[{ "paper_id": "0036b28fddf7e93da0970303672934ea2f9944e7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "005c43980edf3fcc2a4d12ee7ad630ddb651ce6e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For the rapid test, patient throat swab samples were directly applied to assays, and results were read in 20 min.", "There is a critical need for POCT diagnostics in healthcare which can have a positive impact on the quality of life worldwide [20] . POCT devices of interest include smartphones [20] , wearable devices [21] , other complementary metal-oxidesemiconductor (CMOS) imaging devices [22] , and strip readers [23] . Among them, devices integrating with personal computer have revolutionized research in recent decades, and smartphones are now finding increasing application in a wide variety of research domains as they are expedited by the integrated data capture, processing capability (e.g., lab in a phone), operability, compact form, relatively low cost, and very widespread circulation [24] .", "Program of the NRF funded by the Korean government, MSIP (2014M3A9E2064699).", "Supplementary figures. http://www.thno.org/v08p6132s1.pdf", "Despite the versatile tunability of the emission peaks of QDs in multiplexed diagnostic systems, few reports show their application in clinical diagnostics [29, 30] . Since high-fluorescent QDs are usually synthesized at elevated temperatures in organic solvents, they are only soluble in non-polar organic solvents, which are not suitable for biological applications, water compatibility, and bioconjugation. When QDs are covered with hydrophilic shells using tedious processing [31] , the signal is too weak for the visible readouts of POCT requiring encapsulation of many QDs in an individual nanoparticle [32] ." ] },{ "paper_id": "006be99e337c84b8758591a54f0362353b24dfde", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "I would like to thank David Samols, Irving Kushner, and Stanley Ballou for stimulating discussions; Alan Tartakoff, Kenneth Neet, and Cecil Cooper for technical advice; David Bole for the generous gift of anti-BiP antibody and instructions in its usage; Patricia Kalonick, Judith Preston, and Debra Rzewnicki for technical assistance; and Thomas Massella for the EM. This work was supported by grant No. AR34313 from the National Institutes of Health.", "Received for publication 31 January 1992 and in revised form 23 April 1992." ] },{ "paper_id": "00a00d0edc750db4a0c299dd1ec0c6871f5a4f24", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "00e5a723d44eb9f2698c38b518eff85c00f9753b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "01297dffaf94c1314ca46088f7b829b8383c2f73", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "013d9fb8719d3d3d47738f9f0604f3b643c4df57", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "014e31dce7e3f2b1a7020a5debfbf228182f8b5e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The most common hospital-acquired infections are those associated with surgery; in the gastrointestinal tract, bloodstream, or urinary tract via a catheter; and ventilator-associated pneumonia 4, 5) . Ebola virus, Middle East respiratory syndrome coronavirus, hepatitis B virus (HBV), and norovirus are pathogens that have been linked to occupational infection 6 -9) .", "In the case of accidental infection, the most common routes of pathogen entry are aerosol inhalation, percutaneous inoculation through needles or broken glass, animal bites or scratches, direct contact with contaminated surfaces, and accidental ingestion through a pipette 2, 3) .", "Accidental occupational infections occur in laboratories, hospitals, and animal handling facilities as well as in some industries, pharmaceutical and food production, and agriculture 1) ." ] },{ "paper_id": "0167dddb0e2783a60841b8e6f2b4e4cb981904e2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Expansion of the clinical database of bovine EOE is needed to clarify the etiology of this disease.", "The underlying cause and pathophysiologic mechanism of EOE have not been determined in humans and animals [1, 2, 7] ; possible proposed causes include food allergies and endoparasitism. Interestingly, the typical symptoms of chronic diarrhea continued in the heifer in Case 3 from the lactation period to slaughter, indicating that food allergies are a possible cause of EOE from birth to maturity in cattle.", "In conclusion, to our knowledge, these cases are the first JB cattle cases of idiopathic EOE. The excretion of spherical tissues in the feces may serve as an important and identifiable clinical sign in affected cattle. Idiopathic EOE should be considered a differential diagnosis in cases of chronic obstinate diarrhea in Jb cattle.", "The white blood cell (WBC) counts were 8,800 and 10,500 cells/\u00b5l, and the percentages of eosinophils were 3% and 1%, respectively, which indicated no elevation of eosinophils in the peripheral blood. Parameters reflecting hydration status were all within the normal range. Additionally, although the levels of certain serum biochemical parameters were outside the reference range (e.g., in Case 3, the high GGT concentration [37.0 U/l] was considered to reflect cholangitis diagnosed when the animal was slaughtered), no abnormalities in the biochemical profile of the parameters reflecting albumin and electrolyte levels affected by enteritis were observed. Overall, the results of hematological and biochemical analyses prior to slaughter indicated no signs of inflammatory reaction in 2 of the animals with EOE." ] },{ "paper_id": "018b5b5f732e955d349e14a83481739502ae104c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Respondents to the interviews were aged 15 years and older and were considered key informants of the villages where they resided. They included leaders in the community, at children's health centers, and of farmer and/or fishermen groups, as well as religious and youth leaders. ", "Indirect contact, which includes eating fruit contaminated by bats and/or eating domestic animals infected with disease by flying foxes, also poses potential risks for infection. In Bangladesh, the primary pathway of NiV transmission from bats to people is through consumption by humans of raw date palm sap that has been contaminated with bat saliva [16] . In a study in Africa, NiV was detected in 48% and 3-4% of bat and human samples, respectively, by seroneutralization assay [24] . People who butchered bats for consumption were exclusively seropositive for NiV [24] .", "doi: 10 .1292/jvms. to hunt wild boars or as guard dogs, such that the population of dogs in Garut is comparatively high in Indonesia. A huge nature conservation area, Leuweung Sancang (2,157 hectares), is located on the south coast of Garut District [17] , as shown in Fig. 1 .", "The educational attainment of more than half of the respondents in our study was elementary level. This might be associated with the age of most respondents (over 40 years). The educational level in area (c) seemed to be lower than the other two areas, which is probably because area (c) is a mountainous region with limited access to roads and schools." ] },{ "paper_id": "01aa247284f0baf43293d8ea335b70781365a985", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Quantitative results were expressed as mean \u00b1 SD, and groups were compared by using the one-sample t-test. P values < 0.05 were considered statistically significant. MedCalc software version 16.2 (MedCalc Software bvba, Ostend, Belgium) was used for statistical analysis." ] },{ "paper_id": "01af2562df4acf3113843d039c3b82bb801b1427", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "During the 2014 outbreak, RSV infection was diagnosed by reverse transcriptase polymerase chain reaction using respiratory specimens, and genetic proximity was confirmed by a phylogenetical analysis (15). Eight RSV-infected patients", "The clinical information and chest X-ray findings were retrospectively reviewed from patient medical records within one week of the chest CT scan.", "The medical records and radiological images of the collected cases were retrospectively reviewed, with identifying information removed. This study was reviewed and approved by the Clinical Research Ethics Committee of University of the Ryukyus." ] },{ "paper_id": "01b3d789dbd69fff374842fbe2d7f4150fb3d8f5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "SF213-224 were constructed as follows. First the entire BglII-NcoI fragment of pSF2 was replaced by a synthetic dsDNA fragment (5 0 -GATCTTAATACGACTCAC TATA-GGGCTCATTTAAACTAGTTGAGGGGCCA TATTTCGC-3 0 and 5 0 -CATGGCGAAATATGGCCC CTCAACTAGTTTAAATGAGCCCTATAGTGAGTC GTATTAA-3 0 , sequences forming a SpeI restriction site are underlined). The resulting plasmid pSF208 was opened at the BglII and SpeI sites and oligonucleotides SF226 (5 0 -GATCTTAATACGACTCACT-ATAGGGCTCAGG GAAA-3 0 ) and SF227 (5 0 -CTAGTTTCCCTGAGCCCT ATA-GTGAGTCGTATTAA-3 0 ) were inserted. This yielded pSF212, which was subsequently digested with SpeI and NcoI to insert sets of complementary oligonucleotides corresponding to mutants SF213-224. The sequences of these oligonucleotides are available on request. All mutants were checked by dideoxy sequencing and are listed in Table 1 .", "Although the time scale of folding (milliseconds) may at first seem irrelevant compared to the time scale of translation elongation (seconds) it has recently been reported that the conversion rate between two comparatively stable hairpins ranges from a few seconds to several minutes (39) . Also, slow-folding pseudoknots, 5-350 s, limit the activity of the Hepatitis Delta virus ribozyme (40) . Thus the efficiency of a frameshifter pseudoknot may not be solely dictated by its stability but also by its kinetic properties.", "SF222 by still having C24, was capable of shifting 30% of the translating ribosomes. Thus, it appears that depending on the context deleting C24 is not always beneficial for frameshifting.", "Reactions contained 4 ml of RNA solution, 4.5 ml of reticulocyte lysate (Promega), 1 ml of 35 S methionine (ICN, in vitro translation grade), 0.5 ml of 1 mM amino acids (\u00c0Met) and were incubated for 60 min at 28 C. Samples were boiled for 3 min in the Laemmli buffer and loaded onto 12% SDS polyacrylamide gels. Gels were dried and exposed to phosphoimager screens. Band intensity of 0 frame and \u00c01 frame products was measured using Molecular Imager FX (Biorad) and Quantity One software. Frameshift percentages were calculated as the amount of \u00c01 frame product divided by the sum of 0 and \u00c01 frame products, corrected for the number of methionines, multiplied by 100." ] },{ "paper_id": "01bc7fe59fc7feb0e3d23c716aa23a694a4362a2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "01de46a248049d2fbdc049b686ee5b172301d0fa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "021291da7cf3769e4182317703a95b6c5f7c76f9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "022abf5f202c04e2bbf88d829db9844746e0fb71", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "02450c2c82a1511cb5e1639d3b8438f69bbe11f0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "766 | E. Ahat et al.", "For drug treatment, 5 \u00b5g/ml BFA, 500 ng/ml Noc, 100 \u00b5g/ml CHX, 50 \u00b5M MG132, or 2 \u00b5M monensin was directly applied to the medium alone or in combination for indicated times. Cells were lysed and analyzed by Western blotting.", "In all figures, the quantification results are expressed as the mean \u00b1 SEM from three independent experiments, unless otherwise stated. The statistical significance of the results was assessed using a Student's t test. *, p < 0.05, **, p < 0.01, ***, p < 0.001." ] },{ "paper_id": "02522a1b4512e4d2880a6a551a8dff589d4cb393", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Expression plasmids for viral GPs [24, 25] , lectins [24, 26] , Ctype lectin domain family 5 member A (CLEC5A) [27] , NPC1 [7] , TIM-3 [28] , angiotensin-converting enzyme 2 [24] , and folate receptor \u03b1 [29] were described elsewhere. The plasmid encoding Axl was purchased (ImageGenes). Expression plasmids for human TIM-1, TIM-4, and scavenger receptor A (SR-A) were generated by reverse-transcriptase polymerase chain reaction (RT-PCR) and cloning of products into plasmid pCAGGS. The integrity of all PCR-amplified sequences was confirmed by automated sequence analysis. Antibodies against entry factors were purchased from R&D Systems.", "Cell lines were maintained in Dulbecco's modified Eagle medium or Roswell Park Memorial Institute 1640 medium, supplemented with 5%-10% fetal bovine serum and antibiotics. THP-1 monocytes were differentiated into macrophages by exposure to phorbol-12-myristate-13-acetate (Sigma). Primary human monocyte-derived macrophages (MDMs) were cultured in monocyte differentiation medium: X-VIVO 10 (Lonza) supplemented with 1% human fibrin-depleted plasma and antibiotics. All cells were grown in a humidified atmosphere at 37\u00b0C and 5% carbon dioxide.", "depend on parallel expression of Mer, a scenario in keeping with published findings [39] ." ] },{ "paper_id": "025ed2caa0ae1ab7f04d3479116e6ed2a334938d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Hypothesis/Objectives: The objective is to describe the clinicopathological phenotype of affected Holstein cattle homozygous for the causative apolipoprotein B gene (APOB) mutation.", "Methods: This case review included a full clinical examination, a complete blood count, blood chemistry, and measurements of cholesterol and triglycerides. The animals were euthanized and necropsied. A PCR-based direct gene test was applied to determine the APOB genotype.", "Animals: Six Holstein cattle, 5 calves with a clinical history of chronic diarrhea, and 1 heifer with erosions in the buccal cavity and neurologic symptoms were admitted to the Clinic for Ruminants.", "Conclusions and clinical importance: Suspicion of CD in Holstein cattle is based on the presence of chronic diarrhea with no evidence of primary infections. Confirmation of the associated APOB gene mutation is needed. Additionally, the heifer demonstrated primarily signs of neurologic disease providing an unexpected phenotype of CD." ] },{ "paper_id": "0260e364e040cc9b229b2b4f727bfc2e4d68474d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "02d9be8cdb8499cd90f2c9cee8421b02b2bbba76", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "02eb3dc5054c0dd2ce8faa06d6942484900d76c6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nucleic Acids Research, 2017 , Vol. 45, No. 5 2677 ", "Indirect immunofluorescence and direct GFP-fluorescence analysis was done as described before (13) . Images were visualized at a Zeiss Axiophot microscope using a 40\u00d7 1.3 oil immersion Plan-Neofluor objective and processed with NIS-Elements BR 3.10 and ImageJ software.", "Data are reported as mean values from at least three biological replicates with error bars denoting standard deviations (SDs). The two groups were compared using a paired twotailed Student's t-test. The significance level was set at P values *P < 0.05, **P < 0.01. Quantification of western blots and radioactive signals was performed using Image Gauge and ImageJ software." ] },{ "paper_id": "02f267368636c422f19d77d3be96de3c0dcbceef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A reverse transcriptase (RT)-PCR was set up to amplify and biotin-label the nucleic acid of human rotavirus A from these clinical samples.", "The ZipScores from up-and downstream zipping were then added; the final NucZipScore = ZipScore downstream+ZipScore upstream.", "Alternatively, the Brownian movements of the two long non-hybridized sections could mechanically stress the remaining base pairs.", "Supplementary Data are available at NAR Online." ] },{ "paper_id": "0322eccb9230a1aad165702457091eb9ae122d55", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0346cb9d0f5b07fe50d9a3cc0378a53f1a87708c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Citation Yuan S. 2015. Statins may decrease the fatality rate of Middle East respiratory syndrome infection. mBio 6(4):e01120-15.", "Downstream of TLR-MYD88 pathways, activation of NF-B is a hallmark of coronavirus infections, and inhibition of NF-B reduced lung infection and significantly increased mouse survival after SARS-CoV infection (7) .", "Despite the opposite functions of TLR4s in AIV and SARS-CoV infections, MYD88 (myeloid differentiation primary response 88; downstream of TLRs) plays an important role in the survival of respiratory virus infections (Fig. 1) . The MYD88 gene was observed to be highly induced by SARS-CoV infection (1). Interestingly, either excessive expression of MYD88 (1) or a deficiency in MYD88 expression (6) resulted in high mortality rates after MERS-CoV infections, implying that a balanced immune response is crucial for survival of respiratory virus infections." ] },{ "paper_id": "035dc4021101af0a19152cb5ea7b40b0c57ed76d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sia is the name given to the nonulosonic carbohydrate neuraminic acid (Neu) that contains an acetyl group at the fifth carbon position, hence Neu5Ac. In many animal species the acetyl group also undergoes enzymatic transformation to form a glycolyl group -Neu5Gc. Humans lack the enzyme that performs this transformation, however small amounts of Neu5Gc may be incorporated into humans from the diet [18, 19] .", "There are a number of good review articles on this pathway available [59] [60] [61] . These pathways exist in order to distinguish host \"self\" RNA from invading pathogenic RNA (i.e \"non-self\"). The intracellular detection of this RNA was ascribed to two cytoplasmic helicases called RIG-I and melanoma differentiationassociated gene 5 product (MDA5). RIG-I has 2 consecutive caspase activation and recruitment domains (CARD), a central helicase domain and a C-terminal domain (Fig. 3) . Knockout studies showed that RIG-I and MDA5 were able to discriminate between different strains of virus -RIG-I for the ortho, paramyxo and rhabdoviruses and MDA5 for the picornaviruses [62] .", "Nicholls JM \u2022 Influenza and innate immunity www.icjournal.org", "Thus TLR7 appears to play a dual role -the recognition of vRNA in early infection and then in terms of immunization TLR7 is activated in the MHC class II endocytic pathway. As a backup to the late endosomal compartment there are 2 other pathways that recognize vRNA in the cytosolic component -RIG-I and NLR." ] },{ "paper_id": "036a7af6f90c822210bcac1869a5e85303bb0ef6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Setting: A total of 26 dermatology and sexually transmitted disease (STD) departments, 34 obstetricsgynaecology clinics and 28 urology outpatient clinics selected from 34 hospitals of Shenzhen regarded as our study sites.", "Investigators and quality control staff in our study were trained to ensure that their work complied with standards and methods of this survey. Coding labels, supplies, specimen preservation and transportation strictly abided by the ISO17025 laboratory accreditation standards. The operating procedures were performed in strict accordance with the COBAS AMPLICOR CT/NG Test instructions." ] },{ "paper_id": "03a9a21fad1427fc2dbb6a4969627d0a76459597", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "03afd58d8d29e1c6d008e06e38553079bbdc4d02", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "03d003f7c962aa4f0394e79f38a332662105cdb3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "03d3f764353cecb297c318e55b88be1d5664bf5c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "At the individual level, support is needed to help survivors resume normal lives and to address challenges such as emotional distress, health issues, loss of possessions, and difficulty regaining their livelihoods. 103 ", "Folayan et al forgo their freedom for the public good through quarantine and isolation should be compensated. 39 A broad public debate in each country is, however, required on how best to achieve equity. The outcome of the debate should inform policy and guidelines development.", "The authors report no conflicts of interest in this work" ] },{ "paper_id": "03e8628eb61ff4c66a17673745a7b9c33aece853", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "041adbe00a7ca71fcbc38ff4406297ce86e93a6a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The behavior of the epidemic curve followed the seasonal influenza pattern of sustained and self-limiting transmission.", "The signs and symptoms of influenza are nonspecific: sudden fever, cough, headache, muscle pain, joint pain and coryza 1 with clinical characteristics that vary from asymptomatic cases to severe cases leading to death, making it a challenge to the surveillance system.", "The registrations that did not have the required data filled were excluded from the proportions calculation. Frequencies and proportional distributions of reported cases were presented. When appropriate, the odds ratio of exposure and the 95% confidence interval were calculated.", "We had the same limitations described by several authors that conducted studies using secondary data related to: data quality, difficulty and heterogeneity when filling the disease reporting form, underreporting and inaccuracy of the data collected, registration priority of severe cases or cases of people that belong to risk groups.", "We have also taken this opportunity to demonstrate the necessity of urgent improvements in the surveillance of emergent and re-emergent diseases." ] },{ "paper_id": "043aa68f2c784899f71225e8eb233150760a6a54", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The direction of the spread of pandemic influenza was from the southeast to the northwest, indicating how the virus benefited from entering the country through international airports in the coastal areas and spreading further along routes of long-distance domestic travel.", "Analyzing the information gathered and unearthing underlying risk factors provide an opportunity to identify epidemic characteristics and transmission patterns of the pandemic in China, thereby producing useful information for prevention and control measures during future epidemics. In this study, we aimed to characterize the temporal and spatial distribution of pandemic influenza in mainland China, to understand the diffusion pattern of the disease within the country, and to identify risk factors for invasion and local transmission of this disease.", "With the fast-growing public transportation infrastructure and increasing socioeconomic activities, travel has become an important issue in the prevention of emerging airborne infectious diseases such as influenza, especially during the introduction period. Obviously, the presence of airports and high densities of transportation routes coincide with more developed areas (i.e., those with a higher population density and more medical facilities); however, after we corrected for these factors, proximity to airports and the presence of national highways or freeways remained significantly associated with the spread of the infection." ] },{ "paper_id": "04421db3d34e7fd7c7486d66d21b34978a1fb362", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical methods. Mean \u00b1 SEM is depicted in all graphs. A two-tailed unpaired Student's t test was used to determine statistical differences. Statistical significance was assigned to p-values <0.05. All statistical analyses and plots were produced in Prism (GraphPad Software).", "Flow cytometry and cell sorting. The blocking of Fc receptors was performed with 2.4G2 mAb before staining with the indicated surface or intracellular antibodies (BD, BioLegend, and eBioscience). Flow cytometry was performed using an LSR II flow cytometer (BD). NKG2D ligand staining was done using mouse NKG2D-human Ig fusion protein for 30 min at 4\u00b0C, followed by PE-conjugated goat anti-human IgG Fc antibody (Luminex) for 15 min at 4\u00b0C. In proliferation assays, NK cells were labeled with 5-\u00b5M CTV (Invitrogen) before transfer, and labeling was performed according to the manufacturer's protocol (Invitrogen). The data were analyzed using FlowJo software (Tree Star). The enrichment and adoptive transfer of NK cells were performed as previously described (Sun et al., 2012) ." ] },{ "paper_id": "044d6ebfdeacd8fbdd4f039872020cd4adbbe138", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Animals: One hundred dairy calves with naturally acquired BRD.", "Conclusions and Clinical Importance: This study provides guidance for veterinarians selecting diagnostic tests for antemortem identification of pathogens associated with BRD.", "Objective: To evaluate agreement among TTW and NS, NPS, or BAL for identification of viral and bacterial pathogens in dairy calves with BRD." ] },{ "paper_id": "046b480f92a27f809d67c98c77752037f3342d2a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In addition, individuals with low viral load are more likely to be co-infected with other pathogens compared to those with high viral load (57% vs 38.9%) [84] .", "In this review, we examine the current knowledge and recent findings on the taxonomy, biology, epidemiology, pathogenesis and diagnosis methods of HBoV.", "Furthermore, other studies demonstrated that HBoV1 induces IFN-\u03b3 against HBoV VP2 VLPs, IL-10 and IL-13 (Th2 cells) in CD4+ T cells [97, 98] . These findings suggest that HBoV infection can induce production of Th1 and Th2 cytokines. To date, however, the precise mechanisms underlying HBoV-specific T cell immunity have not been defined.", "In conclusion, a better understanding of the natural course of HBoV infection, the implementation of experimental systems to analyse the replication cycle in more detail and the development of specific therapies are important and urgent needs." ] },{ "paper_id": "049364026266fb6b0b8d8a626844823a3036e5b0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In summary, environmental variations constitute an important factor in the occurrence and spread of infectious diseases in general. This is particularly important for arthropod-borne diseases, where environmental changes can influence both their geographic range and the risk of introduction (Sutherst, 2004; Gould and Higgs, 2009; Tabachnick, 2010) .", "www.frontiersin.org", "This work was funded by EU grant HEALTH.2010.2.3.3-3 Project 261391 EuroWestNile.", "Clinical manifestations range from subclinical infection to acute illness that can be fatal. Expression of BT disease reflects a variety of virus, host, and vector factors (MacLachlan, 2004) . Clinical signs in sheep include pyrexia, tachypnea, nasal discharge, and lethargy. Pathology is characterized by generalized edema, hemorrhage, especially in lymph nodes, lungs, heart, and skeletal muscle and necrosis on the surface of the oro-nasal mucosa and gastro-intestinal tract (reviewed in MacLachlan et al., 2009) ." ] },{ "paper_id": "04c77d3ae97fcb0cb3d82480c5f75513f6266662", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The study was conducted as a prospective cross-sectional observational study. A prior sample size calculation was not performed." ] },{ "paper_id": "04e156a83cb3b0b2da2ed07eec1a669be53575b5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "There are several kinds of reporting dyes used for probe-based real-time PCR assays based on fluorescence energy wavelength. This facilitates multiplexing by combining different reporting dyes. Theoretically, multiplex real-time PCR can simultaneously detect up to four different targets in the same sample [18] . Nevertheless, there is a size limit for the PCR product (usually less than 200 bp) in order to maintain stable sensitivity [141] . The primers and probes should thus be carefully designed when a multiplex real-time PCR assay is performed. \"Cross-talk\" between different dyes due to close proximity in fluorescence energy wavelength is another factor to take into consideration when multiplexing.", "6 virus particles per mL) in the specimen for virus detection (i.e., low sensitivity) and cannot concurrently evaluate multiple samples [38] . The collection of fecal samples from clinically ill animals with acute diarrhea is important for successful EM. The cost of electron microscopes and requirement of skilled laboratory personnel is still a challenge for EM use as a routine An overview of calf diarrhea -infectious etiology, diagnosis, and intervention 7 diagnostic test. Nevertheless, EM is a tool to use when diarrhea with an unknown infectious cause is encountered.", "The invasion of C. parvum into enterocytes induces changes in intestinal cytoskeleton structures, such as loss of microvilli and shortening of columnar epithelial cells, leading to severe villous atrophy in infected animal [54] . Damage to the intestinal epithelium causes prolonged malnutrition and reduced growth rates in affected calves due to malabsorption and fermentation of undigested milk in the intestinal lumen [96] . These result in considerable economic losses in cow-calf production.", "Cow nutrition is closely associated with weak labor, amount of milk production, dystocia, and calf growth. Inadequate feed intake and macro-or micro-nutrient deficiencies during the last trimester increase calf morbidity and mortality rates because most fetal growth occurs during last 2 months of gestation [89, 90] . The quality and quantity of colostrum is associated with body condition score (BCS). A BCS near 5 (on a scale of 1\u223c10) is acceptable for multiparous cows and a score of 6 for primiparous cows at calving is desirable [70] . Recently, cow nutrition has been shown to impact the transition of the calf into adult life as well as fetal growth and development [48] . Calves born to underfed cows have poor growth performance, low productivity, and higher susceptibility to disease. In another study, heifer calves born to cows fed supplemental protein during the last trimester were found to have greater pregnancy performance later in life compared to the control group [83] ." ] },{ "paper_id": "05248494136966d79614f475f8e5bb0880a20bf7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "054831a6a11886b5ad44cac71d17e367721a2b5b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Enrichment of Cytoplasmic and Nuclear Proteins by Subcellular Fractionation-Cell pellets were resuspended in a cold cytoplasmic lysis buffer (20 mM Tris-HCl, pH 7.5, 100 mM NaCl, 0.5 mM EDTA, 0.5% Nonidet P-40, EDTA-free Complete protease inhibitor mixture (Roche Applied Science)) and incubated for 10 min on ice. The su-pernatant containing predominantly cytoplasmic proteins was collected after a 3-min centrifugation at 2,000 \u03eb g at 4\u00b0C. The remaining pellet was resuspended in radioimmune precipitation assay buffer (50 mM Tris, pH 7.5,150 mM NaCl, 1% Nonidet P-40, 0.5% sodium deoxycholate, 0.1% SDS, EDTA-free Complete protease inhibitor mixture (Roche Applied Science)) and incubated for 30 min at 4\u00b0C. The supernatant containing predominantly total nuclear protein was collected after a 2-min centrifugation at 13,000 \u03eb g at 4\u00b0C. Both fractions were incubated for 5 min at 4\u00b0C in a sonicating water bath.", "Gel Electrophoresis and In-gel Digestion-Each sample was reduced in SDS-PAGE loading buffer containing 10 mM DTT and alkylated in 50 mM iodoacetamide prior to being boiled, then separated by one-dimensional SDS-PAGE (4 -12% Bis-Tris Novex minigel, Invitrogen), and visualized by colloidal Coomassie staining (Novex, Invitrogen). The entire protein gel lane was excised and cut into 10 gel slices each. Gel slices were subjected to in-gel digestion with trypsin (36) . The resulting tryptic peptides were extracted by 1% formic acid, acetonitrile; lyophilized in a SpeedVac (Helena Biosciences); and resuspended in 1% formic acid.", "Trafficking Analysis of P and M2-1 Proteins-The P and the M2-1 genes were amplified by reverse transcription-PCR from total RNA extracted from HRSV A2-infected cells. Complementary DNA served as a template for PCR amplification and was subcloned into TOPO TA vector pCR2.1 (Invitrogen). The P gene was then cloned into the cyan fluorescent vector pECFP-C1 (Clontech), and the M2-1 gene was cloned into pTri-ExNeo vector (Novagen). The orientation of the insert was confirmed by sequencing (data not shown). A549 cell monolayers were grown on glass coverslips in 12-well dishes, transfected with 2 g/well plasmid using Lipofectamine 2000 in Opti-MEM (Invitrogen) according to the manufacturer's instructions, and added to antibioticfree media. After 24 h at 37\u00b0C, the transfection mixture was removed. The plates were then incubated as described above for a further 24 h. Control wells of transfection only and media only were included to assess any background reactivity. Nuclei were stained with propidium iodide (Invitrogen), and coverslips were mounted onto glass slides with glycerol." ] },{ "paper_id": "0568c55234a6ad2585fe3ac5f3c51260194af7ec", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cross reactions with DENV were evaluated using anti-Den- ", "Nonstructural 1 (NS1) and Envelope (E) proteins were used as diagnostic target of anti-ZIKV. The particular NS1 sequence (354 aa) and E sequence (261 aa) were obtained from the Swiss Institute of Bioinformatics (http://viralzone.expasy.org).", "To produce hybridoma cell-secreted monoclonal antibodies (mAbs), we used a cell fusion technique according to an established protocol [30, 31] . Mouse myeloma cells (SP2/0 cell; ATCC #CRL 1581) were fused with spleen cells from the donor mice using 50% polyethylene glycol (Sigma Chemical Co.). After incubation with hypoxanthine, aminopterin, and thymidine media (Sigma Chemical Co.), supernatants of hybridoma cell culture were screened by ELISA using the recombinant ZIKV NS1 or E proteins (1 \u03bcg/ml) as an antigen. After subcloning with limiting dilutions, selected hybridoma colonies were transferred into 25 cm 2 tissue culture flasks (Nunc, Roskilde, Denmark) with RPMI-1640 medium (Gibco/BRL) containing 10% FBS (Gibco/BRL).", "The recombinant proteins (100 \u03bcg/250 \u03bcl) were mixed with equal volumes of Freund's complete adjuvants (Sigma Chemical Co., St. Louis, Missouri, USA), and the mixture was injected intraperitoneally into 6-weeks-old female BALB/c mice (Samtaco, Suwon, Korea). The second and third injections were followed with the same amount of protein mixed with incomplete Freund's adjuvant (Sigma-Aldrich, St. Louis, Missouri, USA) in the same way at 2-week intervals. After the third immunization, the recombinant proteins (100 \u03bcg/250 \u03bcl) were injected intravenously without adjuvant." ] },{ "paper_id": "058b7249ce7acc1c14c989cb2d8db27435f81363", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "I am very grateful for the help of friends and colleagues that provided valuable input and support for this letter.", "Citation Fouchier RAM. 2015. Studies on influenza virus transmission between ferrets: the public health risks revisited. mBio 6(1):e02560-14.", "I am active in the field of research on influenza virus transmission via respiratory droplets or aerosols between ferrets, funded by the European Union and NIAID/NIH. I am an inventor on a patent related to influenza virus reverse genetics." ] },{ "paper_id": "058e306088e83c58ee30b43f0e102a45463351fe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "When the outbreak of human infections with an emerging avian influenza virus (H7N9) occurred in mainland China in early 2013, inter-and intra-organizational communication in and between government agencies was carried out to control avian influenza virus transmission to humans at poultry farms or wet markets. As a result, Taiwan CDC coordinated with the animal health authorities and local governments to ban vendors from slaughtering and selling live poultry at traditional markets, which has successfully protected people from avian influenza infections since 2013. This was a successful case of communication and engagement across multiple sectors.", "Taiwan has built a comprehensive information network for infectious disease surveillance and reporting. Combined databases, such as the National Health Insurance data and Taiwan CDC's data warehouse for infectious disease surveillance and warning, are routinely used for decision making, risk communication, and epidemic control purposes. Since 2012, a national policy of government open data has further guided health authorities' communication strategies to enhance the transparency and integration of information from diverse resources. 9 In so doing, citizens are provided with increased resources to make well-informed health decisions for themselves and for the wider community through civic participation. For example, people now have easy electronic access to 203 government datasets for information on 14 groups of infectious diseases topics. 10 All of this information is easy to read, free to use, in open document format, and free for value-added analysis.", "A weekly press conference is held to communicate the latest information on communicable diseases to reporters, with a well-trained spokesperson from Taiwan CDC fielding questions from the journalists. In addition to the regular press conferences, during a particular pandemic period 2 special briefing sessions have been organized to update reporters about epidemic situations and what the government is doing RISK AND OUTBREAK COMMUNICATION to prepare for it. This has helped reporters become more informed about the evolution of the public health situation at hand so that, should a pandemic occur, they would be able to produce more accurate and constructive reports.", "There were no confirmed cases of Ebola or MERS in Taiwan, so the purpose of risk communication was to control the infectious diseases outside of the borders and to detect any imported case early to avoid community spread. Several risk communication strategies were implemented, including: (1) issuing travel notices and releasing news to remind citizens going abroad to have greater vigilance, (2) providing travelers with updated information and health education materials at airports and travel clinics to remind them about disease prevention when visiting affected areas, and (3) displaying posters or scrolling texts at quarantine stations of the international seaports and airports." ] },{ "paper_id": "05a12a1fb4a86a4158ad027b911092cfc25bc40b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Natural polymers based on polysaccharide, such as pullulan [73] [74] [75] , alginate [76] , and chitosan [77] [78] [79] [80] [81] [82] , have been explored for nanoparticle vaccine preparations.", "Liposomes are self-assembled, spherical vesicles consisting of a phospholipid bilayer and an aqueous inner core [14, 15] . They are prepared from phospholipids with fatty-acid chains of defined length and saturation. The choice of phospholipids and the addition of cholesterol influence liposomal stability and performance [16] [17] [18] . The vesicles can have a unilamellar structure with one layer of phospholipids or a multi-lamellar structure with several concentric phospholipid shells. This platform is highly versatile for cargoes delivery and allows for incorporation of hydrophilic molecules in the inner core and hydrophobic molecules within the phospholipid bilayers. Antigens and adjuvants may thus be incorporated into liposomes based on their lipophilicity [19, 20] .", "Chitosan-based nanoformulations have been widely adopted for vaccine development, examples of which include vaccines against Clostridium botulinum type-A neurotoxin [56] , Neospora caninum [88] , HBV [77] , and Newcastle disease [81] . The polysaccharide polymer has also been applied to enhance the potency of DNA vaccines against viral, bacterial, and parasite infections [78, 80, 82] .", "Although synthetically prepared nanoparticles have yet to show the level of ordered antigen arrangement found on viruses and virus-like particles derived from cell culture systems [181, 182] , ongoing studies continue to demonstrate emerging techniques to couple antigens of interest to nanocarriers. In the last section of the review, we review commonly used methods for coupling antigens with nanoparticles. These strategies may spur novel approaches for preparing nanoparticle vaccines." ] },{ "paper_id": "05b5ca303bd262f2a8e7d9d05d203f023867d0ed", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The following S. cerevisiae strains were used in this study: SF838-1D-8A1 (MATch, phoSA ::LEU2, ade6, gal2) , pho8A::LEU2, ade6, gal2, , JHRY20-1A-13 AgA (MATot, steJ3A::LEU2, dap2A:: HIS3, , JHRY20-1ASA1 (MATtx, phoSA::LEU2, , phoSA::LEU2, and CRY2-8A (MATot, kex2A::URA3, pho8A:: LEU2, trpl) .", "ALP ~i !i i i !\u0129i i !!~i i i !\u0129!i i i !i !!~i i i i i i \u0129\u0129!!!~!~!i i i i i i i i i !i !i !~!!~i i i i i i i i i i !i i !~!~i !~\u0129i i i DPAP A NI A-ALP NI PEP4 I c C i0", "The JoulTlal of Cell Biology, Volume 121, 1993 " ] },{ "paper_id": "05cc87a56d714cc75ce393c73f3076d3f8a463b5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In this study, for determination of diagnostic criteria of FIP for CNS infected cases using the FCoV antibody test, we examined anti-FCoV antibody titers in CSF and sera from cats with neurological signs.", "We were not able to obtain more detailed information, such as other examination results and clinical signs, from the attending veterinarians regarding the cats examined. Additional epidemiological investigations are necessary to more accurately and efficiently diagnose FIP using anti-FCoV antibody testing of CSF samples.", "Substances with a molecular weight smaller than 160,000, such as immunoglobulin G antibodies and albumin, enter the brain relatively easily from circulating blood, and their levels reportedly range from 1/256 to 1/2,048 of that in serum in subjects with a normal blood brain barrier (BBB) [5, 11, 21] . Hence, CSF antibody should be simultaneously examined with serum antibody." ] },{ "paper_id": "05cf81cc55f7a6f80902a671cac49d85af9782ed", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "I n late 2002, severe acute respiratory syndrome coronavirus (SARS-CoV) crossed the species barrier from animals to humans. SARS first struck in Guangdong Province, China, and was officially recognized by the World Health Organization (WHO) in February 2003. After its introduction into human populations in Hong Kong in February 2003, the virus spread across the globe within weeks. A number of superspreading events occurred in several health care settings during the epidemic. When SARS was declared to have been contained (5 July 2003) , there were 8,098 confirmed SARS cases, and 774 of these patients died from the disease. After this catastrophic event, one of the most frequently asked questions was whether SARS would come back.", "Kindler et al. report that HCoV-EMC has faster replication kinetics than SARS-CoV in HAE cells (5) . SARS-CoV has a mean incubation period of about 5 days in humans. This relatively \"long\" incubation period allowed the identification and isolation of SARS patients before they became highly infectious during the SARS epidemic. If HCoV-EMC has a very efficient replication rate in the upper human respiratory tract, the potential use of quarantine and isolation policy to contain a possible epidemic would be extremely limited.", "It is not known whether HCoV-EMC is going to be fully established in humans. Extensive efforts have been made and will continue to be needed to fight against this possible epidemic. If we are \"lucky\" enough to control this novel disease, more resources should be allocated to different areas of coronavirus studies. Currently, we know some animal coronaviruses in wildlife only at the nucleotide level. In fact, the number of bat species tested for coronaviruses is only a fraction of the total number (\u03fe1,200) of bat species. In addition, there is a lack of biological/biochemical characterization of these animal viruses. Ideally, we should develop an effective universal strategy to treat and prevent human infections caused by animal coronaviruses. The phylogenetic relationships of coronaviruses (Fig. 1) suggest that there have been a number of introductions of animal coronaviruses (e.g., SARS-CoV and 229E) into humans in the past. The great diversity of coronavirus in bats will surely increase the odds of yet another zoonotic event occurring in the future." ] },{ "paper_id": "05df6a79e61e69b9113ffa6a667c3fb9b2680e70", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To clarify this point, we used Akata cells overexpressing a dominant-negative mutant of the adaptor protein MyD88 (DN-MyD88). 16 Table 1 ) by quantitative real-time polymerase chain reaction (qRT-PCR) and confirmed activation of STAT3 by western blot (data not shown).", "qRT-PCR (Taqman). Total RNA was extracted from 10 6 cells with the RNeasy Kit (Qiagen) and DNA was removed with DNA-free (Ambion Europe, Huntingdon, Cambridgeshire, UK). 1 mg of the purified RNA was used to generate cDNA with the High-Capacity cDNA Reverse Transcription Kit (Applied Biosystems, ", "Collectively, we validated our microarray data showing that triggering with ODN CpG-2006 activates Akata cells to induce CD40 and STAT3 expression. Moreover, our results indicated that both ODNs used here act in a MyD88dependent manner and that the ODN lacking CpG motifs activates Akata cells to a similar extent as the ODN containing CpG motifs. " ] },{ "paper_id": "05e5a2bca07922fe0bd52185f4ccaae1b8b154f6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Viral culture MERS-CoV isolates from nasal swabs were grown on African green monkey kidney (Vero) cells. 2,31,32 Samples were inoculated in Vero cells at a multiplicity of infection of 1.0 for 1 h. Unattached viruses were removed by washing the cells twice in serum-free Gibco minimum essential medium (Thermo Fisher Scientific, Inc.). The monolayer cells were maintained in minimum essential medium with 1% fetal calf serum. All infected cell lines were incubated at 37 6 C for 5 days. Cytopathic effects were examined on days 1, 3, and 5 by inverted light microscopy.", "All serum samples were tested for MERS-CoV IgG antibodies using Euroimmun ELISA (Euroimmun AG, L\u00fcbeck, Germany). Samples were applied at a 1:101 dilution and incubated in the wells of microtiter strips coated with the purified spike protein subdomain S1 antigen of MERS-CoV. A ratio of .1.0 was considered to be positive.", "The nucleotide sequence of the genome of the camel MERS-CoV in this study has been submitted to the GenBank sequence database under accession NO KT751244. " ] },{ "paper_id": "0612bb6d157e8cd266943d84daf110c46a56aa23", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All subjects answered a questionnaire to provide basic information such as age, gender, education years, subjective health status, and medical illness status. The subjective health status was scored from 1 (very healthy) to 5 points (very unhealthy), and the medical illness status was answered with disease or no disease.", "Assessment tools for measuring chronotype include selfreport questionnaires such as the Morningness-Eveningness Questionnaire (MEQ) and physiological tools such as Dim Light Melatonin Onset (DLMO) and polysomnography", "Prior to the study, all participants completed informed consent. All questionnaires were interview-based, administered by trained research assistants following a standardized protocol. Participants were administered the Korean version of Mini-Mental State Examination for Dementia Screening (MMSE-DS) 35 to screen for cognitive impairment. This study was approved by the Institutional Review Board of the institute where the research was conducted." ] },{ "paper_id": "06137bb1e53080493b33c1b749b59848cddc05fc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Site-directed mutagenesis was performed using the Quikchange II site-directed mutagenesis kit (Stratagene) according to the manufacturer's instructions." ] },{ "paper_id": "065497953c64b5163eb29e9a4fe78534f244ca26", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "066178ded1d6d540be366e6468bc01e78e605a81", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Avian infectious bronchitis virus (IBV) is a highly contagious pathogen of chickens that replicates primarily in the upper respiratory tract. Secondary replication also occurs in the lower respiratory tract and non-respiratory epithelial cells of the alimentary tract, kidney, and gonads, suggesting various pathologies depend on the type of infected tissue [1] . IBV infection affects egg production of laying hens and growth of broiler chickens, leading to economic losses in the poultry industry that cannot be ignored [3] . IBV is spread by aerosol and is endemic in many countries where chickens are farmed.", "Genotyping of avian infectious bronchitis virus (IBV) was performed on trachea and kidney samples of six chickens obtained from a single farm in Japan. Using two primer sets targeting the spike (S) protein gene, the S1 and S2 regions of DNA fragments were amplified. Sequences of amplified S1 fragments extracted from both organs were identical among the six chickens, showing a JP-I genotype. Sequences of amplified S2 fragments differed between trachea and kidney samples. The kidney profile showed a group IV genotype, whereas the trachea profile showed an unclassified group. This result showed that two different IBVs infected the six chickens. The first IBV infection induced poor protective immunity in this farm, permitting a second IBV infection to occur.", "It is unclear why S2 sequences differed between the kidney and trachea samples of the six chickens, although the S1 sequences were similar (Fig. 1) . One hypothesis is that the primer set for S2 can amplify a wider variety of IBVs than S1. Namely, the S1 primer pair amplified IBV (Far East, JP-I genotype) that is a unique population in kidneys and a minor population in the trachea, but may not amplify the major population of IBV co-infecting the trachea. However, the S1 primer pair, which we used, is synthesized on the conserved region of the S1 gene and is frequently used for IBV genotyping worldwide [1, 9] . Therefore, primer Fig. 3 . Phylogenetic tree based on the partial S gene sequences. Phylogenetic tree analysis based on the nucleotide sequences of amplified S1 (A) and S2 (B) regions were performed using the unweighted pair group method with arithmetic mean (UPGMA) method. Naming of groups followed previous publications [9] [10] [11] [12] [13] . Sequences of representative IBV were either downloaded through NCBI, PubMed, Nucleotide-searching site, or obtained by our own sequencing." ] },{ "paper_id": "06c89f69aa7b5f9648d2c1543b8246fe9c3610cf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "06f075e64c8861491ea4de2f98b606866f54a752", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "None.", "ReFeRenCes" ] },{ "paper_id": "07054fdca599b609a0fd99007a13a5133145449c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "07241235ee553a5b165ed19b2091101128eca805", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "077a70059a89059bace1150d779cc911a2229c60", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "MERS-CoV-infected Vero cell lysates were run on SDS-PAGE and subsequently transferred onto a nitrocellulose membrane as described previously (26, 27) , and detailed information is provided in the Supplementary Material.", "MERS-CoV-infected and non-infected Vero cells were lysed with lysis buffer (0.5% SDS and 1% \uf062-mercaptoethanol) and ", "Four-week-old BALB/c (H-2 b ) female mice were purchased from Nara-Biotec Co. Ltd. The mice were maintained at an animal facility under specific pathogen-free conditions. All the experiments involving the animals were carried out with the approval from the Institutional Animal Care and Use Committee of Hallym University (Hallym2016-51) . The mice were intraperitoneally immunized three times at 10-day intervals with 200 \uf06dl of the Spike-492 peptide (50 \uf06dg) or Spike-492 (L506F) peptide (50 \uf06dg) and the Lipoplex (O) complex (17, 22, 23) ." ] },{ "paper_id": "077d5a9302762a66842c6bdf13912433954ca723", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "where Sc.s. is the mean cell surface on thin-section, The surface to volume ratio was found according to formula:", "SEM. Statistical calculations were performed by determining the SEM for the pooled stereological data for each condition as described in the Results.", "(4)" ] },{ "paper_id": "08079db5747d09016612f319e154ff81c4d9aef5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "PAMs were fixed with cold methanol-acetone ", "All experiments were performed with at least three independent replicates. Data were analyzed with SPSS 16.0 and GraphPad Prism software (version 5.0) by Student's t-test and one-way ANOVA. P<0.05 was considered statistically significant." ] },{ "paper_id": "08f6c419a42b6c922108349af6c1b2aaf2cc62b2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "091b857ba8a07eca145ae411f7202ca3a4d970df", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors declare no conflicts of interest in this work. ", "Different mechanisms might contribute to the debilitation in host defense of the respiratory tract against bacteria following viral infection. Some of the mechanisms have been extrapolated from studies conducted in animal models of sequential infections by respiratory viruses and several bacterial pathogens.", "Hendaus et al relevant to the topic of interest. Finally, the search was limited to studies of disease in humans that were published in English and Spanish from 1918 to the end of 2014 ( Figure 1 )." ] },{ "paper_id": "092880cc76f470dd9cca8233d83c884c0c5edf94", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "096c2c85e046f4ebb34552e0a21bcd69907d1b81", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "097e78073b154805e74de8245008ee3f91c24af2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In addition to their wide variation in viral characteristics, respiratory RNA viruses are also remarkable in their epidemiological variety. They differ in (1) their outbreak calendar, where some are seasonal and others are year-round, (2) their patient profile, whether infant, geriatric, or otherwise healthy adults, and (3) the morbidity and/or mortality associated with infection.", "The first nucleoside analog developed for respiratory viral infection was ribavirin, but despite its approval for use in RSV, its utility for treating severe viral infections remains low. Therefore, the concept of nucleoside analogs against respiratory viruses remains relatively new and needs to be further explored.", "Human metapneumovirus and human RSV are nonsegmented, negative strand RNA viruses from the Pneumoviridae family of the order Mononegavirales. The polymerases from this class of viruses are multifaceted with multiple enzymatic functions contained within a single protein. It exists as part of a ribonucleoprotein complex, or replicase, composed of L, N, P, and M2-1 proteins in complex with RNA. These include RNA synthesis activities carried out by an RdRp domain but also include capping and methylation functions." ] },{ "paper_id": "0994b9aa851f17dc1c6af309973fe189118ab6c5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Abbreviations used in this paper: LC-MS/MS, nano-capillary HPLC ion trap mass spectrometry; PS, phosphatidylserine; rhSLPI, recombinant human secretory leukocyte protease inhibitor; RNAi, RNA-mediated interference; siRNA, small interfering RNA; SLPI, secretory leukocyte protease inhibitor.", "Nano-Capillary HPLC Ion Trap Mass Spectrometry (LC-MS/MS). Membrane protein fractions from monocyte (2-10 \u03eb 10 9 ) or macrophage (2-10 \u03eb 10 9 ) coimmunoprecipitations were pooled and separated on SDS-PAGE. The gels were stained with colloidal blue, destained, photographed, and the desired protein band(s) was marked before storage at 4 \u040a C. The gels were analyzed with LC-MS/MS of in-gel tryptic digests for subsequent protein identification by database searching (Wistar Institute). The output from the National Center for Biotechnology Information and nonredundant database search using SEQUEST consists of peptide sequences matched to protein(s) in the database searched by correlated predicted and observed peptide fragmentation patterns." ] },{ "paper_id": "09c84b9de7fc5c3fed4736e7a3cd45e112377042", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "09cec865941962acf6060e72ef9c477c196c4c3b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "09d9038625c7a2e0aa27f9f04cd7f4b2d7ec6f11", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "09da5dea6fa9b08b2eb1549e85cbc7e29fd3f2f8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "09e6d442b7da6f36e3c7a82a056d8d61e27b1050", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0a098b3876e799d9b21608e26e80d05aa9ec6475", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0a19aacc124c9c42d66d481a9d0c837a76a252e6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0a296d80d8a8c0408c1ea9559c0f0589fb35cb03", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The status of a combination of astrovirus with other gastrointestinal viruses was assessed by RT-PCR.", "The PCR products of expected sizes were purified and then cloned into pMD18-T plasmid vectors (Takara Bio, Inc.), which were then used to transform competent Escherichia coli Top 10 cells. The recombinant plasmids were submitted in duplicate for DNA sequencing to Invitrogen Biotech (Beijing, China). Editing and assembly of nucleotide sequences were performed using the SeqMan program included in the Lasergene 7 Genomics Suite (DNAstar, Inc., Madison, WI, U.S.A.).", "Samples: A total of 211 rectal swabs were collected from calves, aged 0-6 months, with mild to severe diarrhea from five industrial farms (3 dairy and 2 water buffalo) in Guangxi province, China. All samples were collected in sterile tubes containing 10 ml of 1/100 antibiotic 10 mM phosphatebuffered saline and transported on ice to our laboratory within 24 hr. Samples were homogenized by vortexing for 5 min at room temperature and centrifuged at 3,000 \u00d7 g for 15 min at 4\u00b0C, and then, the supernatant was aliquoted and stored at \u221280\u00b0C until assayed." ] },{ "paper_id": "0a2ded6cbd632857d491140a57f2773c3610b10b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This paper was handled and processed by the European Editorial Office (ISFM) for publication in JFMS Open Reports", "MRI of the brain was performed using a 1.5 T magnet (Philips Ingenia CX). All slices were 3 mm thick with a 0.3 mm slice gap. Sagittal, dorsal and transverse T2-weighted (T2W) images were acquired. Transverse images for fluid-attenuated inversion recovery (FLAIR), T2*W, T1-weighted before and after intravenous administration of contrast medium (gadobutrol 0.1 mmol/kg bodyweight [Gadovist;", "Bayer]) and proton-density weighted sequences were obtained." ] },{ "paper_id": "0a449e173239afb38816257e1a53811b47bf13f4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0a64b2c55fc2091358da4f83ac6fdc7701ddb46e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u00c01 PRF (FS%) was calculated as follows:", "The dual-fluorescent reporter system recapitulates data obtained using a dual-luciferase reporter system", "The experiments were repeated using our previously described dual luciferase assay system (39) to compare the results obtained using the dual fluorescent reporter system. Side by side comparisons shown in Figure 3B demonstrate strong agreement between the two assay systems. These results match our previous findings for these conditions where 60 mg/ml anisomycin inhibited \u00c01 PRF, rpl11-Y52\u00c1 promoted increased \u00c01 PRF and rpl11-92-6A promoted decreased \u00c01 PRF. This independent validation underscores the potential for the less expensive and scalable dual fluorescence methodology to accurately detect changes in frameshifting." ] },{ "paper_id": "0aa3eda0fb09bf9f55864fc2b9157b9317f62323", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Because of long geographical distances, two approaches were used for data collection: i) technical visits to the facilities involved with border surveillance, which included questionnaire applications and direct observations of the operational procedures and facility structures; ii) application of online questionnaires for those facilities that could not be visited. For both approaches, questionnaires were developed in English and, subsequently, translated into Spanish and Portuguese.", "Acknowledging the vulnerability of introducing and spreading potential public health events through land borders, the International Health Regulations (IHR) recommends that countries sharing common borders should consider establishing bilateral or multilateral agreements about strengthening surveillance actions at ground crossings 7 .", "The epidemics of severe acute respiratory syndrome (SARS), pandemic influenza (H1N1) and Middle Eastern Respiratory Syndrome (MERS-CoV) hit the world with a high pathogenic potential in recent years, providing a warning to nations of the speed with which these epidemics can move across the globe 1-3 . Everyday, nations are more internationally connected 4 . On February 1, 2016, for the fourth time in history, the World Health Organization (WHO) declared a public health emergency of international concern (PHEIC) to make a joint global effort to control the outbreak caused by Zika virus (ZIKV) in Latin America and the Caribbean 5,6 . These facts reiterated the need for governments and international agencies to build and strengthen the surveillance of infectious diseases at all levels, from national to international, thus facilitating the timely detection, response, and communication of disease outbreaks on a global scale 4 ." ] },{ "paper_id": "0ace222a6c33986dfe57d3f24779fe5f674724c7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0ad29b032fe87db2641893f4cc880c22f2107712", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Safety assessments were in the case of adverse events, and included laboratory tests (hematology, biochemistry, and urinalysis) and vital sign assessments (systolic blood pressure, diastolic blood pressure, and pulse rate).", "Acute respiratory illness (ARI) is a self-limiting viral disease that causes mild symptoms such as fever, shivering, chills, malaise, and dry cough. Rhinovirus and coronavirus (50%-70%) are the most common viruses, followed by influenza virus (20%-35%), and adenovirus (5%-10%) (1, 2) . Most influenza-associated deaths occur in persons aged 65 yr or older with associated chronic disease (3) . Vaccination to prevent influenza is particularly important for elderly persons who are at an increased risk for severe complications from influenza (4) .", "Recently, KRG was shown to be capable of enhancing cellmediated immune responses by T lymphocytes and activating natural killer cells in immunomodulation and anticancer pathways. Two clinical studies for the immune response with ginseng or KRG have been conducted (7) (8) (9) . In addition, treatment of Pseudomonas aeruginosa pneumonia in rats with ginseng was found to reduce bacterial load and lung pathology, as well http://dx.doi.org/10.3346/jkms.2012.27. 12.1472 as to increase immunoglobulin G2a in serum. They suggest that the antimicrobial properties of ginseng are due to its induction of Th1-like responses (10) .", "This study was a 12 weeks, randomized, double-blind, placebocontrolled clinical trial at the onset of the influenza season at the Chonbuk National University Hospital (Fig. 1 ). Subjects who responded and met the inclusion criteria during a telephone screening interview were scheduled for a baseline visit. The evaluation included a physical examination, electrocardiogram, and screening blood parameter study. In addition, subjects were scheduled for a screening visit (within 3 weeks) where the informed consent was reviewed and signed. A random number between 1 and 100 was generated by a computer for each subject. The randomization codes were hidden from all subjects, research staff, investigators and pharmacists until all the data were analyzed." ] },{ "paper_id": "0adc0c7498f0ebbb3c8f1c662da34605d5f91fe2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0adc2dfd5f26656ce3527dbb5dec379d44d0601e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This retrospective study was conducted at the University of Michigan Health System (Ann Arbor, MI) and Karmanos Cancer Center (Detroit, MI). Approval was granted by the institutional review board at each center.", "We conducted descriptive data analyses for all variables. Student's t test, Fisher's exact test, and one-way analysis of variance were used to determine differences between groups. All statistical analyses were completed using SPSS software, version 24.0 (SPSS, Inc., Chicago, IL)." ] },{ "paper_id": "0ae1cad5b20badf8dcea32e8c80209b8948d1e49", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(F) shows representative western blots confirming efficient knock-down, and showing accumulation of IAV proteins under knock-down conditions. ", "Detailed methods are provided in the online version of this paper and include the following: Bercovich-Kinori, A., Tai, J., Gelbart, I.A., Shitrit, A., Ben-Moshe, S., Drori, Y., Itzkovitz, S., Mandelboim, M., and Stern-Ginossar, N. (2016) . A systematic view on influenza induced host shutoff. eLife 5, e18311.", "Chaimayo, C., Dunagan, M., Hayashi, T., Santoso, N., and Takimoto, T. (2018) . Specificity and functional interplay between influenza virus PA-X and NS1 shutoff activity. PLoS Pathog. 14, e1007465. were resuspended in 500 ml RIPA buffer (50 mM Tris-HCl pH 7.4, 150 mM NaCl, 1% Igepal, 0.5% sodium deoxycholate, 0.1% SDS) with protease inhibitor cocktail (P8340, Sigma) and lysed at 4 C for 1 h with gentle agitation, followed by passing through a 21-gauge needle. Lysates were cleared by centrifugation at 4 C for 20 min at 20,000 x g." ] },{ "paper_id": "0ae7bedff3dfbfc1ccaeb5b662bbace00ae16b33", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Blood samples were collected into EDTA and heparin and analysed by an automated haematology impedance analyser (Vet ABC; Scil) and by a VetScan VS2 chemistry analyser (Abaxis), respectively. Only mild hyperproteinaemia (84.0 g/l; reference interval 54-82 g/l) was present. Blood smear examination and urine analysis were unremarkable.", "The first case of FeL was reported in 1912 in Algeria, 8 and it was not until the past two decades that case reports and epidemiological studies established a description of clinical FeL including skin or mucocutaneous lesions and lymphadenomegaly. 1 In contrast, fewer data are available regarding the treatment, monitoring and prognosis of FeL.", "The clinical signs gradually improved by month 1 (Figure 4a ) and resolved by month 2, with no clinical relapses evident at the completion of treatment (Figure 4b ) nor up until the end of the follow-up period at month 14." ] },{ "paper_id": "0afa3ea846396533c7ca515968abcfea3f895082", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Serum SAA was measured by ELISA (ab157723; Abcam, Cambridge, England).", "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.01817-14/-/DCSupplemental. Figure S1 , EPS file, 1.8 MB." ] },{ "paper_id": "0b064096b51c4cada7b64af37eae826b7e7c9649", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "5A), the predominant cell type infected exhibited the morphology and anatomical location of oligodendroglia and was similar in both groups (Fig. 6B) . These data suggested that anti-CD25 treatment did not alter viral tropism.", "Brains were homogenized in Dulbecco's PBS using ice cold Tenbroeck tissue homogenizers (Wheaton Science Products, Millville, NJ). After centrifugation at 450g for 7 min at 4 \u00b0C supernatants were stored at \u221280 \u00b0C. Cell pellets were suspended in RPMI medium containing 25 mM HEPES, pH 7.2 and used for the analysis of CNS inflammation as described below. Brain derived supernatants were used to determine virus titers by plaque assay on monolayers of the continuous Delayed Brain Tumor (DBT) astrocytoma cell line as described (Fleming et al., 1986; Kapil et al., 2009; Phares et al., 2012) ", "CNS derived cell pellets resuspended in RPMI medium containing 25 mM HEPES (pH 7.2) were adjusted to 30% Percoll (Pharmacia, Piscataway, NJ). Cells were separated from myelin debris by centrifugation at 850g for 30 min at 4 \u00b0C onto a 70% Percoll cushion. Cells from the 30%/70% interphase were collected, washed and analyzed by flow cytometry or for cytolytic activity. Single cell suspensions from CLN were obtained as described (Bergmann et al., 1999; Kapil et al., 2009; Phares et al., 2012) ." ] },{ "paper_id": "0b2c383c48f644edcb7c4dcf40046bd58dd5e0f8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Due to the limited regeneration of cardiomyocytes [1] , stem cells have been the premier choice for promoting myocardial regeneration.", "Echocardiograms were acquired at 4 h and 21 days after ischemia/reperfusion surgery with a Philips CX30 ultrasound system and L15-7io transducer (Philips; Amsterdam, Netherlands). The individual who performed the echocardiography and analysis was blinded to the treatment each animal received. Animals were anesthetized with 1.5% isoflurane during echocardiography. Ejection fraction was measured using Simpson's method using B-mode images to measure ventricular volume.", "Supplementary figures and tables. http://www.thno.org/v08p1869s1.pdf" ] },{ "paper_id": "0b627ea5840e5e48709565840313984dc900af8d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In considering what is to follow, several caveats should be borne in mind:", "\"The stepwise coevolutionary process results in extreme specialization and complex defense mechanisms. . .specialization is likely to increase the rate of speciation that may occur in both host and parasite\" (Price, 1980) \"Host specificity thus is an ideal prerequisite for rapid speciation\" (Mayr, 1963) .", "HIV in people was associated with parasites that rarely if ever had been implicated in causing human disease including microsporidia, cryptosporidia, JC virus, and Mycobacterium avium (Kovacs and Masur, 2008) ." ] },{ "paper_id": "0b90f302993b075229dbe5f9bc03a180b2e2632f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0bcc4d843bd37ae1c8623e45dab6fff11263f798", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0c3068b22cb2cb50114316f9fed2738a943d2435", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This systematic review was conducted using the Cochrane Collaboration's approach [20] and was reported complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. [21] Ethical approval and patient informed consent were not necessary because all data were obtained from previous studies.", "We scanned reference lists of each eligible study to find relevant publications fulfilling the inclusion criteria. We also retrieved conference proceedings and dissertation abstracts to identify unpublished studies.", "Retrieved records including titles and abstracts were screened independently by 2 review authors (LP and P-WR) using EndNote 5.0 software after removal of duplications. Studies were selected in accordance with predefined criteria, and full texts of eligible studies were downloaded. Discrepancies were resolved via discussion or in consultation with the lead reviewer (D-YK)." ] },{ "paper_id": "0c83fb7b5413cd36d8ca958f15e7640636c8e730", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Viral titration was conducted in 96-well microplates by using 10-fold serial dilutions, and CPEs were observed under a microscope at 5 days post-inoculation (DPI). The viral titers were calculated according to the Reed and Muench method and expressed as the 50% tissue culture infectious dose (TCID50/mL).", "PED has been reported in many countries including Korea, and PEDV, which causes severe diarrhea in piglets, has led to enormous economic losses in the Korean pig industry. A total of 669 cases of the disease occurred between 2000 and 2015, and two large epidemics were observed in 2003 and 2014 (Fig. 7) . In 2014, 169 PED outbreaks causing high mortality were identified, officially, and more than 33,600 piglets were infected with PEDV at 169 Korean pig farms.", "Animal ethic committee of Animal and Plant Quarantine Agency (APQA; Gimcheon, Korea) approved the animal experimental design (approval No. 2015-283)." ] },{ "paper_id": "0c88aef176b70c6b11a51028124680237a6e5abd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Background. Acute upper respiratory tract infections are a common cause of emergency department (ED) visits and often result in unnecessary antibiotic treatment.", "Immunosuppressed 17 (18) 17 (17) Abbreviations: BMI, body mass index; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; RP, respiratory panel. a Missing BMI measurements due to lack of height measurements for some patients.", "There were also several strengths to this study, including the rigorous experimental study design, relatively rapid TAT given the current state of the art, and generation of preliminary data for future more rigorous multicenter clinical trials evaluating the implementation of rapid respiratory panels in EDs and other acute care settings.", "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.", "The primary and secondary outcome results are shown in Table 3 (Table 4 ). There were no other outcome differences between groups in the post hoc stratified age analysis (Table 4) ." ] },{ "paper_id": "0c92f5b237572a3461ae2205a62ba7622c07a6ab", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Not applicable.", "The authors declare no conflict of interest, financial or otherwise. " ] },{ "paper_id": "0caa109e0faf5c5fefe81a8108e1199058cb3a27", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0ce1f213337247a67628f95cf699bdabddc94d9c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "IFIT proteins (300 nM) were incubated with 40S ribosomal subunits (160 nM) for 15 minutes at 37 C in 200 ml reaction mixtures containing buffer B. The reaction mixtures were then subjected to centrifugation through 10-30% sucrose density gradients in a Beckman SW55 rotor at 53 000 rpm for 90 min. Fractions that corresponded to ribosomal complexes were trichloroacetic acid precipitated and analyzed by sodium dodecyl sulphatepolyacrylamide gel electrophoresis SDS-PAGE using the NuPAGE 4-12% Bis-Tris Gel System (Invitrogen) with subsequent fluorescent SYPRO (Invitrogen) staining. Assembled complexes were separated by centrifugation through 10-30% SDGs as described above. 43S complex formation was analyzed by scintillation counting of an aliquot of each fraction.", "The promoters of most IFIT genes contain one to four IFN-stimulated response elements (ISRE), typically located within 200 bp upstream of the transcription start site, that are recognized by IFN regulatory factors, leading to rapid induction of transcription. A few IFIT genes, including human IFIT1B, lack ISRE-containing promoters and are not transcriptionally induced by IFN or dsRNA (11, 12) . Sequence similarity between the different IFIT proteins within a species is high (44-98% identity) (11), but they are differentially expressed depending on the cell and tissue type, respond differently to IFN and different viruses, and have different effects on replication of individual viruses, suggesting that different IFITs have non-redundant functions in the host response to viral infection (e.g. [19] [20] [21] [22] [23] .", "Native rIFIT1B was purified from RRL on the basis of its activity in binding to cap0-Stem-MVHL-STOP mRNA, which was monitored by primer extension. The 40-50% ammonium sulfate precipitation fraction of the 0.5 M KCl ribosomal salt wash that was prepared from 1 l of RRL (Green Hectares, Oregon, WI, USA) (43) was dialyzed against buffer A (20 mM Tris-HCl, pH 7.5, 10% glycerol, 2 mM DTT, 0.1 mM EDTA)+100 mM KCl and applied to a DE52 column equilibrated with buffer A+100 mM KCl. rIFIT1B was eluted by buffer A+250 mM KCl. This fraction was applied to a P11 column equilibrated with buffer A+100 mM KCl, and rIFIT1B was eluted between 250 and 400 mM KCl. This fraction was applied to a FPLC MonoQ HR 5/5 column. Fractions were collected across a 100-500 mM KCl gradient. rIFIT1B was eluted at $250 mM KCl. rIFIT1B-containing fractions were applied to a hydroxyapatite column. Fractions were collected across a 20-500 mM phosphate buffer gradient. rIFIT1B was eluted at $180 mM phosphate buffer. rIFIT1B-containing fractions were applied to a FPLC MonoS HR 5/5 column. Fractions were collected across a 50-500 mM KCl gradient. rIFIT1B was eluted at $170 mM KCl. rIFIT1B-containing fractions were concentrated on Microcon YM30 (Millipore)." ] },{ "paper_id": "0cea2b0d9b7187e2c5a596ed433be46208186d32", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The IDBD management system allows users to access the biomarker database without registration. However, user registration is required for adding and editing database contents, and user support can be obtained by e-mailing graduate@korea.ac.kr. Readers are encouraged to contact us if they wish to provide new data for inclusion in IDBD, assist with curation or have any suggestions for improvements.", "IDBD was developed as a relational database using Oracle 10g applications (12) on the Windows operating system. Two open source softwares, the Apache HTTP Server and Apache Tomcat, were used as HTTP server and servlet container for Web service, respectively. Perl scripts were used to provide common gateway interface for sequence alignment using ClustalW, and Java applet was used to link Jmol for displaying 3D models. IDBD can be publicly accessed from any Web browser at http://biomarker.cdc. go.kr and http://biomarker.korea.ac.kr.", "In order to advance our understanding of biomarkers and the roles in early infection processes, we have developed an integrated user-friendly relational database that catalogs putative and validated biomarkers relates them to infectious diseases processes. In addition, we have added value by hosting various bioinformatics tools that can be used to analyze and visualize the biomarker data. This freely accessible resource will be a valuable research tool and a contribution to improved public heath." ] },{ "paper_id": "0cf8f70367fc77ea444519b2d9ed108765edd25f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0d0af538cf60b6330d1eb7f5da52bef9ea30fd9c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "W e are gratified that Ron Fouchier has joined (1) the important effort to quantify the risks (2-5) of the creation of potential pandemic pathogens, including ferret-transmissible variants of influenza A/H5N1. However, we disagree with many aspects of his assessment.", "between 0 and the value obtained by dividing 3 by the number of observed lab-years (7) .", "(iii) As with reduced transmissibility, the assertions of reduced lethality are inconsistent with early statements about the experiments. NSABB member Michael Imperiale was quoted in Science as saying in 2012, \"What Ron [Fouchier] is saying now is not what was in the paper. We were led to believe by the paper that aerosol transmission is also lethal.\" (30) . This view was shared by at least one reporter who attended the Malta presentation of the results (36) ." ] },{ "paper_id": "0d0ca66887cfd2b3a09f5205cdcbaa4479f17337", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Thus, to have a more accurate view about the occurring IB viruses a broader scale molecular analysis is necessary from time to time, at least for the S1 gene, of geographically or epidemiologically representative IBV strains.", "Furthermore, two S1 sequences of GenBank origin, Eg/ 12197B/2012 (KC533683) and Eg/12120s/2012 (KC533684), showed the very same recombinant pattern as the D1456-like viruses and, accordingly, grouped together with these on the respective phylogenetic trees (Figs. 1 and 2) .", "The location of the larger recombinant fragment overlapped with two reported antigenic domains of the S1 gene, according to Koch et al. (1990) while the shorter recombinant fragment overlapped with one antigenic domain (Fig. 4) . Both recombinant fragments were located outside the portion that is flanked by the XCE primers.", "Tissue homogenate in PBS (1:10 dilution) was prepared from the organs with Ultra-Turrax (IKA, Staufen, Germany), filtered through Sterile Millex Filter Unit (22 lm, Merck Millipore, Carrigtwohill, Ireland), and 200 ll of the homogenate was inoculated in the allantoic cavities of embryonated chicken eggs, and incubated for 6-7 days at 37 C and candled daily. A sample was considered positive for IBV if the embryos in the inoculated eggs showed typical lesions, that is, stunting and curling of the embryos, and by PCR (Capua et al. 1999 )." ] },{ "paper_id": "0d3de075e16c6d2e02c68e541b4d2654c78bea04", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "On our examination, he had no fever. On auscultation, a widespread reduced vesicular murmur and basilar rales in the left lung were found. On palpation, there was inguinal lymphadenopathy. The remainder of the physical examination was unremarkable.", "Oxygen saturation by pulse oximetry was 93% on room air and blood gas analysis showed a mild hypoxaemia, with an arterial oxygen tension (PaO 2 ) of 61 mmHg with respiratory alkalosis (pH 7.46, carbon dioxide tension 32 mmHg and bicarbonate 23.2 mmol\u22c5L \u22121 ), and therefore with a standard PaO 2 of 48 mmHg.", "What would be your further investigations for a patient with these features?" ] },{ "paper_id": "0dc475f4419836c2dc352073498f56ae982170a0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Chi-square tests and SPSS Statistics 17.0 (SPSS, Chicago, IL, USA) were used for statistical analysis, while P < .05 was considered statistically significant." ] },{ "paper_id": "0dc8d11784da63b899dbb2b404be4efd330e4ac3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This work was supported by grants from the \"Knowledge Innovation Program\" (No: Y014P31503) and the \"100 Talent Program\" (No: Y316P11503) from the Chinese Academy of Sciences and the Shanghai Pasteur Foundation.", "Ebola virus was firstly discovered in 1976 with the outbreaks in Democratic Republic of Congo and Sudan, 113, 114 but the outbreak in Africa in 2013 made it a public concern again. 115 There have been several strategies for the Ebola vaccine development, of which the Ad vectors are selected as a priority.", "No potential conflicts of interest were disclosed." ] },{ "paper_id": "0df0d5270a9399cf4e23c0cdd877a80616a9725e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Coronaviruses are a group of enveloped viruses with a positive-sense, single-stranded RNA and viral particles resembling a crown e from which the name derives. They belong to the order of Nidovirales, family of Coronaviridae, and subfamily of Orthocoronavirinae (Carlos, Dela Cruz, Cao, Pasnick, & Jamil, 2020) . They can affect mammals, including humans, causing generally mild infectious disorders, sporadically leading to severe outbreaks clusters, such as those generated by the \"Severe Acute Respiratory Syndrome\" (SARS) virus in 2003 in mainland China, and by the \"Middle East Respiratory Syndrome\" (MERS) virus in 2012 in the Kingdom of Saudi Arabia and in 2015 in South Korea (Gralinski & Menachery, 2020) .", "A recent coronavirus outbreak has started since December 29th , 2019 in Wuhan, Hubei province, People's Republic of China, and has progressively expanded to various parts of China and has reached as well other countries, including Japan, South Korea, Thailand, Vietnam, Malaysia, Singapore, Nepal, Cambodia, the Philippines, Russia, the United Arab Emirates, Australia, Canada, the United States of America and Europe (France, Germany, Italy, UK, Finland and Sweden). So far, the new virus has infected more than 31,000 people and killed at least 636 of them (National Health Commission of the People's Republic of China, 2020).", "None." ] },{ "paper_id": "0e18097a83b2801c4865c72065b7933fa24face3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0e1c055e39c45d7cef611b6bd17fb67c249ed742", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Since Pr\u00bdAjT; M is independent from the structure , we need to optimize only Pr\u00bdAjT; ; MP\u00bdjT; M:", "where ex-over str () is the expected overlap of with all structures from all sequences. Formally, this is defined by ex-over str \u00f0\u00de", "Here, p u " ] },{ "paper_id": "0e2c97d34c8c6042f26cc11e83e1a2fbac521203", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.00047-14/-/DCSupplemental.", "Text S1, PDF file, 0.2 MB. Figure S1 , PDF file, 2.4 MB. Figure S2 , PDF file, 0.8 MB. Figure S3 , PDF file, 1.9 MB. Figure S4 , PDF file, 0.2 MB. Table S1 , PDF file, 0.2 MB." ] },{ "paper_id": "0e63d19fa3d2ebfcc7cdb06f85225ae0489acf8e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0e78935692851b0466f5a9234adb024e7735c8a3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We thank Tikki Pang, Lee Kuan Yew School of Public Policy, National University of Singapore, for useful comments and suggestions in the preparation of this manuscript.", "Disease or pathogen-specific public health diagnostic laboratories established to support world health organization (WHO)-specific disease surveillance programs and vaccine-preventable diseases, e.g., national influenza, poliovirus and measles laboratories, led to the 'compartmentalization' of laboratory diagnostic services, segregation of functions, and duplication of facilities and equipment. The situation is further complicated by the siting of various pathogen-specific diagnostic laboratories in different buildings or institutes or different locations within a country, thus preventing more cost-effective measures of sharing common equipment and reagents, clinical samples, information and human resources. Finally, the problem is compounded by policy makers and laboratory managers lacking flexibility and not allowing these disease or pathogen-specific laboratories to adopt a more generic approach in the investigation of infectious disease outbreaks.", "Regardless of the category, with some exception for category 4b, effective early detection, identification, characterization, containment, control and ultimately prevention of the emerging infectious diseases will require a good, functional national public health surveillance system. The system needs to be well supported by a network of primary public health and clinical/medical diagnostic laboratories that are coordinated by a national public health reference laboratory with real-time and harmonious communication between the laboratories and epidemiological surveillance units." ] },{ "paper_id": "0e7c4297d1710cac2a64886cb9a748777b0cd03d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Baby hamster kidney cells (BHK-21, clone 15) were cultured as monolayers in Dulbecco's modified Eagle's medium supplemented with 10% (vol/vol) calf serum, 100 units of penicillin/ml, 100 g of streptomycin/ml, and 10 mM HEPES (pH 7.2) at 37\u00b0C and 5% CO 2 .", "Aedes albopictus C6/36 cells were cultured as monolayers in Leibovitz's L-15 medium supplemented with 10 mM HEPES (pH 7.2), 100 units of penicillin/ml, 100 g streptomycin/ml, and 10% (vol/vol) fetal bovine serum at 30\u00b0C.", "Cell fractionation, protein precipitation, and quantitation. Fractionation of cultured cells was performed using the Qproteome cell fractionation kit (Qiagen, Valencia, CA) following the manufacturer's instructions. Proteins from each fraction were methanol precipitated, resuspended in 8 M urea, 100 mM Tris-HCl buffer (pH 8.8), and quantified using the DC protein assay kit (Bio-Rad, Hercules, CA)." ] },{ "paper_id": "0eed9647904ba87a841a177c12a0238faf5c2bd0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0f0bb7346d45679cc1bb2435c66d5ad3ef52c108", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. All the experiments were performed in triplicate. Data are expressed as the mean \u00b1 standard error of the mean. All the data were statistically analyzed using Student's t test. P<0.05 was considered to indicate a statistically significant difference. GraphPad Prism 5.0 software (GraphPad Software, Inc., La Jolla, CA, USA) was used for statistical analysis.", "Sepsis is a systemic inflammatory response syndrome associated with a high rate of mortality (1) . The incidence of sepsis has been increasing over the last two decades. This increase has been more marked in developed countries, where 6-30% of patients in Intensive Care Units suffer from sepsis (2) . Sepsis remains the leading cause of mortality in patients in Intensive Care Units (3) and the associated burden of care incurs financial burden. However, the pathogenesis of sepsis remains to be fully delineated and effective therapies are lacking. A state of immunosuppression induced by sepsis has been demonstrated in clinical and experimental sepsis (3) , with the majority of patients who have succumbed to sepsis-associated mortality showing evidence of immunosuppression and unresolved septic foci (4) .", "Sepsis remains a threat to human health, primarily due to a lack of effective therapies (3). With current treatment options, the mortality rate of patients with sepsis remains high at ~30%, and mortality rates increase directly with disease severity (24) . A previous worldwide survey of relevant pathogens in intensive care units found that the majority of patients with sepsis had blood cultures positive for Gram-negative bacteria (25) . LPS, a component of the outer leaflet of the outer membrane of Gram-negative bacteria, is a key molecule in the induction of sepsis. Therefore, the present study used LPS to simulate sepsis induced by Gram-negative bacteria infection." ] },{ "paper_id": "0f2e41a966ec7d622762dc64ba63009e00a69bd5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "3.578(9) \u00c2 10 5 0.01377 (3) 38.50(7) 2978/10 4.531(4) \u00c2 10 5 4.38(1) \u00c2 10 24 0.967 (3) The number in parentheses is the standard error in the last significant digit.", "Supernatants were harvested following a 25 min spin at 2000 g. The antibodies were purified from the supernatants using Protein G HP columns (Amersham, Piscataway, NJ, USA) by fast protein liquid chromatography (FPLC). The purified IgGs were quantified in BCA protein assays, analyzed on SDS gels, and assayed for the presence of endotoxin using a chromogenic Limulus Amebocyte Lysate test (Lonza, Rockland, ME, USA). If necessary, the preparations were passed through polymyxin B gel columns (Detoxi-Gel, Pierce 20344) for endotoxin removal.", "Sequences in bold indicate codons requiring multiple nucleotide substitutions. Table III . Surface plasmon resonance analysis", "Emerging and re-emerging viruses that cause human diseases are becoming of greater concern for public health. A good example is the SARS coronavirus (SARS-CoV) virus, which first appeared in the human population in late 2002 and eventually infected $8000 people with a 10% fatality rate (WHO, 2003) . Today, the avian influenza H5N1 virus poses a significant threat if effective human -human transmission develops, with the potential risk of a Spanish flu-like pandemic (Juckett, 2006; Tellier, 2006 ; Thomas and Noppenberger, 2007) . The emergence of these viruses and other biothreat agents has raised world concerns for their use in biowarfare/bioterrorism and demonstrates the vulnerability of society to biological threats." ] },{ "paper_id": "0f34670b6327305bb3d66de79d1aa96a5d8de2b2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0f506a74e190c45a399f382c153919612fa1ef5b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In Vivo Mouse DC Stimulation-Two \u03bcg of CpG-A (ODN2216; Invivogen) and 12 \u03bcL DOTAP (Santa Cruz Biotechnology) were mixed with 100 \u03bcL of PBS and administered intravenously (i.v.) by tail vein injection. Control mice received 12 \u03bcL DOTAP with PBS. Spleens were harvested and analyzed 6 hours after inoculation.", "Bar graphs indicate mean \u00b1 SD. Statistics determined by t-test. *p < 0.05, **p < 0.01, ****p < 0.0001.", "Bar graphs indicate mean \u00b1 SD; nd, not detected. Statistics determined by one-way ANOVA with Tukey's multiple comparison test. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. " ] },{ "paper_id": "0f6091029a2cc8ddd6a5c6ee18de7478b73daab2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This work (project code: INV11) was supported by the Consejo Nacional de Ciencia y Tecnolog\u00eda (CONACYT) Programa de Apoyo al Desarrollo de la Ciencia, Tecnolog\u00eda e Innovaci\u00f3n en Paraguay (BID 1698/OC-PR).", "Supplementary material is available on the publisher's web site along with the published article.", "Declared none." ] },{ "paper_id": "0f67baef306ea56d7b574059fb72ff68affb0246", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "These authors contributed equally to the work.", "Nascent transcripts produced by RNA polymerases universally carry a 5 0 triphosphate (5 0 ppp). Processed RNA molecules, such as rRNAs and tRNAs, generated from precursors whose 5 0 segments were removed by nucleolytic cleavage, carry a 5 0 monophosphate (5 0 p). In several types of cellular and viral RNAs, the 5 0 end is further modified enzymatically, by a variety of modification enzymes, to introduce various chemical structures that are collectively dubbed as the \"5 0 caps\". This cap is absent in bacterial and archaeal transcripts." ] },{ "paper_id": "0f8f7f09b42b4b45e128591191176aa358f29b1b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0f90aed025cdf162b89014244740266ce67a3f47", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Baseline characteristics were presented as medians (interquartile ranges) for continuous variables and percentages for categorical variables, as appropriate. All statistics analyses were performed with SAS statistical software, version 9.2 (SAS Institute Inc., Cary, USA).", "We retrospectively assessed data collected 2000 through 2012, from Taiwan NHIRD. Taiwan has implemented a singlepayer, compulsory National Health Insurance program in 1995, which includes reimburses of outpatient visits, hospital admissions, prescriptions for 99% of Taiwanese population. All contracted institutions must file claims according to standard formats, which are subsequently transformed into NHIRD." ] },{ "paper_id": "0f9341750af1f556fdfee5d61d707278005663ca", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0fc5801b4cdc21c018c93aa3cbc9b601491fdeb4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Citation Perlman S. 2013. The Middle East respiratory syndrome-how worried should we be? mBio 4(4):e00531-13.", "Events occurring immediately after MERS-CoV binds its DPP4 Perspective receptor appear to be similar to those reported for other coronaviruses. Cleavage of the surface glycoprotein must occur to expose the fusion peptide and to effect virus-cell membrane fusion and nucleocapsid release into the cytoplasm. Several host proteases, including cathepsin B and members of the TMPRSS family, have been implicated in this process (15) ." ] },{ "paper_id": "102e8dd2d010be4e7f39f8e2d0c84190ee87d9e2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This work was funded by Public Health Service grants P30DA015625 and P51RR000166 from the National Institutes of Health.", "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.00134-11/-/DCSupplemental. ", "RNA preparation and next-generation sequencing. Total RNA was extracted from 5 \u03eb 10 6 cells per sample using a mirVana kit (Applied Biosystems/Ambion, Austin, TX), and the quality and concentration of the RNA were determined by an Agilent 2100 Bioanalyzer. Samples were submitted for sequencing to IlluminaFastTrack Sequencing Services (Hayward, CA). cDNA libraries were generated using Illumina mRNA-SEQ kit. The quality and concentration of these libraries were determined by an Agilent 2100 Bioanalyzer. The libraries were clonally amplified on a cluster generation station using Illumina version 4 cluster generation reagents to achieve a target density of approximately 300,000 (300K)/mm 2 in a single channel of a flow cell. The resulting libraries were then sequenced on a Genome Analyzer IIx using Illumina version 4.0 sequencing reagents which generated single reads of 75 nucleotides (nt). Image analysis, base calling, and error estimation were performed using Illumina Analysis Pipeline (version 2.6)." ] },{ "paper_id": "103228b102f34e60c7057cc68069d00194959837", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Rel. IFITM3 protein", "Immunofluorescence confocal microscopy. Cells were seeded (15,000/well) in Lab-Tek II chamber slides (Thermo Fisher) overnight and treated with DMSO, rapamycin (20 uM), or rapamycin and bafilomycin A1 (1uM) for four hours followed by fixation/permeabilization with Cytofix/Cytoperm (BD) for 20 minutes. Primary antibodies were diluted in Odyssey blocking buffer in PBS (Li-Cor) and incubated with cells for 30 minutes at room temperature. Cells were washed and incubated with Alexa Fluor-labeled secondary antibodies for 30 minutes at room temperature." ] },{ "paper_id": "104e60eede9e4016c243f20f4541a33852ea3d1c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Demographic information and clinical courses of the patients; information regarding combined diseases; results of blood tests; cerebrospinal fluid (CSF) examinations; electroencephalography (EEG); and brain imaging techniques such as MRI (including DWI) were analyzed. Detection of RSV was performed using real-time reverse transcription-polymerase chain reaction, with samples obtained by nasopharyngeal swabbing (AdvanSure, LG, Seoul, Korea).", "We identified a total of 1,193 children who were diagnosed with laboratory-confirmed RSV infection during the study period; 35", "Descriptive statistics were used to analyze demographic data. The continuous variables are presented as mean\u00b1standard deviation. The statistical analysis was performed using IBM SPSS Statistics ver. 21.0 (IBM Co., Armonk, NY, USA). The incidence reported by national RSV surveillance during the study period was used for comparison with the incidence pattern of this study." ] },{ "paper_id": "1052ac76b8c769749a3400eb9479e34a35407eae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "105b993dee9f9e44637daa2d43e66f3ba3039fbf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A number of virologic and", "ON VIRAL DISEASE EMERGENCE.", "Based in references [2, 3, 6, 8, 11-16, 19, 25, 34, 36, 49, 58, 59] ." ] },{ "paper_id": "106203869ac3c318d5ec8a2644d469d71e98f056", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "107ff91ec95dea35a80145aebbe5322c08c57e5e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For rhinoviruses, there are also additional limitations related to the number of serotypes circulating and the lack of broad (14) .", "In this context, we tested three different protocols, including one that differentiated HRV form HEV by nested-PCR (2), in samples that were discordant when tested with two other protocols (17, 20) .", "Virus diagnostic procedures using cell culture are limited by the expertise of the diagnostic laboratory and the time required to obtain a result. As such, viral culture has a limited place in routine diagnostic microbiology, although these assays must still be considered in reference or research laboratories." ] },{ "paper_id": "11217ee4e2bcf58f21011db8ff3d166aad2691ca", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Type Genus-Rhinonicteris J.E. Gray, 1847 Type genus is Rhinonicteris J.E. Gray, 1847:16, which was included in J.E. Gray's (1866:81) supra-generic grouping, the Rhinonycterina, which he called \"leaf-nosed bats\". Correct generic spelling was discussed by Simmons (2005:378) and resolved by Armstrong (2006) , see also Mahoney and Walton (1988:127 ) (see derivato nominis section of the supplementary information for further discussion).", "Overcoming Impediments to Resolution . doi:10.1093/molbev/msu329 MBE because a re-examination of the holotype showed that it was misidentified originally and actually best assigned to Hipposideros ) (see table 1 for full classification) .", "Performance Evaluation: Removal of Outliers and Differential Resolving Power of Introns and Exons?" ] },{ "paper_id": "116c94dd67777e0c9806ef56974157060f5cca4b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The patient signed the informed consent for a kidney biopsy and reporting his case publicly.", "The patient was treated with 180 \u03bcg of pegylated interferonalpha on hospital day (HOD) 1 and 1,800 mg of ribavirin (600 mg every 8 hours) daily from HOD 3 to HOD 7. Anti-viral treatment was discontinued thereafter because of sustained fever and thrombocytopenia (lowest platelet count was 56,000/\u03bcL).", "The IDMS traceable SCr level was 0.9 mg/dL (the estimated glomerular filtration rate was 83.9 mL/minutes/1.73 m 2 ) on HOD 125. A urine dipstick test was negative for albumin and 2+ blood at that time, and the ACR and PCR were 5.8 and 105.6 mg/g Cr, respectively.", "The patient complained of myalgia, dry cough, dyspnea, and nausea-vomiting at the time of admission. His vital signs were as follows: blood pressure, 135/72 mmHg; heart rate, 85/minutes; respiration rate, 20/minutes; and peak body temperature, 38.6\u00b0C. The peripheral capillary oxygen saturation (SpO2) monitor showed 96% with 2.5 L/minute of oxygen via nasal cannula. The results of the laboratory tests were as follows: WBC, 3,400/ \u03bcL (segmented neutrophils 80.4%, lymphocytes 14.5%, monocytes 4.8%); hemoglobin, 13.7 g/dL; platelets, 160,000/\u03bcL; AST/ ALT, 176/97 unit/L; albumin, 2.5 g/dL; and isotope dilution mass spectrometry (IDMS) traceable serum creatinine (SCr), 1.0 mg/dL. A dipstick test showed albumin and blood (negative/negative). We found multiple pneumonic infiltrations in the right upper and middle lobes and in the left lower lobe on a chest radiography." ] },{ "paper_id": "11888535f2eb67c15d08783b164def90aa47a3bd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Six-Seven-weeks-old female BALB/c mice were purchased from Vital River Laboratories (Beijing, China).", "All data generated or analyzed during this study are included in this published article.", "Statistical analysis was performed using two-way analysis of variance with the GraphPad Prism (version 5.0; GraphPad Software, San Diego, CA, USA) software package. P-values < 0.05 were considered representative of statistically significant differences." ] },{ "paper_id": "11a6f813fa996f0baa670ecc66875602f971eef1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In the paper we describe the manifestation and etiology of the respiratory tract infections in five infants in whom the diagnosis of SCID had been established.", "In all the children affected, chest X-rays (CXR) showed bilateral interstitial infiltrations and progressive parenchymal infiltrations with decreased aeration of the lungs. In HRCT imaging, they manifested as a white-glass pattern or as consolidated infiltrations with atelectasis. The radiographic features of destruction of the lung parenchy- ", "The authors declare no conflict of interest." ] },{ "paper_id": "11af78fdd83655124c3b5acce4cfb92f0aafe4f6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "11def60675b38fbb811f2b7a9ad62f5d938c8956", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "11ebffa99e4b093c6304549246b534983012f909", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Among 129 KD patients, respiratory virus polymerase chain reaction was performed in 107 patients. Respiratory virus panel included influenza A and B, adenovirus, parainfluenza virus types 1 through 4, respiratory syncytial virus types A and B, bocavirus types 1 through 4, coronavirus NL 63, OC 43, and 229E, enterovirus, human metapneumovirus, and rhinovirus types A, B, and C.", "All patients with KD were examined for inflammatory markers such as total white blood cell count, neutrophil count, neutrophil/ lymphocyte ratio, ESR, CRP, lactate dehydrogenase (LD), and B-type natriuretic peptide (BNP).", "This was a retrospective study and we evaluated a relatively small number of adenovirus-positive KD patients; further prospective studies with larger numbers of patients are warranted to confirm our results.", "In the study, we did not routinely examine for BNP in the adenoviral infection, so we could not assess the difference between the 2 groups." ] },{ "paper_id": "11f3cdbb678b326042e1d0c38887a34a2177ddfe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Twenty cats and their owners were ultimately included in the trial and pertinent information on each cat is given in Table 1 and on the entire trial group in Figure 1 . Cats presented to the study with varying degrees of pretesting by their primary-care veterinarians. This testing usually included a complete blood count (CBC) with total plasma protein, globulin (G), albumin (A), A:G; serum chemistry profile and analysis of effusions, including total protein, actual or estimated cell count, and type of inflammatory cells. Additional testing had been performed on a small proportion of cats and included FIPV antibody titers, abdominal or thoracic ultrasound, biopsies of diseased tissue and quantitative real-time PCR (qRT-PCR) on effusions.", "The 3CLpro sequences of pretreatment viral RNA obtained 25 days (CT16), 139 days (CT02), 149 days (CT12) and 231 days (CT10) later at the time of necropsy were also compared. No differences were observed in 3CLpro over this time. Sequences also remained unchanged in CT02, CT16 and CT12 from the times of presentation to necropsy. The viral 3CLpro from lung and spleen of cat CT10, which relapsed twice over 8 months and retreated, had an Asp-to-Ser substitution at position 25 and a Lys-to-Asp substitution at position 260 compared with virus from pre-treatment abdominal fluid. The exact effects of these mutations on protease function are currently being investigated. It is reported that genetic evolution of viral protein quasi-species arises over time in patients chronically infected with an RNA virus (HCV) and may lead to sporadic amino acid changes. 11", "Weight gain was a simple and accurate measure of growth and improvement of health. The value of monitoring this parameter was typified by CT04, the oldest cat in the trial (Figure 4a ). Cat CT04 presented with significant weight loss of 30%. It gained weight after each round of treatment, began to lose weight shortly before each disease relapse, and regained and added to its weight after each treatment. It regained all its lost weight after 9.3 months off and on treatment (4.8 kg to 7.19 kg). All kittens in sustained remission steadily gained weight during and after antiviral treatment, indicating normal growth continued with antiviral treatment (Figure 4b ). One long-term survivor was spayed (CT15) and two castrated (CT17, 20) without complications during their disease remissions.", "This study was conducted under protocol 18731 approved by the Institutional Animal Care and Use Committee and the Clinical Trial Review Board of the Veterinary Medical Teaching Hospital Clinical Trials Committee, University of California, Davis. This protocol detailed the conditions of the testing of a novel protease inhibitor, GC376, in client-owned cats. Each owner was required to read and consent to the conditions of the trial (supplementary material)." ] },{ "paper_id": "120be7888e94409082f16c372c818d66e558d33e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Diagnoses: Histologic examination revealed massive fibrinous exudation with organization within alveolar spaces and scattered neutrophilic infiltrates, which was consistent with AFOP.", "Interventions: This patient was treated with prednisolone therapy.", "Outcomes: Chest radiograph improvement and symptom improvement, including fever and respiratory symptoms, was observed after 2 week of oral prednisolone treatment. After 9-month of treatment, the patient was asymptomatic with stable disease and improved quality of life." ] },{ "paper_id": "12267e4378cb6c21255f204fb40b9daaa02ab09b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Animals: Eight puppies from a research breeding facility negative for these pathogens.", "Conclusions and Clinical Importance: Vaccine status should be considered when interpreting respiratory agent PCR results if modified live vaccines have been used. Development of quantitative PCR and wild-type sequencing are necessary to improve positive predictive value of these assays by distinguishing vaccinate from natural infection.", "Results: Nucleic acids of all 3 organisms contained in the topical vaccine were detected from both samples multiple times through 28 days after vaccination with higher numbers of positive samples detected between days 3 and 10 after vaccination." ] },{ "paper_id": "12666bbfb4382c1c684087fa6343d5c03cea8584", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Minor points:", "Major comments:" ] },{ "paper_id": "129fe5d1e963bc655146edf42a382819deca0ce6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "131af5ab50551638e3ce9a8c615b9b4364f2f34e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "dustry in Asia (13, 14) . During this ongoing outbreak, new strategies are desperately needed to understand pathogenic mechanisms and the functions of viral genes and to provide new technologies to combat this disease.", "To generate the ORF3 deletion RFP construct, the tdTomato gene was amplified by PCR with flanking PEDV sequence and then inserted using native restriction sites into PEDV-F. PEDV-F-\u232cORF3-RFP was cultured and sequenced to ensure seamless replacement of ORF3 with RFP containing the ORF3 TRS.", "Little information is available regarding the molecular mecha- a Pigs 2, 5, 7, and 10 were exposed by indirect contact to the pigs which were housed in the same isolator through small holes drilled into the stainless steel divider. The panel was located between the 2 pigs in the shared pig tub isolator unit. b ND, not done because pig 1 was used for hyperimmune serum production; NA, not available; VH/CD, villous height/crypt depth. c Fecal scores were as follows: 0, normal; 1, pasty stool; 2, semiliquid diarrhea; and 3, liquid diarrhea." ] },{ "paper_id": "13531a593bf382e8e4f605622db4f7f2c6ef92a9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1369823dbf5f34fd8e2f5d5bba470711dfca4032", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1376526470f18216200ecd6c375d9913942fa362", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Histology. Tissue samples of intestine, stomach, lung, kidney, spleen, and liver were fixed in 10% (vol/vol) phosphate-buffered formalin for 24 to 36 h, dehydrated in graded ethanol, embedded in paraffin, cut in 5-m sections, and mounted onto glass slides. The sections were deparaffinized, rehydrated, and then stained with hematoxylin and eosin. Slides were examined by conventional light microscopy." ] },{ "paper_id": "138e18baf12e4e92b67ab7dee321d2b149f236ed", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "13b16688b86661a6165f9c688c4f45893b7e47c5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analyses were performed using GraphPad Prism 5 (GraphPad Software, San Diego, CA). Data were analyzed by analysis of variance (ANOVA) or Student's t test. All group results are expressed as mean plus or minus SEM, if not stated otherwise. The paired Student's t test was used for the comparison of group values and discriminatory parameters, where appropriate. Survival data was analyzed with SPSS software (version 16.0; SPSS Inc., Chicago, IL, USA) by using the Kaplan-Meier method and compared using a Log-rank Test. p values less than 0.05 were considered significant.", "Anti-CD4, anti-biotin, anti-CD25 and anti-CD14 magnetic microbeads were from Miltenyi Biotec. All cells were cultured in complete media consisting of RPMI 1640 supplemented with 10% heat-inactivated fetal bovine serum (FBS), penicillin (100 U/mL), streptomycin (100 \u03bcg/mL), 1\u00d7GlutaMAX (Gibco) and 1% MEM non-essential amino acids, 1% sodium pyruvate (Hyclone).", "Peripheral blood mononuclear cells (PBMC) were isolated from adult peripheral buffy coats (Gulf Coast Regional Blood Center) by Ficoll gradient centrifugation. Tregs were purified from PBMC by positive selection using directly conjugated anti-CD25 magnetic microbeads with AutoMACS (Posseld2 program)." ] },{ "paper_id": "13bcbfda70f3fae9fc63e5a041e4f3dba700b95c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Infectious diseases cause approximately one quarter of all deaths worldwide each year (Fauci and Morens, 2012) . These include the \"big three\"-HIV/AIDS, tuberculosis, and malaria-which account for 10% of all deaths. They also include emerging diseases such as Ebola, Middle East Respiratory Syndrome, and methicillin-resistant Staphylococcus aureus. Infections are caused by microbial pathogens from different domains of the tree of life-viruses, bacteria, or eukaryotes. All share the ability to colonize their hosts and cause pathology through their interactions with host cells.", "There are two predominant approaches for combating infectious diseases. One is to stimulate the immune system to prevent or reduce the impact of infection, for example, through vaccination. Another is to reduce or eliminate an existing infection with drugs that kill the infectious agent and/or enhance the immune response.", "Thus it appears that developing drugs that target host components is a viable strategy to combat infectious diseases, and this may prove complementary to the traditional approach of developing antimicrobials that target pathogen proteins. Although potential drawbacks of such a strategy include the risk of toxicity to the host, potential benefits may include an increased flexibility in developing combination therapies and a reduced capacity of the pathogens to become resistant to drug treatment." ] },{ "paper_id": "13cc84dcf620af030f92f4240637ba43a84004e9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The principles and procedures of the fluorescence recovery afar photobleaching (FRAP) technique have been discussed before (22, 23, 33) .", "Since the fluorescence was compared domain by domain (i.e., apical to apical) in unextracted and detergent extracted cells, it was assumed that detergent extraction does not modify the membrane folding and no correction for membrane folding was used. The validity of this assumption was confirmed at the EM level (see Fig. 1 C) .", "extracted from the basal surface under the same conditions.", "A control was performed labeling the cells with primary Ab and fluorescem anti-mouse Ig Fab. The label was measured by flow cytometry in the presence of a large excess of unlabeled Fab. No significant dissociation was observed in 90 min." ] },{ "paper_id": "13e343269547d19b3be05976232fd5cd627e1d80", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ethical approval was obtained from the Clinical Research Ethics Committee of the Shanghai Pulmonary Hospital. Permission to conduct the study in the selected center was also obtained. The subjects participated voluntarily in the study and were informed of its purposes. A written informed consent was obtained from every eligible subject.", "Sputum bacteria culture and sensitivity test 20 were performed before and after the treatment, so did the hematuria routine, liver and kidney function test, and chest X-ray examination. Patients' clinical symptoms, signs and adverse reactions, hemogram and other parameters were recorded daily after treatment.", "The purpose of cost-effectiveness analysis was to determine the treatment plan with the least cost for certain treatment effect, which was represented by the cost per unit of " ] },{ "paper_id": "13e6c9b0730b53139910cfa6835ae4c460a30851", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "13f055e666f5a05c1f18856409f9b8f4ac4ae4ce", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Other analytical procedures Sodium dodecylsulfate (SDS)-polyacrylamide gels were performed by the method of Laemmli (1970) . Protein concentrations were determined by the method of Bradford (1976) .", "Based on the measured inhibition constants, the affinity for the disaccharide was 1000-fold higher than for any of the monosaccharides tested.", "The polymerase chain reaction was carried out using a mouse cDNA panel and Advantage 2 DNA polymerase from ClonTech-Takara Bio Europe (Saint-Germain-en-Laye, France) under the standard reaction conditions described by the manufacturer. Forward and reverse oligonucleotide primers, obtained from Invitrogen (Paisley, UK), were 5ccagggctggacgccaccaccacc-3\u2032 and 5\u2032-ctggggtcactaaagcatgcact ggtcagg-3\u2032. Following an initial denaturation at 95\u00b0C for 1 min, 40 cycles of 95\u00b0C for 30 s and 68\u00b0C for 1 min were executed, and the products were resolved on a 2% agarose gel containing ethidium bromide." ] },{ "paper_id": "140e6d0298bfcd1e825a4b81dcabc50d1658357a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1425915f5f44c6e2bb0753cbe0531cbcbad46d13", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1430ebabc4bb953366b635cd4a8adf9956c2f86b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "143381fcb7566228ad053f619d03efdfbc2668b3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "147de820d90c0ce89fb5ae6836ea1794b808fdf2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "148a0ab3b9bb851a56bbe926abed11c0d71fc61c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The protocols of both studies were reviewed and approved by Royal Canin Internal Ethics Committee." ] },{ "paper_id": "14b07f164039eddabc4f3932a873bcbccb2108f4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Searching for strains based on direct submission metadata for those viruses annotated with such data returns strain records and genome sequences matching the query criteria.", "Supplementary Data are available at NAR Online. Supplementary Table 1 , Supplementary Figures 1-5 .", "The goal of the BRC program is to provide the necessary data, bioinformatics tools and workflows to enhance ongoing basic and applied research. By integrating the data with a variety of computational analysis tools free of charge to the virology research community, complex analyses that take advantage of cross-referenced data within the ViPR database become possible.", "Viral disease outbreaks tend to occur every several years in the human population (1) (2) (3) (4) . During such outbreaks, identification of the causative agent and comparative genomic analysis can be critical to limiting the spread of the virus and identifying suitable treatment options. While the first lines of defense against such outbreaks are clinical reporting and automated surveillance, 'wet lab' experimentation of viral isolates is also important. Bioinformatics tools and database resources that provide information about the genomic structures and phenotypic characteristics of known viruses can make this process more efficient by supporting data mining for the development of hypotheses worthy of in-depth laboratory experimentation on the emerging strain.", "Sequence data deposited in archives such as GenBank are extremely valuable in the computational analysis of emerging viruses. These sequence records can be enhanced through integration with additional knowledge about the viral strains including: gene and protein annotations, immune epitope locations, 3D protein structures, clinical metadata, etc. Database resources and modern computing make storing and retrieving such a wealth of data tractable." ] },{ "paper_id": "14c6f99cf0ec54c78447ad5a8403e3ee2708176f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "HIV was first reported in China in 1985. Since then, the HIV epidemic has been concentrated in most at-risk populations (MARPs), including injection drug users (IDUs), commercial sex workers (CSWs) and their clients, men who have sex with men (MSM) and former plasma donors who became infected because of unsafe donation practices.", "International support has not only been provided to governmental agencies, but also to Chinese domestic NGOs, civil society organization or grassroot organizations. From 2005 to 2008, 11.8 million USD was provided for their activities, including training and prevention interventions.", "A second challenge is accomplishing needed work while still exploring new models. In the past, some locations looked at cooperation projects as a way to provide funding for routine work. These locations failed to take full advantage of innovative projects. It is a challenge for China to take full advantage of international projects requiring the flexible piloting of new ideas and new technology while still completing routine work." ] },{ "paper_id": "14c9ca5bf096d03bde8e8ffe88c7419ef5b79b13", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Given a slippery sequence p in s, a candidate x is a substring of s of the form x = pu, for various lengths of u.", "We downloaded the yeast genome sequences from NCBI (accessions: NC_001133, . . . , NC_001148, NC_ 001224; all versions are dated 24 January 2007) and extracted 6199 annotated ORFs with a total length of 8.76 MB. Each ORF was analyzed by KnotInFrame and for each ORF the five best predictions were stored and used in the comparison.", "Supplemantary Data are available at NAR Online.", "Definitions. Let s be a DNA sequence of length n. We require neither a start codon nor frame information. s i; j \u00bd is a substring of s starting at position i and ending at position j, and s\u00bdi; n is called a suffix of s. A slippery sequence in s is a substring s\u00bdi; i \u00fe 6 that matches the consensus slippery motif of the form X XXY YYZ, where the spacer marks the zero-frame codons, XXX stands for any three identical nucleotides, YYY for either three As or three T/Us and Z for any nucleotide.", "In the middle of the last century, George Beadle and Edward Tatum (1) proposed the 'one gene-one enzyme' theory, stating that one gene holds the genetic information of one enzyme, performing one enzymatic reaction. It was later changed to 'one gene-one polyprotein' to account for the discovery of polyproteins. However, today there are several cases which violate this assumption. By alternative splicing several protein variants are made by selecting different sets of exons from one single gene. With trans-splicing, proteins are synthesized from exons of different genes (2) . Another way of enhancing the information content of an mRNA are translational recoding events. With codon hopping (bypassing) (3), the ribosome skips over a gap in the open reading frame (ORF) and resumes translation at a downstream codon. In procaryotes, UGA codons followed by a characteristic stemloop structure are redefined from stop codons to insertion of selenocystein (4) ." ] },{ "paper_id": "14e7bfe37c331fdf83f54808418cae7129a653a0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Feline infectious peritonitis (FIP) is a common disease in cats and some non-domestic felids that is caused by feline coronavirus (FCoV) 1 . This virus is included in the Coronaviridae family, a group of enveloped positivestranded RNA viruses 1 . Although FIP manifests itself in effusive or noneffusive forms, the basic lesion is the same, a pyogranulomatous inflammation and vasculitis 1 . Testing by immunofluorescence assay, ELISA, electron microscopy, RT-PCR and sequence analysis may be useful in supporting a diagnosis of FIP 1,2 .", "Since 2006, some ferrets with clinical signs and visceral lesions similar to those in cats with FIP have been reported [2] [3] [4] [5] . All cases in these reports were found in either Europe or the United States, and no case had been reported i n J a p a n . R e c e n t l y , w e e n c o u n t e r e d a c a s e o f pyogranulomatous inflammation in the mesentery of a male ferret that was similar to the cases previously reported. This paper describes the histopathological features of our ferret, which is the first reported case of feline infectious peritonitis-like pyogranuloma in ferrets in Japan.", "Fecal-oral exposure seems to be the likely route of transmission for this coronavirus 2 . All the ferrets we purchased were bred in individual cages, and the ferret in this report had a short latency period in our laboratory. Accordingly, we consider that the risk of infection in our laboratory is low but it is unclear how the ferret became infected. To our knowledge, this disease resembling FIP in a ferret has not previously been reported in Japan, and therefore this is apparently the first case in Japan." ] },{ "paper_id": "14e878a6400d8320e2c781a76edc4a14f4cec1df", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Viruses are the most common etiology of ARIs in children. 6, 7 These include rhinovirus (RhV), respiratory www.mjhid.org Mediterr J Hematol Infect Dis 2019; 11; e2019059", "Medical history and demographic data were obtained from the patients and their medical records. A respiratory sample was collected and stored at -80\u00b0C for viral assessment. The study was approved by the Institutional Review Board (IRB) of the AUBMC, and written informed consent was obtained from all parents.", "Nucleic acid extraction and viral detection. Nucleic acid was extracted from clinical specimens by using the QIAamp MinElute Virus Spin kit (Qiagen) according to the manufacturer's protocol. A 200 \u00b5l aliquot of each specimen was used for nucleic extraction. Specimens were then analyzed by the ResPlex II panel (Qiagen) using the manufacturer's protocol." ] },{ "paper_id": "151b29e4b482ad11ee11e83cec4f3faebb8124c5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Reagents 2-iminothiolane (2-IT), m-maleimidobenzoyl-N-hydroxysulfosuccinimide ester (sulfo-MBS), Amino Ethyl-8 Reagent, HRP, and DAB were purchased from Pierce Chemical (Rockford, IL). Fluorescein 5-isothiocyanate (isomer 1), and Slow Fade were purchased from Molecular Probes (Eugene, OR). Glutaraldehyde, osmium tetroxide, and EMbed 812 kits were purchased from Electron Microscopy Sciences (Fort Washington, PA). Cy3.18 was purchased from Biological Detection Systems (Pittsburgh, PA). Balanced salt solutions and other reagents used in the preparation of media were purchased from GIBCO BRL (Gaithersburg, MD). Chromatographic matrices were purchased from Pharmacia LKB Biotechnology (Piscataway, N J). All other reagents were purchased from Sigma Chem. Co. (St. Louis, MO).", "1,1 '-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labeled LDL (DiI-LDL) was prepared according to the method of Pitas et al. (1981) and kindly provided by Drs. J. N. Myers and I. Tabas (Columbia University, NY) .", "each particle of Tfl0 must be displacing several 125I-Tf particles and by inference binding several TfR." ] },{ "paper_id": "153c3a86e8939de3ca0331ea95b68f8bb4a3e395", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Members of the rab/YPTI/SEC4 gene family", "Hiss-tagged rabla(N124D protein was prepared as described (Nuoffer et ai., 1994) .", "After transport in vitro, permeabilized NRK cells were fixed for 30 rain with 3 % paraformaidehyde and 0.1% glutaraldehyde, pH 7.4, in 0.1 M phosphate buffer, washed briefly in PBS, and processed for immunodiffusion or indirect immunogold labeling of ultrathin cryosections." ] },{ "paper_id": "1560d77c8e16b3b283f328b1c3de5513014522e9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +", "Conflict of interest relevant to this article was not reported." ] },{ "paper_id": "157d6b204fdc9b7ea26cdbffea19197b0faaa31f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "15ac0bdac1ae44bf9d833b2156761082915fb642", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Abbreviations: Corona, coronavirus; RSV, respiratory syncytial virus; Para, parainfluenza virus; MFI, median fluorescence intensity.", "involved enterovirus/rhinovirus (78%), consistent with results of previous studies [12, 13] , and 43% of these cases involved enterovirus/rhinovirus and RSV.", "In conclusion, the two Luminex assays performed comparably for most pathogens, with the NxTAG RPP having the advantages of being able to detect atypical bacteria and having better diag-nostic sensitivity for certain viruses.", "The NxTAG RPP detected the presence of M. pneumoniae in one of the samples included in this study. This finding was con-firmed by using a commercial real-time PCR assay for Mycoplasma, the Venor GeM qEP Mycoplasma detection kit (Minerva Biolabs GmbH, Berlin, Germany). Subsequent sensitivity testing using the lyophilized 10 colony-forming units (CFU) Sensitivity Standards (Minerva Biolabs GmbH) showed that NxTAG assay was capable of detecting M. pneumoniae strain down to 10 CFUs/ PCR." ] },{ "paper_id": "15d061338f90460e59acb68d6cd52f5e776e53c1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "15d87194ff22d1a52809b2c2332aa3e11a6fcd4a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For additional Materials and Methods, please refer to the Supplementary Materials.", "Supplementary materials are available at The Journal of 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. ", "Hepatitis B virus (HBV) infection is a severe health burden, with approximately 2 billion infected people and >250 million chronically infected carriers [1] . HBV is the major cause of chronic liver diseases, the primary causative agent of hepatocellular carcinoma, and responsible for 887 000 deaths worldwide annually [2] . Despite the availability of vaccines and drugs, chronic hepatitis B is still an incurable disease. HBV is a small, enveloped, hepatotropic DNA virus belonging to the family Hepadnaviridae [3] ." ] },{ "paper_id": "15e262dad93d5086e9fcb6a1267dec5189f5c1fe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The UNITAID Constitution directs the initiative to dedicate at least 85% of its spending on products for lowincome countries.", "The Open AIDS Journal, 2010, Volume 4 39 more easily and quickly; and patients in developing countries get faster access to better, more affordable treatments.", "Today, however, the treatment landscape is more complex." ] },{ "paper_id": "15f57ae58cbfdd0616c570508ce0471bc4dacebe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "15f99a27eec125edd5f2c431344f01883ff72129", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Phase I studies of a synthetic, consensus DNA plasmid vaccine A single MERS-CoV vaccine candidate, full-length S protein consensus DNA vaccine GLS-5300, has progressed to human clinical trials ( Table 2) . A total of 75 participants were assigned to one of 3 dose levels: 0.67 mg, 2 mg, or 6 mg administered on day 0, week 4, and week 12 via intramuscular (IM) injection and followed by electroporation (EP). Additional studies to assess the relative immunogenicity of intradermal (ID) vaccine administration and followed by EP will provide details as to optimal vaccine dosing.", "Vaccine candidates in development include live-attenuated viral vaccines; live chimeric vaccines; purified inactivated (killed) vaccines (PIV); viral vectored vaccines based on measles, adeno-associated virus (AAV), vesicular stomatitis virus (VSV), and vaccinia platforms; subunit and nanoparticle protein based vaccines; and nucleic acid vaccines using both DNA and mRNA approaches 138, 139 (see also the World Health Organization listing at http://www.who.int/immunization/research/ vaccine_pipeline_tracker_spreadsheet/en/). As of the date of this review, pre-clinical data for one PIV vaccine, an attenuated live-virus vaccine, 3 DNA vaccines, 2 mRNA vaccines, 2 separate AAV-based vaccine (Ad5 and Ad52), and a subunit vaccine have been published. [140] [141] [142] [143] [144] [145] [146] [147] Three DNA vaccines, an mRNA vaccine, and a PIV vaccine have advanced into Phase I clinical trials ( Table 3) .", "Both diseases had the advantage of occurring at a time when multiple platform technologies were existent. 154 Many platforms could respond to a new pathogen after only minimal genetic modification. Experience has allowed more classical vaccines to also undergo rapid modification, although in some cases structural considerations (e.g., protein structure and antigen presentation) or unique adverse events (e.g., eosinophilc pulmonary inflammation induced by whole inactivated SARS virus vaccines at the time of viral challenge 158 ) were required." ] },{ "paper_id": "16320b30b2f068bc2d7bc9cf2f2da87261f041b4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "165792449dc650fba4a923f3a94a851754a7bcb7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1685a03eac1fe5f949aa6b7889e02dadf9d3f90f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.00698-13/-/DCSupplemental. Text S1, DOC file, 0.1 MB. Figure S1 , TIF file, 1 MB. Figure S2 , TIF file, 0.8 MB. Figure S3 , TIF file, 1.8 MB. Figure S4 , TIF file, 1.5 MB. Figure S5 , TIF file, 0.6 MB. Figure S6 , TIF file, 2.6 MB. Figure S7 , TIF file, 3.2 MB. Figure S8 , TIF file, 2.4 MB. Figure S9 , TIF file, 0.8 MB.", "Microarray data accession number. The data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus (58) and are accessible through GEO Series accession number GSE48831 (http: //www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc\u03edGSE48831)." ] },{ "paper_id": "1694b4f8e456f966ff1fe215161bae59e59148df", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "169eb7d3419808c29066e6e5ed091a8d54bc214a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For competition assays, U3 snoRNA was transcribed by T7 RNA polymerase (Fermentas T7 transcription kit K0411) and labelled with [a-32 P]UTP. The labelled U3 snoRNA was preincubated with AtFib2 in binding buffer for 10 min, and then competitors were added and incubation was continued for 10 min. After electrophoresis, gels containing radiolabelled RNA were dried and exposed to a Phosphoimager (Fujifilm Fla-300), and the intensity of RNA bands were quantified (with Aida/2D Densitometry).", "AtFib2 RNA binding was additionally analysed in competition assays. Figure 2G shows that a radiolabelled U3 snoRNA can be released from the complex with AtFib2 by TMV RNA, 18S rRNA and 26S rRNA, although 18S rRNA was a less efficient competitor.", "Supplementary Data are available at NAR Online. " ] },{ "paper_id": "16c8b4fe2b6ae40077de377027c4fdf6a27a0744", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "16d4d6332fb5f17df0c487e2c9202716d01889be", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "16dd2eb417bbac88ac2235efe705761a57807ae6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "There was not off-label antimicrobial use. ", "https://orcid.org/0000-0003-0259-7210" ] },{ "paper_id": "17114faf3bbc2a82ef49762ce4f3f922cb213f4e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "174f63ff45fc7bbecf0f559200761ad76691b6fb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Alaternin-2-O-\u03b2-D-glucopyranoside (29) 34", "Chryso-obtusin-2-O-\u03b2-D-glucopyranoside (7) 36", "Obtusifolin Rubrofusarin (47) 49 Rubrofusarin" ] },{ "paper_id": "176fa00106dc0e7b0ef19c0b606aa80cd14e4057", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "HepG2 cells were reverse-transfected with corresponding constructs using Lipofectamine 3000 and Opti-MEM (Life Technologies).", "I nterferons (IFNs) are an essential part of the innate immune response, which is the first line of defense against pathogens. The induction of IFNs leads to activation of the JAK/STAT signaling pathway and expression of interferonstimulated genes (ISGs) in the infected and the surrounding cells. This response can limit viral spread through mobilization of cellular defense mechanisms and elimination of infected cells (Parkin and Cohen 2001; Levy and others 2011) .", "IFN-l4 protein sequences were analyzed with free online tools-Clustal W for sequence alignment and BoxShade for annotating amino acid similarities. Analysis of leader peptides was performed with online SignalP 4.1Server (Petersen and others 2011) , and PSORT II analysis of nuclear localization signals and intracellular localization was performed with PSORT server (http://psort.hgc.jp/) (Nakai and Horton 1999) . Statistical analysis and graphical presentation of results were done with GraphPad Prism 6 (GraphPad).", "We used information based on our earlier sequencing of the genomic DNA for chimpanzee IFN-l4 (GenBank JX867772 and NM_001276259) and cynomolgus (crabeating macaque; Genbank KC525948). Sequences for orangutan, marmoset, elephant, panda, megabat, cow, dog, and pig were only derived from the UCSC Genome browser and not validated by sequencing. Commercial genomic DNA sample for rhesus was obtained from Zyagen and used for Sanger sequencing of the predicted IFN-l4 ORF." ] },{ "paper_id": "17bfdf17f46ae63e52c3e7c085bac97057e9ae61", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org/ lookup/suppl/doi:10.1128/mBio.00759-15/-/DCSupplemental.", "Text S1, DOCX file, 0.1 MB.", "Transient-replication assay. For quantification of the replication efficiency of subgenomic replicons containing a firefly luciferase gene, luciferase activity contained in cell lysates was determined at different time points after electroporation as described elsewhere (49) ." ] },{ "paper_id": "17c135abc3c6a212ba22ae3d3750e4a396933022", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "17c30925f6e62319c5049126e8fddbc1410e9983", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Several different sources of antisera were initially tested for quantitative immunoprecipitation of lysosomal hydrolases from rodent islets. Based on these trials, experiments using antisera to cathespin L (from Dr. C. Gabel, Pfizer Research, Groton, CT), cathespin B (from Dr. A. Saluja, Beth Israel Hospital, Boston, MA), and cathespin D (from Dr. S. Diment, New York University, New York) were performed in mouse islets. ~glucuronidase, which was too low for reliable detection in mouse islets, was immunoprecipitated from rat islets (antiserum from Dr. R. Ganschow, University of Cincinnati, OH). The precipitation reagent used was either protein A agarose or Zysorbin (Zymed, San Francisco, CA). Immunoprecipitates were dissolved in SDS gel sample buffer and analyzed by 12% acrylarnide SDS-PAGE, followed by fluorography.", "The C-peptidedInsulin (C/I) ratios from media collected during the 60-120min chase period from control islets or those treated with zinc or chloroquine, were measured by specific immunoprecipitation using antisera to insulin and rat C-peptide as described previously (Kuliawat and Aryan, 1992) . Data from the supplier (Linco) and our own preliminary studies indicate that the anti-C-peptide precipitation may under-recover rat and mouse C-peptides, especially C-peptide-1, so that the C/I ratios >unity are nevertheless likely to be underestimates. However, neither ehloroquine nor zinc treatment of islets influences the subsequent immunoprecipitation step per se (data not shown).", "tion of/~-cell secretagogues (Fig. 1) . Thus, although a small fraction of lysosomal enzymes may exist in B-granules (Ira et al., 1989) , mechanisms exist for the selective storage of regulated secretory proteins (Kelly, 1985) and lysosomal enzymes (Kornfeld and Mellman, 1989) in largely nonoverlapping steady-state distributions." ] },{ "paper_id": "17c738edd73de72b15a2ca40132e7747d38fb221", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "17da3a159054b31e3da81a51ab9ccc26e18bd266", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "ACKNOWLEDGMENTS. Authors thank Mr. N. Uchiyama for his efforts in preparing the original design of the PACT device. We also thank Mr. K. Ohnuki for for his instructive suggestions. This research is supported by the Matching Planner Program from Japan Science and Technology Agency, JST. ", "FCV-F9 (VR-782, 40 nm diameter) virus used in the study is a vaccine strain. Crandell Rees feline kidney (CRFK) cells were used for culturing and measurement of the virus. Cells were cultured in Eagle MEM (Nissui, Tokyo, Japan) containing 5% fetal bovine serum (Nichirei Bioscience Inc., Tokyo, Japan), 0.3% Tryptose Phosphate Broth (BD Biosciences, Sparks, MD, U.S.A.), and antibiotics (100 U/ml of Penicillin and 100 \u00b5g/ml of Streptomycin).", "PACT was developed as an air purification technique and, for example, has been shown to be effective in removing toxic substances in cigarette smoke. It has also recently been utilized to inactivate bio-aerosols employing plasma technology [5] . We investigated whether PACT has a virucidal effect against an airborne, infectious virus and found that aerosolized FCV was inactivated by PACT and the FCV titer could be reduced to below the detection limit depending on conditions.", "Airborne infectious diseases, such as SARS, Mycobacterium tuberculosis, and highly pathogenic avian influenza, are serious threats to human health. Infected individuals may visit health care institutions, increasing the chance of infection for both patients and health care workers, in particular, the infection of immunocompromised persons, leading to serious illness and possible death [16] . Infections caused by Mycobacterium tuberculosis, measles, and varicella virus are spread through coughing and sneezing by infected individuals. Scattered droplets dry and form dried droplet nuclei alone or by adhering to particles in the air and infection occurs by inhalation. When droplet nuclei are less than 5 \u00b5m in diameter they can float in the air for a prolonged time and become widely spread [1, 16] . Airborne infection is partially dependent on the concentration of infectious pathogen in the air [8] . Vaporized material from infected person's vomit may also result in airborne infection. A typical pathogen transmitted by airborne infection is norovirus. Cases of infection from an air conditioner 1-2 days after processing vomit from norovirus infected persons have been reported [3, 7, 15] ." ] },{ "paper_id": "17f00e096a5f3ce94278a77011e6f38d7a47c618", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Subsequently, absorbance of the sample was measured at 450 nm in a microplate reader (Tecan). The experiments were repeated three times.", "Authors declare no conflicts of interest for this article. " ] },{ "paper_id": "17fd86bef40a55871ecfc83dc845f3a988bf4aaa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplementary textexperimental procedures Figures S1 to S7 Tables S1", "\u2020 These authors contributed equally to this work www.pnas.org/cgi/", "CedV, HeV and NiV soluble receptor-binding proteins (sG) were each coupled to specific magnetic microspheres following a standard manufacturer protocol (Bio-Rad) and mixed together. Henipavirus sG coupled microspheres were incubated with serial diluted human monoclonal antibody, m102.4, at indicated concentrations and incubated at room temperature with agitation. Wells were washed with PBS-Tween (0.05%) then incubated with biotinylated anti-human IgG (1:10,000), agitated, washed and finally incubated with streptavidin-phycoerythrin (PE). The PE signal for each sG-coupled microsphere -hm102.4 complex was detected as a median fluorescence intensity (MFI) by a Bio-Plex 200 machine (Bio-Rad). The graph is a representation of two independent experiments performed in technical triplicates. Hercules, CA) machine using Luminex xMAP technology." ] },{ "paper_id": "1863b855d1e87b1a2b85a88c71c0b8753619f0b2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "amino-terminal signal sequence or membrane-spanning domains. Analysis by BLAST and COILS2.1 (Lupas et al., 1991) indicated that a region of Vps38 has some probability to form a coiled coil structure (not shown).", "Steady-state levels of Pma1, CPY, and Kex2 were analyzed in cell lysates, prepared from mid-log cultures by vortexing with glass beads, as de-scribed previously (Chang and Slayman, 1991) . Samples were normalized to lysate protein using the Bradford assay (Bio-Rad Laboratories, Hercules, CA). After separation by SDS-PAGE, samples were transferred to nitrocellulose for Western blot with rabbit antibodies against Pma1, CPY, or Kex2, and 125 I-protein A (Amersham Corp., Arlington Heights, IL).", "The Journal of Cell Biology, Volume 138, 1997" ] },{ "paper_id": "18aa7bfcf8b4dfcad03cf4836aaaa5345d6cfdc7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cells. NIH/3T3 murine fibroblasts (CRL-1658) obtained from ATCC (Manassas, VA) were maintained in DMEM containing 10% fetal calf serum. PC-3 human prostate carcinoma cells were maintained in Ham's F12 media containing 10% fetal calf serum.", "Western blotting. Transfected cells were lysed and total cellular protein extracted using M-PER solution (Pierce Biotechnology, Rockford, IL) containing protease inhibitor cocktail (Roche, Welwyn Garden City, UK). Protein concentration was determined by BCA assay; 20 \u03bcg of total protein was loaded onto each well of a 12% SDS-PAGE gel and run at 170 V for 40 minutes. The proteins were transferred to a nitrocellulose membrane and blocked in 5% dried milk in Tris-buffered saline pH 7.4, 0.1% Tween 20 (TBST) at room temperature for 60 minutes. The blot was then washed three times with TBST and incubated with mouse anti-LacI clone 9A5 primary antibody (Millipore UK, Watford, UK) diluted 1 in 1,000 at room temperature for 2 hours. The blot was then washed three times with TBST and incubated with goat antimouse IgG-HRP secondary antibody (Dako, Ely, UK) diluted 1 in 5,000 at room temperature for 1 hour. The blot was washed and the bands visualized by chemiluminescence using ECL western blotting detection reagent (GE Healthcare, Little Chalfont, UK) on a ChemiImager (Alpha Innotech, San Leandro, CA), and analyzed using Fluorchem 8000 software. Each blot was stripped and reprobed with sc-5286 anti-\u03b1-tubulin antibodies (Santa Cruz Biotechnology, Santa Cruz, CA) diluted 1:1,000 as a protein loading control.", "The strategy adopted to develop a lac-regulated luciferase expression model was based on that previously performed by Scrable et al. 33, 34 Briefly, transgenic lines comprising HDLacO-Luc and LacIR were generated and then subsequently crossed to produce double transgenic (HDLacOLuc x LacIR) offspring." ] },{ "paper_id": "18cdd1a1d97483f2cb8a1586b2d4858dab46efa2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Human infection with the Middle East respiratory syndrome coronavirus (MERS-CoV), a positive-sense single-stranded RNA virus of the family Coronaviridae, was first reported in 2012 [1]. Since then, more than 2,200 laboratory-confirmed cases have been described with an estimated 35.5% case-fatality rate [2] . Middle East countries appeared to be mainly affected by the life-threatening pathogenicity of the virus, but some exported cases were also reported in Asia, Europe, and the United States of America [1,3]. Given zoonotic transmission of the virus from dromedary camels to humans and its lethality in humans [1], vaccines and/or antivirals should be prepared, but no approved medical countermeasures are available, yet.", "In line with the pathogenic mechanisms reported with MERS-CoV [4], such as acute respiratory symptoms and local immune responses, viral antagonism against host innate immune responses may be of great significance in terms of the pandemic potential and host range restriction of the virus. Viral antagonism had been already described for , and, of the MERS-CoV proteins, protein 4a was suggested responsible for its role against RNA-dependent protein kinase-mediated antiviral immunity and activation of retinoic acidinducible gene I and Melanoma Differentiation-Associated protein 5 of host cells [6, 7] . The antagonistic effects of MERS-CoV protein 4b were also demonstrated against nuclear factor-\u03baB-dependent immunity and RNase L activation of host cells [8, 9] . As shown for influenza and Zika viruses [10, 11] , the species-specific effects of viral antagonism of MERS-CoV on J Vet Sci.", "The 4a and 4b proteins of the Middle East respiratory syndrome coronavirus (MERS-CoV) have been described for their antagonism on host innate immunity. However, unlike clustering patterns of the complete gene sequences of human and camel MERS-CoVs, the 4a and 4b protein coding regions did not constitute species-specific phylogenetic groups. Moreover, given the estimated evolutionary rates of the complete, 4a, and 4b gene sequences, the 4a and 4b proteins might be less affected by species-specific innate immune pressures. These results suggest that the 4a and 4b proteins of MERS-CoV may function against host innate immunity in a manner independent of host species and/or evolutionary clustering patterns." ] },{ "paper_id": "18d7f4c8e204349b39a037c19874cff1b34d0f97", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The coordinates and diffraction data have been deposited into the Protein Data Bank with accession code 4L72.", "Purified RBD and DPP4 were mixed for 1 h and then loaded to Superdex 200 column. The complex was collected and concentrated to ~10 mg/ml in HBS buffer (10 mM HEPES, pH 7.2, 150 mM NaCl) for crystallization. Crystals were successfully grown at room temperature using the sitting drop vapor diffusion method by mixing equal volumes of protein and reservoir solution containing 25% (w/v) polyethylene glycol 1500. Crystals were frozen in liquid nitrogen with cryoprotectant (well solution plus 20% (v/v) glycol) before data collection. Diffraction data were collected at the BL17U beam line of the Shanghai Synchrotron Research Facility (SSRF). Diffraction data were indexed, integrated and scaled with the program HKL2000 [20] .", "The structure was determined by the molecular replacement method with PHASER [21] in CCP4 suite [22] . The search models are DPP4 extracellular domain structure (PDB code 2G63) and SARS-CoV RBD structure deleting the receptor-binding loop (PDB code 2AJF). Density map improvement by atoms update and refinement was performed with ARP/wARP [23] , and automatic model extension of the missing receptor-binding subdomain of MERS-CoV was carried out with BUCCANNER [24] . At the final stages of model building and refinement, glycans were added based on the electron densities. Structure validation was performed with PROCHECK [25] . All structural figures were made with Py-Mol [26] ." ] },{ "paper_id": "1919f9569a8e073accc1c8a105ec36a56ddf569c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Our hospital has continuously received economic support from the DOH for the 'General Medicine Training Demonstration Center Programme' since 2006." ] },{ "paper_id": "1999185dad27d52562c1dfe77bb72f06bdaf5084", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "19e9fcce4b442e7bef53c6cec0aee71a1c565943", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study was approved by the Institutional Review Board (IRB) of Samsung Medical Center (IRB No. 2017-10-002-003). Informed consent was waived since only overall statistical data was used without review of medical records of individual patients." ] },{ "paper_id": "19fb39e16fc35b4ca36825636d018beda55d3d42", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1a2900a53677a6c68ff37167c31ca33ad219acdb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Five female BALB/c mice (6-week old) were purchased from Orient Bio Incorporated (Korea). The animal room was maintained at 22 \u00b1 2 o C (relative humidity, 50% \u00b1 10%) and illuminated using a 12-h day/12-h night cycle. The experiments were performed in accordance with the Code of Laboratory Animal Welfare Ethics, National Research and Quarantine Service, Korea (NVRQS).Experimental design was approved by the NVRQS Animal Welfare Committee.", "Fluoroquinolones (FQs) have been widely used as human and veterinary drugs, especially for the prevention and treatment of various infectious diseases in domestic animals, poultry, and fish [21] . FQs act through inhibition of DNA-gyrase, abolishing activity by interfering with the DNA rejoining reaction [3, 14] . The widespread use of FQs has led to contaminating residues in foodstuffs derived from treated animals, which can induce unwanted reactions such as erythema, burning, and itching in humans and animals [25] . Furthermore, antibiotics released into the natural ecosystem can modify the local environmental microbiota by changing the composition or activity [1, 23] . Many regulatory agencies have established a maximum residue limit for FQs in milk, meat, and other foods [5, 6] . For example, the maximum sum of enrofloxacin (ENR) and its metabolite ciprofloxacin in muscle was set at 100 \uf06dg/kg for all animal species in the European Union [14] .", "Bovine serum albumin (BSA), enrofloxacin, ciprofloxacin, difloxacin, sarafloxacin, pefloxacin, norfloxaicin, keyhole limpet hemocyanin (KLH), N-hydroxysuccinimide (NHS), triethylamine, carbonate-bicarbonate buffer, Tween 20, glutaraldehyde solution (Grade II, 25%), glycine, Freund's complete adjuvant/incomplete adjuvant, and 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (EDC) were purchased from Sigma-Aldrich (USA). Goat anti-mouse IgG was purchased from Abcam (UK). An EZ-Link Plus Activated Peroxidase kit was purchased from Thermo Scientific (USA). 3, 3', 5, 5'-tetra-methylbenzidine (TMB) solution was purchased from KPL (USA). Amine-functionalized MNPs (160 nm) were acquired from Nanobric (Korea). A HiTrap Protein G HP kit was obtained from GE Healthcare (UK).", "To produce the ascites fluid, hybridoma cells in medium were intraperitoneally injected into a mature female BALB/c mouse that had previously been injected with 0.5 mL of pristine. After 14 days, the ascites fluid was collected, and monoclonal IgG from ascites was purified using Protein G column chromatography (GE Healthcare). The isotype of the purified antibody was determined using a mouse mAb isotyping kit (Roche) according to the manufacturer's instructions. The ENR mAb was conjugated to horseradish peroxidase (HRP) using an HRP labeling kit (Thermo Scientific), then stored at \u221220 o C until use.", "As a light molecule with a molecular mass of 359.4, enrofloxacin must be conjugated with a carrier protein to elicit the immune response, which an animal uses to produce the desirable antibodies. Szurodoki et al. indicated that,among the carrier proteins for immunogens, KLH is generally a potent immunogen [28] . KLH conjugate was also found to much more accurately stimulate the corresponding region of the protein and to induce the synthesis of larger amounts of specific antibody than a BSA conjugate [7, 12] . Therefore, we prepared to conjugate ENR with KLH for an immunogen and ENR with BSA for a coating antigen using the NHS method [15, 22, 29] ." ] },{ "paper_id": "1a39379895d1e136f64c7b79ef2204de094dfa75", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The PLEX-ID/Flu assay has been recently developed to enable the detection and typing of influenza viruses based on the RT-PCR/electrospray ionization mass spectrometry technology.", "The influenza A(H1N1)pdm pandemic in 2009 resulted in the development of a number of assays, such as single/multiplex real-time RT-PCR [3] [4] [5] [6] or microarray systems [7, 8] , allowing the rapid detection and typing of influenza virus in human specimens. Sensitive and rapid diagnostic or typing assays are essential for appropriate patient management, particularly high risk patients, and the use of appropriate antiviral therapy." ] },{ "paper_id": "1a3ac4ed56c42714b04e97e0e5e11a93c5a91508", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "After labeling, monolayers were washed twice with Moscona's PBS (36) and cells were scraped offthe dish into an SDS solution (20 mM Tris-HCl, 7.4, 2% SDS) and sonicated 10-30 s in a Heat Systems-Ultrasonics Instrument with a microtip (Heat Systems-Ultrasonics, Inc. Plainview, NY). The suspension was boiled for 2 min and centrifuged (2 min at 15,000 g) in an Eppendorf 5412 to remove unsolubilized material. The supernatant was diluted fourfold with 50 mM Tris-HCl 7.4, 190 mM NaCI, 6 mM EDTA, 2.5% Triton X-100, 0.02% NAN3, and 100 U/ml Trasylol (Solution A).", "Immuneprecipitation: Cell extracts were incubated with lgG fractions (300 ~g/ml) at room temperature for l h and at 4\"C for 14 h before addition of protein-A-sepharose CL-4B beads. After incubation for 3 h at room temperature, the beads were sedimented, washed three times with Solution A containing 0.2% SDS, and boiled for 2 min in a solution of 10% SDS, l M dithiothreitol, 2 mM EDTA.", "RNA Extraction: Clone 9 hepatocytes or GH 3.1 pituitary cells were homogenized in a solution containing 5 M guanidine thiocyanate plus 100 mM mercaptoethanol at pH 5.0 (58). RNA was separated by centrifugation through 0.2 vol of 5.7 M CsCl2 as described by Liu et al. (32) . Similarly, total RNA was prepared from control rats starved for 18 h or from rats sacrificed 15-24 h after partial bepatectomy (l 6)." ] },{ "paper_id": "1a6e69772e4e79d9106015988c0d6ed48dc25ceb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Although the consequences of several caspase protein cleavages have been elucidated, they remain elusive so far for others (Table 4) .", "Caspase Cleavage as a Way for Viruses to Replicate and Spread: Live and Let Die Unlike the expression of antiapoptotic products, the requirement of apoptosis for viruses to survive is a way more counterintuitive strategy that yet has been evolved by several viruses and involves caspase cleavage (Table 2) .", "Apoptosis induction by infected cells is meant to jeopardize viral replication. Therefore, many viruses have developed strategies to inhibit this process through various mechanisms. Among them, inhibiting caspase activity through the cleavage of viral proteins constitutes an effective way to achieve apoptosis suppression (Table 1) .", "Herpex simplex virus 1 (HSV-1) causes lifelong infections affecting between 50 and 90% of the global population. HSV-1 exerts antiapoptotic properties against numerous stimuli. But some variants including d120 mutant induce apoptosis and under these conditions, infected cell protein no. 22 (ICP22 or M r 37,500 protein) leads to an additional product (M r 35,000) that can result in vitro from ICP22 cleavage by caspase 3. 49 Neither the identity of the caspase site nor the biological relevance of ICP22 cleavage has been further investigated yet." ] },{ "paper_id": "1a7676018fd73150a122c2afb1362324dbab4918", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Frozen prostate cancer samples were sectioned onto slides. Cell nuclei were isolated in situ with ice-cold cytoskeleton buffer (CSK: 300 mM sucrose, 100 mM NaCl, 10 mM PIPES, 3 mM MgCL 2 , 1 mM EGTA and 0.5% Triton X-100) (28) . The slides were fixed by dipping in ice-cold methanol for 3 min, followed by ice-cold acetone. After air drying the slides, they were allowed to age for at least 1 week in ethanol.", "DNA-FISH was carried out according to a method for single copy loci detection (28) . The protocol was adapted with few modifications, using 50-mer oligonucleotides specific to the loci of interest and labeled with a desired hapten. Two probes were used for FISH for breakapart assay. A probe located at the promoter region of TMPRSS2 was labeled with biotin (Bio/GACTCCA GGAGCGCTCCCCAGAATCCCCTTCCTTAACCCA AACTCGAGCC). The other probe at exon 2 of ERG was labeled with 5 0 -6-carboxyfluorescein (56FAM) (56FAM/ GATCTTTGGAGACCCGAGGAAAGCCGTGTTGA CCAAAAGCAAGACAAATG). Detection of probes was achieved by using antibodies conjugated to quantum dots (Qdot) against the hapten label. Conditions were optimized to use a combination of two antibodies (1 : 200) obtained from Invitrogen-Molecular Probes TM (Qdot 655 \u00c3 sheep anti-Bio primary antibody conjugate; Qdot 525 \u00c3 Goat anti-FITC whole IgG primary antibody conjugate). Image acquisition was done with a Zeiss Axioplan 2e microscope (Carl Zeiss, Inc.). All pictures in the corresponding three channels were deconvolved and optical sections merged to produce 2D pictures using Axiovision 4.0 software (Carl Zeiss, Inc.) and Image J (Rasband, W.S., ImageJ, U. S. National Institutes of Health, Bethesda, MD, USA, http://rsb.info.nih.gov/ij/, 1997-2006.)", "Institutes of Health (CA119335 to UCSD NanoTumor Center of Excellence for Cancer Nanotechnology, CA133634 to Y. T. Liu, NS034934 to" ] },{ "paper_id": "1aaa45043de59cda6c14acd355518c688f37b374", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1b58422e266ab9339c919119923229d080f27360", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The levels of various markers in the pleural effusion samples are expressed as the mean \u00b1 standard deviation (SD) or shown as the median (interquartile range). Group comparisons were made using the nonparametric Kruskal-Wallis test. Differences were considered statistically significant when p < 0.05. Statistical analysis was performed using statistical software (SPSS, Chicago, IL, USA).", "Pleural effusions from 125 patients were processed in our laboratory from August 2010 to December 2011. All pleural effusions were designated as transudates or exudates according to Light's criteria [12] . Definitive diagnosis of tuberculous, pneumonia, or adenocarcinoma effusions for the exudate was verified by examining effusion biochemistry, cytology, acid-fast staining, and clinical follow-up. The study was performed with the approval of the Institutional Review Board of Mackay Memorial Hospital. Informed consent was obtained from all patients.", "For each pleural effusion sample, the routine pleural analyses included total protein, lactate dehydrogenase (LDH), glucose, and white blood cell (WBC) count. In addition, the activities of ACE, ACE2, and gelatinases (MMP-2 and MMP-9) in the pleural effusions were measured.", "WBC number, glucose, total protein and LDH concentration in the exudates from of three types, tuberculous, pneumonia and adenocarcinoma effusions, were determined ( Table 2 ). The data show that all of WBC number, glucose and LDH concentration determinations among the three exudative effusions were insignificantly different. " ] },{ "paper_id": "1b7520912fbd483ef60014fe0e7f0d0c2df1d07e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1badb9da3cd92175be22f42538742c07f58eb5f8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1be90a46380a03cc53bacd389834702db88ac79b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The viral space displays enormous diversity but high redundancy", "For this representation, the differences between two codon usages (P\u00bc(p 1 ,y,p 59 ), Q\u00bc(q 1 ,y,q 59 )) were measured using their KL divergences (DKL, Kullback-Leibler divergence), where D KL \u00f0PjjQ\u00de \u00bc P 59 i\u00bc1 p i log p i =q i ; and D KL \u00f0QjjP\u00de \u00bc P 59 i\u00bc1 q i log q i =p i :", "Supplementary information is available at the Molecular Systems Biology website (www.nature.com/msb)." ] },{ "paper_id": "1bed4f8a5412cfa315b0936705a647059ceaec62", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1bf18631b9c161ea2834b3d7c8ea42875319d18c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Specific overlapping RT-PCR reactions were set up to amplify a 1,554-bp fragment covering the gene region ORF3, ORF4a, and ORF4b, and these genes were sequenced from additional MERS-CoV-positive swab samples from which full-genome sequences were not obtainable because of lower viral loads. The primers used were 5\u2032-GAGGAATACGACCTCGAGC-3\u2032 (forward) and 5\u2032-TTGGA-GAATGGCTCCTCTTC-3\u2032 (reverse) for ORF3 to ORF4a and 5\u2032-ACAAAAGCTTTGGCCAAACAGG-3\u2032 (forward) and 5\u2032-CAGC-TAAAGCAGCTACATAGC-3\u2032 (reverse) for ORF4a to ORF4b.", "The full and partial genome sequences were aligned using Geneious V8.0.5 (https://www.geneious.com/). The MERS-CoV full genomes were phylogenetically analyzed using PhyML and BEAST.", "Clonality Classification of Loci Observed in MERS-CoV Genomes. A maximum-likelihood phylogeny of 291 complete or nearly complete MERS-CoV genomes was recovered with PhyML (5) under a HKY+\u0393 (9, 10) model of nucleotide substitution. ClonalFrameML (11) was used to reconstruct ancestral sequences on nodes in the PhyML phylogeny and to map substitutions onto individual branches. Each substitution was classified as apparently occurring once in the phylogeny (likely to have arisen via mutation), more than once (likely to be part of a recombined tract), or a reversion from a substitution occurring ancestrally (even more likely to be part of a recombined tract)." ] },{ "paper_id": "1bfdb418d0771a30669663e4fa7bc18f5745d780", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Each of the subjects' DNA was extracted from whole blood at the time of diagnosis using QIAamp DNA Blood Mini Kit (Gene Company LTD., Chai Wan, Hong Kong). DNA fragments were amplified through polymerase chain reaction (PCR), which was carried out in a total volume of 10 L containing 50 ng of genomic DNA, 200 mM dNTPs, 0.3 mM/mL of each primers (5\u2032 -CTGGAGACCACTCCCATCCTTTCT); (5\u2032 -GATGTGGCCATCACATTCGTCAGAT) in PCR buffer with 0.5 units Taq DNA polymerase (Takara, Shiga, Japan). After the initial denaturation step (10 min at 95\u2103), 35 cycles were repeated for 30 sec at 94\u2103, 30 sec at 52\u2103, 90 sec at 72\u2103, and 5 min at 72\u2103. DNA fragments were then separated by electrophoresis on 2.5% agarose gel.", "Two dimensional echocardiography was done to evaluate cardiac complications. Coronary arterial lesion was defined as following: 1) inner diameter that is >3 mm in children <5 yrs old and >4 mm in children \u22655 yrs old; 2) internal diameter of a segment \u22651.5 times that of an adjacent segment; or 3) lumen with irregular surface. Among these patients, 17 showed coronary dilatations and 38 did not.", "Student's t-test was used to compare the demographic characteristics between the two groups. Chi square test and Fisher exact test were performed to compare the genotype and allelic frequencies between the two groups. Its frequencies were compared by odds ratio. p value less than 0.05 was considered significant.", "Informed consent was obtained from his/her parents prior to the participation in the study. The study was approved by the hospital's ethics commitee." ] },{ "paper_id": "1bfeba839c9c98eb6e49ceb13cfcdba28620a61d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Aprotinin, colchicine, carbonyl cyanide m-chlorophenylhydrazone (CCCP), cytochalasin D, TPCK-trypsin, and soybean trypsin inhibitor were obtained from Sigma Chem. Co. (St. Louis, MO). Brefeldin A was from Epieentre Technologies (Madison, WI). Stock solutions of reagents were stored at -20\u00b0C.", "A useful model protein for studying Golgi retention signals has been the M glycoprotein (formerly called El) of the avian coronavirus infectious bronchitis virus (IBV)k Coronaviruses bud into the intermediate compartment or Golgi complex of mammalian cells (Griffiths and Rottier, Please address all correspondence to Dr. Carolyn Machamer, Department of Cell Biology and Anatomy, The Johns Hopkins School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205.", "Indirect immunofluorescence staining of transiently transfected COS-7 ceils was performed as described (Machamer and Rose, 1987; Machamer and Rose, 1988) . Gml and related mutants were detected using a monoclonal anti-VSV G antibody (5/~g/ml; Lefrancois and Lyles, 1982) followed by Texas red-conjugated, affinity-purified goat anti-mouse IgG (10 /zg/ml; Jackson Immuno Research Laboratories Inc., Avondale, PA)." ] },{ "paper_id": "1c202f2c3924d86f516deecda1d47f55d08337da", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1c3abd60f3deefb350c36d0f51ba2ae27eff56b5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The predicted mVCs are stored as metagenome scaffolds and they remain under their corresponding metagenome datasets (i.e. metagenome 'Taxon OID'). Thus, metagenome 'Taxon OIDs' can also be accessed the same way that any iVG and specific mVCs can be retrieved from the 'Scaffold Search' tool of the 'Find Genomes' tab ( Figure 1) .", "The habitat type classification is based on 11 distinct manually curated habitat terms (e.g. air, freshwater, marine, host-associated human, host-associated plants, terrestrial soil) previously described (11) . This classification allows the selection of mVCs from samples that belong to a single habitat type ( Figure 3C ).", "In order to alleviate some of the existing resource limitations, and enable the community to access and analyze an expanded version of the recently emerging viral genomics data we have developed IMG/VR, an integrated viral analysis system, within the Integrated Microbial Genomes with Microbiome samples (IMG/M) data management system (20) .", "The ecosystem classification is based on a previously developed five-tier hierarchical classification system (21) . All metagenome data sets are organized in three main classes of the top ecosystem tier: engineered, environmental and hostassociated; and then further divided into sub-tiers called ecosystem category, ecosystem type, ecosystem subtype and specific ecosystem (31) ( Figure 3A) . Currently, 78.3% of the mVCs belong to environmental samples, while 16.3% and 5.4% correspond to host-associated and engineered, respectively. Users can navigate through all samples at once or just reduce the search to any specific ecosystem class or category (i.e 'Environmental Terrestrial' Figure 3B ), and from there, select particular types, subtypes or specific ecosystems.", "In total, genomes from 36 bacterial and archaeal phyla were linked to viral sequences (Table 1) . A large number of these connections were previously unknown, including the identification of nine phyla (Atribacteria, Fervidibacteria, Armatimonadetes, Deferribacteres, Parcubacteria, Gemmatimonadetes, Ignavibacteria, Aminicenantes and Saccharibacteria) which were not previously reported to be infected by viruses in the NCBI RefSeq database or as prophages (30) ." ] },{ "paper_id": "1c3d3ea935a9625190ebf6f76b035999b03e03f0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1c468d9576bd22e199c4fe2028856afabb3746a7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Background. Parainfluenza virus (PIV) is a common cause of acute respiratory tract infections, but little is known about PIV infection in children and adults in Africa, especially in settings where human immunodeficiency virus (HIV) prevalence is high.", "Conclusions. Parainfluenza virus causes substantial severe respiratory disease in South Africa among children <5 years of age, especially those that are infected with HIV.", "The 3 PIV serotypes (1, 2, and 3) were found to cocirculate throughout the year and differed from year to year; seasonal peaks were observed for PIV-3 between September and November, which is spring in South Africa (Figure 1 ). The percentage of specimens testing positive for any PIV type varied by year, with a higher proportion of SARI positive for PIV in 2009 ", "The second and third analyses models were built using manual backward elimination in which nonsignificant variables were removed from the model one at a time starting with the variables with smallest magnitude of effect until all remaining variables had a P value of <.05. Covariates with a P value of <.2 at univariate analysis were assessed for significance with multivariable analysis; statistical significance was assessed at P < .05 for all multivariable models. Two-way interactions were assessed by inclusion of product terms for all variables remaining in the final additive models. For each univariate analysis, we used all available case information. For important variables in the HIV association and AF analyses that had substantial missing data, namely HIV infection status, we multiply imputed that variable as well as any variables that were incomplete and associated with HIV using chained equation multiple imputation over 10 iterations. When adjusting for respiratory viral coinfection in our models, we evaluated coinfection with each virus separately and also as a combined variable of coinfection with any of the tested viruses." ] },{ "paper_id": "1ca4dc2cbd2171a1b471d103caa4bb5d1f057eef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1ce2ec3b5d92a3f2ace27a00bde0165ba6761aa0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1ce4231aeefd5ac1caef8246df9984b7455d16df", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Month", "Number of deaths within 7 days (n) Ratio of deaths in 2015 (%)", "A. Monthly number of emergency room visits and deaths within 7 days of myocardial infarction." ] },{ "paper_id": "1cf06efb631fff1394f207cd3ad09376ed85f8cb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1cfa24297a36bcd526ad00635440d59bce705a17", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Fecal samples were thawed and suspended to 0.1 g/mL in chilled extraction buffer (PBS, 0.05% Tween 20, 1x complete protease inhibitor cocktail (Roche)). Suspensions were vortexed, nutated for 30 min at 4 C, cleared of cellular debris by centrifugation at 16,000 \u00a3 g for 10 min at 4 C, and stored at \u00a120 C.", "deviations above the value for the pre-immune serum.", "None. " ] },{ "paper_id": "1cfcdcf2a3783b9adba2b091bd50c5d8ac3252ff", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data were analyzed by unpaired t-test or ANOVA followed by the Dunnett's multiple comparison tests using Prism (Graph-Pad). P-value ,0.05 is considered statistically significant. ", "Vacuolar ATPase-inhibiting anti-influenza nanoparticles of host-directed therapeutics may be enhanced by surface modifications of drug-loaded nanoparticles. 53 For instance, influenza virus targeting by nanoparticles was recently demonstrated with a cell membrane-coated nanoparticle. 54 The strategy may be applied to further facilitate antiviral drug targeting. Future studies are warranted to further validate and improve the nanoparticle-based antiviral treatments.", "For TEM observation, negative staining was applied. First, 10 \u00b5L nanoparticles was added to glow-discharged grid and the droplet was placed on the grid for 30 seconds. Then, 10 drops of ddH 2 O was applied to the grid to wash away the excessive nanoparticles. Subsequently, the grid was stained with 10 \u00b5L of 1% uranyl acetate for 30 seconds and the staining was subsequently removed by wicking with a piece of filter paper. Nanoparticle size and zeta potential were determined by DLS using Malvern Zetasizer Nano ZS (Malvern Instruments, Malvern, UK) following the manufacturer's instructions. Each measurement was made with 1 mL of the nanoparticles at 1 mg/mL in water in a folded capillary zeta cell (Malvern Panalytical, DTS1070)." ] },{ "paper_id": "1d81eea0f16b71d643336838cd22e51125bf05ef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "His-tagged EF-G was purified from pET24b-fusA in E. coli BL21(DE3) as described (41) .", "Standard free-energies at zero force were computed for each trajectory according to", "U-G C-G C-G U-A U-A C-G C-G G-C G-C U-A C-G U-A A-U G-U A-U A-U G-C G-U A A G 12 G C A A46" ] },{ "paper_id": "1d8907508d6c233f454408abbfd624a9fda81f37", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1da4278cead869b78e5bf6205013a8407944f1f6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1dfb38c44ff4bd4534b37c8f42f3e18c282e66e7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "GO-BP enrichment analysis revealed that UBE2D4 and TUBGCP3 were primarily associated with cell differentiation, phylogeny and RNA stability, whereas CENPO may participate in intercellular communication (data not shown).", "Principal component analysis (PCA). PCA is a procedure used to emphasize principal components (uncorrelated variables) in a multivariate dataset. Raw data with k-dimension subspace were mapped to n dimensions space (k1630 cases of MERS-CoV infection and >580 associated deaths had been reported worldwide, mostly in Saudi Arabia [9, 10] ." ] },{ "paper_id": "1f263aae1c1dcc053a85fc4444f0bc02a01e5b68", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1f26b5e8291ea1ddc0a3131e8f93f7272093799e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Additionally, LDPs have performed with a high degree of accuracy and interlaboratory agreement. Blinded PT samples were distributed to 383 laboratories as part of a CAP PT survey for analysis of HSV; 91.6% correctly identified HSV-2, and 7.8% identified HSV, but not noting the subtype; an overall accuracy of 99.4% was obtained. Previous proficiency surveys showed similar results for samples containing HSV1. Over 90% of the laboratories used LDPs. 10 ", "These disorders are heterogeneous, which can lead to clinical diagnostic uncertainty or error; hence, large multigene panels are particularly useful to cover the spectrum of genes that may cause a clinical disorder. Importantly, the identification of pathogenic variants in affected individuals can inform medical management of family members and can identify those at risk early and also release negative individuals from clinical screening. 111 Genetic testing can also identify phenocopies such as Fabry disease, which can masquerade as isolated HCM. While Fabry disease is rare, disease-modifying treatment is available, and therefore, genetic testing provides essential clinical information for these patients.", "A total of 111 laboratories recently participated in a CAPsponsored proficiency assessment of NGS cancer panel testing (NGSST-A-2016), with data collection on 10 gene mutations (AKT1, ALK, BRAF, EGFR, FBXW7, IDH1, KIT, KRAS, NRAS, and PIK3CA). Of 1010 genotyping calls across the spectrum of mutations tests, 993 (98.3%) were called concordantly (unpublished data). 88 ", "In addition to continuous quality assessment of the \"wet laboratory\" procedures, ongoing national and international efforts to share data, and construct and maintain up-to-date curated databases for variant interpretation, are critical for quality care. As new mutations and variants are detected, interpretation and assessment of clinical impact, including determination of the clinical importance of variants of undetermined significance, is critical. Rapid generation of genomic data, disorganized data sharing, and a lack standardization have created challenges, and a more consistent approach to clinical sequence interpretation is needed, along with centralized and openly accessible databases for sequence and clinical information." ] },{ "paper_id": "1f2bfec9b985a04dc2645ceabc4e5e456a9ad9a5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1f3b676368e5c9a1582ab624cbf0884c383fddd2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "DNA templates were linearized by BamHI digestion and purified by successive phenol/chloroform extraction and column filtration (Qiagen, Benelux). SP6 polymerase directed transcriptions were carried out in 50 ml reactions containing $2 mg linearized DNA, 10 mM NTPs, 40 mM Tris-HCl (pH 7.9), 10 mM NaCl, 10 mM DTT, 6 mM MgCl 2 , 2 mM spermidine, 6 U of RNase inhibitor (RNAsin, Promega, Benelux) and 15 U of SP6 polymerase (Promega, Benelux). After an incubation period of 2 h at 37 C, samples were taken and run on agarose gels to determine the quality and quantity of the transcripts. Appropriate dilutions of the reaction mix in water were directly used for in vitro translations. Alternatively, transcripts were purified by phenol/chloroform extraction and isopropanol precipitation and quantified by UV absorption as described previously (14) .", "Ribosomal frameshifting is a translational recoding event in which a certain percentage of ribosomes are forced to shift to another reading frame in order to synthesize an alternative protein. This switch occurs at a specific position on the mRNA, called the slip site or slippery sequence, and can be either forwards (+1) or backwards (\u00c01). The nature and efficiency of frameshifting depends on several factors, including tRNA availability and modifications, and mRNA primary and secondary structure (1, 2) .", "Experiments were carried out in duplicate using seriallyin water-diluted mRNAs with final concentrations of 5 nM. Reactions contained 4 ml of an RNA solution, 4.5 ml of rabbit reticulocyte lysate (RRL, Promega), 0.25-1 ml of 35 S methionine (Amersham, in vitro translation grade), 0.5 ml of 1 mM amino acids lacking methionine and were incubated for 60 min at 28 C. Samples were boiled for 3 min in 2\u00c2 Laemmli buffer and loaded onto 12% SDS polyacrylamide gels. Gels were dried and exposed to phosphoimager screens. Band intensity of 0-frame and \u00c01 frameshift products was measured using a Molecular Imager FX and Quantity One software (Biorad). Frameshift percentages were calculated as the amount of \u00c01 frameshift product divided by the sum of 0 and \u00c01 frame products, corrected for the number of methionines (10 in the 0-frame product and 28 in the fusion product), multiplied by 100." ] },{ "paper_id": "1f475d5dbca18aa9710ca227dad58204cc1f21f3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Graphical Abstract Highlights d We describe cooperative neutralization and in vivo protection d Cooperativity turns non-neutralizing ebolavirus antibodies into potent neutralizers d A hotspot for antibody cooperativity identified on Ebola virus glycoprotein", "was more evident at lower concentrations (CI, 0.05-0.5 and DRI, 35-2 for FVM04 concentrations of 0.05-5 mg/mL; Figures S2D-S2F ).", "The 2014 Ebola virus (EBOV) disease (EVD) epidemic claimed over 11,000 lives, underscoring the need for effective therapeutics for this deadly virus and other members of the family Filoviridae that have caused human outbreaks in the past-Sudan virus (SUDV), Bundibugyo virus (BDBV), and Marburg virus (MARV) (Rougeron et al., 2015) . Monoclonal antibodies (mAbs) targeting the filovirus glycoprotein (GP) are among the most promising countermeasures for filoviruses ." ] },{ "paper_id": "1f541a086ac9bc30df8ee2060f958691fb4a0667", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Blood samples were collected using EDTA containing blood tubes and treated with sucrose lysis buffer and the nuclear cell pellets were stored at -80\u00b0C until DNA extraction. Genomic DNA was extracted from whole blood using the QIAamp DNA extraction kit (Qiagen Hilden, Germany, Cat no. 51304) according to the manufacturer's instructions.", "Statistical Package for Social Sciences (SPSS) version 14.0 was used for statistical analysis. The quantitative results were expressed as means \u00b1 standard deviation (SD). For comparing quantitative results between two groups, independent t-test was used, and for more than two groups ANOVA and post hoc least significant test (LSD) were used. Qualitative results were expressed as number (No.) and percent (%). Pearson chi-square test (\u03c7 2 ) was used for statistical analysis of the qualitative data. Differences were considered to be significant when the p-value was \u2264 0.05.", "Forward primer 5'GCCATTACCTTTGACTCTTCTGT3', Reverse primer 5' CCTGTTGGTAGTCCTTGTATT-TAGTATC3' and the probe sequence was as follows: AGAAACTTCCAGCCCATGAGCCG.", "This was a cohort study; all subjects were selected randomly from the Chest Outpatient Clinic and Pulmonary Function Unit in the National Research Centre and Chest Department of Cairo University over 24 months." ] },{ "paper_id": "1f5c1597a84ed1d4f84c488cd19098a091a3d513", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(https://www.who.int/westernpacific/emergencies/covid- 19) .", "This ", "The author declares no conflict of interests " ] },{ "paper_id": "1f71a8f9029056b6e7656ebd885ccce476e2f623", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "I nfectious diseases continue to be major health concerns worldwide: hepatitis C, AIDS, malaria, and tuberculosis (TB) are ongoing pandemics. A third of the world population is currently infected with the TB bacillus; millions of people are infected by influenza virus annually; and even though therapeutic drugs have slowed the threat of HIV-1, there is still no definitive cure or viable vaccine in sight. Although influenza virus vaccines provide protection, they must be reformulated annually, and the time lag from the spread of a pandemic virus to the availability of a vaccine is far too long. A universal vaccine against influenza virus is needed to limit high levels of morbidity and mortality. Newly emerging infectious diseases, such as swine H1N1 influenza, avian H5N1 influenza, severe acute respiratory syndrome (SARS), and dengue fever are a constant threat; and bacterial infections, such as the recurrent Salmonella outbreaks in the food industry, are costly to society.", "The technologies, computational methods, and genome information needed to successfully implement this approach now exist. Technologies such as next-generation sequencing have opened the door to sequencing total transcriptomes, encompassing mi-croRNAs, long noncoding RNAs, and mRNAs. This has raised the possibility that a previously unappreciated class of RNAs-the long noncoding RNAs-may play important roles in the host response to virus infection (4) . Proteomic technologies and accompanying informatics pipelines are evolving rapidly, with throughput and sensitivity approaching that of microarrays. Metabolomics, glycomics, lipidomics, and phosphoproteomics are young and comparatively undeveloped, but the promise is unlimited and the potential unprecedented. Moreover, the appropriate in vitro and in vivo experimental systems to generate useful pathogen-host interaction models are now available. Each of the four NIAID Systems Biology Centers has taken a unique approach to implementing this new research paradigm as outlined below.", "As highlighted in a recent review, systems biology is already making important contributions to cancer research (7) . The approach has been used to identify network motifs that can accurately predict the development of distant metastases in breast cancer patients-tumors that may develop years after the primary tumor and which frequently prove fatal. A network-centric approach has also identified specific oncogenes in certain types of B-cell lymphomas, and a multiscale mathematical model has been developed to test the efficacy of different radiation protocols, which has led to improvements in radiation therapies for colorectal cancer. The cancer field was one of the first research communities to aggressively embrace (and fund) the use of systems biology. We believe that the infectious disease community will build on the resulting substantial systems biology methodologies and insights to claim similar successes in the near future. We invite your thoughts and comments on this perspective." ] },{ "paper_id": "1f7394c2575f1eb1a196c9f19cd4b57ddd05789b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.00524-12/-/DCSupplemental. Figure S1 , PDF file, 0.4 MB. Figure S2 , PDF file, 0.1 MB. Figure S3 , PDF file, 0.2 MB. Figure S4 , PDF file, 0.1 MB. ", "Citation Chan JM, Rabadan R. 2013. Quantifying pathogen surveillance using temporal genomic data. mBio 4(1):e00524-12." ] },{ "paper_id": "1f7f3e09db31be0bc73e921a1034ec9de0d52ebe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Left: Spotting layout for a multiparameter analysis, Right: False-colored picture of an assay with CRP present as analyte.", "Peptide assay specificity assessed by different antibodies specific against the described targets (Reprinted from (9), License number 2982331327162).", "Results of a on-chip helicase-dependent amplification of two pathogens (Reprinted from (11), License number 2982330906644)." ] },{ "paper_id": "1f8144c7b80bb22a8af2478791657d4cbaa8d802", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Results of the phylogenetic analysis of the deduced amino acid sequences obtained for the 22 Korean strains and 10 reference coronaviruses are summarized in Fig. 1 ", "Korean strains belonged to four genetic clusters based on the description of the reference CCV strains of Table 2 . These included a unique Korean CCV cluster (cluster I), CCV type II and TGEV cluster (cluster II), intermediate cluster between CCV type I and II (cluster III), and CCV type I cluster (cluster IV).", "In summary, genetic differences of the M gene from Korean CCV strains were identified. Data from this investigation provide a platform for the molecular identification of different Korean CCV strains. Further sequence analysis needs to be extended to other parts of the genomes of CCV and FCoV field strains to obtain more detailed information about the predilection sites of such recombination and mutation events." ] },{ "paper_id": "1fe6e8c22714c1484434a2b5b334bedf7f216739", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "ATP concentration wa~s.determined in cell lysates using the luciferinluciferase assay (Boehringer GmbH) according to the manufacturer's instructions.", "In addition, they show that M~ can be resolved as a distinct intermediate between M0 and M3, the Golgi form.", "large number of ~-cop-containing buds and vesicular profiles." ] },{ "paper_id": "200eee0824f97c373a016370a5292af80121f351", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Osteonecrosis is a condition characterized by bone marrow ischemia and cell death which may subsequently lead to insufficiency fracture and secondary osteoarthritis requiring palliative surgery (1, 2) .", "Among 50 included patients, 32 (0.64%) were female and 18 (0.36%) were male with a mean\u00b1SD age of 37.3 \u00b1 12.3 years (range 14-65 years)." ] },{ "paper_id": "2011e171a1664541e88ec5333849781130565135", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2024ea5609babbd8769ee9f1898e825306b49cfe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A strain of Iranian ETEC was isolated from diarrhea samples of newborn calves that was positive for the K99 antigen. It was provided by Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran, and confirmed by biochemical and molecular tests. Genomic DNA of ETEC was extracted by using a DNA extraction kit (Bioneer, Korea). One pair of specific primer was designed and synthesized by Macrogen (South Korea) as follows: FanC-Forward: 5'-CGCGGAT CCGC-GGCGAATACAGGTACTATTAACTT-3' and FanC-Reverse:", "The t-test was used to detect significant differences between means of ELISA absorbance for determination of specific IgY antibody. Also, a repeated measure ANOVA was used to compare the means of ELISA absorbances between weeks. P-value<0.05 was considered significant." ] },{ "paper_id": "2041dc24bd4022a90b0b441ed6f1024f3e16dc77", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CONFLICTS OF INTEREST. The authors have no potential conflicts of interest to declare with respect to the research, authorship, and/or publication of this article.", "Bovine coronavirus (BCoV) is a member of the order Nidovirales, family Coronaviridae, subfamily Coronavirinae, genus Betacoronavirus, species Betacoronavirus-1. This species also includes Human coronavirus OC43, Porcine hemagglutinating encephalomyelitis virus, Equine coronavirus, and Canine respiratory coronavirus [1] .", "The Animal Care and Use Committee of the National Institute of Animal Health approved all animal procedures prior to the initiation of this study (authorization number: 11-083)." ] },{ "paper_id": "2060cb027399ce2ff97b6f9d17b932aa16dd0844", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Here, we propose a study to seek a useful and relatively non-invasive marker (i.e., serum EDN [sEDN] ) to predict favorable responses to nebulized budesonide or montelukast, common treatment options for young children with asthma.", "Montelukast was the chosen treatment for the OBS group because it has been reported that ICS is less effective in non-atopic populations. 21 Furthermore, from our clinical experience montelukast is preferred over ICS by both physicians and patients in Korea and Japan.", "At initial enrollment and when exhibiting asthma or upper respiratory infection symptoms at regular visits, nasopharyngeal swabs were collected and total RNA from common respiratory viruses was extracted and identified using a multiplex PCR system (Seeplex RV12 Ace Detection; Seegene, Seoul, Korea) that identifies adenovirus ( " ] },{ "paper_id": "20a7363b3ad53472952cc80c03489ff56b7178bc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For Canterbury participants, a research team member made phone contact with potential participants within 2 weeks of identification, obtained consent and conducted the first interview. A follow-up questionnaire was mailed at 4 weeks postvaccination.", "An SAE is defined as any untoward medical occurrence that: results in death; is life-threatening; requires inpatient hospitalisation or causes prolongation of existing hospitalisation; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or requires intervention to prevent permanent impairment or damage.", "Since the two regions recruited and collected data in different ways, we have not attempted to analyse any differences." ] },{ "paper_id": "20c05a8e1616b61a78300ee5911bc70bd1c952d3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Corosolic Acid and Lagerstroemin versus Tannic Acid and PGG: Which are More Bioactive?", "Corosolic acid -0", "Insulin 1 nM 156 *Activity of b-PGG was arbitrarily assigned as 100." ] },{ "paper_id": "20dd62d0387e8b4231d67af2eaf757767492656e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In 1986, it was proposed that cytokines released by activated T-lymphocytes initiate and maintain the psoriatic process by stimulating keratinocyte proliferation [3] . Since that time it has become clear that, Hanaa Rasmy, Nancy Mikhael, Somaia Ismail upon stimulation, keratinocytes are also able to secrete an array of different cytokines with a variety of functional effects on both themselves and other cell types, including T-lymphocytes [4] .", "Total RNA was extracted using QIA amp RNA extraction kit provided by QIAGEN worldwide companies. The concentration and purity of RNA was determined by measuring its absorbance at 260 nm (A 260 ) and 280 nm (A 280 ) in a UV visible spectrophotometer. Total RNA (2 \u03bcg) was reversetranscribed to cDNA with High-Capacity cDNA Archive kit provided by Applied Biosystems. cDNAs were stored at -20\u00b0C until real-time quantitative PCR was performed.", "Psoriasis is a chronic inflammatory condition which is the result of persistent stimulation of T cells by antigens of epidermal origin [1] . This persistent stimulation of T cells is the result of interaction between T cells, antigen-presenting cells, i.e. Langerhans cells, and antigens, and comprises the following steps: primary signals (signal 1) including T-cell receptor stimulation by peptide antigen, costimulation (so-called accessory signals) (signal 2) and T helper type 1 (Th1) differentiation and proliferation [2] .", "All data were collected from the patient charts and entered into a computerized spreadsheet. The fit of the data to the normal distribution was tested with Kolmogorov-Smirnov test. Since the distribution of the data was significantly different from normal, nonparametric statistics were further used. Comparisons were made using Mann-Whitney U, Kruskal Wallis and Wilcoxon signed ranks tests between variables adjusted for appropriate covariates, and Spearman rank correlation coefficients were calculated between the assessed variables. The null hypothesis was rejected with a two sided p value of < 0.05. All analyses were performed with SPSS 11.0 for Macintosh (Statistical Package for the Social Sciences. SPSS Inc., Chicago, IL, USA)." ] },{ "paper_id": "20f863c8fc0ff956ea9f902a2f9d1299ab8514a6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In the original GIB, Common Object Request Broker Architecture (CORBA) was used for internal communication. However, CORBA was not needed for GIB-V because of remarkable advances in hardware performance that solved the problems associated with managing the large quantity of data.", "Virus genome analysis has a long history. In 1977, Frederick Sanger successfully sequenced the entire genome of Phage fphiv;X174 (1). Since that time, a huge number of virus genomes have been sequenced. Virus genome sequences provide researchers with important information needed to analyze virus evolution, pathogenicity and diversity (2) (3) (4) .", "GIB-V can be accessed from http://gib-v.genes.nig.ac.jp/. Registration is not necessary, and use of the database is free.", "The functions of GIB-V are described below. Most of these functions are accessed from the main menu bar displayed in the Web page." ] },{ "paper_id": "2105c805d6a0a560348c1bb6bf620685944ba9dc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "of (benzylidene-hydrazono)-1,4dihydropyridines with \u03b2-amyloid, acetylcholine, and butyrylcholine esterases. Bioorg. Med. Chem. 18, 2049 -2059 . Angelisov\u00e1, P., Drbal, K., Horejs\u00ed, V., and Cern\u00fd, J. (1999 . Association of CD10/neutral endopeptidase 24.11 with membrane microdomains rich in glycosylphosphatidylinositolanchored proteins and Lyn kinase. Blood 93, 1437-1439. Araki, W., Kitaguchi, N., Tokushima, Y., Ishii, K., Aratake, H., Shimohama, S., Nakamura, S., and Kimura, J. (1991) . Trophic effect of \u03b2-amyloid www.frontiersin.org", "In the context of this review it is important to mention another cholesterol and ganglioside enriched membrane domain, which share some similarity but are physically and functionally distinct from the lipid rafts, the tetraspanin-enriched microdomains (TEMs). Tetraspanins are a large family of small membranespanning proteins (Yanez-Mo et al., 2011) , numbering at least 32 family members in mammals. They are involved in a whole range of cellular processes, from cell morphology and motility to signaling pathways (Hemler, 2005) .", "It has traditionally been difficult to reach any kind of consensus concerning the definition of lipid rafts. However, in 2006 at the Keystone Symposium on Lipid Rafts and Cell Function in Colorado it was agreed that \"membrane rafts are small (10-200 nm), heterogeneous, highly dynamic, sterol, and sphingolipid-enriched domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through proteinprotein and protein-lipid interactions\" (Pike, 2006) . The long, saturated acyl chains of sphingolipids allow tight packing hence their juxtaposition with the kinked, unsaturated acyl chains of bulk membrane phospholipids leads to phase separation (Brown and London, 2000) . The cholesterol molecules can act as \"spacers,\" filling any gaps in sphingolipid packing (Simons and Ikonen, 1997) ." ] },{ "paper_id": "21337e54a7d02b12aea5f5835648d69aef32701e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "pBS-U6-Apa1. They also thank Johanie Charbonneau, Pascal Chartrand, Dominic Dulude, Alexey Karetnikov and Stephen Michnick for stimulating discussions and for critical reading of this manuscript. ", "Deleting two different regions has an opposite effect on the HIV-1 5 0 UTR IRES activity", "The IRES located in the 5 0 UTR of HIV-1 RNA is functional in Jurkat T cells" ] },{ "paper_id": "214d64d4237818509b17cb5ac82107116407b2e0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "siMDA5, Qiagen validated siRNA (S103649037). siControl and siRIG-I were synthesized by the custom design service of Qiagen.", "Supplementary Data are available at NAR Online: Supplementary Figures 1-7 , Supplementary Methods and Supplementary References (18, (50) (51) (52) ." ] },{ "paper_id": "2159d7f128a1995e7131a8d4f036fcb3cec6e332", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors declare no conflict of interest." ] },{ "paper_id": "216dbed8787845bd23a22cc2dd10964aef95fe71", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2176706829fb93fa471a706137b138e8766b4f32", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Received for publication 10 November 1982 and in revised form 28 March 1983. ", "Rats. Lewis female RT1 ~ rats, 6-8 wk old, were purchased from Harlan Sprague Dawley, Inc., Indianapolis, IN." ] },{ "paper_id": "219fb67386566e8bd98da17b591ae91ffc1f2b0d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "21a164b5e3d241d8d34eb335bf8db56dc945fea6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Similarly, a large proportion of survey respondents reported moderate or great familiarity with many components of the intervention, including accountability agreements (96%), performance targets (98%) and reporting requirements (94%).", "Conditions and processes that offer the greatest opportunity for improvement", "Site-A stood out as a particularly strong example of this:" ] },{ "paper_id": "21a19241ff8c8602a9cd610ceea62e746a6493e2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "No patient involved." ] },{ "paper_id": "22238e30828eb4613d777bea7bd3ff321aae450c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. Extracted data were managed in a Microsoft Access database and were analyzed with standard parametric and nonparametric techniques. Data for categorical variables were compared with Yates' corrected \u03c7 2 analysis, and data for continuous variables were analyzed for significant differences with the Student t test or, in the case of non-normally distributed parameters, the Mann-Whitney rank sum test. Differences between groups of continuous variables were compared using one-way analysis of variance (ANOVA) or Kruskal-Wallis one-way ANOVA on ranks. All statistical tests were 2-sided. Statistical computations were performed with SigmaStat 2.03 software (SPSS Inc., Chicago, IL). The level of significance was set at p < 0.05.", "\u27a3 Many travel-acquired infections are preventable by specifi c behaviours, vaccines, or chemoprophylactic medications, so interventions and policies that encourage uptake of pretravel advice should be promoted." ] },{ "paper_id": "22694a0a131da58c1a82a0d2d1556e0ccd8617c5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2271485cae8757f2abdb1c2d012bb892c5421ba4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "However, despite these efforts, this novel virus was able to spread via infected people traveling within China and internationally. Furthermore, the mechanism of spillover that led to human infection is still uncertain, although it has all the hallmarks of a bat-origin SARS-related coronavirus (SARSr-CoV) [4] . This leads us to two questions that we need to think \u204e Corresponding author. through even now to get ready to prevent the next 2019-nCoV-like pandemic:", "Dealing with the risk of future epidemics and pandemics requires a global effort. China is located within a major 'emerging disease hotspot' in Southeast Asia, but there is also a high risk of future diseases originating in sub-Saharan Africa, South Asia and Latin America [24] . Furthermore, the drivers of disease emergence are human activities that are expanding on a global scale, including deforestation, agricultural intensification and the wildlife trade. This has led to an exponential increase in the frequency of animal-human contact and likelihood of novel disease emergence and spread, suggesting that pandemics will become more frequent and more devastating in the future. These threats face all countries because once diseases emerge, they travel rapidly and freely through our global networks of travel and trade. We look forward to continued collaboration among scientists from China and the rest of the world, and to helping develop these new strategies to preventing the next pandemic.", "The first question is why did this virus spread so rapidly, and how can we deal with this risk? China has changed significantly since the emergence of SARS in 2002-2003. The economy has expanded, and many people have become wealthier, leading to an expansion of air and high-speed train travel. It is estimated that 3 billion individual journeys were planned during the Lunar New Year holiday (Chunyun), around 80 million of these being flights. The flight habits of Chinese citizens have changed alsowith many more flying internationally for business or tourism. In addition, since 2003, there has been an increase in travel between China and African countries, across Southeast Asia and into the New World as part of China's expansion of business and trade. This largely explains why the virus was able to spread out of China much more rapidly than SARS-CoV, which took over 2 months to move to Hong Kong then to the rest of the world." ] },{ "paper_id": "2272b370fe7b1e730af1659f9e3099c451b1a21d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2285bbcea934e093b35c23152a3314aab4969ddd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The TCEM practice guideline was published in 1996. There were about 134 injection types of herbal remedies being used in China.", "The first group of doctorate students in the area of TCEM at Guangzhou TCM University graduated in 1996." ] },{ "paper_id": "22c00b12361acc7b59c2874d165c8f9bcee54b5d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Tzu Chi Medical Mission Project 106-06-03, Buddhist Tzu Chi Medical Foundation.", "Peter S. Temes emphasizes that the following three aspects should be considered in education reform: Keeping it real, making it new, besides, recruiting and retaining the right teacher [25] . Strategies and practices in education reform that are established on the basis of a realistic understanding fulfil ", "A medical education that highly integrates clinical learning in basic curriculum facilitates context-based reflection. By establishing highly integrated courses with case-based learning and integrating the experiential learning of medical students regarding their medical knowledge, skills, and attitude, students can be guided to develop self-awareness and achieve self-regulated learning, which can enhance their confidence in clinical competency.", "Taiwan's medical education program has undergone five main transformations [ Table 1 ], as revealed by an analysis of the program design from various perspectives: First, the program previously emphasized individual discipline, but currently, the program emphasizes clinical case integration. Second, the program was previously based on those of other countries, but currently, the program is witnessing a transformation in accordance with Taiwan's higher education environment. Third, the program involved a one-stage learning process, but it currently involves a two-stage learning course, including undergraduate and PGY. Fourth, the program previously involved a superior elite education approach, and this has currently been transformed into a scientific education approach involving liberal humanism. Finally, the program previously applied a uniform teaching approach, and this has been replaced by a diverse, proactive, and innovative learning environment [9] ." ] },{ "paper_id": "22dce3fab7317bb2a8ff48f0da6f2c9717dc6ed9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Previous studies have reported a significant association between the onset and severity of astrovirus infections and age in young puppies (5-7 weeks old) [7] , mink (3 weeks old) [6] and children (under 2 years old) [20] .", "Between February and December 2010, samples of dog feces (n=91) were collected from two animal shelters and three animal hospitals located in Seoul and the Gyeonggi region of South Korea. All dogs were aged between 1 and 24 months and were suffering from diarrhea. Infection with canine parvovirus (CPV) and canine coronavirus (CCoV) was diagnosed by PCR using previously described primer sets [9, 23] .", "Therefore, the aims of the present study were to examine the prevalence, genetic diversity and geographical relationships between CAstVs and CKoVs in Korean dogs." ] },{ "paper_id": "22f98765239b02e3e5810fd976971ca87bab092b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "231ba154ea0d9a668c5c5e7e5732c4f223608f6d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "23b89b2ee6a5870dd94c479b892cda6a54c8ab6f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Galactosyl transferase assays were done as described in Brew et al . (1975) .", "To identify slowly sedimenting synaptic vesicles, Sl and PIM fractions were applied to 5-25 % glycerol gradients as described in Clift-O'Grady et al . (1990) , except substituting buffer C without BSA for buffer A and adding a 0.4-ml 2 M sucrose pad . After centrifuging 1 h at 218,000 g, gradient fractions were collected, TCA precipitated, fractionated by PAGE, transferred to nitrocellulose, and probed with anti-synaptophysin (SY38), followed by 1251 goat anti-mouse IgG .", "For equilibrium gradients, -0 .2 ml of sample was applied to a 0.5-1 .5 M sucrose gradient with 0.4 nil, 2 M, and 0.4 ml, 2 .25 M buffered sucrose pads and centrifuged 16-17 h at 32 .5 k rpm in a SW55Ti rotor (except in Fig . 6 where the 2 .25 M sucrose pad was omitted) . The density of each fraction was calculated by measuring refractive index of each fraction ." ] },{ "paper_id": "23cc9704b77903e3ec5e9ecb81ebf83b3a231c4c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "23fcb75440f439f30f656e0c6b47c6f565f32ef2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "23ffba1251c42cd4311635ab25afeba065146568", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Using the Bioedit 7.0.5.3 software (6), the GsuI (BpmI) restriction enzyme was selected which is able to cleave the ", "This study aimed to evaluate the use of a restriction enzyme assay as a specific, sensitive and practical tool to differentiate genotypes of BCoV for the molecular epidemiology of BCoV-caused diseases.", "This article reports the use of the GsuI restriction enzyme to differentiate genotypes of Bovine Coronavirus (BCoV), based on an 18-nucleotide deletion of S1-coding region found in one of the two genotypes. It was concluded that this assay can be used as a rapid tool for BCoV genotypes differentiation." ] },{ "paper_id": "2407834245c872e91a78cdb9bd63ac8f81a49231", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Animals. The present study was approved by the Institutional Animal Care and Use Committee of Shanghai University of Traditional Chinese Medicine (Shanghai, China), and all procedures were performed in accordance with the National Institute of Health's guidelines (14) . A total of 46 male 8-week-old Wistar rats with a mean weight of 200\u00b110 g were provided by the Shanghai SLAC Laboratory Animal Co., Ltd.", "Protein extraction and western blot analysis. Plasma membrane proteins were extracted from adipose tissues using a radioimmunoprecipitation assay lysis buffer (cat no. 89900, Pierce; Thermo Fisher Scientific, Inc., Waltham, MA, USA), total protease inhibitor and phosphatase inhibitor, as described previously (16) . Protein concentration was measured using a commercial bicinchoninic acid assay kit and a microplate reader at 570 nm. Subsequently protein (40 \u00b5g/lane) was separated by 10% SDS-PAGE and transferred to a polyvinylidene difluoride membrane (Bio-Rad Laboratories, Inc., Hercules, CA, USA Statistical analysis. All data are presented as the mean \u00b1 standard error of the mean. For multiple comparisons, differences were analyzed using one-way analysis of variance followed by Tukey's multiple comparison test. P<0.05 was considered to indicate a statistically significant difference. All statistics were analyzed using Graphpad Prism version 6.0 (GraphPad Software, Inc., La Jolla, CA, USA).", "Histopathology. Adipose tissues were collected at 11 weeks and fixed in 4% formalin at room temperature for 24 h, embedded in paraffin and sliced serially into sections 5-\u00b5m thick. To determine adipocyte size, hematoxylin and eosin staining was conducted on EATs at room temperature for 30 min. Five visual fields were randomly selected from each section with an Olympus BX51 light microscope (Olympus Corporation, Tokyo, Japan) and examined using Image-Pro Plus version 6.0 (Media Cybernetics, Inc., Rockville, MD, USA) to determine the average adipocyte diameter. Toluidine blue staining was also performed on EATs for 1 h by briefly submerging tissue sections in 0.1% aqueous toluidine blue (Sigma-Aldrich; Merck KGaA, Darmstadt, Germany) at room temperature, the histological images were used to quantify the number of mast cells present, as previously described (15) . Mast cell numbers were counted using a light microscope and were presented as cell numbers/mm 2 ." ] },{ "paper_id": "241348149ec43ddce1d3033145b00307db56aea0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data are expressed as mean \u00b1 SD, and statistical analysis was performed with analysis of variance (ANOVA). A statistical difference was accepted as significant if P < 0.05.", "The rat lung tissues were homogenated using liquid nitrogen, and total lysates were obtained from rat lung tissue by RIPA lysis buffer (Beyotime Inc, Jiangsu, China). Equivalent amounts of protein (30 \u03bcg) of each sample were separated by electrophoresis using 12% SDS-polyacrylamide gels. After being transferred onto 0.22 \u03bcM nitrocellulose filter membranes and blocked in 5% skimmed milk, the bands were then incubated with the corresponding primary antibodies (ACE-2, TGF-\u03b2).", "The concentrations of ANG-(1-7) in lung tissue were measured using ELISA kits (R&D Systems Inc., MN, USA) according to the manufacturer's instructions.", "Total RNA of rat lung tissue was extracted by using Trizol agent (Invitrogen, Carlsbad, CA, USA). First-strand cDNA was synthesized by a M-MLV reverse transcripase kits (BestBio Inc, Shanghai, China) from 2.5 \u00b5g per sample of total RNA according to the manufacturer's instructions. The primer pairs were designed by primer premier 5 (PREMIER Biosoft International, Palo Alto CA, USA), and original infor-mation of cDNA were aligned in the GeneBank. The primers were checked and synthesized by Genescript Company (Nangjing, China). The primer pairs for TGF\u03b21 are GAAGACATGACCCTGCTGGTGA (forward chain) and CTGGTGCTCTGGGCACTTGA (reverse chain); ACE-2 are AATCGTAGGCTCTGGGCTTGG (forward chain) and TTCGATCAACTGGTTTCGGTTGTA (reverse chain)." ] },{ "paper_id": "246f59ddffedd4a166b9317dee38bdf6077b2f3f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Submit your manuscript here: http://www.dovepress.com/drug-design-development-and-therapy-journal Drug Design, Development and Therapy is an international, peerreviewed open-access journal that spans the spectrum of drug design and development through to clinical applications. Clinical outcomes, patient safety, and programs for the development and effective, safe, and sustained use of medicines are a feature of the journal, which has also been accepted for indexing on PubMed Central. 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. ", "Drug Design, Development and Therapy Dovepress submit your manuscript | www.dovepress.com Dovepress 2255 O r i g i n a l r e s e a r c h open access to scientific and medical research Open access Full Text article http://dx." ] },{ "paper_id": "24709e4ba406a998d011ea9b31d33279bbabedb5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "beamsize of between 0.03 \u00c2 0.03 mm 2 and 0.06 \u00c2 0.07 mm 2 , depending on the size of the crystals. On I24, the X-ray beam was homogenized with a 0.25-mm carbon plate and focused downstream from the crystal. Using 0.1 s exposure times and 100% beam transmission, typically 4-15 useful images could be collected from a crystal (Table 1) .", "PaSTRy assay. Thermofluor experiments 25 were performed with an MX3005p RT-PCR instrument (Agilent). SYTO9 and SYPROred (both Invitrogen) were used as fluorescent probes to detect the presence of RNA and the exposed hydrophobic regions of proteins, respectively. Fifty-microlitre reactions were set up in a thinwalled PCR plate (Agilent), containing 0.5-1.0 mg of the CVA16 virus, 5 mM SYTO9 and 3 \u00c2 SYPROred in PBS (pH 7.4), and the temperature ramped from 25 to 99\u00b0C, with fluorescence recorded in triplicate at 1\u00b0C intervals ( Supplementary Fig. S4 ).", "(d-f) Structural differences in VP1 (blue) and VP3 (red) due to capsid expansion and VP1 egress (d, mature EV71; e, empty 80S-like EV71; f, 135S-like CAV16). Note especially the changes in the VP3 GH loop, which is labelled. As appropriate, the rough inner and outer boundaries of the shell are marked as grey arcs (panels (a,d-f))." ] },{ "paper_id": "247161ad51b7f362e9cadfcd39e94dd6a1a26ca3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In panel (f), the 100% represents the count of deaths or cured cases. ", "We summarise the officially reported data from Wuhan, China in Figure 2 . There is an increasing trend of daily new confirmations and deaths. We argue that these data were heavily impacted by availability of medical supplies and health care workers.", "where" ] },{ "paper_id": "24bc853dce27cbe938ca42aefdaa4e788df30481", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Blood samples were collected aseptically for a CBC and blood culture each morning, and feces were collected each morning for culture. Any calf still alive on day 4 was euthanized for sample collection. Samples collected at necropsy for culture included ileal contents, ileal tissue, mesenteric lymph nodes, and bile. Ileal tissue also was collected for histology, immunohistochemistry (IHC), and assessment of barrier function in Ussing chambers.", "An appropriately filled 2 mL EDTA collection tube was used for the CBC.", "Unstained, formalin-fixed paraffin-embedded ileal sections were stained using a mouse monoclonal anti-Salmonella antibody and standard IHC techniques. A serial section was included on each slide in which the primary antibody was omitted and replaced with the blocking serum to assess nonspecific staining. Sections were deparaffinized and rehydrated, then treated with a 3% H 2 O 2 /70% MeOH block followed by a protein block (#MP-7402: normal horse serum, Vector, Burlingame, California). ", "This study was approved by the NC State University Institutional Animal Care and Use Committee (protocol #16-050A). Thirty dry cows (15 control and 15 vaccinated) were given the SRP Salmonella Newport bacterin (Zoetis; Parsippany, New Jersey) or saline SC in the neck at cessation of lactation (dry off) and again 3-4 weeks later with 1.5 in, 18 gauge needles. All cows were identified by a colored neckband and housed together on a grass lot with access to a total mixed ration." ] },{ "paper_id": "24d4cd7729a8df22c9cab12f20e96aa9bf1332a2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Studies have suggested higher incidences of nonspecific reactive hepatitis in men than in women, but no sex-specific differences were found in the present study [11] .", "Comparing respiratory virus-specific differences between the groups A total of 131 patients (24.6%) were infected by respiratory syncytial virus A, 128 patients (24.1%) \u2021 increase rate of AST or ALT was calculated only in in AST or ALT elevated group.", "Statistical analyses were performed using PASW Statistics ver. 18.0 (IBM Co., Armonk, NY, USA). Continuous variables were analyzed using the unpaired 2-tailed t-test or analysis of variance, and categorical data were analyzed by using the chi-square test or Fisher exact test. A p-value less than 0.05 was considered statistically significant in all tests.", "We believe that one of the merits of this study is our exhaustive investigation of all patients admitted to a single university hospital for lower respiratory tract infection, and that it more clearly observed virus-specific features by excluding cases of double infections." ] },{ "paper_id": "24df3883c547f5976077bc7a924eec9ae8fa9e71", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In the replicative cycle of RNA viruses, the crucially important process of RNA-templated RNA synthesis is generally performed by an RNA-synthesizing complex of viral enzymes (1, 2) . Commonly, its core subunit is a single RNA-dependent RNA polymerase (RdRp) that drives the production of template strands for replication, new genome molecules, and-in many RNA virus groupsalso subgenomic (sg) mRNAs. This canonical RdRp is structurally conserved among RNA viruses and widely accepted to drive catalysis of phosphodiester bond formation via a well-established reaction mechanism involving two metal ions that are coordinated by aspartate residues in its motifs A and C (3) (4) (5) .", "Alignments of nsp8 sequences were made using Muscle (16) . Sequences used included the alphacoronaviruses human CoV 229E (NC_002645), human CoV NL63 (NC_005831), and bat CoV HKU8 (NC_010438); the betacoronaviruses SARS-CoV Frankfurt-1 (AY291315), mouse hepatitis virus A59 (MHV, NC_001849) and human CoV OC43 (NC_005147); and the gammacoronaviruses beluga whale CoV SW1 (NC010646), turkey CoV (NC_010800) and avian infectious bronchitis virus (IBV, AJ311317).", "The (functional) implications of these observations are not clear at present, but additional structural studies will likely be required to address these issues in detail, and gain insights that may aid in explaining the in vitro results presented here. Likely, such experiments will also offer further information regarding the residues that are involved in nucleotide positioning, Mg 2+ coordination and RdRp chemistry." ] },{ "paper_id": "24ec3df6486c04e0eb67d213475f3f1b20fe9fec", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "252878458973ebf8c4a149447b2887f0e553e7b5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Infection with N. veterana might have followed inhalation in this dog, or alternatively, it might have followed ingestion of a contaminated penetrating foreign body, especially as the dog had a history of chewing sticks. The latter could also have explained the gagging behavior that was initially observed, which was otherwise unexplained. Additionally, culture of the focal jejunal mass grew Lactobacillus acidophilus as well as Candida, suggesting the possibility of perforation secondary to direct trauma or the inflammatory lesion itself. Histopathology of the jejunal mass revealed no evidence of plant or foreign material. Finally, it is possible that the organism was introduced by direct cutaneous inoculation, such as from a plant awn or other penetrating organic matter.", "Early detection and intervention is critical for patients with opportunistic infections secondary to immunosuppression. The identity of the organism to the species level in this dog was facilitated by MALDI-TOF MS and led to initiation of appropriate antimicrobial treatment sooner than traditional gene sequencing methods. The clinical utility of MALDI-TOF MS could have broader applications, particularly in animals with uncommon infections that are slow-growing and fastidious. In this case, successful treatment of disseminated N. veterana infection was possible with proper antimicrobial treatment and might be facilitated if underlying immunosuppressive drug treatment can be discontinued. ", "On initial evaluation at the VMTH (day 0), the dog was febrile (103.7\u00b0F) and had a moderate right thoracic limb lameness. Pain was elicited on palpation of the caudal thoracic vertebral spine, dorsal and lateral flexion of the cervical spine, and on elbow extension bilaterally. Mild joint effusion was noted in the tarsi, carpi, and elbows. A CBC was performed, and the only hematologic abnormality was leukocytosis (38,350 cells/uL, reference range, 6,000-13,000 cells/uL) characterized by a mature neutrophilia (36,433 cells/uL, reference range, 3,000-10,500 cells/uL). Arthrocentesis of the carpus, tarsus, elbow, and stifle revealed mild-to-moderate nondegenerate neutrophilic inflammation (neutrophils comprised 44-75% of total nucleated cells present). No microorganisms were observed. Examination of CSF obtained from the cisternal space revealed no abnormalities. No other diagnostics were performed. A diagnosis of primary immune-mediated polyarthritis (IMPA) was made, and an immunosuppressive dose of prednisone (1.1 mg/kg PO q12h) and tramadol (2.8 mg/kg PO q8-12h as needed) were prescribed at the time of discharge (day 2)." ] },{ "paper_id": "254270af7f396d35475aee946cc1b3f9a3694e29", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Caspase-3 staining Splenocytes were cultured ex vivo for 4 h in RPMI 1640. Cells were then stained for surface markers, fixed, permeabilized, and stained with PE Active Caspase-3 Apoptosis Kit (BD PharMingen).", "The Gene Ontology Resource website (http://geneontology.org/), AmiGO2 version 2.4.26, was used as source of annotated ISGs. Search criteria were as follows: search \"ontology,\" species \"Mus musculus,\" and GO terms response to type I IFN (GO:0034340), cellular response to type I IFN (GO:0071357), response to IFN\u03b2 (GO:0035456); and cellular response to IFN\u03b2 (GO:0035458; Table S1 ). The downloaded gene sets were filtered for duplicated entries to obtain the numbers of genes listed below. As an additional ISG gene set, the GO set \"response to type I IFN\" was downloaded from MSigDB. This MSigDB gene set contains mouse orthologues of human genes of the Homo sapiens GO gene set.", "Cytokine in vivo treatments C57BL/6 mice were infected with Cl13 (2 \u00d7 10 6 PFU) and recombinant mouse IL-27 comprising both functional subunits (R&D Systems) or recombinant mouse IL-35 comprising both functional subunits (Adipogen), each at the specified concentration, administered daily by intraperitoneal injection on 0-8 dpi.", "Statistical analyses were performed as described in the figure legends. R version 3.4.3 was used for computational analysis and plotting (R Core Development Team, 2008); Prism was used for plotting selected panels." ] },{ "paper_id": "254c09779d5d51cd41becfb1ef4d3fcb08a0ba8f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "25576dd63e9bdf1bef094279010e378d096d40f2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All National Institute of Allergy and Infectious Diseases (NIAID) Integrated Research Facility (IRF) and SAB animal facilities and animal programs are accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International. The study protocols were reviewed and approved by the SAB and NIAID IRF Institutional Animal Care and Use Committees in compliance with all applicable federal regulations governing the protection of animals and research.", "With SAB-139", "For fluorescence reduction neutralization assay-50% (FRNA 50 ) and plaque reduction neutralizing test-50% (PRNT 50 " ] },{ "paper_id": "2559cb0b4a2175212495ab7d44d9305db4a06c05", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "ZBD-HEL1 may have been a critical event to facilitate the genome expansion of ancestral small-sized nidoviruses, thus setting the stage for the subsequent ExoN-driven expansion towards even larger nidovirus genomes (19, 57) .", "The nsp10-nucleic acid complex: towards the dsRNA unwinding mechanism", "Among +RNA viruses, whose RdRps generally have a high error rate, nidoviruses stand out for their large to very large genome size (13-32 kb) . Consequently, the replication fidelity of nidoviruses, in particular coronaviruses, has been the subject of intense study. Most recently, the identification of a unique 3 0 -to-5 0 exoribonuclease (ExoN) activity has provided the basis for the hypothesis that a primitive proofreading mechanism operates to promote the fidelity of RNA-dependent RNA synthesis in nidoviruses with >20 kb genomes (21) (22) (23) (24) (25) (26) (27) ." ] },{ "paper_id": "259f3f6bc30f4fce9f20d4ca222e2d5d04b5377d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Abbreviation EBV, Epstein-Barr virus.", "Monoclonal antibody technology has undergone rapid and innovative reinvention over the last 30 years. Application of these technologies to human samples revealed valuable therapeutic and experimental insights. These technologies, each with their own benefits and flaws, have proven indispensable for immunological research and in our fight to provide new treatments and improved vaccines for infectious disease.", "In the future, monoclonal antibody technology promises to become higher throughput and more efficient, allowing scientists to screen for exceedingly rare antibody specificities and B cell subsets. Furthermore, in combination with technologies evolving in vitro, valuable human antibodies may become further optimized, both in terms of their specificity and stability. For instance, researchers are currently trying to stabilize antibodies so that they can survive extreme temperatures, allowing field medics to have access to these treatments without concern for degradation when ideal storage conditions are not available." ] },{ "paper_id": "25a01c665ab20de80b75d48a2f71081666bca429", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "25a10dcacb257ac926ad42124f605189b3789d3f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "25aad84c22269cf7221d0c22737e2e01a36ec51b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In conclusion, G-rich sequences can have a major impact on slippage and its directionality.", "Interest in the potential of synthetic compensatory frameshifting near the sites of frameshift mutations to ameliorate a subset of genetic disease, prompted the testing of complementary oligonucleotides for frameshift stimulatory effects (60) (61) (62) (63) . Whether sequences that can bind to DNA, such as CRISPR-cas nickase mutants (64, 65) , would create a counterpart partial 'roadblock' structure for slippage stimulation, merits future work.", "Evolutionary selected transcription slippage is utilized in the expression of viruses such as the Paramyxoviruses, Sendai virus and Parainfluenza virus (3, 4) , the Filovirus, Ebola virus (5) (6) (7) , the large Potyviridae family (8-10), chromosomal genes such as Thermus thermophilus dnaX (11) , numerous genes in an endosymbiont (12) , a variety of bacterial Insertion Sequences (13) (14) (15) (16) , several medically important plasmid genes of Shigella flexneri (17) (18) (19) , and counterpart chromosomal toxin secretion genes in Citrobacter rodentium and Yersinia pseudotuberculosis (20) . Further, an extensive bioinformatic analysis of bacterial genomes has revealed many candidates that have yet to be experimentally explored (13, 15, 16) . Transcriptional indel errors are relevant to certain disease states (21) (22) (23) (24) (25) and maybe significant for aging (26, 27) ." ] },{ "paper_id": "25c88fafba786f31d034614ba0f6efce5c687594", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The characteristics of the 14 hospitals are presented ", "Hospitals with an RRS showed a statistically significant ", "The " ] },{ "paper_id": "25fd0362dfe0a62ca9ee6f9f634e24ef9a527dfc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Noticeably, known cases of recoding in Archaea [recently reviewed in (19) ] are limited to termination codon readthrough events that regulate the incorporation of the 21st and 22nd amino acids selenocysteine and pyrrolysine, respectively (20) (21) (22) (23) .", "No archaeal genes regulated by translational programmed frameshifting and ribosome hopping have been identified experimentally so far; therefore, if compared with the others domains of life, the study of translational recoding in Archaea is still at its dawn.", "reported that these elements, alone or in combination, enhance frameshifting by pausing the translating ribosome on the slippery sequence (4, 18) .", "In vitro translation assays were performed essentially as described by Cond\u00f2 et al. (28) . The samples (25 ml final volume) contained 5 ml of S.solfataricus cell extract, 10 mM KCl, 20 mM Tris-HCl, pH 7.0, 20 mM Mg acetate, 3 mM ATP, 1 mM GTP, 5 mg of bulk S.solfataricus tRNA, 2 ml of [ 35 S]methionine (1200 Ci/mmol at 10 mCi/ml) and $10 pmol of each mRNA. The mixtures were incubated at 70 C for 45 min. After this time, the synthesized proteins were resolved by electrophoresis 12.5% acrylamide-SDS gels and revealed by autoradiography of the dried gels on an Instant Imager apparatus." ] },{ "paper_id": "2606e22c2560b4cc0909c102ee356d562d78a9f3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Programmed ribosomal frameshifting (PRF) is a translational recoding phenomenon historically associated with viruses and retrotransposons. A PRF signal stochastically redirects translating ribosomes into a new reading frame (i.e. by +1 or \u00c01 nt) and, in the typical viral context, these signals allow ribosomes to bypass the usual in-frame stop codon and continue synthesis of a C-terminally extended fusion protein. As with most basic molecular mechanisms, although first described in viruses, it is becoming increasingly apparent that PRF is much more widespread and is likely employed by organisms representing every branch in the tree of life [for reviews see (1) (2) (3) (4) ].", "Pknots (24) was used to predict the minimum free energy (MFE) 'fold' of each motif hit identified by RNAMotif. Each motif hit identified by RNAMotif was folded by pknots and assigned a predicted MFE value (MFE in kcal/mol) and a predicted secondary structure.", "randomized ORFs using the observed CDS codon usage bias; diNuc, randomized ORFs generated using the observed CDS dinucleotide frequency. A total of 100 randomized replicate genomes were generated for each of the seven methods (700 random genomes total, $6.5 billion nucleotides). As was done for the natural S.cerevisiae genome, RNAMotif was used to search these randomized genomes.", "All software was compiled and run on one or more of the following systems: Dell Precision 620, 2\u00b7 PIII XEON 866 MHz running Mandrake Linux 10.\u00b7; Apple Power Macintosh, 2\u00b7 G4 1.4 GHz PowerPC running OS X Tiger; SGI Cluster 64\u00b7 MIPS R14K 600 MHz running Irix 6.5; SGI Altix 3000, 64\u00b7 1.5 GHz Itanium II running Linux-64. Supercomputing resources were made available courtesy of The National Cancer Institute's Advanced Biomedical Computing Center in Frederick, MD (ABCC, http://www.abcc.ncifcrf.gov). Unless otherwise noted, data mining and analysis was carried out using scripts written in PERL (www.perl.org), each of which are available on request. In all cases, data is stored in a mySQL 4.\u00b7 relational database (www.mysql.com) referred to as the PRFdb (http://dinmanlab.umd.edu/prfdb)." ] },{ "paper_id": "26360be96ced1f242e01966b0d152c32544f3d60", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "26b49bdf0c3d50386ae603783e9674b7349852df", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "formation which has functional enzymatic activity. It is apparent that the VP7 sequence from amino acids 51-111 is necessary and sufficient for the retention of VP7 in the ER and also serves to retain a normally secreted protein in this compartment.", "dhl/Am) was secreted from the cell (Figs. 5 and 6 ) and exhibited endo-H resistant glycosylation (Fig. 5) . These results along with those in the previous section indicate that two regions in VP7 are necessary for ER retention, namely a segment within the domain of amino acids 51-61 and another within the region 62-111.", "The plasmid pMSal04 (12) containing the full length cDNA coding sequence of mouse salivary a-amylase (a gift from O. Hagenbuchle, Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland), was used in the construction of both the amylase transcription vector Am/ pGEM3 (pGEM3 was obtained from Promega Biotec, Madison, WI), and the expression vector pJC/Am. The plasmid pMSal04 was cut with Pst I and the 1,626-bp fragment containing the full length amylase coding region was isolated and cloned into the Pst I site of the pGEM3 transcription vector." ] },{ "paper_id": "26b944ce8d2f033704c7aeef38b0c128c0dd18be", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Bioactive peptides cleaved from the egglaying hormone precursor in the bag cell neurons of", "Bag cell clusters were isolated and fixed in 1% glutaraldehyde, 2% paraformaldehyde, 1% DMSO, 0.3 M sucrose in 0.1 M Na cacodylate buffer, pH 7.4, for 90 min at 4\u00b0C. The sheath was then dissected from the cluster, and the cluster was washed in 0.05 M Na Acetate, pH 5, and incubated in 0.1% cytidine monophosphate (Sigma Chemical Co., St. Louis, MO) or glycerophosphate (Sigma Chemical Co.) and 0.15 % lead nitrate in 0.05 M Na acelate, pH 5, for 90 rain at 37\u00b0C (Novikoff et al., 1971) . Results were similar for both of the labels, and control preparations without substrate showed no lead precipitate. Clusters were washed with 0.1 M Na cacodylate, pH 7.4, osmicated in 2% OsO4 in 0.05 M Na cacodylate, pH 7.4, for 1 h, and then dehydrated and embedded as described above. Thin sections (80-100 nm) were cut and stained with 2 % uranyl acetate followed by lead nitrate before visualization on a transmission electron microscope (410; Philips Electronic Instruments, Inc.).", "250-750-g Aplysia were obtained from Sea Life Supply (Sand City, CA)." ] },{ "paper_id": "26cb41132d945aa5cff35a80761daf086a4375e0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "26f94b094ce4d39665edddef1942f04dd041f363", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "26fec23192bed03196a134abb20b8b197a2acc42", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Taken together, these results suggest that microglia under acute systemic inflammation present a highly activated state, which is heterogeneous and distinct from neurodegenerative diseaseassociated profiles.", "Adult microglia were isolated from brains of C57BL/6N mice at age ", "Expanded View for this article is available online." ] },{ "paper_id": "276ff0fe5b27771bb52e6fec57cfe7b6430c3b1d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Open Access This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/ ", "The study was designed as a cross-sectional, repeated study over a period from December 2009 to November 2013. It consisted of three different substudies.", "The analyses were performed using JMP V.8 (SAS Institute Inc., Cary, North Carolina, USA)." ] },{ "paper_id": "27c190c3d4fc0884a3b9d79774ee61a0c305c540", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Bands were located on the dried gels by alignment with an exposed X-ray film, excised, rehydrated, and extracted with tissue solubilizer TS1 (Zinsser Analytic, Frankfurt, FRG) as described (58) .", "Published procedures were used for preparing plasmid DNA (35) ; saltwashed, gradient-purified INV (35) ; and an S-135 of a cell extract from Escherichia coli K12 strain MC4100 (38) grown at 30\"C (35) . DNAdependent protein synthesis using the S-135 was performed in 25-/~1 reactions as described previously (37) . When the lacYgene was to be expressed, cAMP was added from a 12. " ] },{ "paper_id": "27d6ec2664104ba3347a3991ce63d20ebae32d39", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "He had a history of cough variant asthma, but did not take any regular medication, and otherwise healthy. On admission (June 2, 2015), the physical examination revealed a body temperature of 38.8\u00b0C, a respiratory rate of 22 breaths per minute, a pulse of 78 per minute, and a blood pressure of 118/71 mmHg. Chest radiography showed patchy consolidation in the upper zone of the left lung. His pneumonia progressed, and on June 8, he developed shortness of breath, his arterial oxygen saturation decreased below 90%, requiring oxygen supplementation, and chest radiography showed multiple con- solidations in the both lungs. On June 10, he was intubated and mechanical ventilation was started. His hypoxemia worsened rapidly, and veno-venous extr acorporeal membrane oxygenation support was started since June 11. On July 2 (day 35 of his illness), real-time RT-PCR for MERS-CoV turned negative, and was removed from the isolation unit. He recovered gradually.", "In summary, we isolated MERS-CoV from a patient with severe pneumonia who had been infected during the Korean outbreak in 2015. We also obtained full-length sequence of the The evolutionary history was inferred by using the maximum likelihood method based on the Tamura-Nei model (16) . Evolutionary analyses were conducted in MEGA6 (17 ", "Middle East respiratory syndrome coronavirus (MERS-CoV) is a betacoronavirus causing a severe acute respiratory infection (1, 2) . It was first isolated from the sputum of a patient with severe pneumonia in Saudi Arabia in 2012 (3) . Since then, 26 countries have reported 1,618 laboratory-confirmed cases of infection with MERS-CoV to the World Health Organization (WHO), including 579 fatalities (4) ." ] },{ "paper_id": "27d9e8f9f893c005e551b219680b7832eac40fca", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The de-escalation approach is generally recommended when high incidence of resistant pathogens in neu-", "The epidemiology of drug-resistant pathogens is important for establishing strategies for prophylaxis and initial empirical antimicrobial therapy. Because domes-tic data are limited to single-institution and retrospective studies, multicenter nationwide studies of the epidemiology of bacterial infections in Korea are required.", "Examples of therapy Antimicrobial prophylaxis" ] },{ "paper_id": "27ee5b4647398fd11e7044166a9d68aca391ebcf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A better understanding of these newly discovered antiviral factors may open new avenues towards the design of drugs that repress the spread of viruses whose genomes have already integrated.", "Keeping the density of glycoprotein molecules on the virus surface low is a property of some viruses that is particularly pronounced for HIV-1, and is thought to provide a selective advantage during immune evasion [20] . It is unclear whether the drawback of reduction of virion infectivity, induced by 90K-mediated paucity of Env embedded in particles, is outweighed by improved immune escape. More work is warranted to fully understand the impact of 90K on HIV-1 infection." ] },{ "paper_id": "280c43e8272c97d38089e567dbf1881430e60dd9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The ability of the copolymers for binding siRNA was evaluated by electrophoresis through 2% agarose in TAE buffer (40 mM Tris-HCl, 1 v/v% acetic acid, and 1 mM EDTA) at 100 V for 20 min. The siRNA bands were stained with ethidium bromide and imaged using a VersaDoc Imaging System (Bio-Rad Laboratories).", "Assessment of siRNA delivery and targeted gene silencing mediated by P1, P2, and P3 copolymers by flow cytometry", "No potential conflicts of interest were disclosed.", "RNA interference (RNAi) mediated by small interfering RNAs (siRNAs) is an exciting, new technology with many potential biomedical applications. siRNAs are generated by cleavage of long, double-stranded RNAs (dsRNAs) by the cytoplasmic enzyme Dicer in plants and worms, 1 but can also be synthetically produced and introduced into mammalian cells to achieve gene silencing. 1, 2 Inside the cells, siRNA targets specific mRNA (mRNA) for enzymatic degradation via association with the RNA-induced silencing complex (RISC). Exploiting this system, siRNAs have been designed as promising therapies to target human diseases including those caused by viruses [3] [4] [5] [6] and cancers. [7] [8] [9] [10] [11] A major challenge of using therapeutic siRNAs in vivo is effective and safe delivery. Typically, siRNAs are 7 nm in length with an approximate molecular weight of 13 KDa 1 and have a high net negative charge. Thus, size and charge make siRNAs unable to readily penetrate cellular membranes. Furthermore, naked siR-NAs are quickly degraded by nucleases in the bloodstream, and have a short half-life of minutes in the plasma. 12 Therefore, different methods have been proposed and examined to protect and deliver siRNAs with varying degrees of success. These include use of viral vectors, cationic liposomes, and polymers." ] },{ "paper_id": "281b4272005dbc998e36b034b7fb528c9ba038cd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CEL I /Surveyor TM enzyme.", "Use TdT enzyme to add oligonucleotide tail (e.g. oligo-dA) to 3\u2032OH ends, to serve as primer anchor", "Un-digested fragments Digested fragments", "Sequencing is often considered the gold standard for comprehensive mutation analysis. Multi-capillary electrophoresis, re-sequencing arrays or pyrosequencing provide platforms for highly parallel genetic analysis (7) (8) (9) (10) (11) (12) (13) . However, the expense associated with these techniques is currently high both for instrumentation and for runningcosts. Since somatic mutations for most genes are relatively rare events it can be inefficient to scan for mutations using expensive approaches that in several cases provide unnecessary data (14, 15) . Another issue with direct sequencing or re-sequencing arrays is the difficulty *To whom correspondence should be addressed. Tel: +1-617-525-7122; Fax: +1-617-587-6037; Email: mmakrigiorgos@partners.org \u00df 2007 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited." ] },{ "paper_id": "2823d7523188f052070c565fc1e5b9c35899f658", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study was approved by the institutional review board of the Keimyung University Dongsan Medical Center (IRB No. 2014-09-054). Informed consent was exempted by the board.", "In order to identify the underlying cause of ALTE, various diagnostic investigations were performed during hospitalization. On the day of admission, blood samples were analyzed for complete blood count (CBC) with bacterial culture, blood gas analysis with electrolytes, and C-reactive proteins. In addition, respiratory virus reverse transcription polymerase chain reaction (RV RT-PCR) using nasopharyngeal aspirate, Rotavirus antigen test in stool, urinalysis with culture, cerebrospinal fluid (CSF) analysis, and chest radiography were all utilized. RV RT-PCR included tests for metapneumovirus, adenovirus (A-F), coronavirus 229E/OC43, parainfluenza virus 1/2/3, influenza A/B virus, rhinovirus, respiratory syncytial virus A/B, and bocavirus. Electrocardiograms (ECG), 2-dimensional echocardiograms, upper gastrointestinal studies, electroencephalograms (EEG), brain image studies, and tests for metabolic disease were ordered on an individual patient basis." ] },{ "paper_id": "284541395ddc07d44ccd2d3da2ba060505a01407", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Aggregated proteins, overabundant proteins, and certain microbial proteins can induce selective autophagy through ubiquitination that binds LC3 via SQSTM1/p62 (sequestosome 1). [78] [79] [80] The autophagic sequestration of invading bacteria is an important innate immune mechanism. Intracellular Salmonella, Mycobacterium, Streptococcus, and Legionella-containing vacuoles or bacteria are ubiquitinated, and subsequent binding of SQSTM1/p62 delivers the bacteria to autolysosomes for degradation. [81] [82] [83] [84] [85] E. chaffeensis inclusions were not ubiquitinated as monoclonal antibody FK2 that recognize both mono-and poly-ubiquitinated proteins did not label the inclusions (Fig. S7 ). Taken together, our observations suggest that E. chaffeensis induces autophagy independent of MTOR, ULK1 or PRKA, and ubiquitination-induced signaling pathways.", "inclusions with RAB5-containing vesicles, suggesting the recruitment and retention of RAB5 endosomes during E. chaffeensis replication and expansion of the inclusion (Fig. 9B to D). In uninfected cells, GFP-RAB5 showed smaller diffuse puncta than in infected cells (RAB5A shown in Fig. 9E ).", "No potential conflicts of interest were disclosed." ] },{ "paper_id": "285423e1a13bb2e1b98795cc6bb0cb6f54c0f8fd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "28698e9d58d0b455cfa1adb28be25bc7f9286859", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The author declares no conflict of interest." ] },{ "paper_id": "2891c813ce4dd156d5f56736db5a10a2065c9167", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "*Address correspondence to this author at the The School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan; Tel: +886-7-6151100 ext. 7063; Fax: +886-7-6155150; E-mail: huangks@isu.edu.tw Compared to a free drug, the advantages of a nano-scale drug delivery system include increasing bioavailability, reduced drug amount and frequency and reduced systemic side effects [39] . In hence, active targeted drug delivery combined nano-technological carrier platforms is a better way to prolong, localize, target with the pathogenic sites and reduction of drug side-effects [40] .", "In modern life, human are always threaten by infectious diseases [1] [2] [3] [4] [5] [6] . Bacteria, virus and fungi are the critical reasons to infectious diseases [7] [8] [9] [10] [11] . Bacteria served many diseases by the food route [12] . In Germany, Escherichia coli in Fenugreek sprouts exported from Egypt caused 48 deaths from 2011 to 2012 [13] . Virus could cause various diseases including human immunodeficiency virus (HIV) [14, 15] and influenza [16, 17] . Fungi like Cryptococcus neoformans could lead to chronic liver disease [18] . Luckily, with the development of safe vaccines and antibiotics, the infectious diseases seemed to be totally cured by these therapies [19] . However, there are some adverse drug effects if patients take these drugs at common dose or overdose such as insomnia [20] , osteoporosis [21] , headache [22] and liver failure [23] . Furthermore, these pathogens with a very fast doubling cycle develop a mechanism for becoming resistant to a specific drug at a glance [24] . In hence, scientists are trying to find new approachs to solve aforementioned problem urgently.", "The authors confirm that this article content has no conflict of interest." ] },{ "paper_id": "2892aee133b8b4037ace7ec6dfe6cab17e466292", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A key question remains \"what is the real number of people infected since many cases may be mild or asymptomatic?\" A recent modelling estimated the population attack rate to be between 0.75 per 100,000 to 15.8 per 100,000 analysing rates down to prefecture level in China . Any determination of incidence will likely be an underestimate since it will not include mild and asymptomatic cases. Accuracy of such estimates will depend on the development of sensitive and specific serologic tests.", "The SARS-CoV outbreak originating from China in 2003 was first reported to the global health community by ProMED (ProMED, 2003; Carrion and Madoff, 2017; Hamer et al., 2017) . It took six weeks for the authorities to acknowledge the outbreak had spread significantly from Guangdong throughout China after cases were reported from Hong Kong, Hanoi, Singapore, and Toronto.", "Li Wenliang, a face to the frontline healthcare worker. The first doctor to notify the emergence of the SARS-CoV-2, (COVID-19), outbreak", "Global public health security is of primary importance to prevent outbreaks of diseases with epidemic potential and every effort to detect, report, and institute infection prevention and control measures should be made. Astute clinicians, access to laboratories with state of the art tools, and openness, transparency and quick reporting are crucial components of this response (Kavanagh, 2020) . This requires an open flow of information and collaboration between laboratory experts and clinicians on the frontline who may be the first to observe unusual clustering of cases or uncommon clinical presentations, both of which should be reported immediately." ] },{ "paper_id": "28d987c4ec40dafc05993e3a209ea4266f270f28", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Text S1. Materials and Methods; Details of Sarcocystis neurona metabolic reconstruction; and apicoplast SNP differences.", "(i) 1. For further details on the implementation of modeling, please refer to (12) ." ] },{ "paper_id": "29445ecd280247f79d6cebe0c3b4d06796e72eb9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Porcine deltacoronavirus (PDCoV) has emerged in several pig-raising countries and has been a causative pathogen associated with diarrheal diseases in South Korea since 2014. In the present study, we were able to isolate and cultivate a Korean PDCoV strain (KNU16-07) in cell culture and investigate its pathogenicity. PDCoV-inoculated piglets showed watery diarrhea accompanied by acute enteritis in the natural host. Sequencing analysis demonstrated the genetic stability of KNU16-07 for at least thirty serial passages.", "The PDCoV nucleocapsid (N) antigen was prepared from PK-PDCoV-N cells stably expressing the PDCoV N protein as described previously [8] . The cell lysate supernatant containing recombinant N protein was purified by using a HiTrap TALON crude column (GE Healthcare, USA) according to the manufacturer's instructions. The purified protein was concentrated with Amicon Ultra centrifugal filters 10K (Millipore, USA) and the final product was used as the antigen. PDCoV N-specific monoclonal antibodies (MAbs) were produced by immunizing 4-week-old male BALB/c mice as described previously [12] .", "Porcine deltacoronavirus (PDCoV) is a newly emerging enterotropic swine coronavirus that causes acute enteritis in nursing piglets [7, 10] . PDCoV was first identified in Hong Kong, China in 2012 and, subsequently, has emerged in most major swine-producing nations in Asia and North America [11, 13, 14] . The presence of PDCoV in South Korea was first announced in early 2014 [7] . Our previous report indicated that monoinfection by PDCoV and coinfection by PDCoV and porcine epidemic diarrhea virus (PEDV) are common in pig herds in South Korea [4] ." ] },{ "paper_id": "29484085aa4df22fec44839b58dcdce03f1c3e82", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "298a64fc7158cb78592bd96d53b4e58fbf562276", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "September 8th, 2018, South Korea reported the first MERS-CoV case since the end of an outbreak in 2015, suggesting that MERS-CoV is still a worldwide threat (WHO, 2018) .", "In their study, mice transfected with the human DPP4 gene became significantly less susceptible to MERS-CoV infection after", "only one animal exhibited moderate ciliary loss in the nasal mucosa ( Figure 9a , Table 1 ) on day 4 p.i.", "| 837 (Cq = 32) was found in cervical lymph nodes, being even less (Cq = 36) in mediastinal lymph nodes and tonsils (Supporting information Figure S1b ). MERS-CoV RNA was not detected in the thymus of llamas on 24 day p.i (Supporting information Figure S1b )." ] },{ "paper_id": "29ead3f1e4f24c9158b65d37a4ba9d839fb9028c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "cattle, colostrum, fecal score, immunity, milk", "Recent legislation, including the Federal Veterinary Feed Directive in 2017 13 and the California Senate Bill-27 in 2018, 14 was enacted into law and recommended judicious use of antibiotics in food producing animals.", "Background: Nonantibiotic alternatives providing local gut immunity have been recommended for managing calf diarrhea." ] },{ "paper_id": "29f72afab8b9894bede98ed862d87595374099c7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(QDYNHDRDIVPPR), Eval162 (IAKTALKVLPQL), Eval418 (LWGEIWNTVKGLI), Eval655", "(IWGALLSGVADLL) and Eval967", "Data are expressed as the mean \u00b1 standard deviation from at least three separate experiments." ] },{ "paper_id": "2a0861490e83f24375ca14187de9617594666850", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "DNA Subcloning and Sequence Determination. Purified )~7_ap clones were subcloned in vivo into pBluescript plasmids using R408 helper phage as recommended in the manufacturer's instructions (Stratagene Inc., La Jolla, CA). The nucleotide sequence was determined using the dye primer cycle sequencing kit and DNA sequencer (373A; Applied Biosystems, Inc., [ABI], Foster City, CA). Oligonucleotide primers were synthesized with a DNA synthesizer (380B; ABI). DNA sequences were determined in both strands and compiled using the alignment program SeqEd (ABI).", "Cell Lines. HeLa (ATCC CCL 2.2; American Type Culture Collection, Rockville, MD); MOLT-4 (human T cell lymphobhstic leukemia; ATCC CRL 1582); HEp-2 (human epidermoid carcinoma ceils), and HepG2 (human hepatic carcinoma, ATCC HB 8065) cells were maintained in RPMI 1640 supplemented with 10% FCS, 2 mM t-glutamine, and 5/~g/ml gentamycin sulfate.", "V 601 AAGAGGGAGCTGGGA~GAAGCT GGGCGAGCTGCAGGAGAAGCTGAGCGAGCTGAAGGA~GGTGGAGCTGAA~TC~T~A~A~A~CA~G 195 K R E L G K K L G E L Q E K L S E L K g T V E L K S Q E A Q S L Q Q Q R D Q Y L 721 GGACACCTGCAGCAGTATGTGGCCGCCTATCAGCAGCTGACCTCT GAGAAGGAGGTGCTC-CATAATCAGCTACTGCTGCAGACCCAGC ~GT~A~A~A~AG 235 G H L Q Q Y V A A Y Q Q L T S E K E V L H N Q L L L Q T Q L V D Q L Q Q Q E A Q 841 GGCAAAGCGGTGGCCGAGATGGCCCGCCAAGAGTTGCAGGAAACCCAGGAGCGCCT GGAAGCTGCCACCCAGCAGAA~ ~AGTT~AT~TC~ 275 G K A V A E H A R Q s 5 Q E T Q E R L E A A T Q Q N Q Q L R A Q L S L M A H P G 961 GAAGGAGATGGACT GGACCGGGAGGAGGAGGAGGATGAGGAGGAGGAGGAGGAGGAGGCGGTGGCAGT~A~T~C~A~~~TG 315 E G D G L D R E E E s D E E E s s s s A V A V P Q P M P S I P s D L E S R s A H 1081 GTGGCATTTTTCAACTCAGCTGTAGCCAGTGCC GAGGAGGAGCAGGCAAGGCTACGT GGGCAGCTGAAGGAGC~T~T~T~A~T ~T~ TC~AG 355 V A F F N S A V A S A g g E Q A R L R G Q L K g Q R V R C R R L A H L L A S A Q 1201 AAGGAGCCTGAGGCAGCAG~AGCCCCAGGGACC GGGGGTGATTCTGTGTGTGGGGAGACCCACCGGGCCCTGCAGGG~T~A~ ~TAT~ATG 395 K E P s A A A P A P G T G G D S V C G s T H R A L Q G A M E K T. Q S R F H E L M 1321 CAGGAGAAGGCAGACCTGAAGGAGAGGGTAGAGGAACTGGAACATCGCTGCATCCAGCTTTCTGGAGAGACAGACACCATT GGA~GTACA~T~A~AGA~A~A~ G 435 Q E K A D v. K E R V E E L E H R C I Q L S G E T D T I G E Y I A L Y Q S Q R A V 1441 CTGAAGGAGCGGCACCGGGAGAAC-GAGGAGTA~ATCAGCAGGCTGGC~AAGACAAGGAGGAGATGAA~T~T~T~~~~ 475 L K s R H R E ) E E Y I S R L A Q D K g E M K V K L L E L Q E L V L R L V G D R", "Human Sera. Sera from patients with Golgi autoantibodies were obtained from serum banks at the University of Calgary (Calgary, Alberta), The Scripps Research Institute (La Jolla, CA), and Immuno Concepts Inc. (Sacramento, CA). The serum samples were stored at -20 or -70~ The specificity of the autoantibodies for Golgi antigens was first identified on the basis of indirect immunofinorescence (IIF) microscopy (4) . Control sera were randomly selected from a bank of 2,000 female Red Cross blood donors (37) or sera pooled from healthy volunteers." ] },{ "paper_id": "2a0dccbe06cd6c48fdafcae920f220b3fdccab41", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "1 . Abbreviations used in this paper: BiP, immunoglobulin heavy chain binding protein; CgB, chromogranin B ; GAG chain, glycosaminoglycan chain ; hsPG, heparan sulfate proteoglycan; PDI, protein disulfide isomerase ; SgH, secretogranin II ; TGN, trans-Golgi network .", "Chanat and Hutwer Aggregation-mediating Sorting of Secretary Proteins 151 1", "vesicles contaminating the fractions of the velocity gradient containing TGN vesicles." ] },{ "paper_id": "2a17719f2c1d211a651060441bda8bc1c052e2aa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "IAP-binding motifs are found in pro-apoptotic proteins and function in the abrogation of caspase inhibition by inhibitor of apoptosis proteins in apoptotic cells LIG_BIR_III_1 LIG_BIR_III_2 LIG_BIR_III_3 LIG_BIR_III_4", "A proline-rich motif binding to EVH1/WH1 domains of WASP and N-WASP proteins LIG_HCF-1_HBM_1", "The AGCK docking motif mediates intramolecular interactions to the PDK1 Interacting Fragment (PIF) pocket, serving as a cis-activating module LIG_AGCK_PIF_2 LIG_AGCK_PIF_3", "protein structure annotated, giving more detailed information about the biological context of the respective motif." ] },{ "paper_id": "2a1c5b2541cb958a6280094aa3c1cd2e414fb468", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A reduction in immune cell infiltration would also result in diminished neuroinflammation. Reactive astrocytosis and microgliosis are considered major hallmarks for neuroinflammation. Staining for astrocytes with GFAP and microglia with Iba-1 can then be used to assess changes in mean area fraction staining to quantify neuroinflammation (Figure 3) .", "Ensure that \"Limit to threshold\" is unchecked and \"Display label\" is checked. Click \"OK\" when complete. 5. To obtain measurements, go to Analyze > Measure. A \"Results\" popup box will appear and this data can be saved as is or copied into another program. For analysis, compare \"Area fraction\" values between treatment groups.", "The authors have nothing to disclose." ] },{ "paper_id": "2a23841a09149d099f936ecc2edf913b9d2dc2ce", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2a2a9ae443755df9e1d930c75c2023f0b1780a51", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2a584d39eb8b164d066dbc8e7496c9a9ff39bc30", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Young mice (6-8 wk) were treated i.n. with LPS (E. coli O111:B4) at 0.1 \u00b5g/mouse in 50 \u00b5l for 7 d.", "Middle-aged mice (10-13 mo) were treated with N-Acetyl-l-Cysteine (Sigma-Aldrich; 100 mg/kg, i.p.) for 7 d.", "In situ CFSE and OVA-FITC staining. CFSE and OVA-FITC were purchased from Molecular Probes. CFSE was diluted to a concentration of 8 mM in DMEM, and then administered i.n. (50 \u00b5l) 6 h before infection (Legge and Braciale, 2005; Zhao et al., 2011) . OVA-FITC was dissolved in PBS, and 200 \u00b5g were administered i.n. in 75 \u00b5l." ] },{ "paper_id": "2a5b2e11c10d35b22cb2965f62ccc79e61eeb77b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2a771153af1b6fd5e71dc23f5db7c83bb5a3f231", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Saccharomyces cerevisiae strains used in this study are listed in Table I . Yeast cells were grown in YPD [1% (wt/vol) Bacto yeast extract (Difco Laboratories Inc., Detroit, MI), 2 % (wt/vol) polypeptone (Nihon Seiyaku, Tokyo, Japan), and 2% (wt/vol) glucose] or in MVD [0.67% yeast nitrogen base without amino acids (Difco Laboratories) and 2% glucose] medium supplemented appropriately. MCD medium is MVD containing 0.5% casamino acids (Difco Laboratories Inc.).", "Yeast Sec12p is a type II transmembrane", "Signals, or special structural motifs, are essential for correct sorting of proteins in a cell. During membrane traffic in the secretory pathway, vesicles dynamically cycle between organelles. The sorting processes in such vesicular traffic should also be understood from the viewpoint of recognition of signals." ] },{ "paper_id": "2aa0a28e4246f367ffe104837e755b28d2021f45", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The in vivo diagnosis of H1N1 infection was confirmed by real-time RT-PCR (rRT-PCR) test using nasopharyngeal swab specimens, in accordance with guidelines from the Centers for Disease Control and Prevention (CDC) [10] .", "In summary, our report of cancer patients highlights the severity of the Influenza A (H1N1) pandemic in this vulnerable population and the urgent need to establish specific protocols of care and management strategies designed to face this health care challenge. funding Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3 gico (CNPq)." ] },{ "paper_id": "2ae023dbcedb660475c4de1033343196265fd42c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A 12-year-old spayed female domestic shorthair cat was evaluated for a 3-week history of abdominal distension. Chyloabdomen secondary to pancreatic carcinoma was diagnosed. The cat was palliatively managed using rutin and a low-fat diet. The etiology, diagnosis and management of chyloabdomen are discussed.", "In human and veterinary medicine, chyloabdomen is a rare condition. It results from leakage of lipid-rich lymph into the peritoneal cavity, secondarily to obstruction or increased permeability of lymphatic vessels. In cats, it is believed to be mostly of neoplastic origin. Medical investigation relies on a systematic approach and definitive diagnosis often requires histopathological samples. This report describes the exploration and management of a chyloabdomen secondary to pancreatic carcinoma in a 12-year-old cat.", "Case Details A 12-year-old neutered female domestic shorthair cat was referred for evaluation of an abdominal effusion. The owners reported an abdominal distension of three weeks duration, with conservation of general demeanor and appetite. The referring veterinarian detected an abdominal effusion. A chyloabdomen was suspected, according to the gross appearance of the liquid. The cat was housed mainly outside. Her vaccination status was not up-to-date. On physical examination, the cat was bright, alert and normothermic. The body condition score was of 4 out of 9 and she had an unkempt haircoat. A marked abdominal distension was noted. No pain was elicited on abdominal palpation. Cardiorespiratory parameters were within normal limits. Abdominocentesis was performed under sedation. Approximately 300 mL of milky fluid were removed. Triglycerides content in the effusion was highly increased (102.84 g/L; reference range 0.30-1.60). The cytologic analysis of the fluid showed 1000 erythrocytes/\u00b5L and 1500 leukocytes/\u00b5L, including neutrophils (48%), monocytes (40%) and small, mature lymphocytes (12%). No bacteria nor neoplastic cells were visualized. Based on these findings, chyloabdomen was confirmed." ] },{ "paper_id": "2b36f467dee97f9675e187cabd4e4585e7ab17f2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "T cell helper type 1", "Supported in part by Serendipity Award SA29/0513 from the Dunhill Medical Trust.", "IFN\u03b3 interferon gamma" ] },{ "paper_id": "2b5a2503522ac52b24f3475d69719626993d9dab", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ausiello et al 35 released a method for extended and controlled delivery of parathyroid hormone to a patient in need, involving implanting a medical device into the patient, the medical device comprising a substrate, a plurality of reservoirs in the substrate, and a release system contained in each of the reservoirs, wherein the release system comprised parathyroid hormone, and controllably releasing a pharmaceutically effective amount of the parathyroid hormone from the reservoirs.", "Drug Design, Development and Therapy 2013:7 945-952 Drug Design, Development and Therapy Dovepress submit your manuscript | www.dovepress.com Dovepress 945 R e v i e w open access to scientific and medical research Open Access Full Text Article" ] },{ "paper_id": "2ba882c9ddb5e9db8ebb0db536788bff66b67f14", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The proteomic complexity of tumors must be fully understood to develop more effective therapeutic strategies.", "Funding SRYC acknowledges support from Fondo de Investigaciones Sanitarias (P1170185 and PI 14/01320), Redes Tem\u00e1ticas de Investigaci\u00f3n Cooperativa en Salud (RTICC, RD 12/0036/0057), Generalitat de Catalunya (AGAUR, 2014, 1131), and CIBERONC 2017.", "Conflict of interest The authors declare that they have no conflict of interests." ] },{ "paper_id": "2bae24fa42f6bd7e9a241b4456296f3af0ee4b2c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As mentioned above, most GBMs present acutely, with relatively few clear indications of the oncoming pathogenesis ", "There is little mention of circulating lipid species as putative biomarkers for GBMs, but 24S-hydroxycholesterol is among ", "submit your manuscript | www.dovepress.com" ] },{ "paper_id": "2bd481afbcdbbc5c78d67ed1f7204b09c1f83da1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Korean J Pediatr 2017;60 (7) :208-215", "No significant difference in LVEDD, LVESD, and FS was found Korean J Pediatr 2017;60 (7):208-215", "No potential conflict of interest relevant to this article was reported." ] },{ "paper_id": "2bfb845e6afaaa4d43ebd7a79dc3e092e0168d29", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2c074099e6063fd2570cb173900da087fba991f5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Respiratory failure following HSCT presents on a spectrum", "Cryptogenic organizing pneumonia (COP) is an interstitial and airspace disease with symptoms mimicking classic pneumonia. Imaging findings include nodular lesions, ground glass attenuation, and patchy peribronchovascular, peripheral, bandlike consolidative distributions [64, 94] . Biopsy reveals chronic alveolar inflammation and exten sive granulation of the alveolar ducts and small airways [94] . Bronchoscopy is useful to distinguish COP from infectious pneumonia, and analysis of lavage fluid reveals a predo minant lymphocytosis [95] . Previously referred to as bron chiolitis obliteransorganizing pneumonia, COP is a distinct entity from the bronchiolitis obliterans syndrome (BOS), which is discussed separately and should not be confused.", "Other therapies with inconclusive utility include inhaled corticosteroids, intravenous immune globulin, TNF\u03b1 in hibitors, cyclosporine, and tacrolimus [4] . Extracorporeal photophoresis is a promising therapy with increasing evidence suggesting its potential benefit [108, 109] . Lung trans plantation for advanced BOS has been reported [110113] ." ] },{ "paper_id": "2c0813f50214197ccbeae857bb05217ade8aae82", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2c2f0107d55f1c770896c982d59e0bfa035fd4d7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All the experiments were conducted in accordance with the Guidelines for the Care and Use of Laboratory Animals of Azabu University.", "In conclusion, Dempo-PCR can identify a wider range of existing pathogens quickly and easily compared to one assayone pathogen test. Considering multiple etiology of PRDC, screening by Dempo-PCR would help us determine treatment and prevention measures. This detection system may provide an alternative testing method that is simpler, faster, and more comprehensive than existing assays.", "The objective of this study is to develop a system based on TaqMan real-time PCR that can detect 17 pathogens, including viruses and bacteria, associated with porcine respiratory diseases in one run." ] },{ "paper_id": "2c70242370bc27a555b206e5bd62b68f1edb772d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "sures to remove or reduce the holes in many other slices in order to effectively prepare against future emerging infectious diseases including MERS. The WHO sent a high-level message to the Korean government including 11 recommendations [5] . These recommendations can serve as references in redesigning the health care and public health systems in Korea.", "Perspective Since the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea (hereafter Korea) began on May 11, 2015, a total of 186 persons have been infected by the MERS coronavirus, 38 of whom have died. With this number, Korea becomes second only to the Kingdom of Saudi Arabia in the ranking of cumulative MERS cases. In this paper Korea's unique experience of an outbreak of MERS will be summarized and discussed briefly.", "Since the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea (hereafter Korea) began on May 11, 2015, a total of 186 persons have been infected by the MERS coronavirus (MERS-CoV), 38 of whom have died [1] . Korea is thus second only to the Kingdom of Saudi Arabia in the ranking of cumulative MERS cases. As the MERS epidemic in Korea has been considered a public health emergency, crisis, or disaster, several policy suggestions for public health system reform are now under discussion [2] . In this paper the unique characteristics of the public health system and social phenomena associated with the MERS outbreak outside the Middle East will be summarized and discussed briefly." ] },{ "paper_id": "2cf45a5a4224dbf38d537eace1f6d49327e3487d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2cf60380bb05becd140053f71fa4cc4e4eaa0d5f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The ortholog groups are further processed to create multiple sequence alignments (MSAs) using MUSCLE (34) with default parameters. Phylogenetic estimations using the neighbor-joining method (35) were created based on trimmed alignments using PHYLIP (36) . Trees were validated by bootstrapping (37) using a minimum of 100 replicates.", "The five categories of viruses studied by PATRIC are all positive-strand ssRNA viruses, with the exception of Lyssaviruses, which have negative-strand ssRNA genomes. While there are no reports of any of these viruses being weaponized, they represent the causative agents for a number of emerging and reemerging diseases including Severe Acute Respiratory Syndrome (SARS), rabies and transmissible gastroenteritis. Recombinant vaccines for these viruses are either still in development or unavailable in areas where these infections are endemic or epidemic, compounding the public health risk.", "Pathway analysis can also yield clues to pathogenesis by comparing virulent and avirulent strains and examining the roles of genes not present in both strains.", "Results of the genome analysis pipeline are merged with original GenBank or RefSeq features for automated interpretation. A decision tree is used to classify genes into categories based on the level of agreement between the various prediction methods. Genes that are unambiguously predicted by multiple methods are automatically 'finalized', creating new 'gene', 'CDS' and/or '[t/r]RNA' features. The remaining genes are marked for manual curation. For viral genomes, an abbreviated pipeline is executed that emphasizes sequence alignment for gene identification and employs GeneMarkHMM optimized for mammalian (host) genomes." ] },{ "paper_id": "2cfdb63ea48ecc4c871cc7d61b5f5361cfd8f287", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Viral gene sequencing and analysis were conducted as follows. In brief, Viral DNA was extracted directly from samples using the AxyPrep\u2122 Body Fluid Viral DNA/RNA Miniprep Kit (Axygen, Wujiang, China), according to the manufacturer's directions.", "Bocaparvoviruses frequently infect animals through the fecal-oral route, causing respiratory and gastrointestinal symptoms in young animals and humans [15] , but are often subclinical in adults [3] . So far, bocaparvoviruses have identified from a variety of vertebrate hosts including humans [8] , cows [4] , pigs [5, 25, 26] , gorillas [10] , chimpanzees [27] , California sea lions [16] , dogs [9, 13, 22, 24] , cats [13, 21, 30, 34] , bats [33] , rats [14] , and pine martens [32] , which suggested that the bocaparvoviruses have a very broad host range.", "Bocavirus belongs to the genus Bocaparvovirus, subfamily Parvovirinae, family Parvoviridae, a small and non-enveloped virus approximately 25 nm in diameter [7] , with a linear single strand DNA genome of approximately 5.4 kb [1, 6] . Bocavirus are unique among Parvoviridae as they contain a third ORF between the non-structural and structural-coding regions [11, 17, 23] . Previously, the genus Bocavirus was originally named according to the initial two members, bovine parvovirus (BPV) and minute virus of canines (MVC) [2, 19, 20, 28, 29] . And now, the genus of bocavirus is reclassified as Bocaparvovirus based on the proposal of Cotmore et al [7] . Currently, the bocaparvoviruses consist of carnivore bocaparvovirus, pinniped bocaparvovirus, primate bocaparvovirus, ungulate bocaparvovirus, and unclassified bocaparvovirus [20] . And the feline bocaviruses belong to carnivore bocaparvovirus 3 and unclassified bocaparvovirus, respectively [20] ." ] },{ "paper_id": "2d1300359d8ec1682b0b6bdb51df4604a7ed4930", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ethical approval was not necessary, because we obtained patients' consent for study before transportation." ] },{ "paper_id": "2d4246494e250c90bb5721a35e2b0a8e20100f20", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We and Prevotella oralis, a Gram-negative member of the class Bacteroidia.", "TMW designed the study, produced Figures 2-6 , wrote the first draft of the manuscript, and interpreted the data; S-RJ produced and curated the required datasets and produced Figure 1 ; MR advised on software tools for all figures, interpreted the data, and edited the manuscript; DWU ensured funding, advised on all figures, interpreted the data, and edited the manuscript.", "Genotypes that have not been described in humans but are isolated from other mammals (e.g., camels) are not considered here. The substitution rate of HEV was estimated between 3 and 5 \u00d7 10 -3 ssy with differences observed between genotypes (Brayne, Dearlove, Lester, Kosakovsky Pond, & Frost, 2017) .", "A provisional phylogenetic tree was constructed (see below), and exceptionally long branches were checked in detail; these were without exception isolates of animal origin, which were subsequently removed. The final datasets contained 134 HAV genomes, 2,542 HCV genomes, and 557 HEV genomes.", "None declared." ] },{ "paper_id": "2d5eaeaa1aa523394ce7697d3cbe98381a2c1559", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Caspase-1 activity was measured using colorimetric assay (BioVision, Mountain View, CA). The assay is based on spectrophotometric detection of the chromophore p-nitroanilide (pNA) after cleavage by caspase-1 from the labeled substrate YVAD-pNA. The pNA light emission can be quantified using ", "Data are expressed as mean AE SD. Statistical comparisons were performed by one-way ANOVA or two-tailed Student t test. Survival rates were analyzed with the Kaplan-Meier test. SPSS16.0 was used for statistical analyses. A P value <0.05 was considered to be statistically significant." ] },{ "paper_id": "2dc628f8092de38b705b1c159ef93a45425f9643", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "How to produce such \"fuzzy vaccines\" is a challenge worth meeting.", "The concepts described here are the product of numerous discussions with my students over many years with whom I have had the privilege to collaborate with. I especially thank Dr. Anna Roitburd-Berman, Dr. Yael Weiss-Ottolenghi and Chen Piller for their critical comments and assistance in making this article possible.", "ARTICLE HISTORY" ] },{ "paper_id": "2def385170922c5786ea00a64f0c139460d23e2c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "sf9 insect cells (Spodoptera frugiperda) (Invitrogen, San Diego, CA) were cultivated as monolayer or suspension in Grace's medium (Invitrogen, USA) supplemented with 10% heat-inactivated fetal bovine serum (Invitrogen, Carlsbad, CA), 1% penicillin/ streptomycine (100U/ml) and 0,1% pluronic F-68 (Invitrogen, USA) and maintained in anaerobic conditions at 27\u00b0C. Cultures in suspension were additionally maintained with constant shaking at 100 rpm. HepG2 cells from ATCC were cultivated in DMEM medium +L-glutamine (Invitrogen, USA) supplemented with FBS and 1% penicillin/streptomycine and maintained at 37\u00b0C with 5% CO2 and 95% humidity.", "Cells and cultures. 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) in anaerobic conditions and incubated at 37\u00b0C . Trophozoites virulence was maintained trough successive passages into hamster\u00b4s liver and recovering trophozoites from the induced ALA.", "Liver histology. Seven days after the challenge, hamsters were sacrificed under anesthesia and the liver excised. General liver damage was recorded by macroscopic features, weight, distribution and size of abscesses. Coronal cuts from whole liver were fixed in 4% formaldehyde-PBS during 24 h, whereas others fragments were included in Tissue Freezing Medium (Leica) and cut in 10 \uf06d for Hematoxylin-Eosin staining.", "Statistical analysis. The comparison of the infection rates between the immunized groups and their respective sham controls was done using Fisher's exact test. The Kruskal-Wallis test was used to compare antibody levels between groups. A P value < 0.05 was considered statistically significant in these analyses. All statistical analyses were performed using SPSS statistical software version 19.0." ] },{ "paper_id": "2dfd4bdcf53215a88599651441351138f99089b6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Aging lung", "The authors report no conflicts of interest in this work.", "Morbidity and mortality " ] },{ "paper_id": "2dfdbf2d6b77426866feaf93486327d372fd27c7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2e16617b3004017c0f1c2fcbb140d70444fee083", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Continuous data were expressed as mean\u00b1standard deviation (SD) and compared using the Mann-Whitney U test. Non-continuous data were expressed as numbers and percentages and were analyzed using the chi-square or Fisher exact test. To evaluated factors associated with a 30-mortality, logistic regression analysis was used. Factors with p-value <0.1 in univariate analysis were entered into multivariate analysis. All data were analyzed using the SPSS software version 18.0 (SPSS Inc., Chicago, IL, USA).", "The aim of this study was to compare the characteristics and clinical outcomes of patients with pulmonary ARDS infected with influenza vs. other respiratory viruses.", "The present study has several limitations. First, this study was conducted at a single center and analyzed data retrospectively, therefore selection bias cannot be excluded. Second, the site obtaining respiratory sample was not the same, therefore, whether respiratory viruses were pathogens cannot be ac-curately distinguished. The miss to detect respiratory viruses by multiplex RT-PCR cannot be ruled out. Third, the change in clinical decision by identifying respiratory viruses was not evaluated as in a previous study 5 . Fourth, the prone position was performed in the low proportion of patients with ARDS compared to a recent study 1 ." ] },{ "paper_id": "2e45740f4d2001e92d14d657feef0191f769cb61", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "NOTE: Data presented as n (%). a Tests performed were cultures of sputum and blood, antigen testing of urine, and PCR analysis of upper airway swabs.", "b Patient reported data." ] },{ "paper_id": "2e85e487853731cc083f75a7b86e7649a7e2272c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "LGTV qPCR primer 5 0 -TGTTCTCCATTGTCGGGTTAG-3 0 IDT N/A", "LGTV qPCR probe 5 0 -/56-FAM/TGAGGTTAA/Zen/ CGTGGCCATGCTCAT/3IABkF-3 0", "Other mRNA LNP vaccines (POWV and controls) Moderna (current paper) N/A (Invitrogen). Vero cells were passaged in DMEM supplemented with 5% FBS and 100 U/mL P/S. Raji B lymphoblast cells stably expressing the C-type lectin DC-SIGNR (Raji-DCSIGNR) were cultured in RPMI 1640 medium (Invitrogen) supplemented with 7% FBS and 100 U/mL P/S." ] },{ "paper_id": "2e8fcc213e690efe461306e2bc37eec6c4151315", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2ea1b31d8e9b2d8e4f980c0fd269f75dad4d1d75", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Implementation project leaders tend to prefer voluntary, intrinsic motivation-focused strategies (26) . For example, supportive strategies such as reminders, decision support, and rewards were mostly effective. Moreover, combined strategies were recognized as more effective than were single strategies (27) .", "Our participants' intentions were positive in terms of willingness, perceived importance, realistic insight, and belief that hand hygiene will save lives.", "Data were entered into SPSS v.20 by a professional data entry clerk and revised and cleaned by another clerk. The data were then analyzed using IBM SPSS software (v.20). Categorical variables were described using frequency and percentages. Continuous variables were summarized using mean9standard deviation. Chi-square test was used for comparing proportions. Student t-test/ANOVA was used for comparing means. Statistical significance was set to 0.05 or less and a confidence interval of 95%.", "Although the English language is the official language of communication in the work environment in KAMC, English is a second language to most HCWs, and this might affect how participants responded to the survey tool. We did not identify any language barriers during the pilot testing of the data collection tool." ] },{ "paper_id": "2ea88246c467b56b00c2a792dbf3120299a624c7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2ead29b6cd37834fcfae2fcd41acbffc821f85ae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "One can take the examples of epidemics of Middle East Respiratory Syndrome Coronavirus -MersCov-and Ebola, for which no secondary case has been reported in France.", "Thus, there is little evidence to support the theories by which migrants would expose the host population to significant infectious risk. However, human diseases acquire a social status based on their perceived risk that determines their acceptability (31) .", "The WHO established a Department of Pandemic and Epidemic Diseases in 2011 to better prepare for and respond to EIDs." ] },{ "paper_id": "2eefde0ef2d54748b892970703c15b798192274e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In recent years influenza viruses have circulated in seasonal (H3N2, H1N1) and avian (including H5N1) forms. There has been concern that Influenza A (H5N1), a worldwide cause of large poultry outbreaks, which by December 2009 had affected 467 persons (282 deaths), would drift or shift to become the next pandemic strain [1] . However in April 2009 'Swine flu' caused by a new strain of influenza A, Pandemic (H1N1) 2009 emerged.", "This has now become the dominant strain producing an illness that is transmitted in the same way as seasonal influen-", "This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. za, which in most cases is mild, which can be effectively treated with antiviral drugs and for which a vaccine is now available. By the end of 2009 many countries were still reporting disease activity and an impact on health-care services [2] .", "Stories about the new H1N1 case in town appeared daily and reflected public anxiety. The media can play an important role in allaying the fears of the community by providing adequate and accurate information. The installation of thermal scanners at points of entry has their limitations, and is not recommended by the WHO. Studies indicate many of its drawbacks, including a low positive predictive value of 3.5% [2] ." ] },{ "paper_id": "2ef7ce66fc8445aa7bfabc121193e2ae0091fecb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2f45403508d925c6fd337bd53f0842e1340a6fcd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2ff89400f9bff213ae066c12daa59d5a40fa6257", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Creatine kinase (normal range 24-173 IU/L) and aldolase (1.0-7.5 IU/L) were determined using an automated kinetic assay. Leukocyte count, lactate dehydrogenase, alanine aminotransferase and aspartate aminotransferase were also assessed. The erythrocyte sedimentation rate and C-reactive protein levels were evaluated using the Westergren and nephelometry methods, respectively. Autoantibodies against cellular components were determined with indirect immunofluorescence using Hep-2 cells as the substrate. Autoantibody anti-Jo-1 was determined using the Western blotting method.", "This study was partially supported by the Federico Foundation.", "Constitutional symptoms, skin changes (e.g., heliotrope, Gottron's papules, ulcers, photosensitive, calcinosis, and vasculitis), joint involvement (arthralgia and/or arthritis), and gastrointestinal (dysphagia) and respiratory (dyspnea on moderate exertion) manifestations were analyzed.", "All of the HZ patients initially received intravenous acyclovir (30 mg/kg/day)." ] },{ "paper_id": "2ffacfd58f57a95344119c15d27560cdeaea2285", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cell culture, transfection, and RNAi HeLa cells were grown in DMEM (Invitrogen) supplemented with 10% FBS. To examine localization of GFP-or mCherry tagged proteins, cells were plated on glass coverslips in a 24-well plate at \ue07a80% confluency and transfected using Lipofectamine 2000 (Invitrogen) according to the manufacturer's instructions. Each transfection contained 400 ng of DNA. Transfected cells were examined 24 h after transfection. For esiRNA experiments, cells were seeded at 50% confluency and transfected using 10 nM of each esiRNA and Lipofectamine RNAiMAX (Invitrogen). Cells were examined 48-72 h after transfection. For RNAi rescue experiments, cells were transfected with esiRNA, incubated for \ue07a36 h until cells had reached \ue07a80% confluency, then transfected with mCherry-Sec61\ue062 and various GFP-tagged EndoU constructs. For siRNA experiments, cells were seeded at 50% confluency and transfected with 5 nM siRNA using Lipofectamine RNAiMAX (Invitrogen). Cells were examined 72 h after transfection.", "Monitoring rate of replication and nuclear envelope formation in CSF extract CSF extracts were depleted of XendoU or control IgG, and Cy5-dCTP (GE Healthcare) was added to extracts at a concentration of 1 \u00b5M. Samples", "Abbreviations used in this paper: CSF, cytostatic factor; esiRNA, endoribonucleaseprepared siRNA; rRNA, ribosomal RNA; snoRNA, small nucleolar RNA; wlm, washed light membrane.", "The resulting reads were reduced to unique reads (we assumed that all perfectly matching reads were the result of PCR duplication) using a custom Perl script. Reads were the aligned to the X. laevis rRNA precursor (gi|65056, gi|64487, gi|65094, gi|65095) using Bowtie (Langmead et al., 2009) . Reads aligning to X. laevis rRNA were subtracted using a custom Perl script. The remaining reads were aligned to a draft assembly of the X. laevis genome (7.0 downloaded from Xenbase, June 2013) using tophat2. Reads aligning to transcripts were counted using Cufflinks." ] },{ "paper_id": "2ffddf5caaef38207b58710a93ee8361518813c9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3041dc5ba951755241ae7e75ade271188033d4de", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "BFA was isolated in crystalline form from FL-24 fungi (Tamura et al., 1968 ", "First, the effect of various glycosidases that do not affect the" ] },{ "paper_id": "304397b339265e6096999d27e83cefb84842e8f2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3061f05203159384dfbb2fd9b1d9a1ca7b98c8a6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "One of the limitations of this plan was the lack of an integrated national structure for recording information and lessons learned from events and crises, resulted in some information being inaccessible.", "Most of the residential structures in the rural areas and the cities of Varzaghan, Ahar, and Herris were mortar and mud or masonry material buildings. The largest casualty in this earthquake was caused by the destruction of mud, mortar or brick rural buildings that simplest technical criteria had not been considered, and non-structural parts such as walls and false ceilings had severe damage. Geological features of the earthquake, the facilities of the area and damage to humans are summarized in Table 1 .", "The following criteria have been used for comparison of earthquakes: The first criterion is the comparison of seismology, geotechnical and texture data; the second criterion is the magnitude of the human damage caused by 3 earthquakes; the third criterion: the notification process and rapid warning system of the medical emergency services system; the fourth criterion: the coordination and pre-hospital Emergency system's surge capacity program; the fifth criterion: distribution system and transfer of patients and injured." ] },{ "paper_id": "3062cebd70447841d68c48fe83f0eb51b07a761d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "DCs were cultured as described elsewhere [21] . Human CD14 1 monocytes were cultured in RPMI 1640 with 20 ng/mL rhuGM-CSF (First Link) and 25 ng/mL rhuIL-4 (eBioscience). The appropriate phenotype of immature DC (ie, lacking CD14 1 but expressing major histocompatibility complex class I and class II and DC-SIGN) was confirmed.", "DENV supernatant was precleared with protein A-agarose for one h at 4\u00b0C. Bead-free supernatant was incubated with 10 lg of 4G2 at 4\u00b0C for 2 h followed by protein A-agarose for 1 h. The beads were washed with .05% Tween/PBS 3 times and eluted with nonreducing loading buffer. The sample was run on nonreducing 10% Sodium dodecyl sulfate (SDS) polyacryramide gels and electroblotted onto nitrocellulose membrane (Amersham). Glycan types on DENV proteins were determined using the DIG Glycan Differentiation Kit (Roche).", "The pcDNA3-LL-SIGN plasmids expressing 7 (N7) and 5 (N5) tandem neck region repeats or a mixture of N7 and N5 plasmids (ratio 1:1) were transfected into 293T cells using the Fugene6 (Roche). L-SIGN expression was verified with L-SIGN-specific antibody (clone 120604, R&D Systems).", "The global prevalence of the dengue virus (DENV) has grown dramatically in recent decades, and it is now endemic in .100 countries, with some 2.5 billion people at risk of infection. Dengue is an arthropod-borne flavivirus that can be subdivided into the 4 major serotypes (DEN-1-DEN-4). Most dengue infections either are asymptomatic or lead to a self-limiting febrile illness, dengue fever. In some cases the illness is more severe, leading to dengue hemorrhagic fever (DHF) with severe plasma leakage and bleeding that can be life threatening." ] },{ "paper_id": "3062fc222bccc8c520612d9d6c9b91f048be12b8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "30c0e6db2173676aae3b5a5fcdf9243903c536c1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study is a cross-sectional study conducted at the Prince Mohammed International Airport in Al-Madinah Al-Munawwarah, Saudi Arabia between August and September 2014. Data were collected by semistructured questionnaires during personal interviews. 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\u202b\u0628\u0627\u0645\u0644\u0637\u0627\u0631\u202c \u202b\u0627\u0644\u0635\u062d\u0629\u202c \u202b\u0628\u0637\u0648\u0627\u0631\u0626\u202c \u202b\u0627\u0644\u0639\u0627\u0644\u0642\u0629\u202c \u202b\u0630\u0627\u062a\u202c \u202b\u0627\u0644\u062a\u0639\u0644\u064a\u0645\u0627\u062a\u202c \u202b\u0644\u0646\u0634\u0631\u202c \u202b\u0622\u0644\u064a\u0629\u202c \u202b\u0628\u062a\u0641\u0639\u064a\u0644\u202c \u202b\u0627\u0644\u0628\u062f\u0621\u202c \u202b\u0648\u064a\u0646\u0628\u063a\u064a\u202c \u202b\u0627\u0645\u0644\u0637\u0627\u0631.\u202c \u202b\u0642\u0637\u0627\u0639\u0627\u062a\u202c \u202b\u0643\u0644\u202c \u202b\u0641\u064a\u202c \u202b\u0627\u0644\u0639\u0627\u0645\u0644\u0646\u064a\u202c \u202b\u062c\u0645\u064a\u0639\u202c \u202b\u0639\u0644\u0649\u202c \u202b\u0627\u0644\u0639\u0627\u0645\u0629\u202c Objectives: To evaluate the knowledge and behavior of workers at a Saudi airport regarding public health emergency measures applied during Hajj season.", "Data collection. Data were collected using a semistructured questionnaire. The questionnaire was constructed by a focus group including 4 consultants from the community and family medicine. Closedended and open-ended questions were utilized, including questions measuring demographics, level of knowledge, practice and attitude relating to public health preventive measures at points of entry. The questionnaire was constructed in Arabic language. The questionnaire was piloted on 20 individuals )10 males and 10 females( and additional questions and choices were conducted according to the piloting findings. All questionnaires were filled out during personal interviews. All interviews were conducted by 3 trained interviewers. There was no audio recording of conducted interviews. However, notes of the open-ended responses were taken during the interviews and were transcribed by the interviewers." ] },{ "paper_id": "30d2d2d37c2a884db55ab21d1cbd92abcff95fa2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data are reported as means \u00b1 SD. The differences were evaluated by a two-tailed Student t-test (2 groups) or one-way analysis of variance (ANOVA) followed by the Tukey post hoc test (3 or more groups) using the SPSS software (version 9.0, USA) (27) . Statistical significance was set at P < 0.05.", "Newborn Sprague-Dawley rats (18-20 g) were supplied by the Animal Center of Guangzhou Medical University. Rats were housed and used in accordance with our institutional guidelines for animal care and the Guide for Animal Care of the National Institutes of Health. Dulbecco's modified Eagle's medium (DMEM), fetal bovine serum (FBS), and TRIzol were purchased from Gibco BRL (USA). Trypsin was obtained from Amersco (USA). Alpha-sarcomeric actin was purchased from Santa Cruz Biotechnology (USA). The SYBR \u00ae GreenPCR Master Mix was obtained from Applied Biosystems (USA). The Thermo ScriptRT-PCR kit was purchased from Invitrogen (USA). [ 3 H]-leucine (Leu) was obtained from the China Institute of Atomic Energy (China) and recombinant Ang II and HGF were purchased from Sigma (Germany).", "The cardiomyocyte medium was changed to serum-free DMEM for 24 h. The cardiomyocytes were then treated with different concentrations of Ang II (0.01-10 \u00b5M) and HGF (1, 10, 100 ng/mL) for 48 h in order to explore the most appropriate concentrations of each factor." ] },{ "paper_id": "30f5bfe5ca79c2e25e5dca95d8dfe473b780a51a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Interestingly, in a previous study [10] , hexon-modified virus with incorporation of the His 6 peptide into HVR8 was reported to be viable. Our result with HVR8 is contradictory, evidently due to the differences in the peptides sequences and their lengths. Further, while the two studies are made with changes within HVR8, the specific locations of the incorporations differ as well. Notably our study uses a foreign sequence inserted between Asn437 and Gly438 ( Fig. 1) , while Wu et al. [10] placed His 6 between Pro431 and Trp439 substituting for 7 aa residues of hexon.", "The virus was amplified by passaging in HEK 293 cells and purified by CsCl gradient centrifugation [23] . The concentration of virus particles (VP) in purified virus preparations was determined by measuring the optical density at 260 nm as previously described [24] , whereas numbers of infectious particles (IP) were determined by the tissue culture infective dose 50 (TCID 50 ) method [25] . ", "Human adenovirus type 5 (hAd5) vector has been shown to be an excellent vaccine delivery system in humans and animals [1, 2] . The replication-defective (E1-deleted) and replication-competent (E3-deleted) hAd5 have both been used as vaccine delivery vectors. For biosafety concerns, a replication-defective hAd5 is considered to be more suitable for vaccination. Replication-defective vectors may also have deletion in the E3 region to increase the amount of foreign DNA that can be inserted. Conventional strategy for the expression of a vaccine antigen by adenoviral vector includes insertion of the foreign gene expression cassette into the E1 region. This antigen is expressed as transgene after the infection of permissive cells with recombinant adenovirus." ] },{ "paper_id": "30fd1c06ba7ba3777ee5a348dfc0ee8343f4fdb2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.", "The author(s) received no financial support for the research, authorship, and/or publication of this article.", "SARI surveillance started in Yemen in October 2010 by establishing 2 sentinel surveillance sites: one site at Al Jumhory General Tertiary Hospital located in Sana'a city (2 500 000 population) and another site at Al Wahdah Pediatric Tertiary Hospital located in Aden city (921 809 population)." ] },{ "paper_id": "310e6155d1d7856c824b0304dea2ca5ec637c2bf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "actin polymerization and phagosome formation in addition to disrupting membrane trafficking in macrophages (5) .", "Statistical analysis. The GraphPad Prism software program, version 4.03 (GraphPad Software, San Diego, CA), was used, and one-way analysis of variance (ANOVA) and Bonferroni tests were applied (P \u03fd 0.01). The microarray data were analyzed applying one-way ANOVA with Benjamini-Hochberg multiple testing correction (P \u03fd 0.01). Colocalization studies were performed using the built-in feature in the Bitplane Imaris 7.5 software program with a threshold of background plus 2 standard deviations (SDs). Colocalization data were accumulated using the GraphPad Prism program as mentioned previously, and an unpaired t test was used to determine significance (*, P \u03fd 0.05; **, P \u03fd 0.01)." ] },{ "paper_id": "31390ea0f2fc73d3cd3fee80ca0de765ddd68429", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "On our study HRSV outbreaks presented defined seasonality, occurring in winter, early spring and late autumn periods, being these data similar to previous obtained results (3, 22, 27 Knowledge about HMPV seasonality is limited in Brazil.", "Knowledge of the trends and seasonality of respiratory viral infections in the community could be a first step to confer information for health care providers, to facilitate the implementation of strategies to prevent and minimize transmission, and also introduce early therapeutic options to high risk patients (13) ." ] },{ "paper_id": "314f4b76581376bc7b40e69a9f0bc9153298cb8e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "317f324d1116fd3d2d4933450d87528207846e36", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "319004f23d1af4357edb2a3862f2619be23a21a6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "319017db7033f2754fd403feb01c1fa2b26f38cc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "319b8c97174d684a0e0f50dff4ecfdab294d2a05", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Pearson's Chi-squared test with Yates' continuity correction was applied to infer non-casual distributions of categorical variables. All statistical analyses were performed using R software, setting the significance level to P < 0.05." ] },{ "paper_id": "31db09417c093cb1d87d4dfbbc2bef73716194e7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study is restricted in that it involved a limited number of patients, and more importantly, this is a retrospective and non-comparative study targeting high-risk patients, for which the conditions for establishing a control group were not favorable.", "\u2212 12 \u2212 ", "No potential conflicts of interest relevant to this article are reported." ] },{ "paper_id": "3230a822ceaf337c5137d32e1505878910621991", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Flu, HRV, PIV 1, PIV 3, PIV 4, ADV and HCoV (except SARS-CoV) usually cause upper respiratory tract infections (URTI), whereas RSV, hMPV and PIV 2 have been frequently associated to lower respiratory tract infections (LRTI) [18] .", "Luminex xTAG \u00ae RVP was the first panel that received the FDA approval. The version RVP Fast has shortened the initial time of 8-10 h required to accomplish the whole procedure. The RVP Fast assay incorporates multiplex RT-PCR using primers with universal tags. The amplified product is hybridized to a bead array conjugated to specific probes. Detection is performed using a streptavidin-Rphycoerythrin conjugate. Each bead population detects a unique viral target by hybridisation to a specific anti-tag. A signal (median fluorescence intensity) is generated for each bead population [40] . These fluorescence values are analyzed by using xTAG \u00ae data analysis software for RVP Fast (TDAS RVP Fast) to establish the presence or absence of viral targets in each sample. A recent version of the xTAG RVP Fast panel (RVP v2) is CE marked and identifies 19 viral types and subtypes, which now includes Flu A(H1N1)pdm09.", "Overall, viral diagnosis in outpatients with mild ARI is not probably cost-effective, and should not be routinely performed, except for studies from surveillance programs or of epidemiological interest." ] },{ "paper_id": "32412ffe52eb41da8ecfed314b703c49fd041f5c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3290019883fad88c1c40279e2783a739dc7363fa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "32b8b12a0247b3413442631d5a1bee05a4e5d689", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "ABBREVIATIONS: ARDS = acute respiratory distress syndrome; BLA = biologics license application; EMR = electronic medical record; IT = information technology; PR = pathogen reduction; SDP(s) = single-donor platelet(s); TA-GVHD = transfusionassociated graft-versus-host disease.", "As the administrative notifications and discussions progressed, we met with physicians caring for both low-and high-risk/-acuity patients (Fig. 1) . The latter represented the patient groups considered the most vulnerable to adverse events of any sort and included stem cell transplant/oncology patients, solid organ transplant candidates/patients, patients admitted to intensive care units (including the neurologic, surgical, medical, and cardiothoracic units), the emergency department, obstetrics, pediatrics (including neonatal and pediatric intensive care units), and geriatric services. Nursing staff and business associates (formerly ward clerks) were also involved in these discussions.", "In this article, we explain the steps and ramp-up strategies we employed to implement PR PLTs on an institutionwide basis. We also address what we believe are some key factors others may wish to consider as they investigate the process of converting to an all PR PLT inventory." ] },{ "paper_id": "32d98992b213139fc36d2ff05af879b112e230f6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 Coronavirus can cause severe immune thrombocytopenic purpura (ITP). \u2022 Intracerebral haemorrhage is an uncommon presentation of ITP. \u2022 Intravenous immunoglobulin and steroids are very effective treatments for severe ITP.", "Immune thrombocytopenic purpura (ITP) is an autoimmune disorder that causes isolated thrombocytopenia. Many viruses have been identified as triggering the autoimmune process, including HIV, MCV, EBV, parvovirus, rubella and measles. However, ITP in association with coronavirus infection has not previously been reported. We describe the case of a healthy man who presented with severe ITP complicated by intracranial haemorrhage following upper respiratory tract infection. An infection screen revealed coronavirus infection.", "Coronavirus is not a well-known cause of immune thrombocytopenia even though it may possibly cause severe ITP. Therefore, a respiratory viral panel test should be used in the initial assessment of a patient with immune thrombocytopenia." ] },{ "paper_id": "32f0f51772fb98f4cdf1a9c3ba578b86e75d79cc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "the digestive system) and replenish ''qi'' to remove ''heat'' and toxic substances, to moisturize the lungs and arrest coughing and to relieve spasms and pain' (2) . In addition, it is widely used as a flavoring adjuvant in drug preparations and an ingredient of cigarettes for its taste and property to reduce irritation (2, 3) .", "Arsenic is present in both pentavalent arsenate and trivalent arsenite. Trivalent arsenite is known to be more toxic than pentavalent arsenate (19, 20) .", "One way analysis of variance (ANOVA) procedures were used to assess significant differences among the treatment groups. For each significant effect of treatment, the Tukey test was used for comparisons of multiple group means. The criterion for statistical significance was set at P50.05 or P50.01.", "Dulbecco's modified Eagle's medium (DMEM) and fetal calf serum (FCS) were obtained from BioWhittaker (Walkersville, MD, USA) and Life Technologies (Gaithersburg, MD, USA). Arsenite, [3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] (MTT) and other reagents in the molecular studies were supplied from Sigma Chemical (St. Louis, MO, USA). Licorice water extract was prepared by boiling 600 g of G. radix (Wolsung, Daegu, Korea) in 5 l of water for 3 h, filtering through a 0.2 mm syringe filter (Nalgene, New York, NY, USA), and storing at \u00c020 C until use. The amount of licorice water extract was estimated by the dried weight of lyophilized water extract of G. radix. The yield of lyophilized licorice from G. radix was 13%." ] },{ "paper_id": "33842ff07428db8111b5c1aa9421d7272f523602", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "33bf14aff364a7ce589e97d8021006f940b1f899", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "T his letter addresses some concerns about two recent articles published by the same authors in mBio (1, 2), specifically many uncertainties regarding the potential applicability of their epidemiological data, which were obtained from dromedary camels (DCs) infected with Middle East respiratory syndrome coronavirus (MERS-CoV), to human public health.", "T his letter addresses some concerns about two recent articles published by the same authors in mBio (1, 2) , specifically many uncertainties regarding the potential applicability of their epidemiological data, which were obtained from dromedary camels (DCs) infected with Middle East respiratory syndrome coronavirus (MERS-CoV), to human public health." ] },{ "paper_id": "3424dfd56dfdf957d0fca5e02da73f1352b84ca0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The process of leukocyte adhesion to endothelial cells is the first critical step in neutrophil migration into an area of inflammation.", "C5a-mediated release of histones Histones are essential regulators of genome function in eukaryotic cells. The NS1 protein of influenza A H3N2 subtype possesses a histone-like sequence (histone mimic), and could target the human RNA polymerase-associated factor 1 transcription elongation complex which has a crucial role in the antiviral response. 56 Thus, the virus used NS1 histone mimic to suppress human RNA polymerase-associated factor 1 transcription elongation complex-mediated antiviral response.", "The severe H7N9 patients were in a state of immune paralysis with general leukopenia, low antigen-presenting capacity and impaired T cell response. 90 Those suffering fatal infections with H7N9 have particularly low proportions of peripheral blood T lymphocyte subgroups. 91 Previous studies have demonstrated that C5a induces thymocyte apoptosis, which in turn results in decreased number of T cells in circulation and attendant immunosuppression. 10, 92 This suggests that in a striking contrast to neutrophils, thymocytes apparently receive pro-apoptotic signals from C5a." ] },{ "paper_id": "344b7576e8d591d39fa83b3fe6d6176a61c0ec9a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data pertaining to the characteristics for each epidemiological cluster is presented in Table 1 .", "The present study was performed after approval from the Institutional Review Board (IRB) of the Pusan National University Hospital (IRB No. 1708-030-058). Informed consent was waived by the IRB.", "These results have considerable implications. First, the overall incidence level in the school population needs to be reduced. Since this population has more contact with the family than that of other collective facilities, it is also necessary to manage the family contacts.", "Here, \u00f6 refers to the cumulative distribution function in the normal distribution with a mean of 0 and a variance of 1, where \u00f6 \u22121 (0.75) is the 75th percentile. 30,31 MOR refers to an indicator that quantifies the variation between levels, by comparison between two individuals between different levels (year cluster in the present study); this is the median value of the odds ratios (ORs) in one group with a higher tendency and another with a lower tendency. MOR is a " ] },{ "paper_id": "34a7701ed25e68579ebbc78052c369ba29bc1fae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Animals: Two hundred and eighty-six calves <21 days. Calves with liquid or semiliquid feces, temperature >39.5\u00b0C, and inappetence were considered as cases, and those that had pasty or firm feces and normal physical examination were designated as controls.", "Conclusions and Clinical Importance: BCoV was more likely to be detected in diarrheic than healthy calves. The PanCoV-RT-PCR assay can be a useful tool to detect CoV samples from diarrheic calves.", "Calves from Southern Ontario Sample Size Calculation A prospective case-control study approach was used, and the sample size was calculated based on an estimated 30% BCoV detection rate in healthy calves. The set parameters to detect an odds ratio of 2, including equal number of cases and controls, with a 95% confidence and a power of 0.8, yielded a total of a 138 calves in each group." ] },{ "paper_id": "34a942268ef93e2776d5074b3fb75879858712b6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The patient and her newborn baby were discharged in stable condition on June 30 with no clinical abnormalities on followup at the outpatient clinic.", "Further studies with a larger sample size will help in understanding of the pathophysiology and perinatal outcome of MERS during pregnancy and the optimal mode of delivery.", "A systematic testing procedure for coronavirus infection, including chest radiograph and serial reverse transcription (RT)-PCR assays with peripheral blood and nasopharyngeal swab, did not demonstrate the presence of MERS-CoV in the newborn. MERS-CoV antibody tests were performed with mother and newborn sera on June 16 and June 28, respectively (5). In the mother's serum, immunoglobulin G (IgG) was detected, albeit weakly, (0.302) via enzyme-linked immunosorbent assay (ELISA; Euroimmun AG, Luebeck, Germany), and via indirect immunofluorescence test (IIFT; Euroimmun AG) with a titer of 1:100. IgM and IgA were not detected through ELISA and the plaque reduction neutralization test (PRNT) result was below the cutoff value. However, MERS antibodies for IgG, IgM, and IgA were not detected in the newborn's blood samples ( Table 1) ." ] },{ "paper_id": "34b3c509de48e972c90694eebad3ff0537f3d10b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Keywords. enterovirus; meningitis; metagenomics; orchitis.", "Schistosoma species a Epididymitis and orchitis typically present." ] },{ "paper_id": "34d485e6c776b7e4e28bab88bdd133aa4d43e4b2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "34dbc74805291ff544a0944fd54d1e4f1a470080", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "34fca1fbc149711e5617126584d1e26f06e94de9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Close relatedness between NiV and these African viruses was also demonstrated by immunofluorescence staining. To this end, Vero cells were infected in a biosafety level 4 laboratory with NiV and incubated with serum from E. helvum before staining with a polyclonal anti-bat antibody. Clear reactivity was seen (Fig. 4c) .", "Next-generation sequencing. Products of random cDNA amplification were loaded on 1.2% agarose gels. Primer dimers and large fragments ( > 700 bp) were removed, and amplicons were extracted from agarose gels. Fragments were endrepaired and a 454 sequencing library was constructed according to the GS Junior Rapid Library Preparation protocol (Roche, Penzberg, Germany). Emulsion PCR and sequencing reaction were performed as recommended by the manufacturer. Primer sequences were trimmed from each read, and all reads were aligned against the NCBI virus database using the tblastx local alignment algorithm in Geneious. All hits were scored and alignments with lengths less than 50 amino acids and a bit-score less than 40 were excluded.", "It was noted that this pattern was very different from that of measles virus in humans 19, 20 .", "T he ability to predict and prevent viral epidemics has become a major objective in the public health disciplines. Knowledge of viral hosts enables the identification of maintenance populations from which epidemics may emerge [1] [2] [3] [4] . From an ecological perspective, the natural host of a given virus may be regarded as its habitat 5, 6 . Unfortunately, unbiased assessment of habitat is impossible, as it requires the investigation of all host species in all possible geographical locations. Moreover, the delimitations of viral species and populations are often not well defined. However, viral phylogenies can identify whether extant viruses encountered in a given host are less or more directly linked to common ancestors, providing clues to virus origins [4] [5] [6] ." ] },{ "paper_id": "35349bb1fc9290338907b7d7f104c9db3951163b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "353852971069ad5794445e5c1ab6077ce23da75d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "357496f6d93f95b8c286882be6bd219ff79f90e1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "357af8bb837fb3521423284fa624316d0965bfa3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cats may live for years with a slowly progressing chronic disease, even without a specific anti-Leishmania treatment. 4, 5, 15 However, in this case, the severity of cutaneous lesions was the clinician's main concern leading her to search for another therapeutic protocol when monotherapy with allopurinol proved to be insufficient.", "Nodular and lymph node aspirates were inoculated in Schneider's Insect Medium (Sigma-Aldrich) supplemented with 0.6% (w/v) of CaCL 2 , 5 mM Hepes, 10% fetal bovine serum, 100 U/ml penicillin and 100 \u00b5g/ml streptomycin. 18 Cultures were maintained at 24\u00baC in a refrigerated incubator (Lovibond) and observed by optical microscopy after 8 days of incubation. Viable promastigotes were observed.", "During and after treatment there were no abnormalities reported by the owner. The cat maintained a normal physical condition 19 and examination apart from the skin lesions." ] },{ "paper_id": "357fe51849c655d37552b3f96c67be8394a9b6e5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "AnS-IC", "LiS-IC*", "AcS-IC*" ] },{ "paper_id": "3588b1ead834ac96e69e3f3e84b422dc3e43c068", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "358ab81c15c1c24b69c02cfa8cf52069a7e2932b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "While critics of blogosphere mining may indicate problems associated with the veracity of the data compiled under this approach, they fail to note that more traditional epidemiological studies also often rely upon limited samples as well. Furthermore, traditional studies are also subject to issues related to response validity. Until empirical evidence demonstrates to the contrary, it must be assumed that blogger posts related to ILI are no more or less accurate than the responses generated by respondents in more traditional surveys.", "The potential benefit of WSM-based flu surveillance far outweighs the potential risk. Before the advent of WSM and blogging, the general public's participation in flu reporting only went as far as calling a public health official (if he or she felt inclined to do so) or visiting a physician who would report ILI to the CDC. Now, if someone has neither the time nor desire to meet directly with a public health official or physician, he or she could, instead, just blog or tweet a statement similar to I'm coming down with the flu. A web-based analytical system such as Subdue will then quickly register the posting." ] },{ "paper_id": "358d351a51c6f7f9ddb86ea3fb468c7fdc601e3d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For construction of pSilencer-siTRAF3, the single-strand oligonucleotides 5= GATCCGCGAGAACTCCTCTTTCCCTCGAGGGAAAGAGG AGTTCTCGCAGA 3= and 5= AGCTTCTGCGAGAACTCCTCTTTCCC TCGAGGGAAAGAGGAGTTCTCGCG 3= were annealed to double strands before being subcloned into the HindIII and BamHI sites of pSilencer 4.1-CMV neo to form the pSilencer-siTRAF3 construct." ] },{ "paper_id": "35ec885b13ad96752433a085e543db81dd1d80df", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "362b77d7f48903a4c2b808cd4edb9013b527e2a3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Lower limit of 95% CI " ] },{ "paper_id": "363b1631ca140d28ca1ba79883e8b339c8a4a68a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Below are several fruitful strategies the author has used herself.", "Research is a long process, and it may take at least a year to complete a research study: Starting from the preparation of a proposal, liaising with clinical partners, going through the ethical approval process, the search for funding support, and carrying out data collection and analysis. Sometimes, it may not be feasible for patients to wait for such a long time before their health needs are met.", "Evaluating and testing an evidence-based intervention involve time, manpower, resources, and effort. Sometimes, nurse clinicians may be reluctant to become involved in research when they are facing a shortage of manpower or are overwhelmed by the workload imposed by existing health services.", "The International Agency for Research on Cancer (IARC) estimated that there were more than 14.1 million new cancer cases reported worldwide in 2012 and 8.2 million deaths from the disease. [1] Moreover, the number of new cases and cancer deaths would increase to 21.6 and 13 million, respectively, in 2030. [2] The cancer burden is not a problem of one single country or region but is a matter for all of us. Although the incidence of cancer may vary from one country to another, people diagnosed with cancer have been reported from all parts of the world. [1] With advances in technology and medical treatment, more people are living longer after cancer treatment. IARC estimated in 2012 that there were about 32.5 million people living with cancer 5 years beyond diagnosis. In fact, 50% of patients survive up to 10 years after diagnosed with cancer. [1] The impact of the disease is not only on people's health but also imposes a heavy financial burden. According to the Global Oncology Trend Report (2015), [3] global spending on cancer medication rose from US$ 75 billion in 2010 to $100 billion in 2014." ] },{ "paper_id": "365b8f727f890a4833a5ab7ca03d443022e7faf2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In order to identify sample-specific variants (say somatic in A when compared with tissue B), LoFreq employs the following approach: (1) variants called in Sample A are then tested in B and (2) variants that are not called in B by LoFreq are further tested to see if this could be because of inadequate read coverage in B (using a binomial test with SNV frequency from A). Variants that pass this test are then reported as being specific to/somatic in A.", "Validation of low-frequency SNVs reported by variant callers is a challenging task and one that has not been attempted before in published methods (21) (22) (23) (24) 27, 29) . The recent availability of micro-fluidic digital PCR systems has made this more accessible but significant cost limitations and technical challenges remain for large-scale validation.", "In order to enable comparisons with the methods described in these publications-which were chosen as representatives for non-model-based algorithms-we re-implemented them and these are now available as part of the LoFreq package.", "Supplementary Data are available at NAR Online: Supplementary Figures 1-6 .", "To study consistency and reproducibility, six library replicates of DENV2 TSV01 viruses were created. The viruses were grown in c6/36 cells and RNA was extracted using the QIAamp Viral RNA Mini Kit (Qiagen). The extracted RNA underwent library preparation as described above. In the final PCR step, the sample was divided into six reactions, which were indexed and multiplexed accordingly.", "Dengue virus samples were sequenced in the Genome Institute of Singapore on an Illumina GA-II sequencer to obtain 35 bp reads. Base calling was done with CASAVA 1.7 and reads that did not pass Illumina's chastity filter (CASAVA 1.7 user guide) were removed." ] },{ "paper_id": "366057ee7dcf005190e239f45cdb054964e828db", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "366d302151fd854813f4519551c7d8c5381c4fd7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3677789674e47d9e9b35f87c659430e5295370e9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Purified RNA fragments were separated on a nondenaturing 1% aga-" ] },{ "paper_id": "369acb7f90ebcfd6e59ab973c97ab233c5642b1a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "36fd2f3dfeec8932ec6e4553bce33222c4380756", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For all T m and free energy predictions, we used the following Unafold settings: [Na+] = 0.2 M, [Mg+] = 0.0015, annealing temperature = 30 C, and strand concentration of each strand = 10 -7 M, making the total strand concentration of both strands = 2 \u00c2 10 -7 .", "For confirmation of amplicon sequence, 9 ml of amplified PCR product was mixed with 4 ml of ExoSap-it (USB, Cleveland, OH, USA) and incubated at 37 C for 15 min followed by a denaturation step at 80 C for 15 min. Sanger sequencing was then performed with the BigDye V3.1 Terminator Kit (Applied Biosystems, Inc., Foster City, CA, USA). Single reactions contained 4 ml of Ready Reaction Mix, 0.2-mM primer, 2 ml 5\u00c2 Sequencing Buffer, 11.5 ml of nuclease free water (Applied Biosystems, Inc.) and 2 ml of post-Exosap-it PCR product. The sequencing reaction used the following thermocycling profile: 1 cycle of 94 C for 1 min; 25 cycles of 94 C for 15 s, 38 C for 30 s and 60 C for 4 min. Two microliters of sequencing reaction product was combined with 18 ml of Hi-Di Tm Formamide (Applied Biosystems, Inc.) and run on the ABI 3130 (Applied Biosystems, Inc.). The results were analyzed using Sequencing Analysis v5.2 (Applied Biosystems, Inc.).", "coverage of 99% and an e-score of 0 (no data shown)." ] },{ "paper_id": "37012151cf80cbbbc5ed684c0473b06b1f48d50a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "372c5fab99bbe7f7862304f94bfaebd3c02f1e1c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study recruited a cohort of 175 children who underwent HSCT at Seoul National University Children's Hospital from January 2007 to March 2010 and were followed for at least 1 yr after HSCT. Clinical and virological data were extracted from a prospectively compiled, integrated database. ", "All specimens were tested by multiplex reverse transcription PCR (RT-PCR) for 12 respiratory viruses; rhinovirus, adenovirus, respiratory syncytial virus (RSV) types A and B, parainfluenza virus (PIV) types 1, 2, and 3, influenza virus types A and B, human coronavirus (hCoV) 229E/NL63, OC43 and human metapneumovirus (hMPV). The 2009 H1N1 influenza virus A was excluded in this study. Viral RNA was extracted from each specimen using MagNA pure LC (Roche Diagnostics, Seoul, Korea) according to manufacturer's instructions and PCR amplification was performed using Seeplex TM RV12 ACE detection kit (Seegene, Seoul, Korea).", "Differences between categorical variables were tested by the chi-squared test or Fisher's exact test. All data were analyzed using SPSS version 17.0 and results were considered to be statistically significant when the P value was less than 0.05.", "Respiratory specimens were obtained during routine patient care. Respiratory samples were collected from patients who visited the emergency room or were hospitalized when eligible subjects had febrile episodes or respiratory symptoms or radiologic abnormalities. In total, 402 respiratory specimens were collected from 358 clinical episodes that occurred in the 116 children of the 175 consecutive HSCT cohort via nasopharyngeal aspiration, transtracheal aspiration, sputum, and bronchoalveolar lavage.", "The proportions of each virus in the clinical diagnosis are summarized in Table 2 . Rhinovirus (76%, P = 0.091) and hCoV (90.0%, Table 3 . Transplantation type, sexual factor, and laboratory findings were not significantly different between URI and LRTI.", "As shown in Table 4 , 66 episodes (74.2%) recovered without pulmonary complications or intervention and 23 episodes (25.8%) developed complications. Prophylactic or therapeutic antibiotics were used in 78 episodes (87.6%). Oxygen was required in 21 episodes (23.6%). Pleural effusion was detected on chest radiograph in 15 episodes (16.9%). Mechanical ventilation in the intensive care unit was used in 11 episodes, and the mean duration of ventilator use was 18.4 days." ] },{ "paper_id": "374f83b1cca6c5caba34833d2cd25febd1cc72f1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Involvement of the posterior structures mostly related to HSV and VZV is potentially sight-threatening. Retinal or optic nerve involvement should be suspected in any child, who complains of an acute onset of blurred vision in the absence of anterior segment inflammation or opacities in the ocular media.", "Optic neuropathy may occur as an isolated sign, although it is more often associated with a more generalised involvement of the central nervous system (77, 78) . While specific therapy is not always available, the early diagnosis of ocular viral disease in children should aid in the amelioration of acute symptoms and in the prevention of long-term complications.", "Children and Ebola infection. EV was first discovered in 1976 and has caused three outbreaks, two simultaneously in 1976 and one in 2014 (48) . The exact mode of transmission of EV remains unknown; however, it seems to be transmitted from the biological fluids of wild animals and subsquently through human-to-human contact (49) . According to the WHO, the 2014 west African outbreak claimed a case fatality, which ranged from 25 to 90% and a total number of roughly 10,000 fatalities; the number of children is unknown (49) . This fact makes it a potential lethal tool in bio-warfare. If used in residential areas or within the public transportation system, as a biological agent, EV can easily affect the welfare and life of children.", "Even though a successful vaccine against HBV has been implemented in 184 countries, the eradication of HBV is still not on the horizon (27) . According to the World Health Organization (WHO), there are 240 million chronic carriers of the virus, globally (28) . The risk of developing chronic hepatitis ranges from >90% in newborns of hepatitis B e antigen (HBeAg)-positive mothers, 25-35% in children under the age of 5 and <5% in adults (29) . HBeAg, a non-particulate viral protein, is conventionally considered a marker of HBV replication (30) . This is the only antigen of HBV, which can cross the placenta (31), leading to the specific unresponsiveness of helper T cells to the hepatitis B capsid protein (HBcAg) and HBeAg in newborns of HBeAg-positive mothers (32) . HBeAg is tolerated in utero and acts as a tolerogen after birth (33) . Thus, perinatal transmission is frequent when mothers are HBeAg-positive, whereas it occurs significantly less frequently when mothers are HBeAg-negative (34) (35) (36) ." ] },{ "paper_id": "376a81a940b9cdc1b10609164d5b1a5edac60956", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "sabe que es algo nuevo, pero no se sabe exactamente qu\u00e9 consecuencias puede tener para la salud a una escala global.", "Si bien la mayor\u00eda de las infecciones por arbovirus son asintom\u00e1ticas o no revisten gravedad, la transmisi\u00f3n del ZIKV durante el embarazo puede ocasionar defectos cong\u00e9nitos graves, como la microcefalia." ] },{ "paper_id": "377786fe05588ea782213fcb92f39a6522f113bd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This work was supported by FAPESP -Funda\u00e7\u00e3o Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo-FAPESP (Grant number 05/ 51484-1; 07/55932-4). We are indebt to the technical team from SADIA-Unidade Uberl\u00e2ndia, MG, Brazil.", "Sequencing of the amplified products revealed a high homology with TAstV-2 North Carolina Q/34/1990 strain for polymerase gene and to TCoV for the 3'UTR of turkey\\UK\\412\\00 strain (FJ178641 and , respectively) .", "All the RT-PCR products were sequenced directly using the BigDye Terminator v3.1 cycle sequencing kit (Applied Biosystems) using the same set of primers in order to confirm the identity of the amplified products. The sequences were deposited as TCoV/Brazil/2006 accession number FJ188401 and TAstV-2/Brazil/2006 FJ178641, respectively (9, 14) ." ] },{ "paper_id": "377e2c575da8f034d4f9f34d7ad6c4395487f348", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Boehringer Marmheim GmbH (Mannheim, Germany), the other antibodies were gifts from the following sources: B. Burke (Harvard University, Cambridge, MA; cx-mannosidase II), E. Berger (University of Ziirich, Switzerland; \u00a2x-galactosyltransferase), S. Prehn and T. Rapoport (Max-Delbriick Institute, Germany; \u00a2x-ERp34), P. Buck and S. Fuller (EMBL, Germany; c\u00a2-PDI), M. Zerial (EMBL, Heidelberg, Germany; c~-rab2), H. P. Hauri (Biozentrum, Switzerland; , and J. Saraste (University of Bergen, Norway; c~-p58). All secondary antibodies, rhodamine or FITC coupled goat anti-rabbit IgG, goat anti-mouse IgG or goat anti-mouse IgM for immunofluorescence and rabbit anti-mouse IgG, rabbit anti-mouse IgM, or rabbit anti-rat IgG for immuncelectron microscopy, were obtained from Organon Technika/Cappel (West Chester, PA).", "The SLO-permeabilized or broken cells were fixed with 1% glutaraidehyde in 0.2 M cacodylate buffer, pH 7.4, for 1 h and processed for Epon embedding.", "Nuclear and viral DNA were visualized by staining with 5 t-~g/mi bisbenzimide (Hoechst No. 33258 for fixed cells and membrane permeable Hoechst No. 33342 for living cells; Sigma Immunochemicais) for 5 rain. After extensive washing in PBS the coverslips were mounted on glass slides using moviol as mounting medium and examined with an Axiophot fluorescence microscope (Carl Zeiss, Inc., Oberkochen, Germany)." ] },{ "paper_id": "37894de51fed87b7b8b323f9ca56cdabdc164a94", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Notably, 35% of infected patients either were asymptomatic or had a mild illness that did not require any medical intervention." ] },{ "paper_id": "37ab0d36dd92298368b797e0770ebfa03a36eca8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "37afb28ad52f876fd3473878e7990165663f3bd2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "37f31338fc1447eb78c6b17f93e700f77728e25d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Apoptosis is a highly conserved and regulated process for eliminating damaged and surplus cells, such as those generated during normal embryonic development and abnormal cancer. 1 Important regulators of this process are the B cell lymphoma 2 (Bcl-2) family of proteins, which include pro-and anti-apoptotic members. Antiapoptotic (ie, pro-survival) members include Bcl-2, Bcl-xL, Bcl-w, and myeloid cell leukemia-1 (Mcl-1), whereas pro-apoptotic members include Bax-like proteins, such as Bax, Bak, and Bok, and BH3-only proteins, such as Bad, Bim, Bmf, Bik, Hrk, Bid, Puma, and Noxa. 2 The interaction of pro-and anti-apoptotic proteins with regulators is a key element of cell survival and death.", "To obtain hierarchal MD clusters, the biomolecular simulation trajectory and data analysis program cpptraj, 32 which is part of the AMBER package, were used. Clustering is a means of partitioning data so that data points inside a cluster are more similar to each other than they are to points outside a cluster. In the context of molecular simulation, this means grouping similar conformations together. Similarity is determined by a distance metric -the smaller the distance, the more similar the structures. One commonly used distance metric is coordinate root mean square deviation (RMSD). Application of this procedure resulted in four main clusters, from which one centroid conformation PDB structure was chosen for subsequent molecular docking.", "Zinc05500896 (-6.64) Zinc33257600 (-8.11) Zinc05521275 (-6.73) 8" ] },{ "paper_id": "37feea85864da899f6c9b22a7d89c8598fa38a29", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cells from Human Donors. Cord blood (CB) was generously donated from the Cleveland Cord Blood Center, Cleveland, for isolation of CD34 + cells and adult mobilized peripheral blood CD34 + cells were obtained from Fred Hutchinson Cancer Research Center Processing and Procurement Core under the approved institutional protocol of the Scripps Research Institute (no. IRB-13-6173).", "Overall, intricate trafficking of membrane proteins regulates specific cellular activities, such as nutrient uptake and signal transduction, and collectively allows cells to rapidly respond to their surroundings. While providing a means for large molecules to access an otherwise impermeable cell, the endocytic network is also exploited as a portal of entry for pathogens. Many pathogenic enveloped viruses infecting humans, including Influenza A virus (IAV), Dengue virus, and Ebola virus, adhere to a life cycle that relies on endosomal movement and maturation. The progressive acidification that occurs during the transition from early endosomes to late endosomes triggers fusion between viral and endosomal membranes, allowing cytoplasmic access and the initiation of viral replication (7) . Endosomes are thus situated at a crucial cellular threshold, and, as a result, they are equipped with elements of the cell-intrinsic antiviral immune response (8) .", "Flow Cytometry. Cells were fixed/permeabilized with Cytofix/CytoPerm reagent (BD) for 20 min and washed in Perm/Wash buffer (BD). Cells were pelleted and resuspended in primary antibodies diluted in Perm/Wash buffer, incubated at room temperature for 30 min, and washed in Perm/Wash buffer. Cells were pelleted and resuspended in Alexa Fluor-conjugated secondary antibodies diluted in Perm/Wash buffer, incubated at room temperature for 30 min, and washed in Perm/Wash buffer, and cells were acquired and analyzed on a LSRFortessa (BD). The following primary antibodies were used to score virus infections: anti-HIV Gag KC57-FITC (BD), anti-p24 Gag (3537; NIH AIDS Reagent Resource), anti-IAV-NP (AA5H; Abcam), and anti-SeV (PD029; MBL). Endogenous IFITM3 was measured by anti-IFITM3 (EPR5242; Abcam) while exogenous IFITM3 WT and mutants, IFITM2, and IFITM1 expressed from pQCXIP were measured by anti-FLAG M2 (Sigma). Endogenous LAMP1 and EEA1 were measured by anti-LAMP1 (H5G11, sc-18821; Santa Cruz Biotechnology) and anti-EEA1 (clone 14, 610456; BD). The following reagent was obtained through BEI Resources, NIAID, NIH: Human Recombinant IFN Beta, rHuIFN-\u03b2 ser17 (NR-3085)." ] },{ "paper_id": "381d5feb501bd762182e76a3fcb4dd3f64c9a261", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Western blot analysis was performed according to our published protocol. 20 Briefly, 1.5 mg purified (His) 6 -tagged rNPs of MERS-CoV, human CoV (HCoV) 229E and HCoV-OC43 respectively were subjected to 12% SDS-PAGE and were transferred to 0.22 mm nitrocellulose membranes (GE Healthcare, Little Chalfont, Buckinghamshire, UK). The membranes were blocked with 5% skim milk in Trisbuffered saline and then incubated with mouse anti-MERS-CoV-rNP immune sera at 37 6 C for 60 min. Antigen-antibody interaction was detected with 1:4000 diluted horseradish peroxidase (HRP)conjugated goat anti-mouse IgG (Novex, Life Technologies, Grand Island, NY, USA) and visualized by 3,39,5,59-tetramethylbenzidine (TMB) liquid substrates system for membranes (Sigma Aldrich, Saint Louis, MO, USA).", "To establish a capture ELISA for MERS-CoV NP detection, two anti-MERS-CoV-rNP-specific MAbs (1F6 and 7C4) were selected. MAb 1F6 was coated onto the microplate and MAb 7C4 was conjugated with HRP. This ELISA showed a high sensitivity, with detection limit to MERS-CoV-rNP of less than 1 ng/mL; and a high specificity, with no detection for the HCoV-OC43-rNP and HCoV-229E-rNP ( Figure 4A ). The high sensitivity was further confirmed with a detection limit of 10 3 ", "Since its emergence in 2012, Middle East respiratory syndrome (MERS) has affected more than 20 countries globally with a total of more than 900 laboratory-confirmed cases and a fatality rate of over 30%. Similar to severe acute respiratory syndrome (SARS), MERS is also caused by a coronavirus (CoV), named MERS-CoV; 1-4 but unlike the SARS epidemic which has rapidly died off after the intermediate amplification animal hosts were segregated from humans by closure of wild animal markets in southern China, the MERS epidemic has persisted for more than two years with no signs of abatement. The persistence of the epidemic may be partly due to the difficulty to control the contact between the people and dromedary camels, a major zoonotic source of MERS-CoV. [5] [6] [7] [8] [9] Since there is still no effective anti-viral agent for the treatment of MERS-CoV infections, rapid and accurate laboratory diagnosis is essential for commencement of infection control measures." ] },{ "paper_id": "3831c263a7c8d673bd839bb390083c0d79003d14", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "384c7676eb08fb530ec399208932513c0fa0c4e3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Primers targeted specifically the nucleocapsid gene of RSV(6), the Matrix protein gene of hMPV (7), the hemagglutinin and neuraminidase gene of PIV-1,2 (8) and PIV-3 (9) the phosphoprotein gene of PIV-4 (10) hemagglutinin (HA) gene of IFV A and B (11) and hexon gene of AdV (12) ." ] },{ "paper_id": "38550290e3c74a86fb0e56ecd69303ff68de55d9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Where new vaccines are required under emergency conditions to prevent or to curtail disease outbreaks, it is essential for developers and manufacturers to work closely with the regulatory authorities and with the WHO to understand the requirements to bring a candidate vaccine as quickly as possible through the development pipeline and into the clinic. It is evident from this review series that much progress in vaccines for emerging pathogens is being made and will continue to be required to counter these serious infections.", "Understanding the interaction of the host with a viral pathogen to expedite vaccine development is a theme taken up in the review contributed by Sharpe et al. [2] . Specifically, they address the targeting of the human leucocyte antigen (HLA)-E molecule, a major histocompatibility complex (MHC)1b molecule, by viral vectors to induce non-classical CD8 + T cell immunity and to inhibit natural killer (NK) cell activity. However, the authors acknowledge that there remain some questions of safety with this HLA-E targeting approach to vaccination; for example, the existence of self-peptides which are able to up-regulate HLA-E activity. The preclinical data, for", "In this two-part series of reviews, we have invited experts in their fields to contribute articles on the status of vaccine research and development for emerging pathogens. This topic has been brought into sharp focus in recent years following significant outbreaks of viral diseases such as those causing severe acute respiratory syndrome and Middle East respiratory syndrome, as well as devastating outbreaks of diseases caused by the Ebola, Marburg, Zika and Lassa fever viruses, to name only a few examples. Additionally, bacterial infections leading to bubonic and pneumonic plague, most notably in Madagascar in 2018, as well as malaria in many tropical countries, melioidosis in south east Asia and tularaemia in northern Europe and North America, have incurred significant morbidity and mortality. In this review series, the life cycle of these pathogens and the epidemiology of disease have been reviewed in the context of potential points of intervention for the prevention of human infection. Many of the emerging pathogens are zoonoses and, as such, there is scope for intervention at the animal/insect/environmental reservoir. Other pathogens covered in this review series are considered to be re-emerging, such as multi-drug resistant tuberculosis." ] },{ "paper_id": "3897a0019d6f54b8c354f32eca68de8f512af39c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "There are no financial or other issues that might lead to conflict of interests. ", "RSV belongs to the family of Paramyxoviridae, and is classified in the genus Pneumovirus. RSV is the most common cause of fatal acute respiratory tract infection in infants and young children. RSV infects virtually everyone by 4 yr of age, and reinfection occurs throughout life, even among the elderly (4-6). Adults infected with RSV tend to have more variable and less distinctive clinical findings than children, and the viral cause of the infection is often unsuspected (7) . This study attempted to verify the seroprevalence of RSV IgG among healthy young adults in their early twenties who had just been admitted to the Korea Air Force basic training camp. Subjects with an RSV IgG seronegative outcome were prospectively observed for vulnerability to respiratory infection, especially during the period of basic training.", "Military recruits admitted to the Air Force boot camp were required to undergo a basic health examination which includes a blood sampling test. In this investigation, RSV IgG immunoassay was added to the basic blood test. All subjects were admitted to the training camp on June 26, 2012. They underwent a blood test on June 27, 2012, which was a day after resting without training on the day of admission. The total number of recruits was 570 and all of them underwent an RSV IgG test. Institutional Review Boards of the Ministry of National Defense (IRB No. AFMC-12-IRB-014). Air Force physicians themselves explained the purpose, method and precautions of this study, and tests were conducted after obtaining an informed consent from each subject." ] },{ "paper_id": "38db3b3d3d82b08a9d95490fd0871d04d7001efe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Competing interests None declared.", "Provenance and peer review Not commissioned; externally peer reviewed.", "Data sharing statement No additional data are available." ] },{ "paper_id": "390dc3c6b8a82c69dddf3395e72846d49f5c4a72", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3920596af370a9e2e4c31d89444c980ceadbc4f8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "RNAs encoding the \u2423-domain gene were mixed with the highly purified reconstituted translation system (30) containing protein (EA reagent, Clontech) and a fluorescent substrate (50 M Tokyo Green R -\u2424Gal, Sekisui Medical, Japan) according to a previous study (31) . The fluorescence at 37 \u2022 C was detected using an Mx3005P QPCR system (Agilent Technologies, USA).", "Supplementary Data are available at NAR Online.", "Funding for open access charge: Exploratory Research for Advanced Technology, Japan Science and Technology Agency. Conflict of interest statement. None declared." ] },{ "paper_id": "39244c86324ed37f0b32222540efeefd2144d458", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All analyzes were performed using SPSS V13.0 software; P<0.01 and P<0.05 were defined as statistically very significant and significant, respectively. One-way analysis of variance (ANOVA) and multiple comparison statistical test were also used.", "TGEV is a coronavirus and contains a positive-sense single-stranded RNA genome [28] , which encodes four structural proteins and three non-structural proteins. Spike (S) protein is the major component of the virion surface and possesses four antigen sites," ] },{ "paper_id": "39708f10658e8e33983d0b2ebb570bdd00c5df46", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "KM is a co-founder of Inserogen, Inc., a plant-based biotechnology company with a focus on the development of orphan drugs for replacement therapy.", "We performed a sensitivity analysis to understand how critical process cost variables impact COGS. The results of a relative sensitivity analysis for the facility are shown in ", "Chinese hamster ovary (CHO) and Escherichia coli (E. coli) cells are the most common type of cells used for therapeutic protein production. The time needed for CHO cell line development has decreased in the past decades, but remains a relatively long and costly process. CHO cell cultures require expensive media and multi-step bioreactor seed trains, and are vulnerable to infection with mammalian viruses and pathogens that can result in shutdown of manufacturing operations. With over 20 years of commercial development and use, the CHO platform only offers shrinking intellectual property opportunities; patent protection for major innovations are held by a relatively small number of consolidated pharmaceutical companies.", "In the pharmactical production and process industries, equipment cost per unit of production capacity scales in proportion to size. This characteristic is observed in the following correlation" ] },{ "paper_id": "39988cf0ce9b1ea1e63e9c3c15de51a9c87fc376", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "39a01111cbf00eb9bf55c7713c1edec443d3e97e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The study was funded by Vice Chancellor Fellowship, the University of New South Wales, 2010-2012.", "By the year 2009, 8563 laboratories (8273 screening laboratories, 254 confirmatory laboratories, 35 confirmatory central laboratories and 1 National AIDS Reference Laboratory) and 84 laboratories hospitals are capable of carrying out CD4 and HIV viral load testing in China [22] . Confirmed diagnosed HIV cases were reported back to referring clinical sites then further integrated into the central database through CISDCP. The hospital-based surveillance in China has cumulatively diagnosed 326,000 people living AIDS and a total of 65,481 people are currently receiving ART in 2009 [23] , which accounted for 62.4% of the AIDS cases [2] .", "Prior to 2004, newly diagnosed HIV/AIDS cases were reported through the National Disease Reporting System (NDRS) (see Table 1 for a list of reportable items in China). The system consists of multiple level of reporting. Villages, being the lowest level of administrative, collected HIV epidemiological data in their allocated areas and reported to prevention units in township hospitals. From the prevention units, HIV data were further sent through county health and epidemic-prevention stations (EPS) to provincial centers and forwarded to the Chinese Academy of Preventive Medicine. With the support from the Ministry of Health and cooperation of provincial centers of health and epidemic prevention, a computerized system had worked effectively to network the monitoring of HIV epidemics at various levels in China and information transfer experienced no substantial changes for about 25 years. However, all communicable disease surveillance systems in China underwent significant upgrade in 2004." ] },{ "paper_id": "39a7144b3eb9ddf5b9076163aa61099d8b58f977", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Our results highlight the importance of carrying out these separate analyses." ] },{ "paper_id": "3ac5e3619d6decbe8deedc18bb939bbfbf0c707c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Our goal was to identify a structural feature of E1 that might be responsible for intracellular accumulation of the protein.", "The process of intracellular transport to the plasma membrane could be governed by positive sorting signals; i.e. pro-C. E. Machamer's present address is Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510. J. K. Rose's present address is Departments of Pathology and Cell Biology, at the same institute.", "Both COS-1 and HeLa cells were maintained in Dulbecco-Vogt's modified Eagle's medium with 5% FCS. The IBV used in these experiments was adapted to growth in monkey cells by nine consecutive passages of egggrown virus at low multiplicity of infection in Vero cells, and was obtained from B. Sefton (The Salk Institute). Tissue culture supernatant from infected Vero cells was used as the inoculum to infect COS-I cells for radiolabeling and inununofluorescence. The multiplicity of infection was approximately 0.1, and infected cells were assayed for IBV-speciflc polypeptides at 29 and 48 h postinfection." ] },{ "paper_id": "3b09cf3b8cc59b5d16c4717c50ffa70edb467046", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Major clinical criteria for PCD diagnosis \u00c3 1) Unexplained neonatal respiratory distress (at term birth) with lobar collapse and/or need for respiratory support with CPAP and/or oxygen for >24 hr.", "Various diseases caused by genetic disorders of nonmotile cilia can result in cystic kidneys, cystic or cholestatic liver, skeletal malformations, developmental delay, hydrocephalus, blindness, or deafness. These include Joubert Syndrome, Bardet-Biedl syndrome, Usher Syndrome, Jeune Syndrome, polycystic kidney disease, and others. The overlap of these non-motile ciliopathies with respiratory cilia dysfunction is unusual, and poorly understood at present, 90,92,93 but increased rates of bronchiectasis are found in polycystic kidney disease. 94 Therefore, consultation with a geneticist or other subspecialists is recommended when patients with possible PCD have features of non-motile ciliary dysfunction.", "Finally, PCD patients should receive recommended vaccinations per local schedules. Annual influenza 127 and pneumococcal vaccinations (per the Advisory Committee on Immunization Practices) 128, 129 are recommended in PCD. In the first year of life, monthly (seasonal) immunoprophylaxis against respiratory synctial virus can be considered for infants with PCD, and more specifically for infants with complicated respiratory courses requiring prolonged oxygen supplementation." ] },{ "paper_id": "3b19c08ee471af50e75d3d2071699e88990cbe68", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplementary materials are available at Open Forum Infectious Diseases online (ofid.oxfordjournals.org). 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.", "In conclusion, this report raises a potential opportunity to widen the diagnostic window for JEV infection. Given the challenges inherent in flavivirus serological diagnosis, especially in the context of lifetime exposures to multiple flaviviruses, a greater capacity for direct virus detection by PCR could be very attractive. Further studies are needed to determine the reproducibility of these findings.", "Electromyogram and nerve conduction studies performed on day 22 were consistent with an acute motor-axonal neuropathy or anterior horn cell pathology. No clinical improvement was evident after 4 days of intravenous immunoglobulin (IVIG) administered at a dose of 1 g/kg daily, and the patient died 30 days after the onset of symptoms.", "Shortly after admission, on day 7 of his illness, he became confused. Cerebrospinal fluid (CSF) obtained by lumbar puncture demonstrated a glucose of 3.5 mmol/L (reference interval, 2.2-3.9 mmol/L), protein of 1.3 g/L (reference interval < 0.45), polymorphs of 280 \u00d7 10^6/L, lymphocytes of 90 \u00d7 10^6/L, and red blood cells of 54 \u00d7 10^6/L. He was commenced on empiric broad-spectrum antibiotics with vancomycin, meropenem, benzyl penicillin, and acyclovir. Due to a deteriorating conscious state, he was intubated the following day and transferred to a tertiary center. Neurological examination upon arrival revealed a generalized flaccid paralysis. A magnetic resonance image of the brain demonstrated no abnormalities. Seizure activity developed on day 10 of his illness, for which anticonvulsant medication was commenced." ] },{ "paper_id": "3b299c75b42f7b4119456256518d2d8753d74838", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3b4bdc3dce8169c30fd1f151713b1f801059c694", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Clearly, m Z g1 gives greater weights to outer vertices/edges than to inner ones in a graph.", ", , , ." ] },{ "paper_id": "3b5c43f1068e79db27adaca5df0bd717851c37cc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "URLs EHCO [132] http://ehco.iis.sinica.edu.tw/ Onco.HCC [133] http://oncodb.hcc.ibms.sinica.edu.tw/index.htm HCVpro [134] http://cbrc.kaust.edu.sa/hcvpro/ HCVdb [135] http://euhcvdb.ibcp.fr/euHCVdb/ Hepatitis Virus Database (HVDB) [136] http://s2as02.genes.nig.ac.jp Los Alamos National Laboratory in the United States [137] http://hcv.lanl.gov LiverAtlas [138] http://liveratlas.hupo.org.cn dbHCCvar [139] http://GenetMed.fudan.edu.cn/dbHCCvar", "J Jo ou ur rn na al l o of f C Ca an nc ce er r 2015; 6(1): 54-65." ] },{ "paper_id": "3b69d402abfb10509e1518f2f2b38e8d8840f34e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Emerging disease is a term used with increasing frequency to describe the appearance of an as yet unrecognized infection, or a previously recognized infection that has expanded into a new ecological niche or geographical zone and often accompanied by a significant change in pathogenicity. 1 The key message is that these are representative of constantly evolving infections responding to rapid changes in the relationship between pathogen and host.", "Considerable international effort is now being made to collect and record samples of viruses and microorganisms from wild animal populations and potential arthropod vectors in order to expand the current molecular databases. By making available extensive catalogues of genome sequences, it is expected that newly emerging agents would in future be more readily identified and thus control measures put in place much more rapidly.", "Viruses must bind to one or more receptors on the surface of the target cell in order to enter and infect cells. New diseases can emerge when viruses evolve the ability to bind to either a new receptor in a novel target host species, or use the homologue of an existing receptor in a new species.", "The preeminent property of the arenaviruses is the establishment of a long-term, chronic infection in their principle murine reservoir. Although rodents are divided into over 30 families worldwide, arenaviruses are found mainly within two rodent families, the Muridae and Cricetidae (e.g. field voles, lemmings, gerbils). Each arenavirus is not necessarily found distributed throughout the populations of any particular host reservoir, however." ] },{ "paper_id": "3b6d953fa2770589cb1f699047f2d94990cfa4ad", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nil.", "There are no conflicts of interest." ] },{ "paper_id": "3b8b2a835cfa770c6cef711d52e1f1e869d8aca8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Reactive oxygen species (ROS) levels in macrophages were monitored using the fluorescent ROS indicator C2 0 ,7 0 -dichlorodihydrofluorescein diacetate (5 mmol/L; Molecular Probes, Eugene, Oregon). Cell-associated fluorescence was detected by fluorescence-activated cell signaling (FACS) using a FACS-Calibur flow cytometer (BD Biosciences, San Diego, California) with FlowJo software V 7.2.5 (Tree Star Inc, Ashland, Orogen). Images of fluorescent cells were acquired under a 710 confocal microscope (Carl-Zeiss, Germany).", "The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.", "Eun Ho Kim, PhD https://orcid.org/0000-0002-6476-163X" ] },{ "paper_id": "3b8d650d6325394ab80ca6c41330f625134680eb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3b8d7417f616e8ba9912423e9b764870d8e2e047", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Live Varroa mites were fixed in 4% paraformaldehyde in 100 mM PBS (pH 7.0) overnight at 4\u00b0C, rinsed in nuclease-free water three times, and then stored in 70% ethanol (200 proof) at 4\u00b0C until used. Tissue dehydration was carried out by successive incubations in ethanol (70%, 95%, and 100%) and xylol (twice for 5 min each) and embedded in paraffin. Paraffin sections were cut 2 to 5 micrometers thick and mounted on poly-Llysinated slides and stored at 4\u00b0C overnight. The sections were then rehydrated through a descending concentration of ethanol (100%, 95%, and 70%), dewaxed in xylol, treated with proteinase K (10 g/ml) for 30 min, and acetylated with 0.33% (vol/vol) acetic anhydride in 0.1 M triethanolamine-HCl (pH 8.0) for 10 min prior to hybridization.", "Virus particles were negatively stained with 2% uranyl acetate on a Formvar-coated Ni grid and viewed in a Hitachi H-7000 electron microscope at magnifications between \u03eb33,000 and \u03eb100,000." ] },{ "paper_id": "3b8ec6abf589bfc9738475e02cb3a6d18eaba5b7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Complement activation plays a critical role in innate recognition and neutralization of pathogens in vivo (3, 4, 58) .", "For survival analysis, Kaplan-Meier survival curves were plotted using Prism software (GraphPad) and analyzed by the log rank test. Statistical signifi cance of complement levels, survival time, viral burdens, antiviral antibody titers, and total number of activated T cells were analyzed by an unpaired t test or Mann-Whitney test." ] },{ "paper_id": "3ba6e62e7ed8c087b34db8520cb1a203a062ded9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In the past, the central Taiwan government has primarily focused on social relief and support efforts during disasters. During the catastrophic earthquake on September 21, 1999, inadequate integrated information and an incomplete response framework resulted in a delayed government response. Thus, it became apparent that the disaster response framework required revision.", "Taiwan is well-versed in responding to natural disasters and has already established relevant, detailed standard operating procedures (SOPs). However, during public health emergencies, such as a dengue fever or rabies outbreak, Taiwan uses a flexible command center structure, and SOPs are not well-established for these types of responses. This is a potential area for future improvement.", "In an emergency, depending on the disaster severity, type, affected area, and other aspects, the CEOC may be activated. When the CEOC is activated, its command structure consists of at least 4 sections, including staff, information, operations, and administration sections as well as 1 on-scene incident office (see Figure 2 ). 17 ", "L ocated on the earthquake-prone circum-Pacific belt and seasonal typhoon impact zone, Taiwan has historically been threatened by natural disasters. Taiwan is a small island with high population and urban density. Disasters in Taiwan can grow into complicated events, causing large impacts on the country's economy, environment, and public health. In 2005, the World Bank report Natural Disaster Hotspots: A Global Risk Analysis indicated that 73% of Taiwan's land and population are exposed to 3 or more hazards, such as earthquake, landslide, or flood, and almost 99% of its land and population are exposed to 2 or more hazards. 1 In fact, Taiwan may be considered one of the most vulnerable areas to natural hazards on Earth. 2 In addition, as climate change con-tinues to affect the world, extreme weather affecting Taiwan may grow worse." ] },{ "paper_id": "3bb1bf62e09f90f586662be381ca7660090400a8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The mammalian Vero, HeLa, and BHK-21 cell lines were maintained in Dulbecco modified Eagle medium (DMEM; Gibco) supplemented with 10% newborn calf serum (Gibco) and 1% penicillinstreptomycin (Sigma) at 37\u00b0C with 5% CO 2 .", "The continuous protease assays were performed using fluorescence resonance energy transfer (FRET)-based substrate representing the CHIKV nsP3/4 cleavage site (34) (Fig. 4D ). Briefly, a peptide substrate with an excitation wavelength of 340 nm and an emission wavelength of 490 nm at an interval of 5 min for a total period of more than 2 h. Finally, the data were normalized to a no-enzyme control and are expressed as relative fluorescence units (RFU)." ] },{ "paper_id": "3bbbbc7190599b47616269323cfbd3659d9dc420", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Step 1, linearization of the fulllength SA 14 -14-2 cDNA at the 3'-end of the viral genome ( Figure 4A) ;", "Step 1, purification of viral RNA from the cell culture supernatant of JEV-infected BHK-21 cells (Figure 1A) ; Step 2, synthesis of four overlapping cDNA amplicons (F1 to F4) spanning the whole viral genome ( Figure 1B); Step 3, subcloning of each of the four contiguous cDNA fragments into a BAC vector, creating pBAC/F1 to pBAC/F4 ( Figure 1C) ;", "The authors have declared that they have no competing financial interests." ] },{ "paper_id": "3be2b917c48e3dc25a4e6bb3028fd5d32e4f2d9d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3bed29e225d41a6617ee40c5bc70c0574388079a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As viral diseases vary greatly in duration and severity, the safety threshold of an antiviral nucleoside/tide needs to be considered in the context of its efficacy and treatment duration. For example, compounds to treat acute and deadly viral infections such as Ebola would likely have different safety criteria than drugs used to control chronic infections such as HIV-1 and HBV. Existing nucleoside/tides are routinely screened against emerging viruses, and it is possible that a compound that failed to achieve an adequate therapeutic window against one virus may be suitable for treating other viral infections.", "Nucleoside and nucleotide analogs have played significant roles in antiviral therapies and are valued for their impressive potency and high barrier to resistance. They have been approved for treatment of herpes simplex virus-1, HIV, HBV, HCV, and influenza, and new drugs are being developed for the treatment of RSV, Ebola, coronavirus MERS, and other emerging viruses. However, this class of compounds has also experienced a high attrition rate in clinical trials due to toxicity. In this review, we discuss the utility of different biochemical and cell-based assays and provide recommendations for assessing toxicity liability before entering animal toxicity studies.", "In certain cases, testing in a specific cell assay is warranted. For example, a number of the first-generation HIV nucleoside analogs showed myelosuppressive effects. As a result, the FDA recommended evaluating this toxicity on the growth of human bone marrow progenitor cells in colony formation assays. 37 The importance of measuring cellular TP levels A nucleoside/tide analog's cytotoxicity is often directly related to its cellular level of the active TP metabolite. BMS-986094 and IDX184 are both 2 0 CMe guanosine nucleotide prodrugs, but the former formed >37-fold higher TP, and this correlated with its significantly higher toxicity. 18 Some nucleoside analogs are poorly phosphorylated in cells, such as balapiravir. Even though it is a specific inhibitor of POLRMT, balapiravir showed little or no toxicity in a large panel of cell lines and primary cells tested, but development of this compound was stopped at Phase II due to toxicity." ] },{ "paper_id": "3c0c493a037dacafd2eda2e37518e0f0dff7955f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Rarely, we used vasopressor support on day 1 following ICU admission (3.2%). Broad-spectrum antibacterial agents were initiated in almost all.", "Chest radiographs demonstrating bilateral mixed interstitial or alveolar infiltrates were found in 90% of patients.", "On admission, 11 of 61 (18 %) patients who were tested had leukopenia, 27 of 61 (42.2 %) had anemia, and 18 of 61 (29.5 %) had thrombocytopenia. Twelve of 61 patients had positive blood and bronchoalveolar lavage cultures.", "The clinical picture in severe cases of pandemic (H1N1) 2009 influenza is markedly different from the disease pattern seen during epidemics of seasonal influenza, in that many of those affected were previously healthy young people. Current predictions estimate that, during a pandemic wave, 12-30 % of the population will develop clinical influenza (compared with 5-15% for seasonal influenza) with 4% of those patients requiring hospital admissions and one in five requiring critical care (6) ." ] },{ "paper_id": "3c39d9aa9e05723ab781cc800c89c69869fd0eeb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3c3a1e707eaf3efae5ae22cced7d4850ffc1f587", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "creased understanding of vaccine-mediated immunity can help scientists be better positioned to identify correlates of vaccine immunogenicity and make progress towards developing new and enhanced vaccines and therapeutics.", "Recent global outbreaks of EIDs, such as Ebola or Zika virus (ZIKV) diseases, reminded the world of the imminent threat of unexpected pathogens. EIDs can result from infectious agents that have recently appeared or have existed, but are rapidly increasing in incidence. 14, 15 Major pathogens include highly pathogenic avian influenza (HPAI) virus, severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV), ZIKV, dengue virus (DENV), and Middle East respiratory syndrome coronavirus (MERS-CoV).", "Emerging infectious diseases (EIDs) are defined as newly appearing infections in a population or diseases that have previously existed, but are rapidly emerging in incidence or geographic range. 1, 2 EIDs are often initiated by pathogens with a change in pathogenicity, and these emerging pathogens are highly likely to be zoonotic, with a broad range of hosts or vector-borne. [3] [4] [5] New human pathogens are especially likely to continue emerging, mainly from mammals and birds, for the foreseeable future. For these reasons, an effective global surveillance system for novel pathogens is needed. Due to the diverse nature of antigenic variation of emerging pathogens and their various strategies to evade the immune system, EIDs continue to pose difficult challenges to clinicians, public health profes-sionals, and researchers globally.", "As summarized above, in addition to virus genetic variation, complex environmental factors, including ecological and behavioral influences, can be important contributing components of the recent emergence of viral diseases. Recent Ebola and Zika outbreaks have shown that the world is unprepared to detect local outbreaks and respond quickly enough to prevent them from becoming global pandemics. Given the great concern for public health owing to the speed and increased volume of global transportation, the ability to rapidly develop and deliver vaccines when new 'unknown' diseases emerge offers our best hope to outpace EID outbreaks, save lives, and avert disastrous economic consequences.", "Southeast Asia has been the epicenter of many emerging diseases in the past decade. 16 Table 1 shows the characteristics of recently occurred or current EIDs occurring in Southeast Asia in the 21st century. Such diseases pose a major threat to public health and have the potential to cause a high incidence of fatality among the global community. Therefore, further investigation into the emergence and pathogenesis of EIDs is required for public health and safety." ] },{ "paper_id": "3c3ab717ef79befde82029b1362348708998d17e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3c47eea51db8f16e9de1d4303cfe054cc39416cc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3c4f6a15937affaf17af8ba34d069cc71968db53", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The following reference compounds were included: tenofovir (PMPA), AMD3100, ganciclovir, cidofovir, acyclovir, brivudin, the lectins Hippeastrum hybrid agglutinin (HHA) and Urtica dioica agglutinin (UDA), dextran sulfate (molecular weight 10000, DS-10000), ribavirin, oseltamivir carboxylate, amantadine and rimantadine, zalcitabine and alovudine.", "The last step involves the removal of the benzoyl protecting groups from O2 0 , O3 0 , and O5 0 positions of D-ribose 4a-j using sodium methoxide (NaOMe) in methanol [30] to afford the desired 1,2,3-triazole nucleosides 5a-j (Table 1 ). ", "influenza A H1N1 subtype, influenza A H3N2 subtype, and influenza B virus in MDCK (Madin-Darby canine kidney) cells." ] },{ "paper_id": "3c6601ba74b263d57b6b7fc0fbb7868d6ad2b107", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In the present study, we described the clinical and histological findings of a feline case of fibrinous pericarditis presumably caused by Moraxella osloensis.", "In conclusion, fibrinous pericarditis is a rare in cats, and empirical administration of antibiotics without surgical management could be insufficient for the treatment of the fibrinous pericarditis. This report described a rarely case of fibrinous pericarditis in a cat secondary to bacterial infection. Based on the morphological characteristics of the bacteria, Moraxella osloensis was suspected ", "A three-year-old spayed domestic short-haired cat, weighing 3.3 kg, presented to a primary care veterinarian with a one-week history of lethargy, anorexia, dyspnea and weight loss. The cat was group fed, liver indoors, and had no history of trauma. Thoracic radiography revealed cardiomegaly and pleural effusion. Due to lack of response to antibiotics, the cat was referred to the Veterinary Medical Center, Obihiro University of Agriculture and Veterinary Medicine (VMC-OUAVM)." ] },{ "paper_id": "3c6ed103b79757989428ac0f837b7a69f0d62b86", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All procedures were done at room temperature. Proteins were separated on 8.5 % polyacrylamide gels (20) and electrophoretically transferred to a dora-pore membrane according to the method of Burnette (8) using a semidry transfer blotter for 2.5 h at 36 V. After blocking with 3% skim milk in TBS for 1.5 h, blots were incubated with primary antibody in 3 % skim milk/ TBS for 1.5 h, and washed four times (5 rain each) with 0.05% Tween-20 in TBS. They were then incubated with secondary antibody (pemxidaseconjugated goat anti-rabbit IgG or anti-mouse IgG) in 0.05 % Tween-20/ TBS for 1.5 h, followed by four washes (5 rain each) with 0.05% Tween-20/TBS. Blots were stained using the enhanced chemiluminescence Western blotting detection system (Amersham Corp., Arlington Heights, IL). Protein bands were quantitated using an enhanced laser densitometer (LKB Instruments Inc., Bromma, Sweden) to evaluate the relative level of proteins in each subcellular fraction. The densitometric scan value was then estimated by multiplying the relative level by the protein yield (milligrams of protein) in corresponding subcellular fraction. In calculating the percent distribution of each immunodetectable protein, the densitometric scan value of the homogenate was defined as 100%.", "All procedures, except for the incubation with antibodies or FITCconjugated lectin at 37\u00b0C, were carried out at room temperature. Cells grown on coverslips were washed gently three times (5 rain each) with PBS, fixed with 4% paraformaldehyde in PBS containing 1 mM CaC12 and 0.5 mM MgCI2 [PBS(+)] for 20 rain, and permeabilized with 0.1% Triton X-100 in PBS(+) for 1 h. They were then rinsed twice with PBS(+), and incubated with 2 % FBS in PBS(+) to block nonspecific binding of primary antibodies for 1 h followed by 45 rain incubation with primary antibody in 2 % FBS/PBS(+). After washing four times (5 rain each) with PBS(+), cells were incubated with secondary antibody in 2% FBS/PBS(+) for 45 min. For localization of the Golgi complex, cells were incubated with FITCconjugated wheat germ agglutinin in 2% FBS/PBS(+) for 45 rain. After washing with PBS(+), they were then mounted on glass slides with 90% glycerol in PBS containing 1 m~/ml paraphenylenediamine, examined, and photographed on a microscope (BH-2; Olympus Corp., Tokyo, Japan) with Ektachrome 400 film (Kodak, Rochester, NY).", "Rat microsomal aldehyde dehydrogenase (msALDH) has no amino-terminal signal sequence, but instead it has a characteristic hydrophobic domain at the carboxyl terminus (Miyauehi, K., R. Masaki, S. Taketani, A. Yamamoto, A. Akayama, and Y. Tashiro. 1991. J. Biol. Chem. 266:19536-19542). This membrane-bound enzyme is a useful model protein for studying posttranslational localization to its final destination. When expressed from eDNA in COS-1 cells, wild-type msALDH is localized exclusively in the well-developed ER. The removal of the hydrophobic", "Frozen ultramicrotomy was performed as described by Tokuyasu (46) . Transfected cells were harvested by centrifugation at 1,000 g for 3 rain, and the pellet was fixed with 4% paraformaldehyde and 0.1% glutaraldehyde dis- Cell fractionation was performed as described in Materials and Methods. In calculating the percent distribution, each value of the homogenate was defined as 100%. The distribution of FP2 and succinate-cytochrome c reductase(SCR) is determined from the specific activities measured. The specific activities of the homogenate fractions are 52.3 + 11.0 nmol cytechrome c reduced/rain per mg protein (the mean + SD n = 4) and 26.9 + 2.8 nmol cytoehrome c reduced/min per mg protein for FP2 and succinate-cytochrome c reductase, respectively." ] },{ "paper_id": "3c919c2857ddedf0a444aa214761e16e4676d50b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Note that Step 4, performed to predict successful outcome, is an optional step. If", ". LCL have been used to present antigens in a variety of immunologic assays 2, 3 . In addition, LCL can be used to generate human monoclonal antibodies 4, 5 and provide a potentially unlimited source when access to primary biologic materials is limited 6, 7 ." ] },{ "paper_id": "3ca41eba26adc5422815f1d8043e76b406e747bd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3cb43b6223f2860048cc7bce8cb0ed0e490ddbda", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "At killing, blood was taken for clinical biochemistry (albumin, globulin, bilirubin, cholesterol, triglycerides, creatinine, glucose, protein, urea, calcium, alanine aminotransferase, alkaline phosphatase, \u03b1-amylase, aspartate aminotransferase, creatine kinase, glutamate-dehydrogenase, \u03b3-glutamyl-transferase, lactate dehydrogenase) and hematology (hemoglobin content, erythrocytes, leukocytes, differential blood count, reticulocytes, platelets, mean platelet volume, red cell distribution width, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration).", "IgG levels were statistically analyzed using GraphPad Prism 5 (GraphPad Software Inc., La Jolla, USA). Normality of data was tested with Shapiro-Wilk test prior to applying either two-tailed Student's t-test or Mann-Whitney test to analyze differences between means of two groups (P \u2a7d 0.05).", "OR, DO, AE and CJ are employees and MS is Chairman of the Executive Board of Mologen AG. CH is employee of IMGM Laboratories GmbH. AW is employee of LPT GmbH & Co. KG. MOLOGEN AG owns a patent for the MIDGE-Th1 vector (PCT/ DE02/03798P74). These affiliations do not alter the authors' adherence to Gene Therapy policies on sharing data and materials. FJS declares no conflict of interest." ] },{ "paper_id": "3ced31e65e14cbd45628ea410b50d4e4841c9f50", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "BMJ Open publishes all reviews undertaken for accepted manuscripts. Reviewers are asked to complete a checklist review form (http://bmjopen.bmj.com/site/about/resources/checklist.pdf) and are provided with free text boxes to elaborate on their assessment. These free text comments are reproduced below.", "3-would it be helpful to add a model consent form and other related documentation given to participants (including instructions on how to use the devices)?", "Answer:" ] },{ "paper_id": "3cf33ae7aecff3052d051eefe7f4d26287c0217d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "How might it impact on clinical practice in the foreseeable future?", "What are the new findings?" ] },{ "paper_id": "3d4c571fcd1ba20b5c25488e82ced70014652cd4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3d5f2ea9eca2aa8acb508626fef27e7b1c087312", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3d6462be232a3f4b4aab41386a74bb8e6a118b44", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3d86ddb1f87053b373d42baadaba6a449fb22fa4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis was performed using the SPSS software (version 10, SPSS Inc., Chicago, IL, USA), and graphs were prepared using Prism software (version 4.0, GraPad Software, Inc., San Diego, CA, USA). Mann-Whitney U test, Chi-squared or Fisher's exact test were performed to assess the significance. A P value < 0.05 was considered statistically significant for all the tests.", "To obtain standard curves for absolute quantification, the PCR product of HBoV was cloned into a plasmid vector pGEM\u00ae-T Easy Vector (Promega, Madison, WI, USA), purified using a QIAprep mini prep kit (Qiagen Inc., Valencia, CA, USA), and quantified using UV spectroscopy (1 genomic copy = 5 \u00d7 10 -12 \u00b5g). Serial 10-fold dilutions of the cloned plasmid were prepared to generate the standard curves.", "Ninety-three (4.8%) of the 1,926 nasopharyngeal aspirates obtained from patients of all age-groups were positive for HBoV. Our detection rate is similar to that stated in other reports [2, 3, 8] . Generally, HBoV is detected in fewer than 8% of respiratory specimens [1, [8] [9] [10] [11] [12] [13] ; however, higher detection rates ranging from 10.3% to 19% have been reported [5, 14, 15] ." ] },{ "paper_id": "3dc1b1e197ec2bdd5ee03a588505a7a7c127c79d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All study-related activities were conducted according to good clinical practice, which includes the provisions of the Declaration of Helsinki.", "A fast, automated POCT, the Cepheid Xpert Influenza+RSV Xpress Assay, was used according to the manufacturer's instructions. 16 A nasal swab was suspended into 3 mL of universal transport medium (UTM, Copan Italia, Brescia, Italy) and 300 \u00b5L of suspension was added into the assay cartridge, which was then loaded into the Cepheid GeneXpert II instrument. After a processing time of 30 min, the test reading was recorded.", "The difference between proportions was tested with a binomial standard normal deviation (SND) test and 95% CIs were calculated accordingly." ] },{ "paper_id": "3dd8351aa51cbbf5dbfbd90a569efbad88b57b36", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "shown in Table 1 . ", "describing adults was realized by Bellei and colleagues (2007) detecting 37.7%.", "Many studies have investigated the occurrence of rhinovirus among community cases but there is a lack of information about the frequency of rhinovirus asymptomatic cases. We investigated HRV infections rates on selected populations of a pair of one child and one family member, health care workers (HCW), and immunocompromised patients with and without respiratory symptoms from June to September." ] },{ "paper_id": "3de90c8c18dbed90408c4a5cc5cb94f856c9f637", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cystoisospora canis, C. ohioensis, and C. burrowsi cause diarrhea in puppies < 6 months of age and immunocompromised dogs [3] . Although C. canis is the prevalent Cystoisospora species in dogs, C. ohioensis is frequently detected in Chinese dogs [4] .", "Recently, Japanese raccoon dogs were identified as the reservoir host of C. ohioensis [5] . However, no clinical cases of canine cystoisosporiasis have been reported to date in Korea although experimental infection and sporulation of C. ohioensis isolates have been performed in Korean puppies [6] .", "It is difficult for veterinary clinicians to diagnose cyclosporiasis and cystoisosporiasis based on clinical signs alone. The morphological similarity of Cyclospora and Cystoisospora oocyst hinders microscopic diagnosis using stools. Thus, both microscopic examination and molecular techniques for differential diagnosis are used [4, 5] . The present study aimed to describe a clinical case in which the protozoan pathogen C. ohioensis was identified in a Korean dog, using microscopy of diarrheal stools and confirmed using phylogenetic analysis of 18S ribosomal RNA (rRNA)." ] },{ "paper_id": "3e039d09e97b28724f19438f21fcebab6c15c986", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3e107cc95d4428962d4fc859f24b87bf0b8433e5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3e1874b3a7b354af8cb25bfcd127ba887afe92c2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org/ lookup/suppl/doi:10.1128/mBio.01461-15/-/DCSupplemental. Figure S1 , TIF file, 2.8 MB. Figure S2 , TIF file, 2.8 MB. Figure S3 , TIF file, 2.8 MB. ", "DENV type-specific PCR and RFLP analysis. Total RNA was isolated from viral supernatants and used as the template for cDNA synthesis using standard molecular techniques. Serotype-specific PCR and restriction fragment length polymorphism (RFLP) restriction endonuclease analyses were performed on cDNA samples in order to validate the purity of the recombinant viral preparations (see Fig. S2A , B, and C in the supplemental material).", "Virus construction. Recombinant viruses were constructed using a four-cDNA cloning strategy, the same strategy used to create wt DENV infectious clones (see Fig. S1 in the supplemental material). Patterned after coronavirus cDNA clones (28, 29) , the DENV-4 genome was subcloned into four separate cDNA plasmids. A T7 promoter was introduced into the 5= end of the A fragment, and unique type IIS restriction endonuclease cleavage sites are introduced into the 5= and 3= ends of each fragment to allow for systematic assembly into a genome-length cDNA from which full-length transcripts can be derived (28) (29) (30) ." ] },{ "paper_id": "3e213ce275307f241723cf26bcb756dcba2a6b5b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The Evolutionary History of Bacterial tRNA Modifications Is Highly Dynamic", "The cmo 5 U modification exists in tRNA molecules for four box codons (Leucine, Valine, Serine, Proline, Threonine, and Alanine) and therefore there were three possible nontarget tRNA in each case. However, tRNA with GNN anticodons (where N is any nucleotide) in each of these codon boxes can also recognize NNU codons via GU wobble pairing. Thus, we only focused on the nontarget tRNA that have CNN anticodons (indicated in fig. 1C ).", "Supplementary data are available at Molecular Biology and Evolution online." ] },{ "paper_id": "3e2e2a0b86f45e26fbd4724a26d74b62a5f7b0e3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Samples of 10-20 ~1 of extracts from whole cells, spheroplasts, or spheroplast supernatants were resolved by SDS-PAGE (Laemmli, 1970) on 8% polyacrylamide gels and then electro-blotted to nitrocellulose filters. For Western blot detection, the following antibodies were used: rabbit antiinvertase at 1:1,000 dilution, mouse anti-M2 (Eastman Kodak Co., Rochester, NY) at 1:10,000 dilution, HRP-coupled protein A (Organon Teknika-Cappel, Durham, NC), at 1:10,000 dilution, and HRP-coupled sheep anti-mouse Ig (Amersham Corp., Arlington Heights, IL) at 1: 10,000. Blots were developed using the ECL detection system (Amersham Corp.).", "For Endo H digestions, 5 vd of boiled protein extract was diluted with 2-3 vol of 50 mM sodium citrate, pH 5.1, containing 100-250 U of Endo Hf (New England Biolabs) and incubated at 37\u00b0C for 2-16 h. Samples were boiled before gel electrophoresis.", "To spheroplast cells, induced cultures of 6 x 107 cells were washed in distilled water, incubated in 0.3 ml of 100 mM Tris-SO4, pH 9.4, 50 mM 13-merceptoethanol for 10 min, washed in 1.2 M sorbitol, resuspended in 60 txl of spheroplasting buffer (1.2 M sorbitol, 10 mM Tris-HCl, pH 7.5) containing 60 U of recombinant lyticase, and incubated for 30 min at 30\u00b0C. The endpoint for complete spheroplasting was determined by >85% cell lysis upon dilution into 1% Triton X-100. Centrifugation at 500 g for 5 min yielded a supernatant fraction containing extracellular enzyme and a spheroplast pellet. Pellets were washed in spheroplasting buffer and lysed by vigorous agitation with acid-washed glass beads. Both supernatant and pellet fractions were boiled in sample buffer. In spheroplasting experiments where protease inhibitors were used, 1 mM PMSF and 0.5 Ixg/ml leupeptin (both Boehringer Mannheim Corp., Indianapolis, IN) were added to the YEP containing 0.1% glucose induction medium, spheroplasting buffer, and lyticase." ] },{ "paper_id": "3e3f1f1b1f7f02523bc38fc9a0c321d1ccc9e1b8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Laboratory variables were determined as previously described. 9 In brief, serum chemistry variables and enzyme activities were determined with an automated analyzer system a and a complete blood cell count was performed with a hematology analyzer (pocH-100iV DIFF, Sysmex).", "Objectives: To describe clinical signs, laboratory variables, and pathological findings of ZDL syndrome and their utility to differentiate ZDL from BHZD and infectious diseases with similar phenotype.", "Histologically, the mucosa of the oral cavity and muzzle was multifocally eroded or ulcerated with many infiltrating neutrophils and many suprabasilar apoptotic keratinocytes in the deep epithelial papillae (Fig 2d) ." ] },{ "paper_id": "3e40cb7055fe5ef148eced8994ff059a0e98aef1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nucleic Acids Research, 2010, Vol. 38, Web Server issue W93", "Description of the i-GSAE4GWAS web server System development, configuration and system overview. i-GSEA4GWAS is written in Java and JSP. The program is running in a high-end computing cluster with six dedicated Intel XEON Quad-Core CPUs at 2.0 GHz and two dedicated Intel XEON Quad-Core CPUs at 3.0 GHz (representing a total of 32 cores) with a total of 96 GB of memory.", "Input data. The input data of i-GWAS are SNP data, mainly P-values. The server will transform the P-value to \u00c0log(P-value). Some other values of association test like odds ratio and statistics are also accepted. Here, we define all these input values as 'association value'. The detailed format of input is a SNP list with two columns, namely SNP identifier and its corresponding association value. A gene list with gene HUGO symbol (http://www .genenames.org/) (18) and along with corresponding association value is also accepted but not recommended due to the limitation of gene variation as described above." ] },{ "paper_id": "3e43db4bbfa0307b42810ceb2b3cd07e2c321e2b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3e5edc4ff36064478e209800a15365cd5f710756", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3e66fa6e5fa282546d206b4d2c55ad15f38f7563", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "other findings when there is extensive involvement by the disease.", "Objetivo: Descrever os aspectos encontrados em TCAR do t\u00f3rax de pacientes infectados pelo v\u00edrus influenza A (H1N1). M\u00e9todos: Foram analisadas retrospectivamente as TCAR de 71 pacientes (38 femininos e 33 masculinos) com diagn\u00f3stico confirmado de influenza A (H1N1) atrav\u00e9s da identifica\u00e7\u00e3o laboratorial do v\u00edrus, estudados no per\u00edodo entre julho e setembro de 2009. A interpreta\u00e7\u00e3o das TCAR foi realizada por dois radiologistas tor\u00e1cicos de forma independente, e, em caso de discord\u00e2ncia, as decis\u00f5es foram tomadas por consenso. Resultados: Os achados de TCAR mais comuns foram opacidades em vidro fosco (85%), consolida\u00e7\u00e3o (64%) ou a combina\u00e7\u00e3o de opacidades em vidro fosco e consolida\u00e7\u00e3o (58%). Outros achados foram n\u00f3dulos do espa\u00e7o a\u00e9reo (25%), espessamento das paredes br\u00f4nquicas (25%), espessamento de septos interlobulares (21%), padr\u00e3o de pavimenta\u00e7\u00e3o em mosaico (15%), espessamento perilobular (3%) e aprisionamento a\u00e9reo (3%). As altera\u00e7\u00f5es foram frequentemente bilaterais (89%), com distribui\u00e7\u00e3o n\u00e3o espec\u00edfica (68%). Derrame pleural, quando observado, foi, em geral, de pequena monta. N\u00e3o foram observadas linfonodomegalias. Conclus\u00f5es: As altera\u00e7\u00f5es predominantes foram opacidades em vidro fosco, consolida\u00e7\u00f5es ou a combina\u00e7\u00e3o de ambas. O acometimento foi frequentemente bilateral e n\u00e3o houve predom\u00ednio quanto \u00e0 distribui\u00e7\u00e3o (axial ou craniocaudal). Apesar de inespec\u00edficos, \u00e9 importante reconhecer os principais aspectos tomogr\u00e1ficos da infec\u00e7\u00e3o por influenza A (H1N1) a fim de incluir essa possibilidade no diagn\u00f3stico diferencial de sintomas respirat\u00f3rios. Descritores: Pneumonia viral; Tomografia computadorizada por raios X; V\u00edrus da influenza A subtipo H1N1.", "features of the disease becomes important in clinical practice.", "As multiple institutions were involved, imaging examination was performed with different tomography scanners, using the high-resolution technique, in accordance with the following protocol: patient in the supine position; 1to 2-mm slice thickness in increments of up to 10 mm, from the lung apices through the hemidiaphragm, at the end of a deep inhalation; and a high spatial resolution reconstruction algorithm. Parenchymal and mediastinal window settings (width = 1,400-1,600 HU; level = \u2212600 to \u2212800 HU; and width = 350-450 HU; level =" ] },{ "paper_id": "3e880727d0c88f982bad7fa677c2a8dc1d837dc7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In-depth literature review was conducted using Cochrane engine and google scholar. The questionnaire Disclosure. Authors have no conflict of interests, and the work was not supported or funded by any drug company." ] },{ "paper_id": "3ef8cc40a38577b24aab94171acf6959598b32c7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dogs were client owned or protection dogs brought to the Kagoshima University Veterinary Teaching Hospital for veterinary care. Residues of heparinized blood samples applied for biochemical tests were used in this study. Information including the patient's signalment, body condition score (5 points scale), diagnosis and undergoing treatment was obtained from the veterinary medical record or from the veterinarians in charge.", "Previous studies have characterized Sir2 protein as a pro-longevity factor for replicative lifespan in yeast [15, 20, 26, 46, 53] . Sir2 orthologs also extended lifespan in other organism species including Caenorhabditis elegans and flies [43, 50] . Because it has been suggested that the beneficial effects of caloric restriction on lifespan are mediated by Sir2 orthologs in higher eukaryotes [4, 7, 8, 44] , sirtuins received significant public interest. Sirtuins are a family of highly conserved nicotinamide adenine dinucleotide (NAD + )-dependent protein deacylases found in eukaryotes. In humans, there are seven sirtuin homologs (SIRT1-7). All sirtuins require NAD + as a cofactor, making them prone to regulation by fluctuations in NAD+ conditions, thus linking them to cellular metabolism in response to nutritional and environmental perturbations such as caloric restriction. Of all the sirtuins, SIRT1 has received the most attention in relation to longevity. It deacetylates key histone residues involved in transcription regulation, and multiple non-histone proteins including p53, FOXO1/3, PGC-1\u03b1 and NF-\u03baB [11, 37, 51] . By targeting these proteins, SIRT1 is able to regulate numerous vital signaling pathways, including DNA repair, apoptosis, muscle and fat differentiation, neurogenesis, mitochondrial biogenesis, hormone secretion, cell stress responses and circadian rhythms [3, 37, 42] . In general, SIRT1 activation triggers nuclear transcription programs that enhance metabolic efficiency and up-regulate mitochondrial oxidative metabolism accompanying resistance to oxidative stress [13, 16] .", "To our knowledge, there are few published studies measuring SIRT1 level in companion animals [17, 18, 30, 31] . In dogs, there are two reports: one is in association with the p53 mutations status in a dog with multiple tumors [31] , and the other evaluated SIRT1 gene expression in a cell line in relation to coronavirus infection [30] . The reason for the low number of studies is, at least in part by, the lack of antibodies to detect canine SIRT1." ] },{ "paper_id": "3f1cfb6b5432c28ba97e2c1fbb8ca341c35f6b4e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3f50d334193fa8cd216e4c4166e43fb0c8109709", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Values are presented as means and standard deviations (s.d.). Statistical significance among different vaccination groups was calculated by Student's t-test using GraphPad Prism statistical software. P values less than 0.05 were considered statistically significant.", "Cellular & Molecular Immunology" ] },{ "paper_id": "3f5d545fbca8b7c83ff7b10f827d772cb0011aa4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3f65b990d1f24de2bf3cd52d8559e8ccba9961af", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3f704d2ac81e0dc4e9e74ffd7d25f790baa6ebe1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Protein structure accession number. Coordinates and structure factors have been deposited into the Protein Data Bank under accession number 5HJ3." ] },{ "paper_id": "3f9572ae671d876279b4d2cd6b6544b24fb3e52d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3f95cd9324e4e68dfac149200521e09981091feb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Overall, evidence justifying the use of E. faecium under these conditions is limited.", "To date, four bacterial strains/products have been examined by the European Food Safety Authority (EFSA) for their safety and efficacy as probiotics or feed additives in dogs. This includes two Enterococcus faecium strains (E. faecium NCIMB 10415 E1705, E. faecium NCIMB 10415 E1707), Lactobacillus acidophilus DSM 13241 25 and Bifidobacterium sp. animalis.", "Infectious and non-infectious acute diarrhoea", "Overall data on improving gut health or immunological status in dogs using lactobacilli or bifidobacteria are not compelling, especially in the light of the fact that it is not known if increasing certain bacterial phyla is correlated with improved GI function or a lower incidence of diarrhoeic diseases." ] },{ "paper_id": "3fa8abac6ce337d7597f4c0d4adac979c4e0b9b7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Coronaviruses are a diverse group of large, enveloped positivestranded RNA viruses in the order Nilovirales, family Coronaviridae, and genus Coronavirus. Typically, they cause respiratory and enteric diseases in humans and animals. Using the open reading frame (ORF) 1a sequences, SARS-CoV was categorized as a subgroup of the group II coronaviruses. 9 The 30 kb poly-adenylated positive-stranded RNA genome 10, 11 has an genomic organization typical of a coronavirus where the first two ORFs (1a and 1b) encode the viral replicase that requires processing by the viral cysteine proteinases to yield the functional membrane-bound replicase complex and a group of 16 non-structural proteins (NSP). 12 Although some functions of these NSPs have been investigated and known, there are many others that still require further characterization (reviewed by Cheng et al. 13 ).", "Although T cell response could be observed for the M protein, current studies seem to suggest that the 3a protein is more immunogenic in comparison, and T cell epitopes identified in it may play an important role in recovery from a primary SARS-CoV infection and in vaccine development.", "Finally, it is important to note that T cells can play a protective and/ or pathological role during an infection. In the case of mouse-hepatitis virus (MHV), an increase of morbidity and mortality in infected mice has been associated with memory T cells. 76 Although no direct evidence have shown that SARS-CoV-specific T cell responses contribute to immunopathology in SARS, it is a question that needs to be further addressed. T cell immune response in SARS coronavirus infection HLJ Oh et al 5" ] },{ "paper_id": "3fad6dea4f2f9afda7699aa3b79d11b4ddfb57fd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Several studies revealed a higher postoperative morbidity, delayed healing, and more frequent secondary infections in malnourished patients with amputations than in non-malnourished patients. Malnutrition encourages dropping sutures. An earlier acute or chronic malnutrition trauma slows healing. Zinc as a trace element is quantitatively the most important one and is involved in the construction of over 200 enzymes with effects as follow: improving cell growth and differentiation, fibroblast proliferation, collagen synthesis, strengthening the immune system and increasing steroid receptors [21, 22] ." ] },{ "paper_id": "3ffe5f150d7f8fe18d126f3c5035ed9425f9f4b6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "where \u03bb is a shrinkage parameter for the L 2 -norm penalty.", "where r k is the 1 \u00d7 m vector of residuals for m samples." ] },{ "paper_id": "40470023462dcfcc8ed653d73a5dd255699abcad", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "404f219ad630336f512bb52d5e6b357adf10e130", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Methods: In total, 44 children aged 0 to 24 months with febrile UTI and 35 age-and sexmatched controls with fever from other causes were enrolled in the study. ELISA was performed to determine the level of YKL-40 in urine collected from each child.", "Background: Given that YKL-40 is a known marker of inflammation, we sought to determine its association with urinary tract infection (UTI) in febrile children.", "ROC curves were analyzed to compare the diagnostic value of urinary YKL-40/Cr with abnormal urinalysis findings (pyuria and positive nitrite) for detecting UTI ( ", "Determining the levels of urinary YKL-40/Cr may help identify true cases of UTI in febrile young children, especially when they have pyuria but not nitrite, or have neither pyuria nor nitrite in the urine. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited." ] },{ "paper_id": "4090c4a0e8cead64dd9e44a1610fb4f557fefdcf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors have nothing to declare." ] },{ "paper_id": "40b2b0e3d2cf519723d858a138e77a26a70f460f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "40c0532640a8bb9d9a0aac07d017d5982af33fdb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "same owner and referred to a veterinary hospital. The analyzed tissues included kidneys, mesenteric lymph nodes, a spleen, and an eye and its vitreous humor. Whole blood samples were treated with ethylenediaminetetraacetic acid as an anticoagulant.", "MATERIALS AND METHODS", "The lengths of truncated 3c proteins expressed by FCoVs were predicted to range from 3 to 235 aa, corresponding to 1.3-99.2% of the length of the wild-type protein." ] },{ "paper_id": "40f79b91682886f0f531b6bb876482a23cd6e400", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In conclusion, our study suggests that initial laboratory findings of patients with acute febrile illness could be potential predictors for MERS-CoV infection during the nosocomial outbreak. Monocytosis with normal WBC count and low CRP level may be useful markers for the prediction of MERS and triage at the initial presentation of acute febrile patients.", "A case-control study was performed to identify clinical predictors for Middle East respiratory syndrome coronavirus (MERS-CoV) infection among patients with acute febrile illness during the nosocomial outbreak. Patients with MERS-CoV were more likely to have monocytosis with normal white blood cell (WBC) count and lower C-reactive protein (CRP) level. Simple laboratory data such as complete blood counts (CBC) with differential count could be a useful marker for the prediction of MERS and triage at the initial presentation of acute febrile patients in outbreak setting.", "In the current study, we found that simple laboratory data such as CBC with differential count could be a useful marker for the prediction of MERS-CoV infection during the nosocomial outbreak. During the nosocomial outbreak of MERS-CoV infection, an unexpected exposure of patients and health care workers can occur, and strict infection control measures are important for the prevention of MERS-CoV spread. Identification of clinical predictors for MERS-CoV infection would be useful in triaging patients into risk categories to determine the likelihood of MERS-CoV infection (7) ." ] },{ "paper_id": "41199e837e1c706b7a8a1a8a0970856974235566", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study investigated the role and mechanism of alprostadil in acute respiratory distress syndrome (ARDS) induced by oleic acid (OA) in rats.", "Thirty male Sprague-Dawley rats (200-300 g weight and 7-8 weeks of age) were purchased from the Animal Center of Yanbian University, Jilin, China (License No.: SCXK" ] },{ "paper_id": "4135ace30ea08a669730959e0f98a4af06537d07", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ethics approval was granted by the Hunter New England Human Research Ethics Committee (HREC), Australia (Ref: HREC/13/HNE/265). To verify the vaccination records of pilgrims, data were cross-checked with another ongoing trial by our team with a separate ethics approval from the Hunter New England HREC (Ref13/05/15/3.05). ", "Twenty-six (14.2%) participants had S. pneumoniae detected by NAT ( ", "Baseline fluorescence was determined using a fluorescence reader (FluorTracker\u2122, Stratagene, La Jolla, CA, United States) before amplification in the Mastercycler Gradient thermocycler (Eppendorf, Hamburg, Germany). The reaction mix was amplified at 95 \u2103 \u00d7 15 min (96 \u2103 \u00d7 10 s; 63 \u2103 \u00d7 1 min) for 45 cycles and 72 \u2103 \u00d7 2 min for one cycle. End point fluorescence was then determined using FluorTracker\u2122, positive samples were defined as a minimum of 2 \u00d7 increase in fluorescence. These results were confirmed by agarose gel electrophoresis on a 2% gel run at 200 volts for 40 min and stained with SYBR-Safe." ] },{ "paper_id": "4178b81e61b88d5cc07ca0253875007e93e9a7f5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nanomicelles stabilize peptides in active biological form (\u03b1-helix), which is preferred for ligand-receptor interactions, and prevents rapid peptide degradation in vivo, thereby prolonging bioactivity [25, 26] . Unlike surfactant micelles, a low critical micellar concentration (\u223c1 \u00b5M) of these nanoparticles prevents their disintegration upon dilution in biological fluids. Importantly, the PEG 2000 moiety of SSM confers steric hindrance in the circulation, while their nanosize mitigates renal clearance and extravasation from intact microvessels. This, in turn, prolongs the circulation time of drug-loaded nanomicelles and promotes preferential extravasation from hyperpermeable lung microcirculation, the hallmark of ALI, into the injured lung.", "To effectively block the expression of TREM1, we developed LP17 peptide nanomedicine, LP17-SSM. LP17 is the soluble TREM1 or extracellular component which binds and inhibits signaling through TREM1 [5] . Control SSMs were prepared by using scrambled peptide. For the TREM1 blocking peptide, LP17, circular dichroism confirmed that there was a significant increase in \u03b1-helicity in the presence of SSM compared to the free peptides in normal saline. This indicated the presence of peptide-micelle interaction where the peptides changed from a random conformation in saline to a more ordered helical structure when associated with SSM. To determine in vivo anti-inflammatory efficacy and the dose-response effect of LP17-SSM, we established the dose and time-dependent effects as with GLP-1-SSM [16] . Mice were given one dose of LP17 nanomedicine, nanoscrambled peptide, PBS, or LP17 subcutaneously in a single dose prior to LPS challenge. The ALI animal model used was based on previous publications [16, 37] . Mice were challenged with aerosolized LPS by nebulization (8 mg LPS dissolved in phosphate-buffered saline at the concentration of 1 mg/mL) administered via DeVilbiss disposable nebulizer (at the continuous air flow rate of 10 ft 3 /h) over 1 h to induce ALI. The animals were sacrificed 12 h after LPS nebulization.", "Studies with other nanomicellar preparations such as 17-AAG, curcumin, and PPAR\u03b3 agonists for treatment of ALI/ARDS are currently ongoing in our laboratory [8] . Together, our studies demonstrate the feasibility of translating the use of these nanomicellar preparations for translational human studies to the clinics to treat this devastating disease. We hypothesize that combinatorial administration of nanomicelles or use of more pleiotropic agents that modulate multiple signaling pathways will prove to be more potent; however, further studies are needed to optimize the administration of the nanopreparations. " ] },{ "paper_id": "417cbe38a2f8a93d0827cd67f4c42076921d6050", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Primary cells are cells isolated directly from tissues or blood using enzymatic or mechanical methods. The cells are characterized by their high degrees of specialization, are often fully differentiated and thus require defined culture conditions (serum-free media) in order to preserve their original phenotype.", "J o u r n a l P r e -p r o o f", "Fifty BSAAs possess not only antiviral but also antibacterial activity ( Figure 4 ; Table S1 ) (Schor and Einav, 2018) . Moreover, 13 of the 50 agents are approved as antibiotics (2 withdrawn ", "This would allow BSAAs to play a pivotal role in the battle against emerging and reemerging viral diseases. that the antiviral activity has not been either studied or reported." ] },{ "paper_id": "418d9334932cd1b03e23fd6e03c01e660fff4bd4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Test strains were grown in 100 ml LB medium containing 100 mg/ml ampicillin in 500 ml flasks at 250 rpm and 37 C. After 24 h, 200 OD 600 units of cells were collected by centrifugation at 4000g and 4 C for 20 min. Cells were lysed and purified by Ni-NTA under native conditions according to the manufacturer's protocol (Qiagen). Purified protein samples were resolved by SDS-PAGE (10% w/v polyacrylamide). Gel band excision and in-gel trypsin digestion were performed using a previously described standard method (33) .", "Fraction of FS m \u00f0%\u00de observed by MS", "where A FSm is the sum of peak areas at different charge states for an FS m target peptide and A FSz is the same for an FS z target peptide in MS.", "Escherichia coli XL1 blue MRF 0 (Stratagene, La Jolla, CA, USA) was used in all experimental studies. All constructs were verified by DNA sequencing at the Cornell Bioresource Center. Construction of the dual fluorescence reporter was described earlier (27, 30) , except that different linker sequences were incorporated into the reporter plasmid ( " ] },{ "paper_id": "41a94f21d4dc3946e1377439a2a3880fb9d33776", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "with four consecutive SNPs spanning the region from 68-91 megabase pairs (Mbp, Fig. 2 Fig. 2 F) , including refined border regions for mice #14 and #28. Mice having apparently discordant levels ( Fig. 2 B , bottom dot plots), which correlated directly with increased or normal CD5 expression, respectively. These results confirmed the existence of a genetic modifier locus/ loci that regulates BCR-induced AICD and CD5 expression.", "phenotypes under low resolution mapping (viable, #2 and 19; nonviable, #44, Fig. 2 ", "Fluorescently labeled HEL protein (Sigma-Aldrich) was made using Pacific blue succinimidyl ester (Invitrogen) according to the manufacturer's instructions, and dialyzed 4\u00d7 against a large volume of room temperature PBS." ] },{ "paper_id": "41d42af9e99779958c80165b6958a1cbeba023a9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "41deae1169912161f5195d978626aa2ca1898994", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All values in the study were presented as the means \u00b1 SD. Statistical significance among groups was determined using a student's-two-tailed t test. A p \uff1c 0.05 was considered to be statistically significant.", "Infectious bronchitis virus (IBV), a member of the coronavirus family, is prevalent in all countries with an intensive poultry industry [8] . IBV is highly infectious and spreads rapidly in unprotected birds [32] . IBV replicates in the epithelium of respiratory tract tissues, as well as in many non-respiratory tissues, such as those from kidneys and gonads [5, 29] . There are a large number of IBV variants worldwide, and they cause great economic losses to the poultry industry.", "Spodoptera frugiperda Sf-9 cells were maintained in Grace's insect cell culture medium (Gibco, USA) supplemented with 10% heated-inactivated fetal bovine serum (FBS), 100 \u03bcg/mL streptomycin and 100 IU/mL penicillin in a 27 o C humidified incubator. IBV strain H120 (accession number M21970) was propagated in 9-day-old specific pathogen free (SPF) embryonated chicken eggs." ] },{ "paper_id": "41df61dc89201d699b23532cbd09da787afa7e84", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The excitatory amino acid glutamate serves as a fast excitatory neurotransmitter in the central nervous system (1) , and excitotoxicity and oxidative toxicity are considered to be two major pathways responsible for glutamateinduced toxicity (2, 3) . Excessive release of glutamate leading to excitotoxicity is responsible for neuronal injury associated with many acute and chronic brain diseases, such as brain ischemia, traumatic brain injury, and neurodegenerative disorders (4, 5) .", "In conclusion, GA protects DPC12 cells against glutamate-induced neurotoxicity mainly through ERK and mitochondria-related pathways. Our findings provide experimental evidence that GA may be a candidate for treating or preventing neurodegenerative diseases.", "One-way analysis of variance followed by post hoc multiple comparisons (Dunn's test) were performed to detect statistically significant differences (P,0.05). Data are reported as means\u00b1SD." ] },{ "paper_id": "41e98d93f0f9f490c34dc4e8f96340cf477e7355", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study was approved by the ethics committee of the Armed Forces Medical Command, which waived the requirement of informed patients consent for this retrospective study.", "A malaria smear and triple antibody tests of Hantann, leptospirosis, and Tsutsugamushi virus were also performed to rule out other potential causes of fever, and revealed no remarkable abnormalities." ] },{ "paper_id": "425e0ee111062385cb630f0ea0659608d5fbec5c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "426da8c3fb9c6792b5d26214d55471099877e337", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data analysis. Data from the genome quantification and TCID 50 assays was analyzed in Prism (GraphPad Software) and CompuSyn (combosyn.com)." ] },{ "paper_id": "426eeb6c4a3047760cd5402f4f4771a317026f95", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The genus Ebolavirus of the family Filoviridae (Order: Mononegavirales) is comprised of five recognized species, with Zaire ebolavirus (ZEBOV) representing the prototype species. ZEBOV is a significant human pathogen with case fatality rates often reaching 90%. To date there have been numerous outbreaks of ZEBOV, 1 the largest of which occurred in West Africa in 2014 and resulted in >28,000 human cases and >11,000 deaths. 2, 3 The high case fatality rate and magnitude of the 2014 outbreak in West Africa illustrates the pressing need for the development of a safe and efficacious vaccine to prevent future ZEBOV outbreaks.", "At 14 days post exposure, to allow plenty of time for dissemination to occur, 48 mosquitoes from each group were anesthetized by cold treatment at 4 C. Legs & wings were removed and transferred into a 2 mL Eppendorf Safe-Lock tube containing 250 mL mosquito diluent, and a stainless steel bead for homogenization. Bodies were placed in a separate 2 ml Eppendorf Safe-Lock tube prepared similarly. Mosquito tissues were prepped and titrated as described above.", "Disclosure of potential conflicts of interest T.P.M. is an employee of New Link Genetics." ] },{ "paper_id": "427e9059167b857c57f420d2fd243be87f6b8a33", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ab 5 antibody; Ag 5 antigen; ALT 5alanine aminotransferase; AST 5aspartate aminotransferase; CFT 5 complement fixation test; EIA 5 enzyme-linked immunosorbent assay; GGT 5 gamma-glutamyl transferase; IFA 5 indirect fluorescent antibody; IgM 5 immunoglobulin M; WBC 5 white blood cell count.", "A brain biopsy of the right frontal lobe revealed features of meningoencephalitis, with inflamed fibrous leptomeninges, scattered microglial nodules, and a perivascular as well as interstitial lymphocytic infiltrate in the cortex (Fig 3) . The white matter also contained a few microglial nodules and small number of perivascular lymphocytes (not shown). The perivascular and interstitial lymphocytic infiltrate was composed predominantly of CD8 1 T lymphocytes. No viral cytopathic changes were seen. Conventional CSF and brain biopsy studies failed to identify a causative organism ( Table 2) .", "The patient is a 34-year-old man from Australia with a history of hypochondroplasia and X-linked agammaglobulinemia (confirmed germline mutations in fibroblast growth factor receptor 3 [FGFR3] and Bruton tyrosine kinase [BTK], respectively). The antibody deficiency was diagnosed in infancy, and the patient commenced lifelong intravenous immunoglobulin (IVIg) therapy. The patient suffered from chronic sinusitis despite IVIg therapy and was treated with clarithromycin prophylaxis. Despite mild developmental delay and associated learning difficulties, he completed school and vocational training and went on to full-time employment as a retail store manager." ] },{ "paper_id": "42d6a33f03497257ad765977dd53d0c4709e5e77", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "433c16daf21bb7f5f0d6379d67fe0917c2aa0281", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "but chest radiography revealed ill-defined opacities in both of his lower lungs.", "Background and Purpose Middle East respiratory syndrome (MERS) has a high mortality rate and pandemic potential. However, the neurological manifestations of MERS have rarely been reported since it first emerged in 2012." ] },{ "paper_id": "43ac139b156b7a9397d9da995694319fdeeba0f4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(2) intervention for difficulty in adaptation, mainly by social psychologists. Among them serious mental problems (e.g. violence, suicide behaviors) must be managed by psychiatrists. Such emotion hypothetical model of psychological crisis intervention is shown in Fig. 1 .", "We propose that the psychological crisis intervention should be dynamic, adapted to suit different stages of the epidemic, i.e., during and after the outbreak. During the outbreak, mental health professionals should actively participate in the overall intervention process for the disease, so that the mental health and psychosocial response can be mobilized in a timely fashion. 12 Specifically, psychological crisis interventions should be integrated into the treatment of pneumonia and blocking of the transmission routes. In this stage, psychological crisis intervention should include two simultaneous activities: (1) intervention for fear of disease, carried out mainly by physicians and assisted by psychologists;", "Based on our experience about the model of psychological intervention practicability and effectiveness, West China Hospital developed and is carrying out the psychological rehabilitation plan, namely the two-stage psychological intervention model (Fig. 6) . The central idea is to integrate Internet technology to the whole process of intervention, and to combine early intervention with later rehabilitation. In order to help patients and general population in the COVID-19 epidemic, we are trying to share it with all mental health hospitals in Sichuan Province to help relieve psychological aftershock of the public emergency. However, there are still many problems with the current psychological interventions, including effective utilization of Internet resources/tools, and efficient cooperation between medical staffs and psychologists." ] },{ "paper_id": "43aeebc83e75673430343bc8f01df5a96793b217", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "43eb920135bc1acb5cb4f1d91b5d06079c53765b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "These results indicate that ABT-263 sensitises cells to death at multiple stages of IAV infection following virus endocytic uptake.", "In conclusion, anticancer therapeutics may accelerate or attenuate microbial infection in cancer patients by targeting host functions essential for host-microbe interplay. However, anticancer programs have neglected the possibility of evaluating the effects of investigational small molecules on this interplay. Preclinical trials are typically performed on pathogen-free mice with xenotransplanted human tumour cells, and early stages of clinical trials focus on tumour regression and long-term survival without taking into account the potential impact of the chemotherapeutic agent in conjunction with underlying or overt viral infection of the patients. Our study sets an example for addressing the impact of anticancer molecules on the microbe-host interplay and the therapeutic outcome in a background of microbial infection. I L 2 IL3 IL4 IL5 IL6 IL7 IL10 IL13IL12 IL16 IL17 IL23 IL27 IP10ITAC KC MCSF T A R C ? IL4 IL5 IL6 IL7 IL10 IL13IL12 IL16 IL17 IL23 IL27 IP10ITAC ", "The infection of macrophages, RPE, MDCK, A549, BHK-21 and Vero-E6 cells with influenza A/WSN/33 (WSN; H1N1) , A/PR/8/34 (PR8; H1N1), A/Sydney/5/1997 (Syd97; H3N2) , B/Shandong/7/97 (InfB), human echovirus 6 (Echo6), sindbis (SINV), semliki forest (SFV), bunyamwera (BUNV), measles (MeV), herpes simplex 1 and 2 (HSV-1, HSV-2), tick born encephalitis (TBEV), dengue (DENV) and vaccinia (VACV) viruses was done as described previously. 31,32 KSHV production was induced in iSLK.219 cells with 0.2 mg/ml doxycycline and 1.35 mM sodium butyrate. 33 Titres of infectious viruses were determined as described. 26, 31 Compound efficacy testing in vitro. The compound efficacy testing was performed in 96-well plates in human macrophages, RPE, A549, MDCK, Vero-E6 and iSLK.219 cells. Typically, cells were seeded in 100 ml of an appropriate cell growth medium and grown for 24 h. The growth medium was changed to an appropriate virus inoculum 31 and the studied compounds were added into the medium; DMSO was added to the control wells. The cells were infected with viruses at a multiplicity of infection (moi) of 0.1-10 or non-infected (mock). Cell viability was measured using a Cell Titre Glo assay (CTG; Promega, Southampton, UK). Luminescence was read with PHERAstar FS plate reader (BMG Labtech, Ortenberg, Germany).", "For a genomic viral RNA (vRNA) transfection experiment, A/WSN/33 virus was grown in MDCK cells. Supernatants were collected at 24 hpi, and the virus was pelleted using ultracentrifugation at 285 000 g for 4 h. Viral RNA was purified using the RNA extraction kit (Qiagen, Hilden, Germany). The RNA was transfected into RPE cells using Lipofectamine 2000 (Life Technologies, Carlsbad, CA, USA) according to the manufacturer's instructions. Six hours after transfection, the Opti-MEM media were replaced with growth media with or without 0.4 mM ABT-263. After 18 h, the cell viability or caspase activity was measured." ] },{ "paper_id": "43fa3923d6ba1d04fb5b0419f617b8c2fbc2f268", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "43fb44b6c809c497fa4e6e7a52e7a3dbbebe4155", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Continuous variables were presented as medians with interquartile range. Categorical variables were presented as frequencies and percentages of the specified group. Comparisons between groups were made with the Fisher exact test or the Kruskal-Wallis test, as appropriate. A two-sided p-value of <0.05 was considered statistically significant. Statistical analyses were performed using SPSS Statistics, version 24, software (IBM, Armonk, NY, USA).", "Secondly, our study showed the existence of a strong association between pneumonia severity and performance of diagnostic testing, in accordance with IDSA/ATS and ERS recommendations. As a consequence, pneumonia severity was also associated with an increased probability of pathogen detection. Exploring the true determinants of pathogen detection would have required a systematic and universal testing strategy and, for this reason, it was out of the scope of this study.", "Community-acquired pneumonia (CAP) is a leading cause of hospitalisation worldwide. Mortality rates for patients hospitalised with CAP approach 30%, especially in those admitted to an intensive care unit (ICU) [1] [2] [3] [4] . Diagnostic testing in CAP has the potential to improve individual patient management, reducing the risk of clinical failure and death, and to generate epidemiological data, informing the selection of appropriate empirical antibiotic therapy. Unfortunately, these advantages are counterbalanced by high healthcare costs associated with diagnostic testing and low sensitivity of these tests to identify pathogens causing CAP [5, 6] .", "We performed a secondary analysis of an international, multicentre, observational, prospective cohort study using the Global Initiative for Methicillin-resistant Staphylococcus aureus Pneumonia (GLIMP) database [13] . GLIMP was conducted among 222 hospitals in 54 countries over 4 days, with 1 day per month randomly selected during March, April, May and June 2015. All adult patients (aged >18 years) hospitalised for CAP at the participating centres during the four study days were screened by GLIMP investigators and included in this secondary analysis. Patients hospitalised with a diagnosis of hospital-acquired or ventilator-associated pneumonia were excluded. The GLIMP coordinating centre was located at the University of Texas Health San Antonio (San Antonio, TX, USA). The coordinating centre received expedited project approval by the institutional review board (number HSC20150184E). The review board waived the need for receipt of informed consent due to the nature of the study. Institutional review board approval was obtained by the site investigators at each individual centre. A detailed description of the GLIMP organisation and methodologies has been previously published [13] ." ] },{ "paper_id": "4476687d4a23df5d5428626f81d9621abf94e679", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Swine kidney cells (IBRS-2) were cultured for 1 day in a 37 o C, 5% CO2 incubator with 10% fetal bovine serum (FBS; pH 7.4) and 1% antibiotics added to minimum essential medium-alpha. Virus titers were determined in IBRS-2 for FMDV. Three days later, the 50% tissue culture infective dose (TCID50) was calculated using the Reed and Muench method. FMDV O/Andong/SKR/2010 (GenBank accession No. KC503937) was used for challenging the pigs.", "Importantly, there are side effects to be considered before undertaking clinical application of ribavirin. It has been reported that all ribavirin-treated pigs show significant decreases in body weight and red-blood-cell counts until 8 dpi [17] . Moreover, in ribavirin-treated FMDV-uninfected pigs, clinical signs of dyspnea, anorexia, weakness, and depression were present until 5 days [17] .", "Pigs that were administered ribavirin with oil adjuvant (water in oil in water) were observed to have the highest clinical score (5 points) within 3 dpc (Table 2 ). Another group that was injected with ribavirin with oil and commercial vaccine did not exhibit any clinical signs during all experimental days, even though the pigs were exposed to approximately 10 2-4 RNA copy numbers from 2 to 3 dpc. The negative control was found to have high RNA copy numbers of viremia (Table 2 ).", "Foot-and-mouth disease (FMD) occurs in animals with cloven hooves. FMD viruses (FMDVs) are a positive-sense single-stranded RNA virus [16] and belong to the genus Aphthovirus, family Picornaviridae [4] ; the size of the virus genome is approximately 8.5 kb. These viruses are classified into seven serotypes-A, O, Asia1, C, SAT1, SAT2, and SAT3and more than 60 subtypes [16] . FMD outbreaks cause a reduction in the productivity of infected animals (e.g., pigs, cows, lambs, and goats) [2, 3] . The culling of infected animals and events such as environmental contamination and loss of revenue from the livestock have emerged as important socioeconomic issues [21, 23] ." ] },{ "paper_id": "44ca0c52f79a893a551da92dd78e599fbc74b060", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The values of Dlat typically are not a normal distribution. Accordingly, geometric mean Dlat were calculated from normally distributed laD. Signifieances of differences between mean InDRit were compared in Student's t test. p < 0.05 was considered significant.", "In experiments with MI2.C3-10-D2, the transfectant that expresses the lowest level of I-A k, recovery of fluorescence was reduced if cells were incubated with goat anti-mouse IgG before measurement (data not shown). This demonstrates that the fluorescence measured is from mAb bound to surface I-A k and is not cell autofluorescence.", "Class II MHC molecules, Ia antigens in the mouse, are heterodimeric transmembrane proteins expressed on B lymphocytes, macrophages, and other antigen-presenting cells. There are two isotypes of Ia antigens in the mouse, I-A and I-E; each consists of a 34-36-kD ct chain and a 27-29-kD/~ chain. Each chain is composed of two external domains (ot~/ot2 or/3,/~2) and a connecting peptide that joins the ex-ternal domains to the transmembmne and cytoplasmic domains. There are two asparagine-linked oligosaccharide units on each c+ chain and one on the B chain.", "The pSV2-Neo construct (27) was a gift from Dr. Ed Palmer (National Jewish Center for Immunology and Respiratory Medicine, Denver, CO). The origin and generation of the a and fl I-A k genomic DNA constructs have been described (28) . In brief, site-directed mutagenesis in vitro was used to introduce double-stop codons that v~uld result in truncated a or fl chains lacking 6 and 12 or 12 and 18 amino acids, respectively. Uamb+nne I RHRsQK Transfectants were generated by introducing pSV2-Neo DNA and ~ and genomic DNA into the Ia-negative B cell iymphoma M12.C3 by electroporation. The transfecled cells were selected and maintained using (3418 (neomycin) at a final concentration of 300 t~g/ml. Transfectants expressing memk k brahe I-A were chosen based on flow cytometry using anti-l-A -specific mAb (Fig. 2) ." ] },{ "paper_id": "44f01ea111fa2b4bd8ce34739f64b17930bb0ea8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The factors which determine probability of transmission from an infectious individual (Ii) to a susceptible individual (Is) are the basic virus transmissibility (\u03b2v), the age-based susceptibility of Is the current level of infectiousness of Ii, and, if the contact between Ii and Is occurs in a household, the household size Household(Ii, Is). These factors are explained below.", "Design A modelling study.", "Setting The towns of Madang in Papua New Guinea (population ~35,000) and Albany (population ~30,000) in Australia." ] },{ "paper_id": "4564dfbcb341f91caefc5a880a127a629416c1c6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Results are reported as means \u00b1 SD. The significance of differences between results for different groups were evaluated using one-way ANOVA with a p-value threshold of 0.05.", "After two weeks, none of the animals in the experimental group exhibited symptoms of FMDV whereas 155 control group cows belonging to 4 different farmers did. Animals in the experimental group were thus completely protected by spraying with Chinese herbal kombucha. These field results clearly demonstrate the potential of Chinese herbal kombucha as a probiotic treatment for the prevention and containment of FMD outbreaks.", "Foot-and-mouth disease virus (FMDV) infects cloven-hoofed animals and has had devastating consequences in many countries (Gibbens et al., 2001; Grubman et al., 2004; Knowles et al., 2001) . Two strategies for its prevention and eradication have been widely adopted. Mass slaughter of animals at risk of infection has been used extensively in developed countries but economic factors have made vaccination more popular in developing countries where the prevalence of FMD is high (Li et al., 2010) . Most countries in the European Union and North America have controlled the disease by slaughtering infected animals and those that may have been exposed, but it remains endemic in many African, Asian, and South American countries (Bayry et al., 2001) . Although the slaughter policy has been highly successful in limiting the extent of outbreaks and eliminating the infection, it has important negative aspects." ] },{ "paper_id": "459c780b398aa89f292490a6b455845448b7d537", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All data were processed using the statistical language R (3.6.2), unless otherwise specified.", "Step 2", "Step 3" ] },{ "paper_id": "459f95218942f624446533e21c9ab2775b8efce3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "45ab08a84c5a80e9ba6a6d21eb814d0ab04a473c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Proteins were separated on 5-10% gradient or 10% polyacrylamide gels (27) . Gels were fixed in isopropanol/water/acetic acid (25:65:10) and soaked in Amplify (Amersham Corp.) before drying and exposure to Kodak XAR film (Eastman Kodak Co., Rochester, NY) at -80~ Protein bands were quantitated using a BioRad densitometer.", "Reagents and supplies were from the following sources: MEM alpha and dialyzed fetal bovine serum (DFBS) were purchased from Irvine Scientific (Santa Ana, CA). Brefeldin A (BFA) was from Epicenter Technologies (Madison, WI). Fibronectin, calcium ionopbores A23187 and ionomycin, SDS, hypoxanthine-thymidine supplement, chloroquine, nocodazole, and BSA were purchased from Sigma Chemical Co. (St. Louis, MO). [3SS]cysteine (800 Ci/mM) was from ICN Biomedicals, Inc. grvine, CA) and 3H- [9, 10] palmitate (30-60 Ci/mM) was from New England Nuclear (Boston, MA). t4C-labeled protein standards and goat anti-rabbit IgGgold conjugate ( ", "CHODG44 ceils which are deficient in dihydrofolate reductase (dhfr) (64) were grown in MEM alpha supplemented with 10% FBS, 0.5x hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ~g/ml streptomycin, and 2 mM glutarnine at 37\"C in a 5% CO2 incubator.", "For routine morphology studies, cells were fixed (1 h) with 2 % glutaraldehyde, 3% paraformaldehyde in 100 mM cacodylate-HCl buffer, pH 7.2, scraped from the culture dish, and pelleted in a microfuge. The cell pellets were then postfixed (1 h) in 2% OsO4 in the same buffer, stained in block (2 h) with 2% uranyl acetate (pH 6.0), dehydrated in graded ethanols, and embedded in Epon." ] },{ "paper_id": "45cf4bcdf80e9ed9e3048485b0c57926028451d3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "45d421f19615b936de0527809bb71e12be89fa7c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To rapidly distinguish Canine distemper virus (CDV), canine parvovirus (CPV), and canine kobuvirus (CaKoV) in practice, a one-step multiplex PCR/RT-PCR assay was developed, with detection limits of 10 2.1 TCID 50 for CDV, 10 1.9 TCID 50 for CPV and 10 3 copies for CaKoV. This method did not amplify nonspecific DNA or RNA from other canine viruses. Therefore, the assay provides a sensitive tool for the rapid clinical detection and epidemiological surveillance of CDV, CPV and CaKoV in dogs.", "doi: 10 .1292/jvms. The one-step multiplex PCR/RT-PCR was performed in a 25 \u00b5l reaction mix with the PrimeScript\u2122 One Step RT-PCR Kit Ver. 2 (Takara, Dalian, China), according to the manufacturer's instructions. The components of the reaction were: 0.75 \u00b5l of CDV, 1 \u00b5l of CPV or 2.5 \u00b5l of CaKoV RNA; 2.5 pmol each of primers CDV-F, CDV-R, and CPV-F, and 10 pmol each of primers CPV-R, CaKoV-F, and CaKoV-R; 12.5 \u00b5l of 2 \u00d7 1 Step Buffer; 0.5 \u00b5l of PrimeScript 1 Step Enzyme Mix (Takara); and 4.75 \u00b5l of RNase-free dH 2 O. The cycling parameters were: 50\u00b0C for 30 min; predenaturation at 94\u00b0C for 5 min; 30 cycles of denaturation at 94\u00b0C for 30 sec, annealing at 55\u00b0C for 30 sec, and extension at 72\u00b0C for 30 sec; and a final extension step at 72\u00b0C for 10 min. The specificity of the one-step multiplex PCR/RT-PCR was assessed against other major canine viruses: CAdV-1, CAdV-2, CPIV and CCoV. To evaluate the sensitivity of this method, 10-fold serially diluted DNA/RNAs (the original concentrations were 10 7 copies for CaKoV (RNA copies for CaKoV were determined by one step SYBR Green Real-time RT-PCR assay (data not shown)), 10 6.1 TCID 50 for CDV and 10 5.9 TCID 50 for CPV) were used as the templates in the multiplex PCR/RT-PCR. The assay detected CDV, CPV and CaKoV, evident as bands of different sizes on agarose gel electrophoresis (Fig. 1) . No PCR products were amplified from CAdV-1, CAdV-2, CPIV and CCoV. The limits of detection were 10 3 copies for CaKoV (Fig. 2) , 10 2.1 TCID 50 for CDV and 10 1.9 TCID 50 for CPV.", "The viral DNA/RNA of fecal samples collected from dogs with clinical symptoms of diarrhea were extracted and tested in parallel with both the one-step multiplex PCR/RT-PCR and the commercial Rapid CDV/CPV Ag Test Kit (Bionote, Gyeonggi, Republic of Korea) for CDV or CPV, according to the manufacturer's instruction, and a traditional simplex RT-PCR for CaKoV, as described previously with minor modification [4] . Of the 66 fecal samples tested, four (6.06%) were positive for CDV, eight (12.12%) were positive for CPV, and four (6.06%) were positive for CaKoV. Among these, two were mixed infections of CDV and CPV and one was a mixed infection of CPV and CaKoV, detected with the one-step multiplex PCR/RT-PCR. The results for the commercial CDV/CPV Ag Test Kit and the traditional simplex RT-PCR were three (4.55%) samples positive for CDV, seven (10.61%) positive for CPV, and four (6.06%) positive for CaKoV; among these positive samples, one was a mixed infection of CPV and CaKoV. For the CDV and CPV, the positive rate of clinical samples tested by one-step multiplex PCR/RT-PCR was higher than the commercial CDV/CPV Ag Test Kit. The main reason may be that the nucleic acid detection methods are more sensitive than the antigen detection methods, But statistically, we cannot conclude that the multiplex PCR/RT-PCR established in present study is more sensitive than the commercial CDV/CPV Ag Test Kit or the traditional simplex RT-PCR. The more clinical tests need further to be done to evaluate it. For one sample, the CPV was positive tested by CPV Ag Test Kit, but negative by the " ] },{ "paper_id": "4615c0a2b164f98ac850d2c16f24cfe5a33db75d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "that imaging ellipsometer enables quantitative, label-free, rapid, high-throughput and low-cost analysis of biological interactions.", "Detection of interactions between SNAREs with imaging ellipsometer. The cytosolic regions (without the transmembrane domain) of Sso2p, Sec22p and Ykt6p were expressed in E. Coli and purified to high quality (Fig. 1 ). To detect their interactions, we designed the microfluidic array as illustrated in Fig. 2a and Fig. 2b .", "The agreement between the SPR and imaging ellipsometer results demonstrated the interactions between the three SNARE proteins. The interactions at protein level were also consistent with Y2H result at domain level 7 . Previous study also showed that the R-SNAREs Sec22p and Ykt6p can substitute for each other in the fusion of ER-derived transport vesicles with the cis-Golgi 25 .Their similar interaction pattern with the Q-SNARE Sso2p observed in our study reinforces that the two R-SNAREs are functionally identical." ] },{ "paper_id": "461bd946be4c4280c46eb9a7b163e9f3da0a734a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Male C57BL/6 mice weighing 20-25 g were procured from Biological Resource Centre (Singapore) and housed in groups of five, in cages with Corncob bedding Experiments were conducted in animal biosafety level 3 rooms. Cages were placed in an isolator maintained at -100 Pa pressure with a supply of high-efficiency particulate air-filtered air. Mice were provided with commercial rodent diet (Harlan-Teklad, Bicester, UK) and drinking water ad libitum. All animals were handled in strict accordance with good animal practice and all animal work was approved by the Institutional Animal Care and Use Committee, Biological Resource Centre (Institutional Animal Care and Use Committee #070236).", "Rolipram and oseltamivir were obtained from Kemprotec Ltd (Middlesbrough, UK). Sertraline was obtained from Atomax Chemicals Co. Ltd (Shenzen, China) and enzyme-linked immunosorbent assay reagents were from R&D Systems (Minneapolis, USA). Minimum essential medium and bovine serum albumin was obtained from Gibco (Life Technologies, Singapore) and L-(tosylamido-2-phenyl) ethyl chloromethyl ketone-treated trypsin, penicillin and streptomycin were from Sigma.", "Thus, the interactions mediated by competition for these enzymes are unlikely to rule out an essential problem of drug-drug interactions." ] },{ "paper_id": "464e444443d007ddd7b577c9e878c12eeaf7829e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "46768e7c839a7f4de0d5a73d25897f948b4eac30", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "46bf124930f3ef18bc9dd2d4ae356a45d3bae461", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All patients underwent a baseline digital anteroposterior chest radiography at full inspiration using a mobile chest radiograph machine (FLUOROSPOT Compact FD, Siemens Healthineers; DRX-Revolution Mobile X-ray System, Carestream Health, Rochester, NY, USA; or Optima XR220, GE Healthcare, Milwaukee, WI, USA).", "This retrospective study was approved by the Institutional Review Board of the participating hospitals, and the requirement for informed consent was waived.", "The authors have no potential conflicts of interest to disclose." ] },{ "paper_id": "46c2b3f4e85af8b1e30ac3c5be7b72a1412eec46", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "46c58d9482fd8d00108402c45033131561eb8921", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The \u2423 2,3 sialyltransferase, \u2423 2,3 SAT (O),", "Reactivity of Peanut Lectin with Live Cells. Cells were incubated with or without neuraminidase and analyzed by FACS \u00ae can for Arachis hypogaea peanut agglutinin (PNA) (Sigma Chemical Co.) lectin binding as described previously (Burchell and Taylor-Papadimitriou, 1993) .", "Detection of the Tagged Sialyltransferase in Permeabilized Cells. Cells were stained with 9E10 mAb after incubating the cells with 0.3% saponin for 20 min. Subsequent steps were as previously described (Burchell and Taylor-Papadimitriou, 1993) with the exception that 0.1% saponin was included in all incubations and washes, which were carried out at room temperature. The reactivity of an mAb (LE61) to keratin 18 (Lane, 1982) was included as a positive control for staining the permeabilized cells." ] },{ "paper_id": "46e88010c4a926b35d981984c673bb834c17f7d2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Recommendations regarding the optimal duration of antibiotic therapy have changed over time, and there are discrepancies on this issue across guidelines (Table 1) .", "Community-acquired pneumonia (CAP) is the leading cause of death worldwide." ] },{ "paper_id": "46eecf9daff1ef854fd51a8e6963d58126d35a2b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The mean fluorescence (MF) value obtained in the wells without competitor peptide was regarded as maximal binding and equated to 0% inhibition; the MF obtained from the wells without reference peptide was equated to 100% inhibition. Percentage of inhibition of binding was calculated using the formula: [1 \u03ea (MF 150 nM reference and competitor peptide \u03ea MF no reference peptide) / (MF 150 nM reference peptide \u03ea MF no reference peptide)] \u03eb 100%.", "Our findings demonstrate the potential of HCV to induce autoreactive CD8 \u03e9 CTLs by a molecular mimicry of CYP2A6/2A7 by the core protein and therefore show a possible mechanism by which HCV may trigger AIH. Further studies analyzing the cross-reactivity pattern of HCV core-specific CTLs derived from untreated patients with active HCV-associated autoimmune hepatitis are required in order to establish this mechanism.", "Competition-based MHC Class I Peptide Binding Assay. Peptides were tested for their binding affinity using the previously described peptide binding assay (26) . In brief, cells were stripped (see above) and resuspended at 7 \u03eb 10 5 cells/ml in IMDM plus 1.5 g/ml \u2424 2 -microglobulin. A fluorescein (FL)-labeled reference peptide (FLPSDC(FL) FPSV), 25 l (end concentration, 150 nM), was incubated with 25 l of competitor peptide (different end concentrations) in a 96-well V-bottomed plate. 100 l of mild acid-treated JY cells was added to these wells. The mixture was incubated for 24 h at 4 \u040a C, washed twice with PBS containing 1% BSA (PBA1%), resuspended in PBA1% containing 0.5% paraformaldehyde, and analyzed by FACScan \u00ae (Becton Dickinson)." ] },{ "paper_id": "46ef984b54bda15d5f23858a2d0a0eb64f39f5d8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "471aa6c890ce013986b2f55f65bde5b06615f456", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We now report a dominantly inherited variant that affects LMAN2L's ER retention, in a second similarly affected family (Fig. 1A ).", "Additional supporting information may be found online in the Supporting Information section at the end of the article. Table S1 . Current neuropsychological testing data. Table S2 . Summary of shared heterozygous, protein coding variants with high confidence in the linked region amongst affected patients.", "Whole exome sequencing (WES) was as previously described. 5 The human LMAN2L NM_001142292.1 cDNA was cloned into pcDNA3.1. The EQKLISEEDLA myc epitope was introduced downstream of the signal sequence cleavage site between codons for amino acids 44 and 45 ( Fig. 2A) . Site-directed mutagenesis on this wild-type (wt) construct generated the mutated version. Following sequence verification, the constructs were transfected into HeLa cells. Lysates were fractionated for cytosolic and light and plasma membrane proteins as previously described. 6 For microscopy, 24 h post-transfection cells were treated with 10 mg/mL cycloheximide for 2 h, fixed in 4% paraformaldehyde, and incubated with anti-myc antibody followed by Alexa 488-coupled anti-mouse IgG.", "The proband (II-1) was born term without complications. At 6 months tremor was noted with reaching, which disappeared by adolescence. At 6 years he developed generalized tonic-clonic seizures; EEG showed sleep-enhanced bilateral independent centrotemporal spike-and-slow waves. Seizures were controlled with carbamazepine, from which he was weaned at 10 years with no further recurrence and with normalized EEG. He sat at 5 months, walked at 1 year, but was delayed in fine motor and intellectual (below) development. His father and two brothers had a similar course with onset of intention tremor in infancy, seizures in childhood, EEG as above, remission of all these by adolescence, and persisting intellectual disability in the boys and low-average function in the father (below). Mother is healthy. Neurological examination in all is unremarkable, except in the youngest, examined in pre-adolescence, exhibiting a kinetic and intentional tremor interfering with fine motor activities, but no dysdiadochokinesia." ] },{ "paper_id": "477645a85a65fb72adc9d17a09bf6d53ca3f24fd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4776a30b2dc8da97b0c419d7577dd959231bbd61", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "47772f3e98d8c61bb9782531a0338ba85f27bf3f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "An epidemic of a novel coronavirus emerged from Wuhan, China, in late December 2019 and has since spread to several large Chinese cities. Should a scenario arise where this coronavirus spreads more broadly across China, we evaluate how patterns of international disease transmission could change.", "A novel coronavirus emerging from Wuhan, China in late December 2019 is currently spreading to other provinces in mainland China and international destinations across East Asia. At the time of writing, cases have been confirmed in Beijing, Shanghai, Hong Kong, Macau and multiple cities in Guangdong province, with more than 500 cases confirmed across China. 1 Furthermore, several cases have spread internationally via air travel 2 to Japan, South Korea, Taiwan, Thailand and the USA. A recent modelling study concluded that for these international exportations to be observed, the outbreak in China should be substantially larger than is reflected by confirmed case counts. 3 Currently, many public health interventions are based on scenarios where Wuhan is the primary source of new cases. 4 While there are currently no documented transmission chains outside of the Wuhan region, should a scenario arise where this novel coronavirus spreads more broadly to and within other Chinese cities, we evaluated how global patterns of disease dispersion might change.", "We analyzed international airline passenger trips from the following 10 cities: Wuhan, Beijing, Shanghai, Kunming, Chengdu, Xiamen, Haikou, Guangzhou, Shenzhen and Hong There currently are numerous unknowns including the presumed animal origins of the virus, the efficiency of humanto-human transmission, an understanding of the full spectrum of clinical illness and an incomplete epidemiological picture of disease activity in China. While our analysis does not account for the potential effects of the epidemic on changing travel behaviours, it reflects worldwide flows of airline travellers at the same time of year in 2019, including the Lunar New Year in February 2019. At the time of writing, flights and land transportation in and out of Wuhan have been suspended, and it is uncertain how this will impact disease transmission in China. Our findings could support public health planning and readiness for different scenarios should the current epidemic spread more widely across mainland China and neighbouring cities." ] },{ "paper_id": "4790e3eb0374a7f159014ef77ec42a6b9de91c29", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "47bd7df352db2b1b093566b04fc328d6f0292c1b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "participants (large and medium) wore model 1860, and 7 (small size) wore model 1860S." ] },{ "paper_id": "47ceb56d266552a6cc6c3c0eb153bab3b99a1e98", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Disclaimer. The findings and conclusions are those of the authors and do not necessarily represent the views of the US Centers for Disease Control and Prevention.", "Financial support. " ] },{ "paper_id": "480e5240848f603d3c04a1e21cecfe502a13cd89", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "well as in important, prespecified subgroups. ALIC 4 E is likely therefore to enhance the evidence base supporting and important and common area of clinical practice.", "There is no requirement for participants to attend a faceto-face follow-up visit as part of their study participation, as all subsequent measurements will be ascertained by self-completed diary-based questionnaires and through telephone calls from the local trial team.", "Participants who have visited the hospital with complications possibly related to ILI and who have had a chest X-ray will have their primary care clinical records examined by the trial team for confirmation of relevant diagnoses of complications, including pneumonia.", "A manuscript with the results of the primary outcome will be published in a peer-reviewed journal. Additional manuscripts will report secondary outcomes and be submitted for publication in peer-reviewed journals.", "The local implementation of the trial has built-in flexibility, and local network recruitment processes vary. For example, medical students may assist with recruitment tasks in certain practices, whereas others will incorporate triage systems or additional trial-specific clinics and/or research support staff in their recruitment processes." ] },{ "paper_id": "485169c3d48f25be33434505f0e9b5ea5c1256f9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A chymotrypsin-like cysteine proteinase, 3C pro , is the main cleavage protein found in all picornaviruses and contains a conserved cleavage site aiding in the identification of cleavage sites of newly discovered viruses (Lendeckel and Hooper 2009) . The 2A pro is another protease encoded by entero-and rhinoviruses, that folds spontaneously into an active form, performing a primary cleavage (Ehrenfeld et al. 2004; Lendeckel and Hooper 2009) .", "Picornavirus evolution is determined by their high mutation rate, which is predicted to range between 10 \u00c03 and 10 \u00c05 mutations per nucleotide, per genomic replication (Domingo and Holland 1997) . In addition, the often reported recombination events are crucial to shape their genomic architecture (Simmonds 2006) .", "Supplementary data are available at Virus Evolution online.", "First-and second-strand synthesis and random PCR amplification were performed for 17 cycles using a modified Whole Transcriptome Amplification (WTA2) kit procedure (Sigma-Aldrich). Denaturation temperature was increased to 95 C to allow for the denaturation of dsDNA and dsRNA. WTA2 products were purified with MSB Spin PCRapace spin columns (Stratec) and were prepared for Illumina sequencing using the Nextera XT library preparation kit (Illumina). Libraries were quantified with the KAPA Library Quantification kit (Kapa Biosystems) and sequencing of the samples was performed on a HiSeq TM 2500 platform (Illumina) for 300 cycles (150 bp paired ends), generating 67,251,870 reads." ] },{ "paper_id": "48545476b719bbb0efc851c4bb4da881b8244cc2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "[22]", "A sample size of 30 was chosen to:", "[2] The severity of symptoms 77 typically peaks two to three days after symptom onset." ] },{ "paper_id": "485f987d1d6344a2982cd356cc2116b4221ad3fe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The patient was later diagnosed as Vici syndrome, which consists of agenesis of the corpus callosum, cataracts, oculocutaneous hypopigmentation, cardiomyopathy, and a combined immunodeficiency (molecular testing revealed biallelic mutations in the EPG5 gene).", "Angiotensin converting enzyme inhibitor therapy was initiated, and his urine protein/Cr ratio decreased to 0.6 on a follow-up nephrology visit. He continued to have intermittent episodes of proteinuria and acute kidney injury during subsequent hospitalizations. The patient expired following a hospitalization for respiratory failure due to severe pneumonia, and acute respiratory distress syndrome (ARDS) which was associated with a disseminated fungal infection.", "In this article, we report 3 pediatric patients with renal biopsy showing TRIs. Evaluation of these patients did not reveal HIV, SLE, or any other viral illness that has been reported in association with TRIs." ] },{ "paper_id": "488c028f6d7b11c0eda9224a28685fcc192e151e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "496bfe6fe82dca285afe74c0202ad9498b41370c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ ".", ", 10% , [2, 3] . , ,", "( )." ] },{ "paper_id": "497065a88412aca3ce4d3de9ebad13ce175e5f18", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The data were analyzed using the PASW Statistics software program for Windows, version 18.0.", "Suicide is a grave public health issue with a global mortality rate of 16 per 100,000 individuals. 1 Suicide is one of the top three leading causes of death, particularly among individuals aged 15-44 years, which is a productive age group. 1 Suicide is a complex event that is influenced by biological, cultural, psychological, and socioeconomic factors." ] },{ "paper_id": "49a7701b214e24e40679127c598881fa579f97dd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The abstracts of the identified studies were independently reviewed by two readers (AB and SJ). Differences were resolved through discussions for a consensus to be reached. Percentage agreement and Cohen's Kappa (k) statistic 45 were calculated and interpreted in accordance with Landis and Koch's benchmarks 46 for assessing the agreement between reviewers as poor (<0), slight (0.0-0.20), fair (0.21-0.40), moderate (0.41-0.60), substantial (0.61-0.80), and excellent (0.81-1.0). The agreement on the inclusion between the two reviewers was 86%, with k=0.72 (95% CI 0.58-0.85).", "The methodological quality of each study was evaluated as previously described 47 with some modification. Quality of the study was based on four criteria: (a) the number of study subjects (n; at least the median of 157 for H1N1 and 17 for MERS-CoV), (b) comprehensive reporting of patients' demographic information, (c) describing a minimum of 3 disease-associated symptoms and (d) reporting at least 2 comorbidities (in addition to diabetes). For each criterion, each study was given a score (0 or 1, with 1 fulfilling the criteria). The total score was calculated for each study (score range 0-4). Quality scores of 1, 2, 3, and 4 were considered poor, fair, good and very good, respectively.", "A search was conducted in PubMed, Ovid MEDLINE, Embase and Embase Classic databases to the last week of July 2015 using the search terms (MeSH) H1N1 or MERS-CoV (Middle East respiratory syndrome coronavirus) and Diabetes. The search resulted in 123 articles selected for title and abstract review as they satisfied our selection criteria (see below). We limited the studies into those in humans and excluded reports published as review articles, letters, case studies, editorials, conference abstracts, vaccination trials or family-based studies. After eliminating duplicate listings and only considering articles in full text, a total of 44 peer-reviewed original studies were selected for full text review. Full article review resulted in the further exclusion of 8 reports that were not documenting the prevalence of diabetes in H1N1 or MERS-CoV (i.e., no association studies), examining only a small number of travellers as a case report (n=2 subjects), reporting seasonal influenza alone, reviewing already reported cases (MERS-CoV), or simply documenting national surveys. A bibliography search of the remaining articles identified two additional studies. A total of 38 peerreviewed articles (29 studies for H1N1 3-5,14-39 and 9 for MERS-CoV 6-9,40-44 ) were identified for this article (Figure 1 )." ] },{ "paper_id": "49c8f45d390502809816b630ee23375427ea0fb6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Intestinal tumors are generally rare in cats. Lymphomas account for nearly 30% of all feline tumors and are the most common intestinal tumors [20] . Adenocarcinomas are the second most frequent tumors in cats, followed by mast cell tumors. Gastrointestinal stromal tumors (GISTs) are thought to originate from the interstitial cells of Cajal (ICCs), which form a network that coordinates peristalsis in the gastrointestinal tract [11] . Many of the smooth muscle tumors in human and canine patients have now been reclassified as GISTs, which by definition express CD117 (KIT) [13, 15] . GISTs have been described in humans, dogs, horses, Spanish ibex, a ferret, a rat, and nonhuman primates [5, 18, 19] . These occur most frequently in the jejunum, cecum and colon [16] . To the authors' knowledge, only one report has described \"a feline GIST\" in the stomach [17] .", "(approximately 5.0 mm) (Fig. 2B ) and performed cytological examination of a fine-needle aspirate. It revealed the lymph node had reactive hyperplasia. Biopsy examination of a hepatic nodule was not performed, because the owner declined it. After surgery, the cat was administered total parenteral nutrition through a central venous catheter." ] },{ "paper_id": "49d10e98d15b16cd6d0b522b21714401d767dcc2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "described (6) (7) (8) (9) . These cases have raised concerns about adenovirus infection in the general population, but there is still limited information on the condition.", "The institutional review board approved our retrospective study, and written informed consent was waived for the use of patients' medical and imaging data. All of the patients' information was anonymized prior to the analysis.", "Diagnosis was confirmed in five patients based on positive viral culture for adenovirus in BAL fluid. Diagnosis via lung biopsy specimens obtained by video-assisted thoracoscopic surgery (n = 4) or transbronchial lung biopsy (n = 1) was made in another five patients. The specimens were evaluated using hematoxylin and eosin immunohistochemical staining (10, 12) . In nine patients, BAL fluid was analyzed using the one-step multiplex realtime AdvanSure RV real-time PCR kit (LG Life Sciences, Seoul, Korea) or conventional multiplex reverse transcription PCR (RT-PCR) assay (Seeplex RV12 Detection Kit; Seegene, Seoul, Korea) (13, 14) ." ] },{ "paper_id": "49fb495cd0efde647aa99ec56606432699b1e88e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Disclosure. Authors have no conflict of interests, and the work was not supported or funded by any drug company.", "Echocardiography showed mild tricuspid regurgitation with normal cardiac function. He was switched to highfrequency oscillatory ventilation. He was afebrile, and laboratory investigations showed a C-reactive protein of 24 mg/L (normal value [NV] -0-6 mg/L), white blood cell count of 9.600/mm 3 (NV -5-14.5/mm 3 ), hemoglobin of 10.9 g/dL (NV -11.5-15.5 g/dl), and platelet of 32000/mm 3 (NV -150-450/mm 3 ). His coagulation profile was initially within the normal range but later become prolonged ", "Discussion. Since the emergence of MERS-CoV, the Prince Sultan Military Medical City in Riyadh has taken extensive measures (the \"no risk\" policy) to prevent further spread of the disease. Apart from extensive infection control measures, a vast education campaign for the staff and the community including parents and their children was initiated." ] },{ "paper_id": "49fbca70a4e7e3018cab7eb445683c58fd06bce2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Background. Beginning in December 2013, an epidemic of chikungunya virus (CHIKV) infection spread across the Caribbean and into virtually all countries in the Western hemisphere, with >2.4 million cases reported through the end of 2017.", "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.", "Methods. We monitored a cohort of school children in rural Haiti from May 2014, through February 2015, for occurrence of acute undifferentiated febrile illness, with clinical and laboratory data available for 252 illness episodes." ] },{ "paper_id": "4a17794fa919d411ae351c9d671d4d1a6d64cc99", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We thank Roselyn J. Eisenberg and Gary H. Cohen for generous donation of the recombinant gB-1 protein. This work has in part been funded by the Bundesministerium f\u00fcr Bildung und Forschung (BMBF; 01EZ0934), and the Klaus Tschira Stiftung (KTS, 00.150.2009).", "Neutralizing activity of LYNDAL antibodies was determined in a plaque reduction assay as described previously. 49 The humanized version of a highly potent HSV-neutralizing antibody was used as positive control. 49", "No potential conflicts of interest were disclosed." ] },{ "paper_id": "4a32929dbc801a7e96e900f42f242f93057211ab", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The application of FISH is growing rapidly in genomics, cytogenetics, prenatal research, tumor biology, radiation labels, gene mapping, gene amplification, and basic biomedical research, as well as clinical applications, for diagnostic purposes. As a gene expression assay, FISH is used for localization and detection of specific RNA targets (mRNA, lncRNA and miRNA) in tumor cells and tissues.", "With a sample processing fee of as little as $0.50 for a single gene, an experimental time of about 5 hours that includes RNA isolation and purification, as well as PCR and data analysis, qRT-PCR offers the cheapest and quickest assay for processing an individual clinical sample for 1-50 genes. Small laboratories such as a hospital lab or a clinic lab suited to a clinical processing environment can purchase a thermal cycler for as little as $25 000 to process and analyze their sample.", "The quantitation of results generally requires the study of the output dissociation curve, which allows a graph of known RNA concentration to be used as a reference for a curve constructed from the unknown RNA quantity. This approach is known as the standard curve method. The comparative Ct method involves comparing the Ct values of interest with a control, such as a non-treated or normal sample, which are both then normalized to a housekeeping gene. 9, 11 A biostatistical analysis can also be done where the final gene expression values are log-transformed for a normalized or symmetrical data distribution." ] },{ "paper_id": "4a3701d8545be96ceb7d7b0625ca1702b3de2634", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "From patient electronic medical records the following information was obtained: Demographics (age and sex), month of hospitalization, and geographical origin.", "FilmArray testing. NPSs were collected according to a standard procedure, kept in viral transport medium, and stored at -20\u02daC prior to analysis." ] },{ "paper_id": "4a8852f2970eadd44d677311548ca6eea1c5079f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4a9469fd152806179cbbf936e6ec7df22930efce", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4aa30aa1b955b36fda673d75c1a37f386f5823c4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4aa64b68fec8e053f6abcc1594eee14507853618", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4af614b04d5df393575c749cd953aa3855fa8b44", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4af62711ee4cca0c90baf73be3e83ea95e68c045", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "No conflict of interest to declare.", "None.", "Approval was not required." ] },{ "paper_id": "4b1b2e95b29b2fb4926c6c0191689f86537985bb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "15-#1 translation mixtures were adjusted to pH 11-11.5 by adding an appropriate volume (pretitrated) of 0.1 N NaOH. After a 10-rain incubation on ice the samples were separated into a pellet fraction and a supernatant fraction by centrifugation through a 100-#1 alkaline socmse cushion (Gilmore and Blobel, 1985) for 10 rain at 30 psi in an airfuge (Beckman Instruments, Inc., Palo Alto, CA) using the A-100/30 rotor and cellulose propionate tubes precoated with BSA (1% solution). The entire supernatant was removed, neutralized with 1 N HCI, diluted 2.5 times with water, and then precipitated by adding 3.5 vol of acetone. These precipitated proteins and pelleted membranes (obtained from the airfuge tube) were taken up in 4% SDS by incubating at 56\u00b0C for 15 min and then processed for immunoprecipitation reactions as described below.", "(1987a) have suggested a translocator protein model in which the signal sequence helps to keep the machinery open for chain transfer.", "Total translation mixtures were adjusted to 4% SDS, then boiled for 4 rain and diluted 1:2 with water. 4 vol of immunoprecipitation buffer (2.5 % Triton X-100, 190 mM NaC1, 60 mM Tris-HC1, pH 7.4, 6 mM EDTA, and 20/~g PMSF/rni) and 2 #1 of antibody were added for 16 h at 40C. The mixture was briefly centrifuged (2-3 min in an Eppendorf minifuge) and to the supernatant one fifth volume of a 1:1 slurry of protein A beads were added and incubated at 24\"C for 2 h under constant agitation. The beads were collected and washed four times with 1 ml RIPA buffer (Gielkens et al., 1976) by centrifugation, followed by a single wash with a buffer containing 150 mM NaCI, 10 mM Tris-HCl pH 7.4, and 20 t~g PMSF/ml. The beads were then taken up in excess gel loading buffer (Cutler and Garoff, 1986) , heated at 95\u00b0C for 5 min, and cleared by centrifugation before loading the immunoprecipitate on the gel." ] },{ "paper_id": "4b34166a75b4835a2743fabba60bf7ff23cf0087", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Being a case report, our institution does not require formal ethical approval. Informed written consent was obtained from the patient for publication of this case report and accompanying image." ] },{ "paper_id": "4b36607cdbc54f8006161a9a1839489dd0a51269", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "-'Two bats flew into our room, so we caught them to eat' (female peasant farmer, 60-y-old, Guangxi).", "I am on the way to interview a potential participant, currently going through a small local market, here they sell fresh vegetables, fruits, pork and live poultry on both sides of the street. Live chickens, ducks and geese are mixed and kept in cages, I can smell the faeces. A vendor (female) is slaughtering a chicken for her customer who just selected one from the cage, she seems very proficient, only wears an apron but no gloves, the ground is covered by blood and feathers. Not far away, there is a woman wearing an orange uniform who is cleaning the street. " ] },{ "paper_id": "4b3d6bca8bfe315d03331cba07299570e2ce7fad", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Autophagy has inexorably been linked to the host cellular response to diverse intracellular pathogens. Indeed, autophagy frequently serves as an innate mechanism that sequesters or clears offending pathogens from the host cell, termed xenophagy. In response to infection, pathogen-and damage-associated molecular patterns stimulate pattern recognition receptors, which then activate ATG proteins to induce autophagy or promote recognition of the microbe by the LC3-positive autophagosome (Deretic et al., 2015) . Nevertheless, the autophagy trafficking process can be subverted by pathogens that have adapted to avoid or use autophagy to their own benefit (Deretic and Levine, 2009 ). One example is poliovirus, which utilizes LC3 to promote its nonlytic viral release, potentially by the fusion of LC3-positive vesicles containing poliovirus with the plasma membrane (Bird et al., 2014) .", "During Brucella abortus infection, multiple ATG proteins implicated in the early steps of autophagosome initiation, such as ULK1 and Beclin 1, are involved in the formation of a B. abortus-containing vacuole (BCV) with autophagic features (aBCV), which promotes bacterial proliferation. Double-membrane crescents reminiscent of the autophagosome engulf BCVs late in infection but do not degrade or clear the bacteria. Instead, ULK1, Beclin 1, and class III phosphatidylinositol 3-kinase activity are all required for the conversion of BCVs into aBCVs. However, the ATG conjugation pathways involved in autophagosome elongation play no role in aBCV formation. Furthermore, these aBCVs facilitate bacterial release and infection of neighboring cells, demonstrating that very specific components of autophagosome initiation promote B. abortus infection (Starr et al., 2012) ." ] },{ "paper_id": "4b55b2415bd2adff96e6013f792d281693bf4587", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Human embryonic kidney 293T cells were maintained in Dulbecco's minimal essential medium, supplemented with 10% fetal bovine serum (PAA), 100 U/mL penicillin, and 100 \u00b5g/ mL streptomycin (Cytogen). RD cells stably expressing a C-terminal fragment of Gaussia luciferase (GLuc) were generated by selection of transfected cells in Dulbecco's minimal essential medium containing G418 at 1 mg/mL. Monocyte-derived macrophages (MDMs) were cultured in X-Vivo 10 medium (Lonza).", "Supplementary materials are available at The Journal of Infectious Diseases online (http://jid.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.", "For the production of human MDMs, monocyte-enriched cells were isolated from thrombapheresis rings by Ficoll density gradient centrifugation. The amount of platelets in the preparations was reduced by centrifugation, and monocytes were collected by adhesion-mediated enrichment on plastic dishes followed by culture in monocyte adhesion medium (Roswell Park Memorial Institute 1640 medium supplemented with 7.5% human fibrindepleted plasma and antibiotics). The next day, the cultures were washed with phosphate-buffered saline, and cells were detached and seeded in monocyte differentiation medium (X-Vivo 10 supplemented with 1% human fibrin-depleted plasma and antibiotics) and cultured for 6 days. Differentiation into MDMs was controlled by flow cytometric analysis of CD14 expression." ] },{ "paper_id": "4b938c2f60ce863541ac9ca19fe0a98cd9a8730e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Depending on the type of experiment, recombinant trapping mutant was applied to cytosolic preparations, human serum ultrafiltrate or intact cells. A detailed description of the different substrate trapping protocols is provided as Supplementary information.", "Cell culture BL-41, CCRF-CEM, HDLM-2, Jurkat, RMA and U937 cells were cultured in RPMI 1640 (Gibco) supplemented with 10% heatinactivated fetal bovine serum, 2 mM L-glutamine, 100 U/ml penicillin and 100 mg/ml streptomycin (Gibco). LCL-721.220 and YT cells were cultured in IMDM (Gibco), HeLa and A431 cells in DMEM (Gibco) with the same supplements.", "Supplementary data are available at The EMBO Journal Online (http://www.embojournal.org)." ] },{ "paper_id": "4b9e5d0ffdac80fba0ea840f8f14e359ad4c43f1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4bae83e2441c3738d96e49c21c9be0a4c85b4a92", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis was performed with SPSS (ver. 17.0; IBM, USA). Differences between the groups were analyzed with a one-way repeated measurement ANOVA and least significance difference test.", "In the present study, we evaluated the protective effect of three plasmids expressing the S1, N, and M proteins of the virulent IBVSX16 strain that we previously constructed [22] . Chickens were immunized monovalently with each individual plasmid (pVAX1-16S1, pVAX1-16M, and ", "A T cell proliferation assay was performed as previously described [1] with some modification. Peripheral blood mononuclear cells (PBMCs) were isolated by Lympholyte-Mammal (Cedarlane, Canada). Briefly, 2 mL freshly heparinized whole blood was diluted with Hanks' balanced salt solution in a ratio of 1\uff1a1 and carefully add on top of 2 mL lympholyte-mammal separation medium, centrifuge at 400 \u00d7 g/min for 20 min, aspirate coat of leukocyte, add 4 mL KPMI 1640 (Invitrogen, USA), centrifuge at 400 \u00d7 g/min for 20 min, discard supernatant and wash precipitation cell twice by the same method. The cells were resuspended in RPMI 1640 medium (Invitrogen, USA) supplemented with 5% fetal bovine serum (Invitrogen, USA), 100 \u03bcg/mL penicillin (Invitrogen, USA), and 100 \u03bcg/mL streptomycin (Invitrogen, USA) at a concentration of 1 \u00d7 10 7 cells/mL. The freshly isolated PBMCs (10 " ] },{ "paper_id": "4bbb0c59babc718f67953fae032dad6ae0d7aeb1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In conclusion, the Genome Detective Coronavirus Typing Tool is a webbased and user-friendly software application that allows the identification and characterization of novel coronavirus genomes.", "The tool uses a novel and dynamic aligner, AGA, to allow submitted sequences to be queried against reference genomes, using both nucleotide and amino acid similarity scores. This allows accurate identification of other coronavirus species and the tracking of new viral mutations as the outbreak expands globally. It also performs detailed analysis of the coding regions and proteins. Moreover, it can easily be updated to add new phylogenetic clusters if new outbreaks arise or if the classification nomenclature changes. The tool has been able to correctly classify all the recently released SARS-CoV-2 genomes, as well as all the 2002-2003 SARS outbreak sequences", "We developed and released the Genome Detective Coronavirus Typing tool as a free-of-charge resource in the third week of January 2020 in order to help the rapid characterization of COVID-19 infections. This tool allows the analysis of whole or partial viral genomes within minutes. It accepts assembled genomes in FASTA format or raw NGS data in FASTQ format from Illumina, Ion Torrent, PACBIO or Oxford Nanopore Technologies (ONT) can be submitted to the Genome Detective Virus Tool (Vilsker et al., 2019) to automatically assemble the consensus genome prior to executing the Coronavirus Typing Tool. User effort is minimal, and a user can submit multiple FASTA sequences at once." ] },{ "paper_id": "4be09649912765a96eb17e54d40b4b777b3413c6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4bf7428a3d7bd1625f0e945398eb8ff045ea4b71", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The proteins found in plaques or neurofibrillary tangles are from two proteomics studies yielding 488 proteins in plaques [85] and 90 in tangles [86] .", "Viruses are transported via the microtubule network [128] , which is also exploited by C. pneumoniae, T. cruzi, and T. gondii to reorganize cellular organelles to the pathogens' advantage [129, 130] . Phosphorylated tau is a hallmark of neurofibrillary tangles and is induced by many pathogens. Tau inhibits the motility of the kinesin-1 motor protein that transports cellular organelles (or viruses) along the microtubules and tau phosphorylation counteracts this inhibition [131] , but it is not clear whether this benefits or deleteriously affects the pathogens.", "Two separate case reports have shown remission from an initial diagnosis of dementia or AD in patients subsequently diagnosed with and treated for C. neoformans infection [278, 279] ." ] },{ "paper_id": "4c13be11a41de81fb7066f7993da218c463cfa1e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "www.nature.com/scientificreports SCIENTIFIC REPORTS | 3 : 3311 | DOI: 10.1038/srep03311 both genders and found no such differences in our results for MDS patients.", "ELISAs. Utilizing ELISA kits we measured plasma levels of AKT3 (dilution 1:5, PathScanH Catalog No. #7934, Cell Signaling), FCGR3A (dilution 1:10, Catalog No. E91278Hu, Uscn Life Science Inc.) and ARL8B (dilution 1:10, MyBioSource Catalog No. MBS946943), using samples from 20 subjects (80 total) for each of s-MDS, t-MDS, L and healthy subjects tested in triplicate, following each manufacturer's instructions (Fig. 3c) .", "M yelodysplastic syndromes (MDS) encompass a diverse range of hematological disorders, with variable clinical outcomes resulting from individual patients' clinical and biological features 1, 2 . MDS pathogenesis involves multifaceted factors, related to intrinsic hematopoietic precursor cell abnormalities. The prevalent shared pathogenesis causing the ineffective hematopoiesis in MDS involves varying degrees of apoptosis of the hematopoietic cell linage [3] [4] [5] . Recent genomic approaches have concentrated on the effects of specific gene mutations and their associated signaling pathways, and their role in MDS development and outcome, including the tendency of transitioning to more aggressive disease stages 6, 7 . Currently, the prognosis of patient outcomes is greatly facilitated by the establishment of the International Prognostic Scoring System (IPSS 8 , recently revised as IPSS-R 9 ). The IPSS takes into account multiple clinical markers to classify lower risk patients (Low, Intermediate 1) as having improved prognoses compared to those with higher risk features (Intermediate 2 and High).", "In our study we compared different patient subgroups to one another. We were specifically interested in signals showing increased reactivity in the retrospectively analyzed MDS patients versus the healthy control group, particularly s-MDS, and assessed statistical significance through a two-tailed Mann-Whitney test (Mathematica 9.0; multiple hypotheses Bonferroni adjusted P , 0.01)." ] },{ "paper_id": "4c565559fff97813a77571986c4c0b34fa3f4d46", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 Optimization and preclinical analysis of a bacterial natural product.", "From the 1940s to 2007, 73% of the 155 small molecules approved as anticancer drugs were of natural origin, either directly or derived 1 . As opposed to this, few natural products had been approved for use in antiviral therapy, although they were the inspiration for antiviral nucleoside analogues 2 .", "Anti-HCV assay in Huh 5-2 cells was performed by seeding 6.5\u00d710 3 cells per well in a tissue culture treated white 96-well view plate (Packard, Canberra, Canada) in Dulbecco's modified essential media (DMEM) supplemented with 250 \u00b5g/ml G418. Following incubation for 24 h at 37 \u00b0C (5 % CO 2 ) medium was removed and 3-fold serial dilutions in complete DMEM (without G418) of the test compounds were added in a total volume of 100 \u00b5l. After 4 days of incubation at 37\u00b0C, cell culture medium was removed and luciferase activity was determined using the luciferase assay system (Promega, Leiden, The Netherlands); the luciferase signal was measured using a Safire2 (Tecan, Switzerland). Relative luminescence units were converted to percentage of untreated controls. The 50 % effective concentration (EC 50 ) was defined as the concentration of compound that reduced the luciferase signal by 50%.", "Stocks of NL4-3 (X4 virus) were prepared by transfection of 293T cells and collection of supernatants on day 2. Supernatants were filtered, aliquoted and frozen at \u221280 \u00b0C until use. Amounts of virus were quantified by p24 ELISA and infectivity of viral stocks verified using CD4+ HeLa-betagalactosidase reporter cells.", "Refer to Web version on PubMed Central for supplementary material." ] },{ "paper_id": "4c5c841e4ad3fbf9b31d6c0c282dfec035f716bb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4c819d4002a693bae0a39b5d0a282c4feac3f184", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4c8bac1e65d1fd2effec0b45c143a97cef99aebd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4ca26be0493fc360519e7586ec0392760846d662", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "ISDS Annual Conference Proceedings 2017. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0/), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.", "Phylogenetics; Transmission Graph; MERS-CoV; Syndromic; Genetic", "Here we use novel methods of phylogenetic transmission graph analysis to reconstruct the geographic spread of MERS-CoV. We compare these results to those derived from text mining and visualization of the World Health Organization's (WHO) Disease Outbreak News." ] },{ "paper_id": "4d186611ecffce20666431e3e9988308833c0236", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Considering a dropout rate of 30%, the sample size increased to 77 individuals, which was then further rounded up to 80 (per group) to enhance the accuracy. According to our CONSORT diagram (Fig. 1) , after the dropout, each group ended up to contain 60 samples.", "The use of positive end-expiratory pressure is one of the ways to treat atelectasis after cardiac surgery. It is not as a preventive method for the atelectasis. It's also a controversy about its beneficial level." ] },{ "paper_id": "4d9b7d6b31a252255d427fd463344c162ae7c690", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4db442dee5f7675795f576b1f6b7be277decf03b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Since all continuous variables were skewed, medians and ranges were calculated to describe the data. Numbers and percentages " ] },{ "paper_id": "4de882602b82e20b2b7d9c7cb136de860a4f8634", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "HEK293T (human embryonic kidney epithelial cell line) and Raw264.7 (murine macrophage cell line) cell lines were cultured in Dulbecco's modified minimal essential medium (DMEM) supplemented with 100 U penicillin-streptomycin and 10% fetal bovine serum at 37 o C in a humidified atmosphere containing 5% CO 2 .", "Group comparisons were performed by a paired Student's t-test in Prism 7 (GraphPad Software, USA). Differences were considered significant when P values were less than 0.05." ] },{ "paper_id": "4e0773d0ae56a69211b358144a99bbecbad56bac", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. Statistical analysis was performed using SPSS version 17.0 (SPSS, Inc., Chicago, IL, USA). Continuous variables were compared using analysis of variance (ANOVA) and one-way ANOVA was used to evaluate the differences among groups. Non-continuous variables were compared using a Mann-Whitney U test between two groups and Kruskal-Wallis H non-parametric test among groups. Correlation was evaluated using Pearson's or Spearman's correlation analysis. P<0.05 was considered to indicate a statistically significant difference.", "Determination and image capture. The specimens were evaluated semi-quantitatively by two pathologists in a blinded-manner (22) . The frequencies of positive cells to total cells at x200 magnification were scored as follows: 1, \u226425%; 2, 26-50%; 3, >51%. The staining intensity above the background level was scored as follows: 0, no staining; 1, light yellow; 2, yellow-brown; 3, brown. These scores served as measures of target protein expression. The final score was the product of the above two scores: 0, negative (-); 1-2, weakly positive (+); 3-4, positive (++); 6-9, strongly positive (+++). Slides were mounted with gum for examination and captured using an Olympus BX51 microscope (Olympus Corp., Tokyo, Japan) and a Nikon Digital Camera System (80i; Nikon Corp., Tokyo, Japan) for study comparison. For this evaluation, five fields were randomly selected per section (magnification, x200).", "Detection of viral load. Blood was processed within 2-4 h post-collection by centrifugation for 10 min at 1,100 x g for plasma separation, followed by HIV RNA extraction by using a Roche Cobas AmpliPrep/Cobas TaqMan automatic analysis system (Roche Diagnostics; Basel, Switzerland, USA). The viral load was quantitatively measured using a Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test kit (version 2.0; Roche Diagnostics) according to the manufacturer's instruction." ] },{ "paper_id": "4e14a0bdb3702f1c98145da4335c327a99b7275c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The institutional review board at Seoul National University Hospital reviewed the study protocol and provided study approval. The board waived the requirement for written consent (IRB re- " ] },{ "paper_id": "4e2387a88720584e25e0f6418be2491523e288af", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4e5e41c6bee286394aab9998f7c4b2401a80333b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4e9acd476a5b8224baf48582bd4f4c095feafe27", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4ea10ee40e0ecf02db0667f87ed9ee4e2bd6aa9c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data are expressed as mean \u00b1 SD (number of mice). Statistical difference between groups was determined using the unpaired two-tailed t test. When there were more than two groups, differences were analyzed using analysis of variance if the variances were equal, and the Mann-Whitney nonparametric test if variances were unequal [16] . Linear regressions were calculated using a statistical computer package, Number Cruncher Statistical Systems [16] . A value of P < 0.05 was considered statistically significant.", "HEK-293 T cells were cultured in DMEM medium containing 10% fetal bovine serum (FBS) in air and 5% CO 2 atmosphere at 37\u00b0C. CaCo-2 cells were cultured in DMEM medium containing 10% FBS, 4.5 g/l glucose, 2.292 mg/ml glutamine, 10 nmol/l pyruvic acid sodium, = and 1% unsaturated amino acid in air and 5% CO 2 atmosphere at 37\u00b0C.", "In conclusion, polyethylenimine is a new human TLR5 agonist with potential application in radiation protection, including, but not limited to, offering protection for cancer patients who receive radiotherapy or radiosurgery, and could serve as a new compound for protecting the health and safety of people in radiation-related accidents." ] },{ "paper_id": "4eb6e165ee705e2ae2a24ed2d4e67da42831ff4a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The program can be obtained free of charge for research purposes by contacting the authors.", "A resequencing microarray (RPM v.1) was designed previously for detection and sequence typing of 20 common respiratory and 6 CDC category A biothreat pathogens known to cause febrile respiratory illness based on ProSeqs without relying on predetermined hybridization patterns (15, 16, 18 ", "In this paper, target pathogens are the organisms the assay was specifically designed to detect. The sets of probes that represent reference sequence selected from target pathogen genomes are referred to as a Prototype Sequence or 'ProSeq' for brevity. The set of resolved bases that result from hybridization of genomic material to a ProSeq is referred to as the hybridized sequence or 'HybSeq'. The HybSeq is split into possible subsequences or 'SubSeqs'." ] },{ "paper_id": "4ebe630a2d802a7d6f2402a88c3dc88e7497dcfd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "F.J. and C.C. designed the research, performed the experiments, and analyzed the data. F.J. wrote the paper. M.H. supervised the study and edited the paper." ] },{ "paper_id": "4ec7c4ec545371f4b8c4a40db7d28fc534674c39", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4ecbacf61daab591e76f7471eb6e7fc1a4e0ed70", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4edda548e89522b4df20e723e29c63f309857b10", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Microarray data accession numbers. Raw microarray data have been deposited in NCBI's Gene Expression Omnibus under accession number GSE45042." ] },{ "paper_id": "4ee0f8eb93dda0ff3512556fbb784c3859cc156f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Leishmaniasis is present in countries around the Mediterranean Sea where the insect vector is present. The ", "Numerous studies have suggested the importance of companion (pet) animals to the physical and mental well-being of their owners. 74 This includes the need to travel with ", "Publish your work in this journal Submit your manuscript here: http://www.dovepress.com/veterinary-medicine-research-and-reports-journal Veterinary Medicine: Research and Reports is an international, peer-reviewed, open access journal publishing original research, case reports, editorials, reviews and commentaries on all areas of veterinary medicine. The manuscript management system is completely online and includes a very quick and fair peer-review system. " ] },{ "paper_id": "4ef096e83734058dd9385a5d65b0c63c080df563", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Is RlmM dependent on rRNA substrate for closing the AdoMet pocket?", "Prior to methylation reactions, 200 nM rRNA (23S in vitro transcript or transcribed domain V) was suspended in 40 mM HEPES pH 7.6, 100 mM NH 4 Cl, 10 mM MgCl 2 , 12 mM b-mercaptoethanol, 20% glycerol and 0.1% Triton X-100 and warmed for 10 min at 50 C followed by 15 min at 37 C (9). A final concentration of 1 mM AdoMet was then added as the methyl donor followed by addition of Ni-purified RlmM to a final concentration of 100 nM. The reaction was carried out at 37 C for 90 min or as noted otherwise. Reactions were quenched in 50:50 phenol:chloroform followed by ethanol precipitation. Precipitated RNA was dissolved in H 2 O prior to primer extension. For time course analysis, 10 ml aliquots were quenched in 50:50 phenol:chloroform at 0 s (before enzyme addition), 30 s, 1, 2, 4, 8, 20, 45 and 90 min. Primer extension analysis was used to detect the modification.", "Of the other similar structures, archaebacterial fibrillarins take part in guide-mediated ribose methylation in rRNA and tRNA, RrmJ is a bacterial 23S rRNA 2 0 Oribose MTase and Nsp5 is involved in capping of viral mRNAs. Thus, similar structures are used for ribose methylation of a variety of substrates in viruses, bacteria and archaea using different mechanisms of substrate recognition.", "Pdb entries 4auk, 4atn, 4b17." ] },{ "paper_id": "4f03e55d6a48282637116273820d4114459abfb0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4f3e689f3806b2047b5f5a70df6ce9d3581dcc97", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Details and examples further describing the three disease emergence categories are provided in subsequent sections.", "Distinctly different from the above three disease emergence categories is the disease behavior that that normally plays at the population level. All diseases feature a certain degree of plasticity in terms of their behavior in time and space, responding to host demographic cycles, host immune status, spatial population structure, seasonality or health protection measures ( Figure 1 , numbers 1, 2 and 3).", "The drivers of disease emergence in a novel landscape facilitate access by existing pathogens to host resources elsewhere distributed. More complex scenarios involve introduction of infected host populations or infected vectors becoming newly established upon arrival." ] },{ "paper_id": "4f7e3be54c93d119c3a1ddb753aa5394878a2bbe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Besides performing clinical clerkships, students attended lectures held in classrooms located at the main teaching hospital (SMC). Thus, SKKUSOM students faced a greater risk than those of other medical schools with a school building separate from their teaching hospital.", "(1) ensuring student safety, (2) minimizing loss of student learning, and (3) reducing anxiety and concern on the part of staff and students. Details of SKKUSOM's actions are discussed below.", "At the end of May 2015, the first Korean patient with MERS was reported at the SMC, and several nearby patients were subsequently identified as having MERS." ] },{ "paper_id": "4f8881d84a2dc68828437d1778e841a3fbf6e2b4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4f8d0dce755f89c22c48c301fe55a457c8ed715b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The ", "who were active in notifying cases to FLU-CIN. S.J. Brett and P.J. Openshaw wish to acknowledge the support of the UK NIHR Biomedical Research Centre scheme." ] },{ "paper_id": "4fab9d6fcfd7daca9ed2e0f89c2433955d34e553", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4fd25cc19b106e5c8a69f89162ca37719192330d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Pneumocystis pneumonia highly unlikely The following findings 'do not' represent pathogens causative for lung infiltrates:", "Previous exposure to antifungal therapy may reduce the sensitivity of the galactomannan as well as quantitative PCR assays [103, 104] ." ] },{ "paper_id": "50005544cba05adf4b743e0ec11f39bd8d903cbd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "No potential conflicts of interest were disclosed.", "This work was supported by NIH grants AI089716 to CG and GM053396 to DJK.", "ADP ribosylation factor 1 ATG autophagy related BECN1 Beclin 1 BFA brefeldin A ER endoplasmic reticulum GTP guanosine triphosphate LC3 microtubule-associated protein 1 light chain 3 MEF mouse embryo fibroblast" ] },{ "paper_id": "500e585afac01e4b3847aa138db86b04352484c5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5036d9acb850bbb3705be78b3ab64dec35d68b27", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "History, signalment, and physical examination findings were recorded for all 78 cats examined. Laboratory analysis (<3 days before laparotomy) for all 78 cats included fecal parasitological examination, CBC, a serum biochemistry profile: albumin (ALB), b blood urea nitrogen (BUN), b creatinine (Crea), b alkaline phosphatase activity (ALP), b alanine amino transferase activity (ALT), b c-glutamyl transferase activity (cGT), b aspartate transaminase activity (AST), b total bilirubin (TBIL), b lipase activity (LIPA), b calcium (Ca), b phosphorus (P), b potassium (K), c sodium (Na), c blood coagulation profile including prothrombin time (PT) d (76/78) and partial thromboplastine time (PTT) d (76/78), serum total thyroxine (T 4 ) concentration, e free thyroxine (fT 4 ) concentration, e serum feline pancreatic lipase immunoreactivity (fPLI measured by Spec fPL \u00d2f ) [32] [33] [34] [35] (76/78), trypsin-like immunoreactivity (fTLI g ; 77/78), and FIV, h FeLV, h and feline coronavirus i testing.", "Diagnostic imaging included thoracic and abdominal radiographs g (69/78) and abdominal ultrasonography k (76/78).", "Cholangitis Score Pancreatitis Score n Median (Range) Median (Range) Median (Range) " ] },{ "paper_id": "50641a70bd884557e33cd969cd77a0f724f4dda6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A cross-sectional survey was conducted of qualified nurses between 18 April and 18 October, 2010. Qualified nurses attending continuing professional education courses at a large university in central London were invited to participate in the study. Potential respondents were given a study information sheet and a questionnaire by the investigator. Completed questionnaires were collected immediately by the investigator or returned by mail to the research team using Freepost addressed envelopes. Questionnaire completion was anonymous so that it was not possible to follow up non-response. Ethical approval was obtained from the University Ethics Committee.", "Further comparisons were performed to explore whether there were differences across the different items of knowledge and risk perception in the clusters.", "For the above reasons, the World Health Organization (WHO), United Kingdom Department of Health (DoH) [8] , United States Centers for Disease Control and Prevention (CDC), other healthcare professional organizations and many countries' government agencies [1, 9, 10] strongly recommend the annual seasonal influenza vaccination of HCWs. However, studies suggest that influenza vaccine uptake in HCWs is often low worldwide [11] [12] [13] [14] . For example, the overall seasonal vaccination rate in England for HCWs was 26 . 4% for the 2009/2010 season [15] . Nurses, as the group having the most patient contact, are more reluctant to be vaccinated than other HCWs [16] [17] [18] [19] [20] [21] [22] [23] ." ] },{ "paper_id": "509eaf8fb436b60e6d84da002b3630d62b39309e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Citation Lipkin WI. 2015. Middle East respiratory syndrome coronavirus recombination and the evolution of science and public health in China. mBio 6(5):e01381-15.", "The paper is important in two respects. First, the recombination event may have resulted in the evolution of a new lineage of MERS-CoV with different transmission properties. Additional field work in epidemiology and studies of recombinant viruses in culture and in animal models will be required to determine whether this proves true. However, the paper itself is evidence of an evolutionary advance in scientific expertise and transparency that is at least as important for microbiology and public health. China has come a long way since the emergence of SARS-CoV in 2002/2003.", "Recombination is common in coronaviruses and has been implicated in the emergence of pathogenic coronaviruses in poultry, cats, and pigs (2, 3). It would not be surprising, therefore, if recombination were to occur in MERS-CoV and to result in enhanced transmission or virulence. Wang et al. clearly demonstrate through bootstrap scanning and single-nucleotide polymorphism analyses that the viruses found in South Korea and China represent a recombinant virus that contains a clade B group 3 coronavirus sequence in the 5= portion of the genome and a clade B group 5 coronavirus sequence in the 3= end of the genome, with a site of recombination between nucleotide positions 17206 and 17311, a region that spans the junction between the ORF1a and S genes. They note that the recombination is evident in recent strains identified in human cases of MERS in Saudi Arabia and estimate that the recombination occurred in Saudi Arabia in the later months of 2014." ] },{ "paper_id": "50a6717377c416aadc6204e0e92f96d12ab4b0e7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This review will focus on the therapeutics currently available for treating viral hepatitis of all forms. In addition, the potential of new therapeutics and targeted inhibitor-based therapies against viral membrane-penetrating peptides and viroporins, a group of virally encoded proteins involved in facilitating replication and other specific steps in the viral life cycle, are also discussed.", "We further investigated the non-structural 2B protein of HAV, which was found to contain a stretch of 60 residues in its C-terminus, and which has viroporin-like activity. 97 A combination of crosslinking studies, biophysical assays and simulation was employed to determine that 2B probably forms dimers and generates ;3 nm pores in membranes. The resulting alteration of membrane permeability is thought to be essential for HAV replication. It is probable that inhibition of the membrane activity of 2B would negatively impact the viral replication process. Thus, a treatment regimen against HAV, which includes a combination therapy targeting VP4 and 2B, could be a very promising and effective approach.", "Given the essential roles played by viroporins and viral membrane penetrating peptides in enhancing several aspects of the virus life cycle, targeted inhibitor therapy holds promise for development of virus-specific drugs. Establishing the commonalities between the structures and functions of these membrane active components might make it easier to design small molecule inhibitors. Finally, given the promise of p7-based therapy against HCV, it is essential to pinpoint such potential candidates in other hepatotropic viruses, in order to expand therapy options against chronic and acute viral hepatitis. " ] },{ "paper_id": "511cd67bbeb3835b5feb25ace6582b7d758debe4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Human rhinoviruses \u2022 Human rhinoviruses (RVs) are the primary etiological agents of the common cold, but can cause serious illness and increased hospital admissions in immunocompromised individuals or those with pre-existing respiratory conditions.", "This work was supported by a funding award from the Chief Scientist Office (ETM/389) awarded to PG Barlow and C Stevens. FH Sousa is supported by a 50th Anniversary PhD studentship from Edinburgh Napier University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.", "Vitamin D is known for its positive effects on bone mineralization and calcium metabolism, and severe deficiency has classically been linked to rickets. Mounting evidence now points to a key immunomodulatory role for vitamin D and to a link between vitamin D deficiency and increased susceptibility to acute viral infections [90] . Furthermore, despite conflicting reports and heterogeneity within studies, a recent systematic review encompassing 10933 participants in 25 randomized controlled trials concluded that vitamin D supplementation reduced the risk of acute respiratory infection, with stronger protective effects in patients with baseline 25-hydroxyvitamin D levels <25 nmol/l [91] .", "No writing assistance was utilized in the production of this manuscript." ] },{ "paper_id": "51485c1b5e3ce7050422a81c6a16ed00faa768fd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Moreover, lower respiratory infections (LRIs), including acute lower respiratory tract infections, pneumonia, atypical pneumonia, bronchitis, bronchiolitis, and severe acute respiratory syndrome (SARS), continue to threaten the health of children worldwide and especially in developing countries, where poor nutrition prevails and access to health care is scarce [11] .", "Student's t-test or one-way analysis of variance (ANOVA) was used for normally distributed variables, while the Mann-Whitney test was used for variables not normally distributed. Values of p < 0.05 were considered as significant.", "Re f e r e n c e s" ] },{ "paper_id": "5157ee00e0ee6c807ca321c405baf2d8b9bd8a4f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Barral-Netto, M., Barral, A., Brodskyn, C., Carvalho, E. M., and Reed, S. G. (1995) . Cytotoxicity in human mucosal and cutaneous leishmaniasis. Parasite Immunol. 17, 21-28. Basu, R., Roy, S., and Walden, P.", "Interestingly, CD8 + T cells do not only participate in primary responses to L. donovani, but are also the major mediators of resistance upon reinfection (Stern et al., 1988) . Indeed, protection was abrogated following CD8 + T cell but not CD4 + T cell depletion.", "www.frontiersin.org" ] },{ "paper_id": "517698251b94fac6d80edcc4644e2448a4efd4ef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "and recursions for the p-variables reduce to:", "Supplementary data are available at Molecular Biology and Evolution online. ", "By separating out the first and last term in the sum above, and using the y-variable recursions, a nearly direct recursion can be written for the x-variables:" ] },{ "paper_id": "51a24b884e01df122d889f1133e7727e2478be24", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The exchange of genetic material generates variations among natural populations and demonstrates their role in evolution and adaptation (Awadalla 2003) . Populations of RNA viruses usually harbor genetic diversity due to high mutation rates, recombination, turnover rates, and large variability (Simon-Loriere and Holmes 2011). Genetic RNA recombination contributes to viral evolution and biogenesis (Koonin, Dolja, and Krupovic 2015) , evident in many groups of plus-sense RNA viruses in animals (Weiss and Schlesinger 1991; Graham and Baric 2010; Lukashev 2010) , plants (reviewed in Bujarski 2013) , and bacteria (Palasingam and Shaklee 1992) , in negativesense (Han and Worobey 2011) , double-stranded (Krupovic, Dolja, and Koonin 2015) , and retroviruses (Delviks-Frankenberry et al. 2011) , and in defective-interfering RNAs (Sandoval et al. 2008) .", "The PCR-generated cDNA products were cloned into the pGEM-T Easy vector (Promega). Digestions with strain-specific restriction enzymes were used to select the insert-carrying cDNA clones and to confirm the ratio of F to R strains in the coinoculated plants. The insert-carrying clones were sequenced using the Sanger protocol at The University of Chicago DNA Sequencing and Genotyping Facility (http://cancer-seqbase.uchi cago.edu/).", "Supplementary data are available at Virus Evolution online.", "Column four presents the corresponding P values that reflect the reliability of the Pearson correlation coefficient. A P value of 0.05 and lower means a 95 per cent chance the stated correlation being correct. The fifth column displays the degrees of freedom, which was used to calculate the correlations; they simply represent the number of fragments being analyzed minus 2.", "A few sites that were polymorphic in the GenBank sequences proved to be monomorphic in our hands. It is likely that the parental strains had become monomorphic through genetic drift. The monomorphic sites included position 3194 in RNA1, positions 1920 RNA1, positions , 1984 RNA1, positions , 2430 RNA1, positions , and 2582 in RNA2, and positions 1324 and 1350 in RNA3. These sites were not scored for recombination." ] },{ "paper_id": "51a25686ff156fa8b99d72204eb04a10079a0a74", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "51d37c55030f7c7570f83c8a75f5e6a97209a6c5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study was conducted in accordance with the amended Declaration of Helsinki and was approved by the Institutional Review Board of Seoul National University Hospital (protocol no. H-1705-019-851). The requirement for informed consent was waived because of the retrospective study design and because all patients records and information were anonymized prior to analysis.", "Isolation beds were isolated with walls and a door, whereas open beds were divided by curtains. The patient to nurse ratio was 2:1 during the day and evening and 3:1 at night. Routine cleaning of the floors was performed every day with 4% sodium hypochlorite and was done more frequently when visual contamination was observed. When a patient left the ICU bed, every surface of the patient's medical equipment was cleaned with 50% benzalkonium chloride.", "Categorical variables are described as numbers and percentages and compared using either the chi-square test or Fisher exact test. Numerical variables are described using the median and interquartile range (IQR) and compared using the Mann-Whitney U-test. IRs are described as numbers per 1,000 patient-days with 95% confidence intervals (CIs) and compared using Poisson regression analyses or negative binomial regression analyses. All statistical analyses were performed using STATA version 13.0 (Stata Corp., College Station, TX, USA). The P-values of less than 0.05 were considered statistically significant." ] },{ "paper_id": "51fff92f21f050e40ae7214b2b0b3a51e9079918", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data were described using percentages and means (SD). The differences between the proportions were compared using chi-square test. Data were analyzed using IPM-SPSS version 23. A P value of less than .05 was considered as statistically significant.", "A cross-sectional study was conducted among resident doctors who were working in MOH and university teaching hospitals in Jordan during the period September 2017 to January 2018. The 4 main MOH hospitals out of 32 hospitals and 2 teaching hospitals that have residency programs were selected. All residents in the selected hospitals from all specialties including emergency medicine, internal medicine, pediatric, and family medicine were visited by the researcher and invited to participate in this study." ] },{ "paper_id": "52069d14f038d493dce5d6cc1fdcdc7c1f0823f9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "52566dccb4bd8044edc87b1a0aa268320a6ea3d4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Full characterization for all the compounds described below can be found in the Supplementary Data.", "A total of 102 unrelated Centre Etude Polymorphism Humaine DNA samples were obtained from the Coriell Institute of Medical Research (http://locus.umdnj.edu/) after specifying that the DNA samples should be used for research purpose only. The list of templates used is available at http:// snp500cancer.nci.nih.gov.", "I FL1 R 1 -R 7 \u00bc H; n \u00bc 0 0.97 0.0031 313 II FL2 R 1 \u00bc R 3 \u00bc R 4 \u00bc R 5 \u00bc R 6 \u00bc R 7 \u00bc Cl; R 2 \u00bc H; n \u00bc 0 0.93 0.0012 775 III FL3 R 1 \u00bc R 3 \u00bc R 5 \u00bc R 6 \u00bc Cl; R 4 \u00bc R 7 \u00bc H; R 2 \u00bc CH 3 ; n \u00bc 0 1.04 0.0010 1040 IV FL4 R 1 \u00bc R 3 \u00bc R 5 \u00bc R 6 \u00bc Cl; R 4 \u00bc R 7 \u00bc H; R 2 \u00bc CH 3 ; n \u00bc 1 1.90 0.0260 73 - - - - - - - - - - - - - - - - -4 - - - - - - - - - - - - - - - -2 - - - - - - -3 - -5 3'-GCTGAGCCGGGAACGGGCGGTGTAACCGTGGCTGACACTGA -5' |||||||||| 5'-Q-CTCGGCCCTT Dye", "Apurinic/apyrimidinic (AP) sites in DNA arise via spontaneous or mutagen-induced hydrolysis of the N-glycosylic bond, or through the repair activity of DNA glycosylases (10) . If left unrepaired, AP sites are potentially lethal or mutagenic (11). To cope with the deleterious consequences of AP sites, organisms possess AP endonucleases that initiate the repair of these DNA lesions (10) . Class II AP endonucleases initiate repair by catalyzing the hydrolysis of the 5 0 -phosphodiester of an abasic site to generate a 3 0 -OH group and a 5 0 -abasic phosphate residue (10) . The substrate specificity of human apurinic endonuclease on synthetic substrate analogs has been reported previously (12) ." ] },{ "paper_id": "528411eebd9d3c1b16ab5ec425724551e7837c5d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Venous blood gas analysis revealed a mixed acid-base disorder with pH 7. 43 An abdominal focused assessment with sonography for trauma scan revealed a moderate amount of echogenic fluid with small suspended particles, diagnosed as a septic exudate on cytology and later confirmed with bacteriologic culture to contain E. coli.", "One day after surgery, the cat developed mild dyspnea. A thoracic ultrasound revealed minimal pleural and pericardial effusions. Echocardiography revealed mild inhomogeneity of the ventricular wall, suggestive of possible myocarditis, and minimal pericardial effusion. Pleural fluid real-time PCR for feline Corona virus was negative. Cytology revealed a septic exudate, confirmed to be hemolytic E. coli on bacterial culture. Blood cultures were negative. The pyothorax was treated with intermittent thoracocentesis followed by placement of bilateral chest drains and intermittent lavage during 4 days. Bacterial culture and sensitivity revealed that E. coli cultured from both body cavities was sensitive to marbofloxacin but E.coli cultured from the peritoneal cavity was resistant to ampicillin and rifampicin, and E.coli cultured from the pleural cavity was resistant to all penicillins and 1st-and 3rd-generation cephalosporins. Monotherapy with marbofloxacin was, therefore, continued.", "Necropsy, performed with the owner's consent, revealed mild myocardial arteriosclerosis, and bilateral diffuse adrenocortical hyperplasia and hypertrophy with moderate cytoplasmic vacuolization, but no lesions explaining the cause of death were identified." ] },{ "paper_id": "52cc80efbb69d917fa6d4ad3f34f73124ea27ee8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Records from subsequent visits were then examined to determine if any follow-up testing was performed to confirm the positive FeLV results. For cats that were euthanased or known to have died, the date of death was recorded. For all other cats, the most recent date the cat was known to be alive (either through a clinic consultation or other forms of client communication) was recorded.", "Separate multivariable logistic regression models were then constructed for FeLV and FIV to identify risk factors associated with test positivity. Univariable analyses were performed using a \u03c7 2 test (for variables with more than five observations in all cells) and Fisher's exact test (for variables with fewer than five observations in at least one cell) to identify risk factors associated with the outcome of interest at a P value <0.2 for inclusion in the multivariable analysis.", "Most veterinary practices never (70/112; 62.5%) or rarely (29/112 or 25.9%) vaccinated against FeLV. Only an estimated 0.2% of cats were vaccinated during the 2015 calendar year with the most common reasons being requested by the owner (29.7%), exposure to infected cats (25.3%), routine vaccination (25.3%), cat at risk being outdoors (5.4%) and other reasons (21.3%). The low perceived prevalence of disease was highlighted as the main reason for not vaccinating against FeLV in the Likert-rating questions (Table 1) and free-text survey comments." ] },{ "paper_id": "52e323d1ed2d4a0dfbe4f68d15d20430a33de8bf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Raw and summarized microarray have been deposited to the NCBI GEO and are available under accession numbers GEO:GSE65075. H K / H K 6 : 2 P a n / P a n 6 : 2 H K / P a n 6 : 2 P a n / H represented as mean with SD. An asterisk (*) indicates statistically significant differences (P < 0.05) between HK wt and HK +II virus.", "The quantitative real-time PCR-based cytokine/chemokine analysis (RT 2 Profiler PCR Array; human NFkB signaling targets [PAHS-225Z]; QIAGEN) was conducted according to manufacturer's protocol. Data analysis was conducted by RT 2 Profiler PCR Array Data Analysis software on QIAGEN webpage.", "For determination of virus titers and cytokine/chemokine protein levels, mouse lungs were collected in PBS, homogenized using a FastPrep-24 homogenizer with Lysing Matrix D (both from MP Biomedical), and adjusted with PBS to obtain a 10% tissue homogenate. The samples were cleared of debris, and supernatants were used for virus titer determination in standard plaque titration and for measuring the concentration of interleukin 6 (IL6), tumor necrosis factor (TNF), and chemokine (C-C motif) ligand 2 (CCL2) using a custom multiplex cytokine/chemokine assay (Millipore) analyzed with a Luminex xPOTENT 3.1 system (Bio-Rad) following manufacturer's protocol.", "For analysis of lung physiology upon influenza virus infections, animals were anesthetized with 1 mg/ml xylazine (Vedco) and 7 mg/ml Euthasol (Virbac) prior to surgical intubation and attachment to the flexiVent FX1 small animal ventilator (SCIREQ). Using the ''mouse inhaled dose response'' script, baseline and responses to 25 mg/ml acetyl-b-methacholine (Sigma-Aldrich) were gathered. Software-generated values for the respiratory system resistance (Rrs), compliance (Crs), and elastance (Ers) and Newtonian resistance (Rn), tissue damping (G), and tissue elastance (H) were recorded. The mean for each was calculated for each animal prior to obtaining the mean and SD of the mean for the group." ] },{ "paper_id": "5322d3b9f5ee17d5b931f0c32173125d6a7304ed", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We washed cells in PBS and lysed them in radioimmunoprecipitation assay buffer (25 mM Tris, pH 7.6, 150 mM NaCl, 1% NP-40, 1% Nadeoxycholate, and 0.1% SDS) with added protease inhibitors. We resolved", "Abbreviations used in this paper: BiP, immunoglobin-binding protein; FRT, ferritinlike protein recombination target; hIre1, human Ire1-\ue061; MEF, mouse embryonic fibroblast; qPCR, quantitative real-time PCR; RIDD, regulated Ire1-dependent decay; Tm, tunicamycin; UPR, unfolded protein response." ] },{ "paper_id": "5335dd626c2c607a3a6f7abefb0d341f0fd63164", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "533f8d39de2e16fb92614d2441621e8fddd85bbe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Abbreviations: see Table 1 ." ] },{ "paper_id": "53c5b444db5bde8e975a22df9e3c80250e8ad3d1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "53cf48ec1726de4e093378e48a74632bf485cca6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/)", "NOTE", "Virology" ] },{ "paper_id": "53f05daf7342372ab5fbeb2f4f5710254fcad893", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "53f9b02ce4cc149507a9d402dcf9d4c191b3bb29", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All human protein sequences were retrieved from Refseq database ftp site (ftp://ftp.ncbi.nlm.nih.gov/genomes/H_ sapiens/protein/) and essential proteins were subjected to BLASTP search against the human proteins with BioEdit. Only the non-hit proteins at e-value cut off 10 \u221210 , were ", "Drug target identification by subtractive genome analysis approach selected as non-homologous proteins to avoid any functional similarity with host proteome.", "As no exact protein data bank (PDB) structure was available for dnaE in PDB, it was subjected to BLAST search against PDB structures using 0.001 e-value cut off. The template for homology modeling was chosen considering X-ray diffraction resolution and highest sequence similarity. Homology modeling was done on ESyPred3D server. 43 " ] },{ "paper_id": "5407b1aabede9eeed76c59a7b890be9f513712b7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Primers for EGFP-P1 fusion", "ARTICLE HISTORY", "To assess the reproducibility of our pseudoviral neutralization tests, we selected sera with high, medium, and low titers in the assay development, with each sample tested six times. The reproducibility of pNT assay was evaluated by calculating the coefficient of variation using Graph Pad Prism 5.0." ] },{ "paper_id": "541efff1146fcb123189ad615099b67769ed41c5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The interviews were transcribed and translated into English. The English translations were thematically coded using the qualitative research software, NVivo 10. Data on specific topics of interest were systematically compared across interviews and variations by gender and site noted. ", "American people through the United States Agency for International Development (USAID).", "Six types of respondents (aged 20 years and above) were included in the study, for a total 67 interviews:" ] },{ "paper_id": "543ac2431685616436dfe9f7ff063a02a741686f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sophie L. Nixon https://orcid.org/0000-0003-4375-434X" ] },{ "paper_id": "544a005c6288491bc6229435fddcdec62d6e24b9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "544a170a18bae9bf44c531c2b0b4bdc5e85ea8f5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "54560eb4cc2e0affe21b8b21435c907232764c8a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors declare that there is no conflict of interests regarding the publication of this article. ", "Coronaviruses belong to the Coronavirinae subfamily. Currently, this subfamily is classified into the four genera Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus, which fall into distinct groups on the phylogenetic tree. (5, 11, 26) . The taxonomy of swine coronaviruses is shown in Table 1 . ", "PEDV is easily inactivated by heating to 71\u00b0C for 10 min. At lower temperatures, pH is a factor in PEDV inactivation. The resistance of PED virus in different pH values is given in Table 3 . PEDV-inactivating disinfectants are oxidising agents, bleach, 2% phenolic compounds, 2% sodium hydroxide, formaldehyde and glutaraldehyde, 4% sodium carbonate, ionic and nonionic detergents, iodophors in 1% phosphoric acid, and lipid solvents such as chloroform (15, 24) . " ] },{ "paper_id": "545cc28cf80d7f18232d1eafdcd3a7e9680a4b9f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "RNA interference (RNAi) is a short, double-strand RNA induced-process that can target the mRNA of a specific sequence for degradation [9, 10] . Post-transcriptional gene silencing can be mediated by endogenous microRNAs (miRNAs), exogenous small interfering RNAs (siRNAs), and short hairpin RNAs (shRNAs). RNAi technology is recognized as a promising, novel nucleic acid-based tool for use against various diseases, including cancer, infectious diseases and genetic disorders. RNAi reagents have also been reported to potently and specifically inhibit the replication of different viruses, including HIV, HBV [11] , HSV [12] , SAR-CoV [13] , influenza virus [14, 15] , coxsackievirus [16] and others. Thus, the development of RNAis as possible antiviral agents for hantavirus infection is of considerable interest [17] .", "At the experimental point of 5 dpi, the brains, lungs and kidneys were harvested, weighed and homogenized into a ~10% (weight/volume) suspension in test medium. The homogenates were frozen and thawed twice and centrifuged at 3000 rounds per minute for 10 min. The virus titers were determined as described above.", "Oligos Sequences", "All of the data were analyzed with SPSS 17.0 software. The data are expressed as the mean\u00b1SD for all experiments. Oneway ANOVAs were used to assess the significance of the differences between the means. P values below 0.05 were considered statistically significant.", "This study was approved by the Ethics Committee of Wuhan University School of Medicine. All work with infected mice was performed in the Animal Biosafety Level 3 (ABSL-3) Laboratory of the Animal Research Center at Wuhan University and was humanely conducted in compliance with the Chinese Animal Protection Act and the National Research Council criteria." ] },{ "paper_id": "54e77bff1912076bccf12a6b099e48a59f634d5f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "54e82ae1126dc9eed820d7a255cb4edca68a9f82", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Characterisation of the monoclonal antibody was conducted by indirect immunofluorescence assay (IFA). For IFA, Vero cells inoculated with PEDV, ST cells inoculated with transmissible gastroenteritis virus (TGEV) or porcine respiratory coronavirus (PRCV), and MA-104 cells inoculated with porcine rotavirus were grown in cell culture chamber slides. The slides fixed with cold acetone were incubated with the PEDV mAbs at 37\u00b0C for 45 minutes. After washing, the slides were reacted with goat antimouse IgG conjugated with FITC at 37\u00b0C for 45 minutes and examined under a fluorescence microscope.", "The sensitivity of ICA was evaluated by comparing the detection limit using real-time RT-PCR as previously described with some modifications. 13 Briefly, real-time RT-PCR was carried out in a total volume of 20 \u00b5l containing viral RNA, PEDV forward (5'-CGC AAAG ACTG AACC CACTAATTT-3') and reverse (5'-TTG CCTC TGTT GTTA CTTGGAGAT-3') primers, probe (6-carboxyfluorescein", "Piglets inoculated with the PEDV strain experienced moderate to severe diarrhoea starting on 1 dpi. Most infected piglets showing clinical signs died between 2 and 9 dpi except for one piglet, which recovered from clinical signs at 9 dpi and survived during the experimental challenge (Table 4 ). In a comparison of the diagnosis methods, examination with the ICA kit using swab samples showed consistent results with real-time RT-PCR in identifying PEDV." ] },{ "paper_id": "550738a7abf0b8378627958a3a5c429f36586d69", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Such issues are not limited to infectious diseases. For example, while it has long been known that human exposure to unsafe levels of methylmercury is predominantly through dietary consumption of contaminated fish and shellfish, recent technological advances in high-resolution mass spectroscopy now provide a means to \"fingerprint\" the contributing mercury and determine its source [26] . For example, many locations are impacted by both point-source releases as well as nearly ubiquitous atmospheric fallout of mercury. This new fingerprinting capability has extended the capacity to determine which mercury sources contribute to fish, wildlife, and human exposures, thereby informing environmental decision makers of the most effective means to reduce such exposures.", "The US surveillance program for HPAI in wild birds is also seen as a model of One Health collaboration through its communication and outreach efforts to stakeholders and the public. The Interagency Steering Committee and its member agencies have produced numerous fact sheets, frequently asked questions, webinars, presentations, and web pages to keep scientists, policy makers, industry, and the public up-to-date on the global status of avian influenza and the US HPAI surveillance program, on how producers can minimize the risk of transmission to poultry, and on how hunters and poultry workers can minimize the risk of acquiring diseases from handling birds.", "As a demonstration of an interconnected system, bats contribute up to 50 billion USD annually to the United States of America (US) agricultural economy through their part in insect control [4] . However, the emergence of white-nose syndrome has resulted in the death of over 6 million bats in North America resulting in a marked decrease in insect control [3] . Additionally, while bats are critical components of world ecosystems, they are also potential reservoirs of zoonotic viruses, including rabies, Marburg virus, and Nipah virus [27] . In today's age of dynamic changes in the emergence of infectious diseases associated with increasing interactions among humans, domestic animals, and wildlife, the need to consider these interactions fully becomes crucial for effective management that balances the needs of humans, animals, and the environment." ] },{ "paper_id": "551d200fafe21b575108018aeb0f39b995c99dce", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "55eb127fae1e7e297c11baca53a758cac2a77329", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The human colon cell line Caco-2 was purchased from the Type Culture Collection of the Chinese Academy of Sciences, Shanghai, China. Cells were placed into 75 cm 2 tissue culture flasks and grown at 37\u2103 under a humidified 5% CO 2 atmosphere in DMEM medium with high glucose, 10% FBS, 100 units/mL penicillin and 100 units/mL streptomycin.", "The", "In vitro anticancer efficiency study" ] },{ "paper_id": "55f664e8e3b18388964ec14c61a7b655b786ef31", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This research was submitted to our university institutional review board and was approved. The IRBNet ID is 1083099-2.", "As pediatricians, we follow the guidelines published by the American Academy of Pediatrics. The 2014 guidelines dealing with evaluation and management of viral bronchiolitis promote supportive care, and note that routine radiographic or laboratory studies are not necessary. 3 While these guidelines are paramount to treating viral illness, it is imperative that the physician recognizes at what point further investigation is warranted. Missing a secondary pneumonia could result in delay in antibiotic treatment, transfer to the pediatric intensive care unit (PICU), or intubation.", "Susan Flesher https://orcid.org/0000-0002-3208-7097" ] },{ "paper_id": "562e3acb22b8ed4cf3edec403ade2e3e425af531", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Three of the 12 HBV-and HLA-related SNPs (Fig. 2B , dotted lines; rs9276370, rs3128917, and rs9380343) also showed significant differences between LWK in Africa and GIH in South Asia ( Table 2 ; P < 0.001). In contrast, we found the allele frequency of NPC-related SNPs (18) (19) (20) to be relatively stable among different populations (Fig. 2C ).", "Among two HBV-and immune-related SNPs in the CFB and CD40 regions (14, 15) and three hepatitis C virus-related SNPs in the IFNL4 regions, (16) (17) (18) allele type differences can be found between Africa and Europe or between Africa and South Asia ( Fig. 2A ). All these immune-related SNP genotypes differed significantly between Esan in Nigeria and Toscani in Italy and between Luhya in Webuye, Kenya (LWK) and Gujarati in India (GIH) ( Table 1 ; P < 0.001).", "Based on a literature review, 12 HBV-and HLArelated SNPs, (7) (8) (9) (10) (11) (12) (13) five hepatitis-and immune-related SNPs in complement factor B (CFB), clusters of differentiation molecule 40 (CD40), and interferon lambda 4 (IFNL4) loci (14) (15) (16) (17) (18) , and five nasopharyngeal carcinoma (NPC)-related SNPs in HLA regions (19) (20) (21) were selected for this analysis (Tables 1 and 2 ). These SNP data from around the world were downloaded from the phase 3 data of 1,000 genomes (http://www. 1000genomes.org/). (22) The subjects participating in the 1,000 genome project were older than 18 years and had three out of four grandparents who identified themselves as members of the group. The location of the 26 populations evaluated in the 1,000 genomes are shown by abbreviation on a global HBsAg prevalence map reported by Hou et al. (2) (Fig. 1) . The allele frequencies of different geographic groups in viral hepatitis-related SNPs and NPC-related SNPs are illustrated in Fig. 2 . The SNP genotype differences between groups are listed in Tables 1 and 2 . We used interactive chi-square tests to calculate the difference in genotypes between groups (http://quantpsy.org)." ] },{ "paper_id": "5644db6f53b8425eedbdb33ae2c8924e02cdf447", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5650690daf962117b9831c42178ffd6a6a969300", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.00515-12/-/DCSupplemental. Figure S1 , TIF file, 0.1 MB. Figure S2 , TIF file, 0.2 MB. " ] },{ "paper_id": "5667ab8a8565a702defd98b5736e32a3bb9c5ad4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "567a4ae944e5286ed25f8ab20dc098ed570b74d8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5699971f98dab3c45f237878901e4c8b247bc234", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Methods. This was a retrospective study at a tertiary care adult and pediatric teaching hospital. Study patients met a priori criteria for definite or possible nosocomial respiratory viral infection.", "This was a retrospective, Institutional Review Board-approved study of patients who developed laboratory-confirmed respiratory viral infections and whose symptoms began during hospitalization at Rhode Island Hospital and Hasbro Children's Hospital (HCH) between April 1, 2015 and April 1, 2016. Rhode Island Hospital is licensed for 719 beds, 87 of which are licensed for HCH. The two hospitals are located in adjoining buildings on the same campus as part of the Lifespan Hospital System." ] },{ "paper_id": "56ac158658a5eb9ee2efbc07d6ec1474417fe8ba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Patients and samples A prospective study was performed of 28 children, aged from 5 months to 14 years (12 males and 16 females), hospitalised for PPE between April 4, 2007 and March 30, 2009 in the paediatric intensive care unit of Hospices Civils de Lyon (Lyon, France). This study was approved by all participating institutional review boards (CE 06-139) and signed informed consent was obtained from all parents. 28 nasopharyngeal aspirates were obtained using disposable mucus extractors within 48 h of admission. 25 pleural effusion samples were collected at the time of chest drain insertion. The samples were kept frozen at -70uC until further study.", "This study reports the description of replicative TTMV-LY isolated from parapneumonic effusions of children hospitalised with PPE, suggesting a potential role of the virus in the pathogenesis of pneumonia.", "A pathogen discovery protocol based on random RT-PCR was performed on the five negative pleural effusion samples, and several short sequences related to TTMV were obtained for three of them. The characterisation of TTMV required the amplification and sequencing of the full-length virus genome.", "Taken together, these results suggest that TTMV-LY isolates can invade the alveolar cells, where they replicate and induce innate immune imbalance in the respiratory tract. Further studies aimed at understanding the physiopathological implications of TTMV as an aetiological agent in respiratory diseases are necessary, as required for every newly discovered pathogen. These investigations would allow to us learn about the presumed need to enlarge the range of researched pathogens to the anelloviruses in the case of PPE, in order to improve the efficiency of diagnosis and treatment of this pathology." ] },{ "paper_id": "56f69c9790f32dd7649fa2e14be26ae099321ee6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "570064e6a308ec28efcc76ef74ba3f0e6ea5e5a5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The author(s) received no financial support for the research, authorship, and/or publication of this article. ", "In silico screening of DPP-4 inhibitors Virtual screening has been seamlessly integrated into drug discovery and development 75 and its success significantly relies on compound library, 76 especially the structural diversity of compound library. 77 For instance, microalgal metabolites were screened for DDP-4 inhibitors. 78 Compared with the synthesized chemicals, natural compound libraries generally consist of more structurally diverse compounds than their synthetic counterparts, 79 providing a better screening resource. As such, numerous studies have adopted various natural compound libraries to find novel DDP-4 inhibitors as listed in Table 2 .", "Traditional Chinese Medicine Database (TCM Database@Taiwan) Chen 80 Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database (NPACT)" ] },{ "paper_id": "571e8706c0aff7482c60e60cad9d1334c917df12", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "idly than do boas, which may survive for months or years after symptom onset if provided with supportive care. Although there is evidence that IBD is transmissible, the precise mode of transmission is unknown (3) . Conclusive identification of an etiologic agent or agents has the potential to enable IBD treatments, vaccines, diagnostics, and prevention policies.", "In addition to being worthy of study in their own right, animal viruses are of great relevance to human health. The simple reason for this is that humans are animals, and many viruses that infect other animals also infect humans. Some of the most medically important human viral pathogens originated from animals or have animal reservoirs, including influenza viruses, HIV-1 and -2, severe acute respiratory syndrome (SARS) coronavirus, henipaviruses, West Nile virus, rabies virus, hantaviruses, filoviruses, and arenaviruses. Furthermore, animal viruses and their hosts often provide excellent models for the study of pathogenic mechanisms, immune response to infection, host-pathogen interactions, treatments, and vaccines." ] },{ "paper_id": "5738e88fe3a742f9f6f69919bd4e6b094d52eded", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The outbreak of the SARS (severe acute respiratory syndrome) epidemic in 2003 exposed serious deficiencies in Taiwan's health care and medical education systems. 1 The Department of Health (DOH), Executive Yuan therefore focused effort on implementation of the \"Project of Reforming Taiwan's Medical Care and Public", "Senior professors and trained lectures also hosted CbD meetings five times each", "Rarely (1) Occasionally (2) Often (3) Frequently (4) Always (5) -outpatient department (OPD) teaching training 6. Articles should list each author's contribution individually at the end; this section may also include contributors who do not qualify as authors. 7 . Any checklist and flow diagram for the appropriate reporting sttement, e.g. STROBE (see below). 8 . Any article that contains personal medical information about an identifiable living individual requires the patient's explicit consent before we can publish it.", "The expectations of the early year's postgraduate training of doctor are that residents are competent in the six-core competencies." ] },{ "paper_id": "5777ec2785cb535789796e239cc3627e92e24b83", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "using single stranded G template from E. coli JM103 and screening plaques by differential hybridization. The following oligonucleotides were used for mutation of El (with mutated nucleotides underlined) :", "The Journal of Cell Biology, Volume 115, 1991", "NIZZ : 5'-AAAGAGTATATCTTATTTATAACTG-3' ; T133 : 5'-GTTGTTCTTAATTATAAATACTTCAG-3' ; QI37 : 5'-CATAATACTTATATATGGCTATGC-3' ; mlins : 5'-ACTGCATTCTTGATAATATTGTTCTTAACC-3 ; and LQ30 : 5'-CTGCATTCTTGCAGTTCTTAACCA 3 ." ] },{ "paper_id": "57a30fc4f036048830b77fa87c64358c48c946d6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A chest radiograph showed multi-node and patchy consolidation in the lower and middle lobe of both lungs on 4 February (Figure 1 (a)), with rapid progression of groundglass opacities and consolidation in both lungs on 6 February ( Figure 1(b) ).", "The authors declare that there is no conflict of interest. " ] },{ "paper_id": "57b32baae9c8cfd1be336a341fe0df2a55ad57bb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistics. The Student's t test was used for a comparison of the means between sample groups. Error bars represent one SD.", "Antibodies. The following monoclonal antibodies were used for flow cytometry: PE-conjugated anti-TCR \u2424 (clone H57-597), hamster anti-IgG (clone Ha4/8), rat anti-IgG (clone R35-95), anti-CD3 (clone 17A2), anti-V \u2424 8.1,8.2 (clone MR5-2), and anti-V \u2423 2 (clone B20.1); FITC-conjugated anti-CD44 (clone IM7), anti-IgG (clone R35-95), anti-CD3 (clone 500-A2), anti-CD4 (clone GK1.5), anti-CD8 (clone 53-6.7), anti-TCR \u2424 (clone H57.597), and anti-CD45RB (clone 16A); biotin-conjugated anti-TCR \u2424 (clone H57.597), anti-CD49d (clone R1-2), anti-IgG (clone R35-95), anti-V \u2424 8 (clone MR 5-2), anti-CD45R (clone RA3-6B2), anti-CD8 (clone 53-6.7), anti-V \u2423 2 (clone B20.1), anti-CD4 (clone RM 4-5), anti-CD45RB (clone 16A), and anti-CD62L (clone MEL-14); and purified anti-CD16/CD32 (Fc \u2425 III/II receptor, clone 2.4 G2). All monoclonal antibodies were purchased from BD PharMingen except anti-CD3, which was purchased from Caltag. Biotin-conjugated primary monoclonal antibodies were detected by streptavidin-conjugated Tricolor from Caltag.", "Splenocytes were purified over a lympholyte M gradient (Cedarlane) and RBCs were lysed before staining. LNs (cervical, inguinal, brachial, and axillary) were teased with tweezers and filtered through wire mesh (Small Parts) to create a single-cell suspension. In some experiments, cervical and inguinal LNs were harvested separately." ] },{ "paper_id": "57b3f365b56a5db10967e1e3f16ade5a85eb296d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All data were entered into a standardised, secure REDCap (Research Electronic Data Capture, Vanderbilt University, Nashville, Tennessee, USA) database. 13 We performed data quality checks on a minimum of 10% of the charts and verified data from all case report forms after entry.", "Nasal and throat swabs were collected and combined in transport medium (M4RT, Remel, USA), aliquoted into MagMAX Lysis/Binding Solution Concentrate (Life Technologies, USA), snap-frozen and then stored at \u221280\u00b0C. Aliquots were shipped on dry ice to Nashville, Tennessee, USA, and were tested by RT-PCR for 11 viruses: RSV; human rhinovirus (HRV); human metapneumovirus (HMPV); influenza (influenza) A, B and C; parainfluenza virus (PIV) 1, 2 and 3; adenovirus (AdV) and Middle East respiratory syndrome coronavirus (MERS-CoV). [14] [15] [16] Blood was placed directly onto filter paper and air dried for \u226530 min before storage at room temperature and kept dry through shipment to ZRT Laboratory (Beaverton, Oregon, USA) for 25(OH)D (vitamin D) level measurement (techniques published previously). 17 statistical analysis Descriptive statistics were presented as frequency (percentage) or median and IQR where appropriate.", "Written informed consent was obtained from parents or guardians.", "Here, \u03c0 is the proportion of the Amman population that is eligible to be sampled, which accounts for the market share m and the sampling intensity (5 days out of 7):" ] },{ "paper_id": "57b88add1645a89614742dc32b0e11922c5f37d2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Immunohistochemistry was performed using formalin-fixed, paraffin-embedded tissues. Four \u03bcm-thick sections were cut and dewaxed in xylene, rinsed in graded ethanol, and rehydrated in distilled water. After antigen retrieval with sodium citrate buffer (10 mM sodium citrate, pH 6.0), endogenous peroxidase activity was blocked with 3% H 2 O 2 . Then the sections were added with the appropriate antibody at appropriate dilution, then DAB staining solution was added. The sections were counter-stained with hematoxylin, dehydrated, and sealed. For immunofluorescence, antigen was retrieved with EDTA buffer (1 mM Tris/EDTA, pH 9.0) and endogenous fluorescence was eliminated with AutoFluo Quencher (Servicebio, Cat# G1221). The details of the antibodies used for immunofluorescence and immunohistochemistry are given in Table S6 . Staining for each marker was scored using Image-pro plus (v.6.0). Integrated optical density (IOD) to area ratio was calculated for each marker to assess the staining intensity.", "ARTICLE HISTORY" ] },{ "paper_id": "57d3826bb67ec3a479bc58f5e9210de44845b802", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Gammacoronavirus, and its genome encodes four structure proteins, spike glycoprotein (S), and membrane, envelope and nucleocapsid (N) proteins [2, 11] . New variant IBV strains in chickens continually emerge worldwide owing to the high mutation rate of its genome [4] . Various vaccines have been developed but the disease still occurs, because different serotypes of the virus do not cross-protect and vaccine failures are often associated with the emergence of antigenic variants that differ from the vaccine viruses [9, 14] .", "All the tracheas from the slaughterhouses and from LC flocks were free of obviously gross lesions. Sixty-six flocks were sampled in the study period. Twenty tracheal samples per flock were taken for a total of 1,320 tracheal samples. The lower prevalence in LC flocks might be due to sampling differences, because 20 tracheas were sampled from each broiler flock but only one trachea was sampled from each LC flock.", "The samples that were IBV positive with the N-specific primer were subjected to RT-PCR and sequencing using the S-specific primer, oligo5/rC3-r for genotyping [17] . The sequences of these primers are as follows: oligo5: 5\u2032-AAACT GAACA AAAGA CAGAC TTAG-3\u2032 (20251-20274, H120 numbering, GenBank accession number: FJ888351) and rC3-r: 5\u2032-(A/G) CAAT GTGTA ACAAA (T/C) ACT-3\u2032 (20655-20637). The same RT-PCR procedure was performed, except the annealing temperature for this primer set was 52\u00b0C. For LC field cases, one trachea from each flock was subjected to RT-PCR using the same method described for broilers. The prevalence differences among different seasons or chicken types were analyzed using chi-square tests or Fisher's exact tests when any cell having expected value less than 5 [12] . The level of a significant difference was set at \u03b1 0.05." ] },{ "paper_id": "57f7bd687c1b968f782d3a1aa7f7fd051acdcaee", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We have created a library of flavonoids to systematically investigate SARS-CoV 3CLpro inhibitory compound by a FRET method.", "ARTICLE HISTORY" ] },{ "paper_id": "582505fda401e9da61e9632a110b2e57806d2e61", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Methods. Setting and participants. Four tertiary hospitals in Riyadh, Kingdom of Saudi Arabia (KSA) were included in this study: King Khalid University Hospital, King Fahad Medical City Hospital, King Abdulaziz Medical City Hospital, and King Faisal Specialist Hospital. We included all Saudi Board Internal Medicine residents who rotated into these hospitals between November 2015 and January 2016. Data were collected using self-administered questionnaires, which were distributed and collected before resident education activities. The questionnaire contained a short description of the study aim and objectives. The study was conducted after obtaining ethical approval from the King Saud University Research Center (Research Project Number E-16-1873).", "Statistical analysis. All data were summarized as frequencies (percentages) or medians (interquartile ranges [IQRs]). We examined the relationships between age and the main variables (emotions, attitudes, and knowledge) using Spearman's rank correlations. Spearman's correlations were also used to determine the relationships between work-related concerns and knowledge of an MERS outbreak. All statistical analyses were performed using the Statistical Package for the Social Sciences (IBM Corp., Armonk, NY) version 21.", "\u202b\u0631\u0627\u062a\u0647\u0645\u202c \u0651 \u064f \u202b\u0648\u202c \u202b\u0635\u064e\u202c \u064e \u202b\u0648\u062a\u202c \u202b\u0631\u0647\u0645\u202c \u202b\u0634\u0627\u0639\u0650\u202c \u064e \u202b\u0648\u0645\u202c \u202b\u0627\u0645\u0644\u0642\u064a\u0645\u0646\u064a\u202c \u202b\u0627\u0621\u202c \u0651 \u064e \u202b\u0627\u0623\u0644\u0637\u0628\u202c \u202b\u0645\u0648\u0642\u0641\u202c \u202b\u062d\u062a\u062f\u064a\u062f\u202c \u202b\u0627\u0623\u0644\u0647\u062f\u0641:\u202c \u202b\u0641\u064a\u0631\u0648\u0633\u202c \u202b\u0639\u0646\u202c \u202b\u0651\u0627\u062c\u0645\u0629\u202c \u064e \u202b\u0627\u0644\u0646\u202c \u202b\u0651\u0633\u064a\u0629\u202c \u064f \u202b\u0627\u0644\u062a\u0646\u0641\u202c \u202b\u0627\u0623\u0644\u0648\u0633\u0637\u202c \u202b\u0627\u0644\u0634\u0631\u0642\u202c \u202b\u0645\u062a\u0627\u0644\u0632\u0645\u0629\u202c \u202b\u064a\u202c \u0651 \u202b\u062a\u0641\u0634\u0650\u202c \u202b\u062c\u062a\u0627\u0647\u202c \u202b\u0643\u0648\u0631\u0648\u0646\u0627.\u202c \u202b\u062c\u0631\u0649\u202c \u202b\u0629\u060c\u202c \u0651 \u064e \u202b\u0630\u0627\u062a\u064a\u202c \u064d \u202b\u0627\u0633\u062a\u0628\u064a\u0627\u0646\u0627\u062a\u202c \u202b\u0634\u0643\u0644\u202c \u202b\u0639\u0644\u0649\u202c \u202b\u0629\u060c\u202c \u0651 \u064e \u202b\u0645\u0642\u0637\u0639\u064a\u202c \u064c \u202b\u062f\u0631\u0627\u0633\u0629\u202c \u202b\u0647\u0630\u0647\u202c \u202b\u0627\u0644\u0637\u0631\u064a\u0642\u0629:\u202c \u202b\u0627\u0645\u0644\u0642\u064a\u0645\u0646\u064a\u202c \u202b\u0627\u0621\u202c \u0651 \u064e \u202b\u0644\u0623\u0644\u0637\u0628\u202c \u202b\u0629\u202c \u0651 \u064e \u202b\u0627\u0644\u062a\u0639\u0644\u064a\u0645\u064a\u202c \u202b\u0627\u0623\u0644\u0646\u0634\u0637\u0629\u202c \u202b\u0621\u202c \u202b\u064e\u062f\u0652\u202c \u202b\u0628\u202c \u064e \u202b\u0642\u0628\u0644\u202c \u202b\u0647\u0627\u202c \u064f \u202b\u0648\u062c\u062a\u0645\u064a\u0639\u202c \u202b\u0647\u0627\u202c \u064f \u202b\u064e\u0648\u0632\u064a\u0639\u202c \u202b\u062a\u202c \u202b\u0627\u0644\u0633\u0639\u0648\u062f\u064a\u0629.\u202c \u202b\u0627\u0644\u0639\u0631\u0628\u064a\u0629\u202c \u202b\u0628\u0627\u0645\u0644\u0645\u0644\u0643\u0629\u202c \u202b\u0627\u0644\u0631\u064a\u0627\u0636\u060c\u202c \u202b\u0641\u064a\u202c \u202b\u0645\u0633\u062a\u0634\u0641\u064a\u0627\u062a\u202c \u202b\u0623\u0631\u0628\u0639\u0629\u202c \u202b\u0641\u064a\u202c 2015 \u202b\u0646\u0648\u0641\u0645\u0628\u0631\u202c \u202b\u0634\u0647\u0631\u064a\u202c \u202b\u0628\u0646\u064a\u202c \u202b\u0627\u0627\u0644\u0633\u062a\u0628\u064a\u0627\u0646\u202c \u202b\u0628\u064a\u0627\u0646\u0627\u062a\u202c \u202b\u0639\u0644\u0649\u202c \u064f \u202b\u0627\u062d\u0644\u0635\u0648\u0644\u202c \u202b\u0648\u062c\u0631\u0649\u202c \u202b\u0628\u0627\u0644\u0628\u064a\u0627\u0646\u0627\u062a\u202c \u202b\u0642\u0629\u202c \u0651 \u0650 \u202b\u0645\u062a\u0639\u0644\u202c \u202b\u0623\u0633\u0626\u0644\u0629\u064d\u202c \u202b\u0639\u0644\u0649\u202c \u202b\u0627\u0627\u0644\u0633\u062a\u0628\u064a\u0627\u0646\u064f\u202c \u202b\u0627\u0634\u062a\u0645\u0644\u202c .2016 \u202b\u064a\u0646\u0627\u064a\u0631\u202c \u202b\u0648\u202c \u202b\u0648\u0645\u0648\u0642\u0641\u0647\u0645\u202c \u202b\u0648\u0645\u0634\u0627\u0639\u0631\u0647\u0645\u202c \u202b\u0642\u064a\u0645\u0646\u064a\u060c\u202c \u064f \u202b\u0644\u0644\u0645\u202c \u202b\u0645\u064a\u0648\u063a\u0631\u0627\u0641\u064a\u0629)\u202c \u0651 \u202b(\u0627\u0644\u062f\u0650\u202c \u202b\u0627\u0646\u064a\u0629\u202c \u0651 \u064e \u202b\u0627\u0644\u0633\u0643\u202c \u202b\u0645\u0644\u062a\u0627\u0644\u0632\u0645\u0629\u202c \u202b\u0628\u202c \u0651 \u0650 \u202b\u0627\u0645\u0644\u0633\u0628\u202c \u202b\u0643\u0648\u0631\u0648\u0646\u0627\u202c \u202b\u0641\u064a\u0631\u0648\u0633\u202c \u202b\u064a\u202c \u0651 \u202b\u062a\u0641\u0634\u0650\u202c \u202b\u0625\u0644\u0649\u202c \u202b\u0628\u0627\u0644\u0646\u0633\u0628\u0629\u202c \u202b\u0631\u0627\u062a\u0647\u0645\u202c \u0651 \u064f \u202b\u0648\u062a\u0635\u0648\u202c \u202b\u0651\u0633\u064a\u0629.\u202c \u064f \u202b\u0627\u0644\u062a\u0646\u0641\u202c \u202b\u0627\u0623\u0644\u0648\u0633\u0637\u202c \u202b\u0627\u0644\u0634\u0631\u0642\u202c" ] },{ "paper_id": "584690fd413d25e55ee5599071bd23b1be00add0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Multivariate analyses in a forward stepwise manner were performed with P = 0.050 as the threshold for entering and removing variables. For all analyses, a 2-tailed P value of 0.05 was considered significant. Statistical analyses were performed with PASW for Windows (version 18 software package; SPSS, Inc., Chicago, IL, USA).", "The Institutional Review Board at the Seoul National University Hospital approved the study. The board waived the requirement for written consent (IRB registration number 1607-062-775)." ] },{ "paper_id": "5856a3f4b9fc9b0947bf045feb20d32d581221dc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "58a0c3ad6fd3ce5eae8b1199bd8e04ad8dadac81", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Among HSCT recipients, hMPV was associated with 19% mortality.", "Screening of all positive laboratory results for hMPV by both direct fluorescent antibody (DFA) and real-time reverse-transcriptase polymerase chain reaction (RT-qPCR) was performed to identify patients between the ages of newborn to 19 years who were diagnosed at Seattle Children's Hospital in Seattle, WA during the years 2006-2010. Of 368 total patients with positive hMPV laboratory results, we performed retrospective chart review to identify a subset of 55 patients with immunocompromised conditions. We defined an immunocompromised condition as presence of hematologic malignancy, solid tumor, rheumatologic disease receiving immunosuppressive therapy, solid organ transplant, primary immunodeficiency, receipt of chronic immunosuppressive therapy, or receipt of a hematopoietic stem cell transplant (HSCT). Using electronic chart review, we abstracted sociodemographic variables, symptoms, laboratory and radiologic values, clinical course, and treatment outcomes for these patients.", "Human metapneumovirus infections in our immunocompromised patient population was associated with high rates of LRTI at presentation, and an attributable mortality of 5%, rates substantially higher than that in the general population where hMPV is most commonly a self-limited URTI. In our study, 12 (23%) of immunocompromised children with hMPV were classified as having severe disease, and neutropenia was identified as a significant risk factor for disease severity. This rate is comparable or even higher than previous rates reported in seriously immunocompromised adult patients [13] .", "A prospective randomized study of ribavirin and IVIG administration, or of newer therapeutic agents under development for treatment of paramyxovirus infections [24, 25] , would be helpful given the high morbidity associated with hMPV in the immunocompromised population. In particular, a study of the use of novel agents, including fusion inhibitors [26] , could be studied in this population given their potential to serve as postexposure prophylaxis in high-risk individuals. The documentation of severe hMPV disease in immunocompromised children supports previous data documenting severe and fatal hMPV disease reported in adult HSCT recipients [9, 13] and highlights the need for treatment options in this population." ] },{ "paper_id": "58b5c77c9fb3f68a3ad84a3f15275dc0e4554192", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "58b95b98f9016190301e31fa9809932a4d8169c2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Codetection was defined as a positive detection of >1 microbe from the sample, and it was used instead of coinfection since coinfection means all the detected microbes must contribute to the pathogenic effect, whereas codetection may not indicate the necessary causative role." ] },{ "paper_id": "58be092086c74c58e9067121a6ba4836468e7ec3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "58c87ea90b23dc0d106427b76bb5525b6aa01b77", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In six of the nine cases reported, the patients were Japanese. This may be due to racial differences in the risk of drug-induced lung injury and better recognition of the complication by clinicians in Japan because of better awareness. An additional contributory factor may be the difficulty in excluding viral syndrome with high accuracy by performing a viral panel test, because the test is not approved by the Ministry of Health, Labour and Welfare and is not commercially available in Japan. However, the involvement of these factors is purely theoretical, and the real reason is currently unclear.", "Our findings suggest that clinicians should be aware of the possibility of interstitial pneumonia as a complication of the influenza vaccine, ask closed questions about vaccination in medical interviews, and educate patients about this complication, as these will facilitate early detection and treatment. Although the safety of this vaccine has been confirmed, relatively newer drugs warrant further investigation to confirm their association with interstitial pneumonia.", "The authors state that they have no Conflict of Interest (COI)." ] },{ "paper_id": "58ef15f083c00ee3ae8e604a9c6e258576b7c7af", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Infectious diseases are a major health concern worldwide, causing millions of illnesses and deaths each year. Newly emerging viral diseases, such as swine H1N1 influenza, severe acute respiratory syndrome (SARS) and bacterial infections, such as the recurrent Salmonella and Escherichia coli outbreaks not only lead to wide-spread loss of life and health, but also result in heavy economic losses. To better navigate this landscape of infectious diseases, it is important to not only understand the mechanisms of individual diseases, but also the commonalities between them. Combining knowledge from related diseases will give us deeper insights into infection and host immune response, will enhance our ability to comprehend new diseases and lead to efficient development of therapeutics.", "we present a novel way of combining experimental PPI data coming from several organisms we incorporate domain knowledge in designing a prior that causes the learned models to exhibit the requisite common structure across the tasks to optimize the resulting non-convex objective function, we implement a concave convex procedure (CCCP)-based method", "Algorithm 1 CCCP procedure 1: Initialize w \u00bc w 0 2: repeat 3: Compute rG using w k 4: Compute current value L approx 5: Solve w k\u00fe1 \u00bc argmin w \u00bdF\u00f0w\u00de \u00fe w T rG 6: Set k \u00bc k \u00fe 1 7: Compute new value L 0 approx 8: \u00bc L approx \u00c0 L 0 approx 9: until 5" ] },{ "paper_id": "58f660cec9eb4423fc12e1b14bc70a951a5edad0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sample handling and preparation for mass spectrometric analyses was performed according to Wulfmeyer et al. (54) . Peptide mass fingerprinting was performed by trypsin digestion of proteins 'in-gel'. Obtained peptides were analyzed with matrix-assisted laser desorption/ionization--time of flight on an Axima Performance mass spectrometer (Shimadzu). Identity of selected peptides was confirmed by sequencing with high energy collision induced dissociation. Mascot MS/MS search software (Matrix Science) was used to identify the proteins.", "Secondary structure of DDX1 protein constructs was predicted with psipred (55) and analyzed by recording circular dichroism (CD) spectra from 200 to 260 nm using a Jasco J-810 CD spectropolarimeter (Jasco Corp.). A typical measurement was performed with 5 M ( = 0.42 mg/ml) protein in 200 l total volume of storage buffer and the cuvette was thermostated to 298 K. Melting curves were recorded at 222 nm by heating the sample cuvette from 293 K to 368 K at a rate of 1 K per min and potential refolding was monitored by returning to the start temperature. Melting curves were fitted to a two-state-unfolding equation (56) .", "Binding affinities for nucleotides were determined by fluorescence equilibrium titration, using N'-methylanthraniloyl (mant)-labeled nucleotide analogs. Fluorophores were excited at 356 nm, emission spectra were recorded from 370 to 520 nm and the fluorescence sig-nal at 448 nm was used to plot binding curves. Titration data of protein binding to mantADP/mantdADP were fitted to a quadratic binding equation (57):", "The specificity of DDX1 toward oligonucleotide sequence and the impact on binding affinities was tested by performing nucleotide titrations in the presence of 40 M RNA. Two different RNA oligonucleotides were tested for their influence on DDX1, a 10mer polyA RNA and a 13mer RNA of mixed sequence (5 -AGCACCGUAAAGA-3 ; according to (59) ). All RNAs were purchased from biomers.net GmbH (Ulm)." ] },{ "paper_id": "591779cb69e83083aa7b2d9b031983c802ba2405", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Diameters of coronary arteries were converted to Z scores by using previously published regression equations 9) . All statistical analyses were performed using SAS ver. 9.1 (SAS Institute Inc., Cary, NC, USA), and P values of <0.05 were considered statistically significant. The median value with interquartile range was used to summarize data. Numerical variables were compared using the Wilcoxon rank sum test, and Fisher's exact test was used to compare categorical variables.", "We obtained informed consent from the parents of all 133 subjects, and the Institutional Review Board of the Asan Medical Center, Seoul, Korea, approved this study (2010-0467).", "Nasopharyngeal swabs were taken by flocked swab and were submitted in Universal Transport Medium (COPAN, Brescia, Italy). Viral RNA was extracted from the swabs with NucliSENS easyMAG (Biomerieux, Marcy l'Etoile, France). cDNA was synthesized using a Revert Aid First Standard cDNA Synthesis kit (Fermentas, York, UK), and each cDNA preparation was subjected to three sets of multiplex PCR with an RV15 ACE Detection kit (Seegene, Seoul, Korea). The RV15 ACE Detection kit targets 15 respiratory viruses, including respiratory syncytial viruses A and B, adenovirus, rhinovirus, parainfluenza viruses 1 to 4, influenza viruses A and B, metapneumovirus, bocavirus, corona viruses OC43/229E and NL63, and enterovirus. This set of 15 respiratory viruses corresponds exactly to the set of viruses causing respiratory infections in Korea that is monitored weekly by the Korea Centers for Disease Control and Prevention 8) ." ] },{ "paper_id": "595ec9383d19b691e17362abb472fa1103074014", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data are presented as the mean \u00b1 standard error of mean (SEM). Statistical significance was assessed using one-way analysis of variance (ANOVA) and post hoc Tukey's multiple comparisons test.", "To detect S0-specific IgG levels, sera were analyzed by ELISA. 96-well immunoplates (SPL, Korea) were coated with 10 \u03bcg/mL of purified recombinant S0 (100 \u03bcL/well) in carbonate- ", "Porcine epidemic diarrhea (PED) is one of the most catastrophic swine diseases and is characterized by severe diarrhea, vomiting, dehydration and even death [1] . The mortality rate of PED is up to 80-100%, especially in neonatal piglets [2, 3] , resulting in large economic losses for swine farms across the globe, including Europe, Asia and the USA for the past three decades [1, 4, 5] , and making the development of an effective PED vaccine a necessity." ] },{ "paper_id": "59a6b0bbb0666fddb456723c185f04bb97858b08", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "COMMENTARY", "837", "Janko Nikolich-ugich \u017d" ] },{ "paper_id": "59c84e06ac8246b44efc595cafef84b946f24219", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5a0058a8f5c282059a2cc172807b09340161ae77", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5a0937374802cad6f72576fb6c511715aa884b18", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The study included a total of 206 patients.", "The results of this study suggest that sex and the presence of an implant significantly affected PC-SPT.", "\u2022 ", "Before SPT was started, patients were grouped on the basis of the periodontal treatments performed. Scaling and root planing (SRP) and flap operation (FO) were defined as periodontitis treatments. Implantation (including bone graft) and mucogingival surgery (e.g., keratinized gingiva widening, root coverage, gingivectomy, and gingivoplasty) were defined as other treatments." ] },{ "paper_id": "5a1a3d864a2110b730b3cbf6b7a1c01a0870be42", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In this analysis, we have rejected those phytochemical ligands that violate Lipinski's rule of five [41] . That is, ligands with MW > 500 g/mol, hydrogen-bond-donating atoms > 5, hydrogen-bond-accepting atoms > 10, or ClogP > 5, even though they may have strong docking energies, were not considered.", "The purpose of this work was to examine whether higher plants may serve as a source of antiviral agents for treatment of dengue fever. A molecular docking approach was used to examine a selection of phytochemicals from our virtual library (2194 different compound structures) with the protein targets of dengue virus.", "In addition to docking energies, it is useful to consider proximity of electrophilic ligands (e.g., epoxides or enones) to nucleophilic residues in the active site. A search of the docked ligands with DENV protease has revealed three sesquiterpenoid -methylene lactones that dock in close proximity to the -OH group of Ser196. Ineupatorolide A, bigelovin, and 2-de-ethoxy-2-methoxyphantomolin (Fig. 2) dock with the methylene carbon within 3.6 \u00c5 of the serine -OH. These ligands can presumably undergo conjugate addition with the -OH group and form a covalent intermediate thereby inhibiting the protease." ] },{ "paper_id": "5a9de698acd2aea68074eb45c0925d4377a41011", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5aaa0dfb49b42f8fab7ce125f89360b828ee9298", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Detection of HBs and HBe Antigens. HBs antigen was quantified by enzyme-linked immunosorbent assay (ELISA) as described previously. 23 HBe antigen was detected by a Chemiluminescent Immuno-Assay (Mitsubishi Chemical Medience).", "Additional experimental procedures are included in the Supporting Information.", "However, CsA did not affect the entry of HCV, in contrast to the inhibition of HCV entry by heparin, bafilomycin A1, or an anti-HCV E2 antibody (Fig. 3B) ." ] },{ "paper_id": "5ab92ddf1bb39b6863b28e2e9946415f7a5adf34", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "V ALID RESPONSES WERE received from 303 hospitals (58.6%)." ] },{ "paper_id": "5af9c3bce43b90c81887d5102c0e5c114d40f5dc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Citation Holmes KV, Dominguez SR. 2013. The new age of virus discovery: genomic analysis of a novel human betacoronavirus isolated from a fatal case of pneumonia. mBio 4(1):e00548-12.", "A new human betacoronavirus in lineage c, tentatively called HCoV-EMC, was isolated from a patient from the Kingdom of Saudi Arabia who died from acute severe pneumonia and renal failure. The viral RNA has been detected in eight additional cases. Sequencing and bioinformatic analysis of the viral genomic RNA showed that it is a novel virus not previously detected in any other species and that its closest relatives are two Asian bat coronaviruses. HCoV-EMC may represent a sporadic spillover to humans from an unknown animal reservoir. In a recent article, van Boheemen et al. demonstrated how state-of-theart sequencing technology and bioinformatic analysis can quickly provide critical insight into the viral genome sequence, phylogeny, replication strategy, and potential drug and vaccine targets and generate tools to evaluate the possible epidemic risk associated with this novel human virus.", "What can analysis of its RNA genome tell us about this new human coronavirus? Analysis of the HCoV-EMC genome was able to distinguish whether HCoV-EMC was a known human coronavirus with mutations that increased its virulence or a product of recombination between two or more known coronavirus species or, like SARS-CoV, a spillover of a zoonotic coronavirus that was transmitted, either directly or indirectly, to humans from an animal reservoir. The genomic analysis showed that HCoV-EMC is a new coronavirus that had never before been detected in any other species." ] },{ "paper_id": "5b0eeabeded14c9e02fc7bcfacb52a8fa0b3ae3c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Pt2L4. Cassava storage roots differentially produce an interesting Pt2L4 protein 238 with low sequence complexity characterized by a reduced amino acid alphabet (just 13 amino acids). This 107 residue-long protein contains 56 glutamic acids, 30 alanines, 24 valines, 20 prolines, 18 serines and 15 lysines, but does not have any arginines, asparagines, cysteins, histidines, phenylalanines, tyrosines and tryptophanes.", "PPE antigens. Proline and glutamic acid rich proteins (or PPErepeat containing proteins, or PPE proteins) are important T-cell antigens produced by Mycobacterium avium subsp Paratuberculosis (Map). 237 One of the PPEs is a 34.9 kDa protein (359 residues, pI 4.31) which following recombinant expression in E. coli was shown to elicit significant delayed type hypersensitivity skin reaction in mice sensitized with Map, suggesting that this recombinant PPE protein of Map was definitely associated with cellular immune response. 237 Curiously, this PPE contains 73 alanines, 44 glycines, 37 prolines, 20 aspartic acids but just 10 glutamic acids.", "No potential conflicts of interest were disclosed." ] },{ "paper_id": "5b25c21a882848393a88f2036871db32f76c7a80", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All statistical analyses were conducted using GraphPad Prism 5 (GraphPad Software, Inc., La Jolla, CA). Differences between groups were analyzed using the two-tailed Student's t-test of means. " ] },{ "paper_id": "5b2945b68e31dfe32f721791a52b95f09b6a31bc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Rickettsial species, such as Coxiella burnetii, causative of Q-fever, comprise bacteria which exist within another cell, and as such Q-fever is contracted when humans are exposed to aerosolized droplets from the urine, milk, faeces or birth detritus from infected sheep, goats and cattle [50] .", "In contrast, EA submissions are for products used under an IND or a protocol (treatment plan), or submitted as a protocol amendment to an existing or new IND. The EA categories cover use under either an individual patient IND or protocol, individual emergency EA use, or EA for an intermediate-size population or for widespread use (large populations). Other US regulatory programmes for biologicals and drugs to treat serious or life-threatening conditions include fast-track designation, breakthrough therapy designation, accelerated approval pathway and priority review designation." ] },{ "paper_id": "5b2c74eaf9dc747307ec2d91ba16771cd505e44c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The samples consisted of conjunctival, nasal and, Table 2) .", "As previously noted, the female/male ratio was comparable, whereas the viral isolation frequency was twice as frequent in females as in males (Table 1 and Results). The large amount of positive samples obtained from females was not an expected result. In quite a few studies performed in cat populations from numerous locations, no gender difference was observed (11, 25) .", "With regards to the origin of the cats, females were positive in 16 locations, males in 9 locations and both male and female in 3 locations (data not shown)." ] },{ "paper_id": "5b355d4f9adcfca08906339ef42a4990b1e9c8b0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The quantitation of [ 35 S]sulfate-labeled macromolecules was carried out as previously described (33, 34) .", "Neutral oligosaccharides were analyzed on an AX5 anion-exchange column using a 40-80% gradient of acetonitrile in 25 mM NaPO4, pH 6.5, in 30 min at a flow rate of 1 ml/min. Fractions of 0.5 ml were counted . Each run included an internal standard of \"C-fucitol and an ovalbumin glycopeptide, [\"C]AcAsnMan6GlcNAc2 . 0-galactosidase digestions were carried out in 50 Al of 100-mM citrate-P04 buffer at pH 4 .5 for 16 h at 37\u00b0C using 0.05 U of enzyme .", "We are grateful to Sandoz Pharmaceuticals (Basel, Switzerland) for the gift of brefeldin A . " ] },{ "paper_id": "5b7753b6a659e6afa0a46fe171a372e682b07010", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The KEMRI Ethical Review Committee in Kenya and University of Warwick Biomedical Research Ethical Committee in the United Kingdom approved the study. Verbal assent was sought from participants aged <18 years, and written informed consent obtained from all participants or their parents/guardians.", "Supplementary materials are available at The Journal of Infectious Diseases online (http://jid.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": "5b96fac306b9b57121152798668506aabb688cac", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The purpose of these organelles remains uncertain, but it seems logical to predict that DMVs help to concentrate viral proteins and their precursors and may offer some protection from the antiviral detection and elimination machinery of the cell.", "Previous DMV studies reported that while the outer DMV membranes open onto a network of connecting tubules that is connected to the endoplasmic reticulum, the inner DMV membranes contained abundant viral RNA (2, 8) but generally did not have visible openings (2) .", "A solid-walled DMV would be a tomb for any RNA synthesized inside and is difficult to reconcile with the generally understood role of DMVs in supporting viral replication. Furthermore, it was difficult to imagine how a closed DMV architecture could have evolved." ] },{ "paper_id": "5c1dd2b19bb6b3016ba2654f69905bf4ec65bd54", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The translation of basic biomedical research discoveries into robust pipelines of products yielding licensed, appropriate, usable, affordable, equitable and accessible tools, such as diagnostics, vaccines, drugs or devices, is essential to achieving universal and global health.", "The funding to develop new NTD vaccines comes from government, philanthropic funding and occasionally from biotech funds. Seldom is any funding raised from private equity.", "ARTICLE HISTORY", "Because our PDP is embedded within an academic health center, the Texas Medical Center, and it is a key research and training arm of the National School of Tropical Medicine at Baylor College of Medicine, 27 we have established a hybrid model (of biotech and academic cultures) to train the next generation of vaccine researchers. Trainees can learn both at their site or via short exchanges the ins and out of " ] },{ "paper_id": "5c49361dc3511c5c14855745fedcbafc97d9ca96", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5ca05808cfc6d2139bc1ab6112d67dff9411f9ce", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Historically, research articles were placed under dissemination embargo until final publication. 1 This served to protect copyright and preserve the novelty of data. It also ensured that the public and the media were not privy to datasets and analyses that had the potential to change significantly between prepublication status and final article publication.", "Prepublication data release increases the risk of having data \"scooped,\" with \"scooping\" defined as \"when 2 independent groups studying the same system produce the same or similar results, and 1 group publishes their results first.\" 12 There is a concern that being \"scooped\" decreases the prestige of the original author. The medical literature has limited discussion of this phenomenon. However, publications in biology 4, 12 and the life sciences 13 cover the topic extensively, in part due to the enormous surge in clustered regularly interspaced short palindromic repeats (CRIS-PR)/Cas9 publications and a recent scandal in which multiple simultaneous developers of CRISPR technology were scooped. 25 The literature suggests that scooping not only does not harm the reputation of the authors, but also adds Table 2 ", "Of the 10 surgical conferences, authors were cautioned or prohibited against submitting work which would be published before presentation by 5 societies. The use of social media while at the conference was generically encouraged by 3 (Table 1 ). No specific guidelines or cautionary statements about how data should be disseminated by the authors or used by the audience were provided.", "Presentation and publication guidelines of 10 national surgical society meetings and 13 major surgical journals were reviewed for mention of embargo and social media policies. National meetings were chosen as being probable sites of presentations by society members and those likely to be attended by a wide representation of the respective society. Journals were chosen as being the official organs of the specialty or those very likely to be read by members of a specialty." ] },{ "paper_id": "5cba1e45c2829cb0ebaa7bf5384fa685f543c6d6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Since demonstration of FCoV RNA in ascites of FIPsuspected cats using RT-PCR was a useful indicator to diagnose FIP [3, 10] , the results of this study likely represent the epidemiology of effusive FIP in domestic cats in Japan. However, whether or not cats negative for the 3'-UTR gene were infected with FCoV was unknown. This status needs to be investigated further, such as by antibody test and quantitative RT-PCR.", "Ascites was obtained from a total of 854 privately owned domestic cats that were clinically suspected of having FIP from veterinary clinics throughout Japan in the period of June 2008 to October 2012. Viral RNA was extracted using a QIAamp Viral RNA Mini Kit (Qiagen, Tokyo, Japan). Detection of FCoV RNA was performed using a QIAGEN On-eStep RT-PCR Kit (Qiagen) with the P205-P211 primer pair providing a 223 bp amplicon of the 3'-untranslated region (UTR) gene of FCoV [10] , according to the manufacturer's instructions. FIPV strain 79-1146 (American Type Culture Collection, Rockville, MD, U.S.A.) was used as a positive reference virus. Furthermore, for samples in which the 3'-UTR gene was detected, genotyping was performed with the nested RT-PCR reported by Addie et al. [4] , providing 360 and 218 bp amplicons of FCoV types I and II, respectively. FIPV strain UCD1 (kindly provided by Azabu University) and FIPV strain 79-1146 (same as above) were used as positive reference viruses for the types I and II, respectively. Gene positivity was analyzed by chi-square test (StatView, Adept Scientific, Herts, U.K.), and a P value of <0.05 was considered statistically significant.", "Then, the positivity was investigated in various purebreds. As shown in Table 1 , the positivities in the Norwegian forest cat (92.3%) and Scottish fold (77.6%) were significantly higher than the average for purebreds (62.2%) (P=0.0274, \u03c7 2 =4.9 and P=0.0251, \u03c7 2 =5.0, respectively), whereas that in the American shorthair (30.0%) was significantly lower than the average for purebreds (P<0.0001, \u03c7 2 =26.3); the positivity in the American shorthair was also lower than that in crossbreds, although the difference was not significant. The The breeds that consisted of fewer than 10 cats were classified together as others. A significance test (\u03c7 2 test) was performed between each breed and the average of purebreds (62.2%)." ] },{ "paper_id": "5cded487793694de49b640b3972285bfc8431cfb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The focus so far has been on those genes/cytokines that have, historically, been regarded as of particular interest and/or have been selected for interrogation. The advent of global transcriptome profiling has helped to identify genes whose function maybe less well understood. However, in time, some of these genes and their respective pathways could be particularly important in determining the susceptibility or resistance of chickens to diseases. Table 2 outlines some genes, and their functions, from NE studies that maybe particularly relevant in determining disease susceptibility/resistance based on consistent (relative) up or downregulation in more resistant birds.", "Coccidiosis and necrotic enteritis (NE) are major intestinal disorders of chickens and were identified as the top two issues affecting broiler production by US poultry veterinarians in a recent survey (Hofacre and Mathis, 2015) . It is estimated that coccidiosis and NE cost the poultry industry around US$ 3 and 6 billion per annum, respectively, through lost productivity, prevention strategies, and/or therapeutic interventions (Wade and Keyburn, 2015) . The true cost to the industry may, C The Author(s) 2018. Published by Oxford University Press on behalf of Poultry Science Association. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ oup.com.", "Overall, this review highlights some of the genes more consistently associated with relative resistance (or susceptibility) to some of the most important diseases and foodborne pathogens of commercial poultry and helps to inform/support appropriate immune-based strategies to optimize poultry health and productivity. The optimum immune response is balanced to effectively counteract the pathogen and minimize tissue damage and associated nutrient costs. However, it does seem that steering the immune system towards a more proinflammatory capability (in different compartments) provides better protection against pathogens and (thus) improved growth performance. Global gene expression profiling is providing a greater overview of genes and pathways involved in the bird's response to pathogen challenge and mechanisms of resistance. Further studies, particularly incorporating bird growth performance, are, however, necessary to better develop our understanding and application of informed outcomes.", "Coccidiosis is caused by species of the Eimeria parasite and is probably the most significant enteric disease affecting chickens. Eimeria are ubiquitous and can persist in the environment for long periods (Blake and Tomley, 2014) . There are seven species of Eimeria that are known to infect chickens, with Eimeria acervulina, Eimeria maxima, and Eimeria tenella being the most prevalent and pathogenic for broilers (McDougald, 1998) . Each Eimeria species is recognized for targeting specific regions of the gut. E. acervulina affects the proximal small intestine, E. maxima affects the mid-intestine, and E. tenella affects the ceca (Hammond and Long, 1973) . Following ingestion of a sporulated Eimeria oocyst, mechanical disruption and digestive processes release four sporocysts and subsequently their sporozoites, which attach to, and invade, epithelial cells in the susceptible region of the intestine (Blake and Tomley, 2014) . The sporozoite then proceeds through further developmental phases (e.g., trophozoite, merozoite, gamete, zygote, etc.,) in the host before the formation of an unsporulated oocyst that is excreted into the environment, where it eventually sporulates. Invasion of epithelial cells causes damage to the epithelium and leads to haemorrhagic or malabsorptive disease, which results in poor growth performance or even death. Whilst good husbandry can play a part in managing coccidiosis, anticoccidial drugs and vaccination are necessary options for coccidiosis control, but each has their own drawbacks. Resistance to anticoccidial drugs has been a problem for many years, and vaccination costs can be prohibitive for the broiler industry (Blake and Tomley, 2014) ." ] },{ "paper_id": "5ceca9883a0930498d29cdfc09b942f6a9c6bf89", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5cf53c279192e23b92dd29e74cf9bdbb3b598244", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Contributors MA, MH, MMH and MAH were the main researchers, with the major roles in data collection, data analysis and manuscript preparation. TMR, MEH, MHR, LBP and MAS contributed to study design, data collection and preparation of the final manuscript.", "Funding This work was supported by the University Grants Commission of Bangladesh (grant number UGC 22, 2014) .", "The cortisol hormone was determined using an ELISAbased technique using the commercial kit of Monobind with its protocol (http://www. monobind. com/ site/ index. html, accessed on March 12, 2015) .", "Diarrhoea was assessed by inspecting the perianal area for adhesion of faeces, observing faeces characteristics around the animal holding area, and history taken from the cattle trader on increased frequency and volume of defecation (if the trader observed and recalled this information). 18 Dehydration was evaluated by looking at the condition of the eyes (sunken eye) and by performing skin fold test 19 (Table 1) ." ] },{ "paper_id": "5d2201d0059d6b9e0702278a74cb46e036434053", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Infectivity titers for both the seed virus and material recovered from infected mice were determined by plaque titration on Vero E6 or LLC-MK2 cells using an overlay supplemented with 1 mg TCPK trypsin/ml and expressed as plaque-forming units. SeV serially diluted in sterile phosphate-buffered saline (PBS) was inoculated onto the wells and incubated at 37 C for 45 min with agitation every 15 min. Wells were overlaid with 3 ml of 2\u00c2 MEM (Life Technologies, Gibco) with 100 IU/ml penicillin/100 mg/ml streptomycin (Gibco), 2% BSA (Gibco), 2 mg/ml of TCPK trypsin (Sigma), and 1.6% agarose. Plaques were visualized at day 3 by staining with crystal violet in 20% methanol processed as described earlier.", "SeV strain 52 was obtained from ATCC (Manassas, VA; VR-105). Seed virus was prepared by inoculation of 10-day embyonated chicken eggs, harvesting allantoic fluid 2 days later and storing aliquots at \u00c080 C.", "Formalin-fixed tissues were embedded in paraffin, sectioned at 5 mm and sections stained with hematoxylin and eosin. An experienced veterinary pathologist evaluated tissues and score for pathology. Tissues were scored as follows: 0 \u00bc no change; 1 \u00bc minimal change (or possibly non-specific background or appearance compounded by lung collapse, i.e. not inflated); 2 \u00bc mild inflammation and/or pneumocyte hypertrophy; 3 \u00bc moderate inflammation and/or pneumocyte hypertrophy; 4 \u00bc marked inflammation and/or pneumocyte hypertrophy; 5 \u00bc severe inflammation and/or pneumocyte hypertrophy affecting <50% of lung lobe; 6 \u00bc severe inflammation and/or pneumocyte hypertrophy affecting >50% of lung lobe.", "Cytokine expression was also measured using a cytokine multiplex assay. Lung homogenates were processed according to manufacturer instructions and then analyzed using a Bio-Plex 200 system (Bio-Rad, Hercules, CA). Briefly, tissue homogenates were centrifuged for 10 min at 1,000 rpm at 4 C to remove cellular debris. Aliquots of the cleared supernatants were transferred into 96-well round bottom plates and processed for use on the Bio-Plex system. The cytokines/chemokines were coupled to cytokine/chemokine specific multi-plex beads (R&D Systems, INC., Minneapolis, MN) . This panel measures the concentrations of cytokines and chemokines IL-1b, IL-4, IL-6, IL-10, IFN-c, CCL2 (MCP-1), CCL3 (MIP1a), CCL4 (MIP1b), CCL5 (RANTES), CXCL10 (IP-10), and tumor necrosis factor-a (TNF-a).", "Structural comparisons of HN proteins of Paramyxoviridae (hPIV3, Simian PIV5, NDV, Nipah, Hendra) showed strong conformational similarities (above 60% of structure similarity measured by LGA_S score (Zemla 2003) ) even for proteins with sequence identity as low as 21% (Fig. 7) ). The strongest structural similarity was seen in conserved regions forming the neuraminidases six-bladed beta-propeller fold, with some deviations observed in more exposed loop regions. The receptor-binding site is located in the center of the propeller." ] },{ "paper_id": "5d352d8eaadb17dc1ed4cd7501e3533d366c939c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The result obtained above implicated that low pH treat-ment removes IBAV outer capsid proteins from the particle and initiates its infection. Figure 3b shows the viability of HmLu-1 after a series of treatment without virus infection, and no significant difference was observed (P=0.983, Welch's t-test).", "Ibaraki virus (IBAV) is one of the strains of epizootic hemorrhagic disease virus (EHDV) serotype 2, a member of genus Orbivirus in Reoviridae family [11, 19] . It is known as a causative agent of Ibaraki disease characterized by the paralysis of swallowing muscles. Although the effective vaccine is widely used, the recent reemergence of Ibaraki disease in combination with the co-circulation with other EHDV raised the alert level for the epidemic of Ibaraki disease [13] . In addition, orbivirus family contains many viruses causing severe loss in the livestock industry. Therefore, it is important to understand the detailed molecular mechanism of their infection.", "Virus infection is initiated by the release of viral genome to the intracellular compartment of target cells. Several mechanisms are known for the genome release to cytoplasm, and one of the most well known mechanisms is the direct fusion mechanism utilized by several enveloped viruses, such as human immunodeficiency virus-1, mouse hepatitis virus and Paramyxoviruses [5, 6] . Enveloped viruses are also known to use host endosomal pathway to facilitate their infection [12] ." ] },{ "paper_id": "5d38ec30f0a4ea9b504808bc6bb2c8793db72e7a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5d3cad66ff27b7d70f1895c653f79d63379af069", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Environment (RIVM, the Netherlands). Poliovirus Sabin 1, 2, and 3 strains were obtained from the late B. Rombaut (Vrije Universiteit Brussels, Brussels, Belgium) . Human rhinoviruses 2 and 14 were a kind gift of Joachim Seipelt (Medical University of Vienna, Austria). ERAV (NM11/67) was kindly provided by David Rowlands and Toby Tuthill (University of Leeds, United Kingdom). Virus titers were determined by endpoint titration according to the method of Reed and Muench and expressed as 50% cell culture infective doses (CCID 50 ).", "Briefly, cells were seeded at a density of 5 x 10 3 cells per well in a 96-well cell culture plate in complete DMEM. Following incubation of 24 hours at 37\u00b0C, serial dilutions of the test compounds in complete DMEM were added in a total volume of 100 \u03bcL. Replicon RNA levels after 3 days of incubation were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Primers used for detection of HCV replicon RNA were: 5'-CCGGCTACCTGCCCATTC-3' (forward primer), 5'-CCAGATCATCCTGATCGACAAG-3' (reverse primer) and 5'-FAM-ACATCGCATCGAGCGAGCACGTAC-TAMRA-3' (probe).", "HeLa R19 cells (2 x 10 3 cells/well of a 96-well plate) were reverse transfected with 2 pmol of small interfering RNA (siRNA) per well using Lipofectamine 2000 (Invitrogen) according to the manufacturer's instructions. Scramble siRNA (AllStars Negative Control; Qiagen) was used as a negative control, siRNA against PI4KIII\u03b2 (5'-UGUUGGGGCUUCCCUGCCCTT-3') was from Qiagen, and siRNAs against OSBP (two siRNAs mixed at a 1:1 ratio, 2 pmol total per well, 5'-", "Purified OSBP (3,3 \u03bcM) was incubated at 30\u00b0C under constant agitation in the presence of 2 \u03bcg/ml trypsin, and the reaction was stopped 5 min after trypsin mixture by addition of 2 mM PMSF. Absence of residual full-length protein and accumulation of the ~35kDa ORD fragment [as identified in (Mesmin et al., 2013) ] was checked by 15% SDS-PAGE before DHE or PI4P transfer assay." ] },{ "paper_id": "5d492015c79953419dd1cfc47ebf6b50297e0334", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. All data were analyzed using an unpaired two-tailed t test and GraphPad Prism statistical software (GraphPad Software Inc., San Diego, CA, USA). A value of P , 0.05 was considered statistically significant (*, P , 0.05; **, P , 0.01; and ***, P , 0.001)." ] },{ "paper_id": "5d4f1f02d0e731966dddd635e8fa7bfdc169d3b9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This is a case report requiring only chart review and literature review, without any direct intervention or harm to the patient referred to in this case, and as such, informed consent and ethical approval was not needed.", "At outpatient follow-up, very long chain fatty acids were normal, eliminating adrenoleukodystrophy as a possible etiology for the adrenal insufficiency. The diabetes autoimmune test group was normal, but the TSH remained elevated with a normal T4, confirming autoimmune hypothyroidism. Follicle-stimulating hormone and luteinizing hormone were normal, eliminating concomitant hypogonadism, but tissue transglutaminase immunoglobulin A was elevated, raising suspicion for celiac disease. Levothyroxine was started and he was referred for intestinal biopsy to confirm celiac disease.", "In a study of 18 pediatric patients with primary adrenal insufficiency, hypotension was the presenting sign in 13, hyperpigmentation in 12, hyponatremia in 16, and hyperkalemia in 9. Of 15 who underwent a cosyntropin stimulation test, all failed. 16 Our patient did not have hypotension, yet he had hyperpigmentation, hyponatremia, hyperkalemia, and failed a cosyntropin stimulation test." ] },{ "paper_id": "5d58ccdb0252429f7c74ece67b505a2afd7e08c9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Twenty-five patients underwent transbronchial lung biopsy (TBLB) and 2 underwent video-assisted lung biopsy. Histological samples showed intraluminal organization (n=21), alveolitis characterized by thickened alveolar septa and infiltration of the inflammatory cells to the alveolar septa (n= 26), intraalveolar hemorrhage (n=12), and fibrin exudate (n= 3) (Fig. 4d-f ).", "The number of cases of virus infection diagnosed each month was higher in the winter months and lower in the summer months (Fig. 3) ." ] },{ "paper_id": "5d78b139da9ef9b2070d532b2bd773c367656ca8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org/ lookup/suppl/doi:10.1128/mBio.01265-15/-/DCSupplemental. Figure S1 , TIF file, 1.7 MB. Figure S2 , TIF file, 1.6 MB. Figure S3 , TIF file, 1.5 MB. Figure S4 , TIF file, 2.7 MB. Figure S5 , TIF file, 2.6 MB. Figure S6 , TIF file, 0.7 MB. Table S1 , DOCX file, 0.1 MB. Table S2 , DOCX file, 0.1 MB. Text S1, DOCX file, 0.1 MB.", "ELISA. IFN-\u2424 in the supernatant of ivtDVG RNA-transfected TC-1 cells was determined by enzyme-linked immunosorbent assay (ELISA) in accordance with the manufacturer's instructions (PBL Assay Science).", "Cell lines and viruses. LLC-MK2 rhesus monkey kidney epithelial cells (ATCC catalog no.CCL-7), A549 human type II alveolar cells (ATCC catalog no. CCL-185), and wild-type, Ddx58 \u03ea/\u03ea (RIG-I \u03ea/\u03ea ) and Mavs \u03ea/\u03ea MEFs (kindly provided by J. Kagan and J. Chen) were cultured in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, 1 mM sodium pyruvate, 2 mM glutamine, and 50 mg/ml gentamicin or penicillin and streptomycin (all from Invitrogen). TC-1 mouse lung epithelial cells (ATCC catalog no.CRL-2785) were cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum, 1 mM sodium pyruvate, 2 mM L-glutamine, 2 mM nonessential amino acids, 10 mM HEPES, and 50 mg/ml gentamicin or penicillin and streptomycin (all from Invitrogen). All cell lines were treated with mycoplasma removal agent (MP Biomedicals) before use. SeV Cantell HD and LD (SeV HD, high DVG particle content; SeV LD and 52, low DVG particle content) were prepared in embryonated chicken eggs as described previously (25) . Influenza A/PR8/34 virus (IAV) was grown in 10-day-old embryonated chicken eggs (Specific-Pathogen-Free Avian Supplies, Charles River Laboratories) for 40 h at 37\u00b0C.", "Statistical analysis. Statistical analysis was performed with GraphPad Prism version 5.0 (GraphPad Software, San Diego, CA). A statistically significant difference was defined as a P value of \u03fd0.05 by either one-way analysis of variance (ANOVA) or Student's t test with or without a post hoc test, as indicated in each figure legend, on the basis of the specific data set." ] },{ "paper_id": "5d98d889c1739957886a3c27dc6552e695fee2f7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This review aims to summarize our current knowledge and to discuss the gaps in knowledge regarding AR in early childhood.", "Non pharmacological therapy with saline nasal rinses has also shown modest improvement in rhinitis symptoms in those above the age of 6 years [49] .", "Allergen immunotherapy is another therapeutic strategy that is attractive in that it reduces new sensitizations, reduces the risk of asthma and has a long term carry over effect even after cessation of therapy [2] ." ] },{ "paper_id": "5da2c99de592512c4295cc5c1b941e5f6548f065", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All in all, we believe that research on new antibacterials should meet the needs of the day-to-day clinicians working in hospitals, where fast responses should be granted within easy technological access to user-friendly databases. If we could conceive such a scenario, then novel avenues will open to explore real novel drugs.", "Editor: Grzegorz Wegrzyn" ] },{ "paper_id": "5db655de0fdc5e28e3fc13f279b5068c30e9cdc2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5dd80841cfa8fbf952df8516dd9ff3e4233b977f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All constructs were made using standard cloning procedures (Maniatis et al., 1989) .", "For immunoprecipitation, the in vitro translation reactions were diluted fivefold with dilution buffer (50 mM \"his, pH 8.0, 1% NP-40, 150 mM NaC1, I mM PMSF) and incubated with 5/~1 of control guinea pig serum or anti-p58 guinea pig serum (Worman et al., 1988) . The immune complexes were precipitated with protein A-Sepharose (Pharmacia Fine Chemicais), washed three times with dilution buffer, and then analyzed by SDS-PAGE as described above.", "A pepfide containing amino acids 2-17 of chick p58 was coupled to keyhole limpet hemocyanin (Calbiocbem Behring Corp., La Julia, CA) through an additional carboxy-terminal cysteine with maleirnido bis succinimide (MBS; Pierce Chemical Co., Rockford, IL) as described (Green et al., 1982) and used for the preparation of rabbit pelyclonal antisera as described (Harlow and Lane, 1988) . The p58 synthetic peptide was coupled to SulfoLink coupling gel (Pierce Chemical Co.) according to the suppliers protocol. Anti-p58 IgG were then affinity purified by passing crude serum over the peptide resin, washing with 0.5 M NaCI, eluting with 0.1 M glyeine, pH 2.5, and dialyzing against PBS." ] },{ "paper_id": "5e2fc4aaa3045d5c12525483a0f18010601b015a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Technical data: Table 1 .", "Analysis of risk factors and a plan for actions allow to improve a program for ECMO transport of persons affected by ALI or ARDS to a referring centre. In order to achieve this goal, four factors seem to be crucial: identification of a vehicle with specific tech features, systematic and precise settings of equipment, a toolsystem to sort out equipment and a dedicated training program for nurses involved in these missions.", "In addition, it must be underlined the importance of clinical stabilization of the patients before transport (29) . The number of adverse events observed in our patients during transport were comparable to those reported by other centers or networks that have implemented similar programs aimed at the centralization of ECMO candidates (7, 8, 12, 30) ." ] },{ "paper_id": "5e3baaac3cdc7bfad5ed84c6e7cc324a8396ebb9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5e8abc62533a447422d5ead64d4ae4991cc99052", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5ea02beeb65f975de027e3b6fedc6b239e9f2e8f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "39 primer: 59-GGCAAGCTGACCCTGAAGTTCTTTTAGGAGTGACGTA-AAC-39 59 primer: 59-TAATACGACTCACTATAGGGAGGACGATGCGG-39" ] },{ "paper_id": "5ea6161f1a3799d02f910658992bc4df2a1cefae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5eb49e806422f7b236b088d46352af5874b52700", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "One-way ANOVA and independent t-test were used for statistical analyses in IBM SPSS Statistics 21 software (Chicago, IL, U.S.A.). Results were considered as statistically significant at P<0.01. Graphics were created with GraphPad Prism software (San Diego, CA, U.S.A.).", "SBV titration is performed on Vero cells as described previously [17] with some modifications. Briefly, Vero cell line was inoculated in 12-well cell culture plate and after 18 hr cells were infected with SBV dilutions. After 3 hr of incubation of virusinfected cells in 37\u00b0C incubator with 5% CO 2 virus dilutions, inocula were removed and 1:1 mixture of 2\u00d7 DMEM and 2% carboxymethyl cellulose (CMC) were dispersed to all wells. After incubation for 6 days cells were fixed with 10% neutral buffered formalin solution and stained with crystal violet. Plaques were counted and stock virus titration was calculated as PFU/ml.", "CONFLICTS OF INTEREST. The authors declare no conflicts of interest. ", "Vero cell line is maintained in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum and penicillin/ streptomycin at 37\u00b0C incubator with 5% CO 2 . Schmallenberg virus is kindly provided by Dr. Wim H. M. van der Poel (Wageningen University in the Netherlands). Vero cells were infected with 0.1 and 0.01 MOI of SBV and excess virus not adsorbed was removed after 1 hr of incubation. Cell viability examined with trypan blue (15250061, Thermo Fisher) exclusion method." ] },{ "paper_id": "5ed43fc646fb368da6a9cf9d0029891a4b8248d1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Epithelial cells accumulate distinct popula-", "permeabilized before incubation with the primary antibodies, this technique ensures that all membrane domains will be equally accessible to labeling. The linearity and accuracy of similar methods have been previously established (Vega-", "zymes occupy distinct membranous domains within the gastric parietal cell." ] },{ "paper_id": "5f071d0350cb9013deb98f9a52070bbf0f70bb84", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5f2fed24630132d29e1336b240edc9ab68e459aa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5f3fc1bf0b828ea47a282433d84726eb5b25447c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5f4261729c0f4fadccac90a0da2c995f13b65802", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A prior study with a commercial AKAP7 antibody (from Pro- ", "Supplemental material for this article may be found at http://mbio.asm.org/ lookup/suppl/doi:10.1128/mBio.01312-14/-/DCSupplemental. Figure S1 , PDF file, 0.7 MB. Figure S2 , PDF file, 2 MB. Figure S3 , PDF file, 2.4 MB." ] },{ "paper_id": "5f52ac4738312fdb215ad06e5a2e886a6fb63efd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5f56a9b712608c599a21191b06b78bfa70ad523f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "No potential conflict of interest was reported by the authors.", "This work was supported by the Science and Technology Innovation Talents in Universities of Henan Province (No. 17HASTIT050) and", "Science and Technology Research Key Projects of Education Department of Henan Province (No. 14A310008)." ] },{ "paper_id": "5f7bc4da553becc28ba03a2ac4a98133d4689adc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Contributors All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published.", "Other relatively common clinical findings in KD include arthritis, aseptic meningitis, pneumonitis, uveitis, gastroenteritis, meatitis and dysuria and otitis. 2 9 Relatively uncommon abnormalities include, hydrops of the gallbladder, gastrointestinal ischaemia, jaundice, cranial nerve palsy, renal involvement (pyuria, proteinuria, tubular disturbances, tubulointerstitial nephritis and renal failure), petechial rash, shock syndrome, febrile convulsions and encephalopathy or ataxia. 2 9 Additional rare complications of KD include macrophage activation syndrome (secondary haemophagocytic lymphohistiocytosis), and syndrome of inappropriate antidiuretic hormone secretion resulting in hyponatraemia. 45 46 ", "Provenance and peer review Commissioned; externally peer reviewed." ] },{ "paper_id": "5f88b4180ba190e37e27776b11432d61770529ef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Digital materials such as tweets are also a potential tool for communication in public health [18, 19] with hopefully an improvement of knowledge and attitudes. However, the indicators and the methods to be used for evaluating social media must be adapted to this specific context. Digital tools used in epidemiology need to be validated as any other measure [20] .", "Public Health and Epidemiology Informatics reviewed the 97 references and drafted a consensual list of 14 candidate best papers. All pre-selected 14 papers were then peer-reviewed by Yearbook editors and external reviewers (at least four reviewers per paper). Two papers were finally selected as best papers (Table 1) . A content summary of these selected papers can be found in the appendix of this synopsis. Lamy et al. [10] describe the whole selection process.", "A comprehensive literature search was performed using two bibliographic databases, Pubmed/Medline (from NCBI, National Center for Biotechnology Information), and Web of Science\u00ae (from Thomson Reuters). The search was targeted at public health and epidemiology papers that involve computer science or the massive amount of web-generated data. References addressing the topics of the other sections of the Yearbook, such as those related to interoperability between data providers were excluded from our search. The study was performed at the beginning of January 2018, and the search over the year 2017 returned a total of 843 references.", "Articles were separately reviewed by the two section editors, and were first classified into three categories: keep, discard, or leave pending. Then, the \"keep\" and \"leave pending\" lists of references built by the two section editors were merged, yielding 97 references. The two section editors jointly Table 1 Best paper selection of articles for the IMIA Yearbook of Medical Informatics 2018 in the section 'Public Health and Epidemiology Informatics'. The articles are listed in alphabetical order of the first author's surname." ] },{ "paper_id": "5fbe76b0ae7ef869d483dfa3844a8d4f66f65c8f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.", "To make a useful comparison, this review will investigate the ", "However, no inflammation was observed in those organs. This experiment proved that hamsters develop a more severe syndrome than mice.", "CoV, reaching the viral replication peak at 2 or 3 dpi and viral shedding by 10 dpi. There was histochemical evidence of pneumonia but no clear clinical symptoms. In addition, recovered hamsters produced high levels of neutralizing antibodies to resist subsequent infection. 39 Unlike mice, the hamsters developed temporary viremia and viral replication in the liver and spleen." ] },{ "paper_id": "5fc9523915b057c03afa54f111fe9fd1995dd1ad", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This article does not contain any studies with human participants or animals performed by any of the authors. ", "The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.", "Background: Viruses are obligate parasites that depend on the cellular machinery of the host to regenerate and manufacture their proteins. Most antiviral drugs on the market today target viral proteins. However, the more recent strategies involve targeting the host cell proteins or pathways that mediate viral replication. This new approach would be effective for most viruses while minimizing drug resistance and toxicity. Methods: Cytomegalovirus replication, latency, and immune response are mediated by the intermediate early protein 2, the main protein that determines the effectiveness of drugs in cytomegalovirus inhibition. This review explains how intermediate early protein 2 can modify the action of cyclosporin A, an immunosuppressive, and antiviral drug. It also links all the pathways mediated by cyclosporin A, cytomegalovirus replication, and its encoded proteins. Results: Intermediate early protein 2 can influence the cellular cyclophilin A pathway, affecting cyclosporin A as a mediator of viral replication or anti-cytomegalovirus drug. Conclusion: Cyclosporin A has a dual function in cytomegalovirus pathogenesis. It has the immunosuppressive effect that establishes virus replication through the inhibition of T-cell function. It also has an anti-cytomegalovirus effect mediated by intermediate early protein 2. Both of these functions involve cyclophilin A pathway.", "There are several CsA derivatives ( Figure 2 ) that interact well with viruses and do not cause serious side effects. [194] [195] [196] Among these derivatives, alisporivir (Debio-025) (Figure 2(a) ), a non-immunosuppressive analog of CsA, was synthesized to contain sarcosine instead of d-methylalanine at position 3 of the PPIase domain and methyl-leucine instead of ethylvaline at position 4 of the calcineurin domain. These modifications have altered the PPIase activity and calcineurinbinding ability of the derivatives. 197 However, alisporivir still results in side effects including reversible hyperbilirubinemia and pancreatitis when used in combination with PEG-IFNa2a and ribavirin to treat hepatitis C virus (HCV) infection. 198 NIM811 ( Figure 2 (b)), another nonimmunosuppressive analog of CsA, is similar in structure to the parent molecule with one modification: methyl-leucine at position 4 being replaced by methyl-isoleucine. This derivative has antiviral effects 195 while exhibiting the same pharmacokinetic profile as CsA without nephrotoxicity. 196, 199 In 2010, SCY-635 ( Figure 2 (c)) was synthesized. 200 This CsA derivative inhibits HCV infection 201 without detectable inhibition of calcineurin phosphatase. Treatment with this drug is associated with transient increases in interferon a, k1, and k3, the cytokines responsible for the clearance of the viruses. 202 Another derivation of CsA, EDP-546, is metabolically stable with favorable pharmacokinetics that allows for less frequent and low therapeutic dosing of the drug. It is also an effective bilirubin transporter without affecting CYP450, a major protein in drug metabolism. 203, 204 Sanglifehrin A (SFA) (Figure 3 ) is a new immunosuppressive agent 205 isolated from the Streptomyces strain A92-308110. This protein interacts strongly with CyPA 206-208 but not with calcineurin phosphatase. 209 It is also a potent inhibitor of mitochondrial permeability transition and heart reperfusion injury. 210." ] },{ "paper_id": "5fedd08f111b588bface2d146740bad23bbbb3e3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For a set of coupled ordinary differential equations", "Step 4: Record (X, t) as desired. Return to Step 1, or else end the simulation.", "Step 2: Draw two random numbers r 1 and r 2 from the uniform distribution in the unit interval, and take Step 3: Replace t \u2190 t + t and X \u2190 X + c j ." ] },{ "paper_id": "6005b8055730f4625c1995a57def5c32fa3f4ec7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "601d3c7ae4ebcd2d835e9cf8d7427ebd0b5db83f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplementary data to this article can be found online at https:// doi.org/10.1016/j.meegid.2020.104272.", "This work was supported by the MEXT-Supported Program for the Strategic Research Foundation at Private Universities (grant number S1511028 to T.I) and the Takeda Science Foundation.", "Coronaviruses are enveloped RNA viruses that infect many species, including humans, other mammals, and birds. After infection, the host may develop respiratory, bowel, liver, and neurological diseases (Weiss and Leibowitz, 2011; Cui et al., 2019) . Coronaviruses are members of the order Nidovirales and subfamily Orthocoronavirinae. This subfamily is divided into four genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. Generally, Alphacoronavirus and Betacoronavirus tend to infect mammals, while Gammacoronavirus and Deltacoronavirus typically infect birds. However, some Gammacoronavirus and Deltacoronavirus can infect mammals under specific conditions (Woo et al., 2012) ." ] },{ "paper_id": "602981d75e74595af0e2de9e046a9cc9e05a1c0e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.00198-11/-/DCSupplemental. Figure S1 , PDF file, 0.1 MB. Figure S2 , PDF file, 0.1 MB. Figure S3 , PDF file, 0.1 MB. Figure S4 , PDF file, 0.3 MB. Figure S5 , PDF file, 0.8 MB. Figure S6 , PDF file, 0.1 MB. " ] },{ "paper_id": "6050d0c1b7c6990972e6cdfca89f79745b13cc14", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Immunoprecipitates were released from the protein A-Sepharose beads by boiling for 3 min in 30 Ixl 200 mM Na-citrate, pH 5.5, 2% SDS in the presence of protease inhibitors, frozen at -20\u00b0C for 30 rain, and boiled again for 3 min. Then the samples were diluted with an equal volume of distilled water containing protease inhibitors and incubated with 4 mU endoglycosidase H (endo H) for 22 h at 37\u00b0C.", "ERGIC-53 is a lectin-type membrane protein that continuously recycles between the ER, ER-" ] },{ "paper_id": "60522266645f5d89d709c2a6dc0f45a072f64dfd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Categorical variables are expressed as numbers and percentages. Fisher exact tests and the chi-square tests were used to evaluate statistical significance. Continuous variables are expressed as means and standard deviations (SD). Independent t test was used to evaluate statistical significance. All statistical analyses were performed using SPSS version 21.0 (IBM Corp., Armonk, NY, USA). A p-value of <0.05 was considered statistically significant.", "The primary study subjects were 5,298 patients, who underwent multiplex real-time polymerase chain reaction (PCR) for simultaneous detection of respiratory viruses, among who visited the emergency department or outpatient clinic with respiratory symptoms at Ulsan University Hospital from April 2013 to March 2016 ( Figure 1 ). The medical records of all these patients were retrospectively reviewed in detail.", "No potential conflict of interest relevant to this article was reported." ] },{ "paper_id": "606233835c3d6d195b7d230745ccb0fded626aa7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(1) Data model" ] },{ "paper_id": "6092602066323176223cd6d8deadfb8f689c0ea0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "60b766c8bbe49fb1702f0784263e8a258ed067f3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In vitro measure of ability of PBMCs to promote either Th1 or Th2 immunity", "In vitro measure of ability of immune cells to produce/release cytokines in response to an immune stimulus.", "An allele at \u00fe 874 is associated with reduced IFN-g production and consequent reductions in Th1 activity \u00fe 874 A predisposes for hepatitis B and C persistence and negatively affects clinical course of these diseases. 290 Reference numbers in Table 3 correspond to reference numbers in paper bibliography.", "Reduced PBMC production of IFN-g and IL-12 is associated with increased severity of respiratory syncytial virus symptoms in infants under 1 year of age. 277 Increased activity alleles of the IL-10 gene (i.e., \u00c01082G)" ] },{ "paper_id": "60bcf8aea7134c49453a05d2b9d52728cc6edcd6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. Experimental data are presented as means \u00b1 standard error of the mean. Significant differences of the variability among different groups were analyzed by two-way ANOVA test or t-test using GraphPad Prism (version 5.0; GraphPad Software, Inc., La Jolla, CA, USA) software. A P<0.05 was considered to indicate a statistically significant difference.", "Porcine reproductive and respiratory syndrome (PRRS), which is characterized by reproductive disorders in pregnant sows and respiratory diseases in growing pigs, is a viral disease caused by PRRS virus (PRRSV) (1, 2) . Since its first outbreak in 1987 in USA (3), PRRS has spread to the major pig-producing countries and regions (4) , causing tremendous economic losses to the world pig industry. The emergence and prevalence of highly pathogenic (HP)-PRRSV with a 30-aa discontinuous deletion in its nsp2-coding region devastated the Chinese swine industry in 2006 (5, 6) . PRRSV, a single positive-stranded RNA virus, is classified into the genus Arterivirus of family Arteriviridae in the order Nidovirales (7) (8) (9) . This virus can be divided into two genotypes, namely types 1 and 2 (10) (11) (12) .", "F and R, primer pairs were annealed and inserted into pmirGLO dual-luciferase miRNA target expression vector digested with PmeI and XbaI; b NotI restriction endonuclease site is underlined; MRE, miRNA recognition elements; IFN-\u03b2, interferon-\u03b2; 3'UTR, 3' untranslated region." ] },{ "paper_id": "60cc55d9df1b0ff215bcaefe413b7b6edc5eb182", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "KEY WORDS: avian coronavirus, cell-mediated immunity, humoral immunity, mucosal immunity, oil adjuvant", "Inf.", "Ep. Dec." ] },{ "paper_id": "60e51d3d13b027492b9f3b8693c58dd8b5385ada", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "60f1455bed921da2e4f3df7aae854cb8e142ff44", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We calculated gap entropy at each position as:", "For all nonparametric bootstrap calculations, we used 100,000 bootstraps, and chose groups of sites without replacement; that is, if calculating a statistic for a group of 17 residues, we would choose 17 different residues for one sample, and resample 100,000 times.", "One possible problem with this analysis would occur if indels themselves disproportionately contributed to branch length, thereby causing an artificial correlation between branch length and these mutations. This possibility can be ruled out: when FastTree estimates branch lengths, positions with gaps are either ignored (when comparing two sequences) or weighted by their proportions of nongaps (when comparing two sequence profiles)." ] },{ "paper_id": "6101fcc0282d2e355b5e094de10aafaa05e749c6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Because many reports are contradictory on the relationship between transfusions and NEC, additional studies are necessary involving larger patient groups. In addition, the patient's general condition and the risk of NEC based on the transfusion must be considered when treating preterm infants <1,500 g.", "PDA was diagnosed based on echocardiographic findings. The number of transfused patients, the frequency of transfu sions per patient, Hgb level at the time of transfusion, and cases in which the NEC diagnosis was made within 48 hours of transfusion were also analyzed. The Statistical analysis was performed with SPSS ver. 12.0 (SPSS Inc., Chicago, IL, USA) using the t-test, and logistic regression. P value under 0.05 was considered significant.", "No potential conflict of interest relevant to this article was " ] },{ "paper_id": "6107c0ccde81ea8fb7c6a10fc39048eedf5c2447", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The systematic characterization and classification of knots has engaged scientists since the introduction of Tait's knots table, whose first entries are shown in Fig. 1A . It is readily seen that the different types of entanglement are permanently trapped in the closed curves. In fact, any two curves cannot be continuously deformed into one another unless they are cut open, rearranged and resealed.", "In our everyday life, the knots that typically surround us differ from these well-defined mathematical ones because they are tied in open chains (Fig. 1B) . These knots are clearly not permanently trapped and hence are termed \"physical knots\". Many of the physical knots that we encounter have been purposely introduced in, for example, the yarn of sewn clothes or in ropes secured to anchoring points. Not infrequently, however, we have to deal with their unwanted spontaneous occurrence, as in the earphone cords pulled out of our pocket.", "No potential conflicts of interest were disclosed." ] },{ "paper_id": "611a37c75e97cd0e251685d63fbbb42dbe3827b9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The results are presented as the mean 6 standard deviation (SD). Statistical significance between different vaccination groups was calculated by Student's t-test and Kaplan-Meier analysis using the statistical package for the social sciences (International Business Machine Corporation, Armonk, NY, USA) statistical software. P-values less than 0.05 were considered significant.", "Viral RNA copies in mouse lung homogenates were measured by quantitative reverse-transcription polymerase chain reaction (QRT-PCR) as described previously. 23 Briefly, viral RNA of mouse lung homogenate was extracted using the RNeasy Mini Kit (Qiagen, Valencia, CA, USA). The extracted viral RNA was reverse-transcribed to cDNA using Superscript II (Invitrogen, Waltham, MA, USA) and primer Flu12 (AGC AAA AGC). The viral RNA copy numbers in the samples were determined using a Lightcycler 96 (Roche Applied science, Penzberg, Germany) with SYBR green I master (Roche Applied science, Penzberg, Germany). Primers specific for influenza viral M gene (forward primer: 5-CTT CTA ACC GAG GTC GAA ACG-3; reverse primer: 5-GGC ATT TTG GAC AAA KCG TCT A-3) were used in the QRT-PCR assay.", "Virus titers were detected by TCID 50 assay as described previously. 20 Briefly, the infected allantoic fluid and mouse lung homogenates were serially diluted 10-fold in minimum essential medium (Invitrogen, Waltham, MA, USA) containing a cocktail of antibiotics. The diluted samples were added to PBS-prewashed Madin-Darby canine kidney cell monolayer in a 96-well plate. The cell cultures were incubated at 37 6 C for 1 h, and the supernatants were replaced with fresh minimum essential medium containing a cocktail of antibiotics. The cytopathic effect that appeared in the infected Madin-Darby canine kidney cells was observed daily and recorded on the third-day post-infection." ] },{ "paper_id": "61316d789f66022b466f2924837aaff7f0bf65f5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "61610467351ceab87933d94e3c6e487654d316a8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "These two scenarios can result in a monophyletic distribution of the blue gene (D) without a de novo origin within an overlapping reading frame. Figure S4 : Phylogenetic relationships among coronavirus sequences. A phylogenetic tree based on the full protein sequence of the ancestral gene and the corresponding genomic maps are shown. The tree was inferred using the BIONG method (Gascuel 1997).", "are the results of two independent origins, is less parsimonious. Because the black gene has no significant sequence similarity with the other genes in the clade, we did not use it for calculations of relative divergence and selective constraint. This scenario corresponds to taxa (4, 5, 6, 8, and 9) in which one (taxa 4, 8, and 9) or two (taxa 5 and 6) de novo genes within a monophyletic clade have no sequence similarity." ] },{ "paper_id": "616cdd0a8b488fcf0b28781f710cc7fba8625a4d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The phylogenic tree was constructed using the neighbor joining method and MEGA software (version 4.0; Biodesign Institute, Tempe, USA). The topological stability of the tree was evaluated by 1000 bootstrap replications.", "The cDNA was synthesized using PrimeScript TM RT reagent kit (Takara, Tokyo, Japan) according to manufacturer's instructions. 8 A fragment of the S1 gene (464 bp) was amplified using a pair of specific primers including XCE1 (5'-CACTGGTAATTTTTCAGATGG-3') and XCE2 (5'-CTCTATAAACACCCTTACA-3'). 9 The PCR reaction and its thermal condition were set up as previously described. 10 The PCR products were electrophoresed on 1.00% agarose gel.", "Extraction of RNA from the allantoic fluid was carried out using RNX-plus Solution (CinnaGen, Tehran, Iran) according to manufacturer's instructions. The isolated RNAs were stored at -80 \u02daC." ] },{ "paper_id": "616d2117cb63fecdaa5ae2901cca9d1b610dd799", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "617197cc751a9208cb0af1b4e31baeddc8d2e985", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "618a793838421a7bf238e8f6ae2635ca3d2f5a25", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "61ad64021b0e34d5e3a82a4310cc92d123a7061c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org/ lookup/suppl/doi:10.1128/mBio.00019-16/-/DCSupplemental. Figure S1 , TIF file, 0.2 MB. " ] },{ "paper_id": "61b8415c8659a58c24af2b8a2456bed96b61b609", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As-GST-1", "Trichuris trichiura is a parasite of the superfamily Trichinelloidea, known as the common whipworm of humans and nonhuman primates. Due to its host specificity, there is no established laboratory animal model for this pathogen. Fortunately, the closely related Trichuris muris parasite, specific for rats and mice, has emerged as a useful surrogate for immunogenicity and efficacy models. Additionally, animal models for Trichinella spiralis (a cause of trichinellosis), also a member of the Trichinelloidea superfamily, exhibit some immunological similarities for Trichuris sp. Both Trichuris sp. and Trichinella sp. possess a unique stichosome -a modified esophagus and esophageal gland that contains longitudinally arranged cells known as stichocytes -which is a rich source of ES Photo courtesy of Florian R\u00f6 ber, originally published in [85] \u00d3 Florian R\u00f6 ber.", ". Avoiding the potential allergic responses by down-selecting antigens that elicit IgE among endemic populations.", ". Scaling-up soluble and appropriately refolded recombinant proteins that could be manufactured under current good manufacturing practices and identifying a suitable manufacturing partner." ] },{ "paper_id": "61c1d57c318f5a10b2d31abd543d55e24d1fa47c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "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. The total score was obtained by adding the relative weight of all comorbidities. For each decade > 40 years of age, a score of 1 is added to the sum of the abovementioned scores. [34] [35] [36] [37] ", "All statistical analyses were performed using the statistical package STATA for Windows (version 11.0). A P-value of .05 was considered to represent statistical significance." ] },{ "paper_id": "61c74b574c1b33ece0ca2f53861597d70c61a720", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "and to facilitate implementation of CID policy in the PHSs regions.", "Because of limited experience with and exposure of infectious disease, extensive investment in developing protocols and training in, for example, donning and doffing of personal protective equipment was necessary. \"The fear of contamination, we really were afraid that the fear of EVD would cause more casualties than EVD itself.\" \"It took us months to install the correct personal protective equipment procedures.\" Peripheral hospital", "The EVD laboratory tests were negative for all patients, and alternative confirmed diagnoses were malaria (n = 7), bacterial sepsis (1), norovirus (1), and no diagnosis (4) ." ] },{ "paper_id": "61d0aa9a148a88e0354e36508c925eeb87a6b685", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "61d252869a226c4393e4637cb90fa3b4df082ae3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "61f4cc62aa5a8b65d63664101a7e4af71a7c1df4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6214d0592f9322221375a64360716a1cae0add5f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6220d2580a3a4a5c86ea58944be947b5d4c0bc0b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Consistent with the distal signal being closely related to the CD33, chain di-leucine signal, Ile s could be modified to leucine without loss of activity. Interestingly, the nonconservative mutation of Pro ~5 to leucine did not reduce the internaliTation activity of the membrane-proximal signal (Table HI) .", "Immunoprecipitates were quantitated on a model 425 Phos-phorImager (Molecular Dynamics). The data shown are from one of two similar experiments.", "Finally, Dintzis and Pfeffer (1990) observed that the M6PR cytoplasmic tall was not sufficient to target the epidermal growth factor receptor to prelysosomes and suggested that additional sorting information in the M6PR transmembrane region and/or extracellular domain may be required." ] },{ "paper_id": "62219dc0553022e4faac2b1523e7e0a2d1eaec30", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Abbreviations: AST = aspartate transferase, MELD-Na = model for end-stage liver disease with incorporation of serum-sodium.", "The general, socioenvironmental, and clinical factors of 263 patients were as follows ( " ] },{ "paper_id": "622504276a8cd63e834d19f7b3c26ca4c2bbcb40", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For epon embedded sections animals were perfused with 4% paraformaldehyde and 2.5% glutaraldehyde in Sorensons phosphate buffer. Spinal cord segments were placed in fixative overnight, post fixed in Osmium tetroxide, and processed to Epon by standard procedures. Cross-sections of cervical, thoracic, and lumbar cord segments were cut on an ultramicrotome at a thickness of 1 micron and stained with toluidine blue.", "This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. 2106 V C 2015 The Authors. Glia Published by Wiley Periodicals, Inc. enhances astrocyte migration, and improves functional recovery (Okada et al., 2006) .", "Morphological differences in focal versus expanding lesions were examined in Epon embedded sections at day 31 p.i. (Fig. 3C,D) . Demyelination was confined to relatively small areas at the outer perimeter of the WT spinal cord (Fig. 3C ). Debris filled macrophage/microglia were not prominent 2110", "Volume 63, No. 11 TCTCGGCCTGTT-3 0 ; Arginase-1 (Arg-1) sense, 5 0 -TGGGTG GATGCTCACACTGA-3 0 , Arg-1 antisense, 5 0 -CAGGTTGC CCATGCAGATT-3 0 ; IL-1 receptor antagonist (IL-1Ran) sense, 5 0 -AGATAGACATGGTGCCTATTGACCTT-3 0 , IL-1Ran antisense, 5 0 -CATCTCCAGACTTGGCACAAGA-3 0 . For IFN-g (Mm01168 134_m1) and GAPDH (Mm99999915_g1) expression levels were determined using Applied Biosystems gene expression arrays with Universal TaqMan Fast master mix (Applied Biosystems). PCR conditions were 20s at 958C followed by 40 cycles of 958C for 3 s and 608C for 30 s. Transcript levels were calculated relative to the levels of the housekeeping gene GAPDH using the formula 2 [CT (GAPDH) -CT(target gene)] 3 1,000 where C T is determined as the threshold cycle at which the fluorescent signal becomes significantly higher than that of the background." ] },{ "paper_id": "626bcea8ab6811ee19f946cb84a273601cfd7bcc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 General practitioners are the first line of defense against antibiotic resistance within communities.", "\u2022 Antibiotic resistance mechanisms in general practice are diverse.", "This publication was supported by a Horizon2020 EU grant under grant agreement GA-633780 ('DIAGORAS' -www.diagoras.eu)." ] },{ "paper_id": "62cd5be77a70a55d18199836987e521d4b992cbd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In some TCRs, the two different orientations (a-P2A-b and b-P2A-a) resulted in nearly equal expression. This similarity between orientations was primarily observed in TCRs with the highest TCR V beta expression (.25% of CD8 T cells). These TCRs may be particularly stable and thus expression is not influenced so significantly by endogenous TCRs. The end result is that a majority of the TCR cassettes have an optimal orientation and testing both can be an easy solution that significantly increases expression.", "PBMC were stimulated with 600 U/ml interleukin-2 (IL-2; R&D Systems) and 50 ng/ml anti-CD3 (OKT-3; eBioscience, San Diego, CA) for 48 h. Untreated 24 well tissue culture plates were coated with 30 ug/ml Retronectin (Takara Bio) overnight at 4uC one day prior to transduction. Wells were then washed with HBSS and blocked with PBS 2% BSA. Lymphocytes were harvested, washed, counted and 5 3 10 5 cells plated into retronectin coated wells and mixed with 1.5-2 ml of unconcentrated retroviral supernatants collected as described above. After 24 h, the viral supernatant was replaced with Aim-V medium with 2% human AB serum, supplemented with 100 U/ml IL-2. TCR surface expression was tested with HLA-pentamers (ProImmune), HLA-tetramer produced by peptide exchange 39 or anti-Vb antibodies 72 h post transduction. Functionality of TCR redirected T cells was tested 7 days post transduction as described below.", "We then tested whether the inflammatory environment led to increased Th1 polarization or caused non-specific bystander activation to account for the increase in IFN-c1 T cells. Unlike figure 4 , where HLA-pentamer and IFN-c staining were performed in separate assays, we measured IFN-c production in HLA pentamer1 or TCR Vbeta1 cells to measure cytokine production in TCR transduced cells." ] },{ "paper_id": "62d641575bf71e839a2c4f4c7a6dc398ef2b5a0a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Animal Model Exp Med. 2018;1:247-249.", "None." ] },{ "paper_id": "62f47ced8c3249f702f0058dc3b6cdb93ca083eb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Note that 5S rRNA, tRNA and miRNA are pseudoknot-free.", "KnotSeeker due to the inclusion of pseudoknots with one interrupted stem.", "DotKnot has excellent accuracy for simple H-type pseudoknots as those reported in many viral 3 0 -UTRs and frameshifting regions. We found that the energy models CC06 and CC09 used for predicting such " ] },{ "paper_id": "62f8fe75756cfe9bee96096f566d79994b7ff5de", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors report no conflict of interest in this work.", "Finding novel therapeutics to treat and cure diseases is a fundamental challenge in biomedical research due to the high cost and failure rate. Drug repositioning is considered a promising strategy to revitalize the slowing drug discovery pipeline due to shorter development time and lower failure and toxicity risks. Although drug repositioning has its intrinsic limitations, it represents an alternative pathway to achieve therapeutic success in the postgenomic era." ] },{ "paper_id": "630a6b5851e9d6362eb68f157fa704bfd97f1705", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6328beb961554b05276359e9c5b26d2e57cd52e9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The Journal of Cell Biology, Volume 102, 1986 2154", "Parallel immunoprecipitations of detergent extracts with antibodies directed against either u or K chains demonstrated that excess free heavy or light chains were detectable immediately after synthesis (Fig. 4, lanes 4 and 6) and not at later times (Fig. 4, lanes 2, 3, 8, and 12) appeared complete as early as 30 min after synthesis, since the ratio of Um:K at this and all later times of chase (Fig. 4 , lanes 8-15) closely resembled the steady-state ratio of the two polypeptides (data not shown). These results indicated that in our pulse-chase experiments, we were examining assembled IgM molecules rather than a pool of free ~mS blocked in transport in rough ER due to a deficiency of association with K light chains. Similar rates of intracellular transport of urnS have been suggested for IgM molecules synthesized in murine spleen cell populations (60) .", "Oligonucleotide-directed mutagenesis was" ] },{ "paper_id": "632bcacf9702ee34c5424827ab7e5449dd21ddcf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All ethical issues including plagiarism, Informed Consent, misconduct, data fabrication and/or falsification, double publication and/or submission, redundancy, etc have been completely observed by the authors.", "Respiratory virus infections in children are a leading cause of morbidity and mortality worldwide. Methods: A total of 897 clinical specimens were collected from February 2007 to January 2008 and transported to the National Influenza Center. Two hundred and two samples belonged to children under the age of six from 897 specimens, described above, were selected. Then they were tested for influenza virus types and subtypes by real time PCR assay subsequently, the specimens were tested for RSV and hMPV by hemi-nested multiplex PCR and parainfluenza viruses type 1-4 by hemi-nested multiplex PCR and adenovirus by hemi-nested PCR. Results: The throat swab was taken from the Kawasaki case with the history of chicken`s contact. The specimen was tested for all influenza subtypes especially H5N1 and the results were negative. Meanwhile PCR was done for screening of other respiratory viruses that results came out positive for RSV and hMPV. Conclusion: In the present study, we demonstrated the possibility to detect dual infection caused by RSV and hMPV, but because of the extravagant pattern of this case, more investigation is suggested specially on Kawasaki patients.", "In the present study, we demonstrated the possibility to detect dual infection which caused by RSV and hMPV. Due to the lack of sensitivity of conventional methods detection of co-infections with different respiratory viruses had been un-derestimated (13) . Severe RSV bronchiolitis in small patient series had been recognized because of co-infection with other viral pathogens (14) . Some previous studies have lighted up increased clinical severity in case of dual infection caused by RSV and hMPV (8, 9) . Greensill et al. observed a 70% co-infection rate with HMPV and RSV and a 90% co-infection rate among intubated infants with hMPV and RSV admitted to their PICU (8) . Although Greensill et al. did not include an appropriate control group in their study, these findings suggest that co-infection with both hMPV and RSV is common and that together the two viruses may contribute to increase the severity of disease (9, 14) . Whereas in other reports hMPV did not contribute to the severity of RSV infection (15, 16) . The basis of the pathogenesis of severe RSV disease is multifactorial. Since severe RSV disease may develop in apparently healthy children, known host risk factors cannot completely account for instances of severe illness. Preexisting or maternally acquired immunity, innate immunity, viral factors and genotypes and environment all likely contribute to disease pathogenesis. We detected co-infection of hMPV and RSV in Kawasaki patient without special respiratory sign and symptoms, we could not find the patient to follow up her and study more about the immunity status and other possibilities of this scenario. More investigation is suggested specially on Kawasaki patients to detect the viral pathogens." ] },{ "paper_id": "634128ea7d7736750e1c3cd0a48bb37843d06dac", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cooccurrence. Patterns of association/disassociation were explored with the Fortran software program PAIRS (11) , utilizing the C score statistic as our measure of species cooccurrence. PAIRS implements a Bayesian approach (Bayes M criterion) to detect nonrandom associations between pairs of species (12) .", "viruses can exist in a single sample. Not only does this reveal information about the carrying capacity and composition of discrete viral niches within an individual bat, it also demonstrates the number of different viruses that could potentially spill over to a new host from a single exposure event.", "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.00598-13/-/DCSupplemental. Text S1, DOCX file, 0.1 MB. Figure S1 , PDF file, 0.1 MB. Figure S2 , PDF file, 0.3 MB. Table S1 , PDF file, 0.6 MB.", "All analyses were conducted with the fossil package (62) implemented in R (63). We followed Chao et al. (10) to calculate how many additional samples would be required to detect any proportion (including 100%) of the asymptotic virus richness. All statistics were incorporated into a single plot." ] },{ "paper_id": "636a2debbb56c9142bbf960d9a200665c556e05a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "637939a0f462b9e821ff62fc20e9fedfe78df73e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The ethical approval or individual consent was not applicable.", "Not applicable. ", "All data and materials used in this work were publicly available." ] },{ "paper_id": "6380762dca586738fd20d4b1c4bbdc3722a313aa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "638c624925ed19a692dcd98a7285191537b1c7c0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "63aed9fa99e7df7846c24993fbf4d7aebb4d957a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A demyelinating disease induced in Dr. Friedrich's current address is Brookdale", "A segment of each spinal cord was excised with a sterile razor blade before glial cell isolation. Segments were fixed by overnight immersion in 1% glutaraldehyde and 2% paraformaldehyde in 0.1 M phosphate buffer. The tissue was then washed for 1 d in buffer, postfixed with 2 % osmium tetmxide for 2 h, dehydrated in graded alcohols, cleared with propylene oxide, and embedded in Epon resin. Transverse sections (1 ~m) were stained with toluidine blue.", "Female C57B1/6N mice, without prior exposure to MHV-A59, were obtained from the Frederick Cancer Research Facility (Frederick, MD). At 28 d of age each mouse was injected intracranially with 1,000 plaqueforming units of coronavirus (MI-IV-A59), which had been propagated in the 17 CI 1 line of spontaneously transformed BALB/c 3T3 cells (Sturman et al., 1980) . This age and inoculation dosage op \"ttmized the proportion of mice developing demyelinating lesions ('069 %) relative to the incidence of acute mortality (,o11%)." ] },{ "paper_id": "63c64ba93501a9ec60ab113b55c23d5bc602a13c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Finally, a filter referred to as the replicate combination filter is applied, wherein results from two independent replicates are combined and SNPs present in both the experiments are accepted. This step is performed after the other filters have been applied to individual data sets generated for any single sample.", "Whole-genome sequencing is probably the most accurate and reliable method to identify and type strains of a species. SNPs and other polymorphisms that serve as informative genetic characters are globally determined and therefore enable a more complete evaluation of inferred evolutionary relationships. The cumulative differences between two or more sequences provide a larger framework upon which reliable phylogenies may be established. Strain genotypes that are built upon SNP variation are highly amenable to evolutionary reconstruction and can be readily analyzed in a phylogenetic and a population genetic context to: (i) assign unknown strains into well-characterized clusters, (ii) reveal closely related siblings of a particular strain and (iii) examine the prevalence of a specific allele in a population of closely related strains that may in turn correlate with phenotypic features of the infectious agent (1) . More directly and for a variety of purposes such as forensic investigations or epidemiological investigations, SNPs provide potential markers for the purpose of strain identification.", "Detection, identification and typing of infectious microorganisms are crucial in many areas of basic and translational research. There is an urgent need for accurate, high-resolution microbial genotyping methods, in spite of the existence of a number of widely used typing methods. That is because the current methods offer only low-resolution and limited genotyping. Single nucleotide polymorphisms (SNPs), horizontal gene transfer and/or intragenic recombination are all known to lead to variations and genome plasticity in an organism. The diversity of an organism can be explicitly understood provided these events are identified and analyzed quantitatively and qualitatively at the whole-genome level." ] },{ "paper_id": "64026e37a33880c07a23deabc68e8e0d8d790c59", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Leishmaniasis is a disease caused by the protozoa Leishmania, which affects 12 million and threatens 350 million people in 88 different countries. There can be different clinical presentations such as cutaneous and visceral (42) . Leishmaniasis is transmitted by the vector phebotomine sandflies. When rural migrants bring their domesticated animals to urban settings, often slums, they create favourable conditions for an urban transmission (43) . It has been shown that it is a growing health problem and the ongoing urbanization has contributed to the increase (44) .", "The rapid urbanization has also interfered in previously untouched ecosystems. These new settlements create new and closer encounters with wildlife, which can be a potential source of zoonotic diseases. These can be both previously known or new pathogens, which make the shift from their animal host to generate infections in humans. Surveillance is of primary importance to monitor the burden of disease and will give both local authorities and the global community a chance for a quick response to public health threats. ", "The zoonotic disease dengue is endemic in most tropical and subtropical regions, which often are also popular tourist destinations. Travellers to endemic countries can contribute to the spread of the disease. The burden of disease is on the rise, and estimations are that in returning travellers from Southeast Asia, dengue is now a more frequent cause of febrile illness compared to malaria (49) . Dengue is now an urban health problem, which is one of the major reasons why the rise is exceptional.", "Numerous of the neglected tropical diseases play a major role in the developing world, which is currently experiencing a much faster pace of urbanization compared to the developed world. The WHO's call for help is important and, for example, dengue is now turning into a global crisis. Safe and targeted assistance can be a huge factor for overall health; such assistance could be an effective vaccine or safe and easy vector control programs." ] },{ "paper_id": "64212980bf5953f369ec10e8a54517ec6ce10227", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Inflammatory bowel disease (IBD) has been long ago recognized as a systemic inflammatory entity and as such, it is anticipated to induce changes exceeding the boundaries of bowel mucosa, being reflected in a broader spectrum of tissues, including blood [1] [2] [3] [4] [5] [6] [7] .", "AHSG serum levels were determined in treatment-na\u00efve newly-diagnosed patients, 96 with ulcerative colitis (UC), 84 with Crohn's disease (CD), 62 with diarrheapredominant or mixed irritable bowel syndrome (IBS, D-and M-types) and 180 healthy controls (HC), by an enzyme linked immunosorbent assay (ELISA).", "To investigate the impact of inflammatory bowel disease (IBD) on \u03b12-Heremans-Schmid Glycoprotein (AHSG/fetuin A) and potential associations with disease and patient characteristics." ] },{ "paper_id": "643f2dd329f342e9e85753ab315722bc1120d0ef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "On admission, he was fully conscious and oriented. Vital signs showed a blood pressure of 88/51 mmHg, heart rate of 97 beats/min, respiratory rate of 27 breaths/min, and body temperature of 38.7 o C. His heart beat was regular without murmurs, and breath sounds were clear on both lung fields. His abdomen was soft and flat with normoactive bowel sounds. However, there was tenderness in the right upper quadrant region and hepatomegaly of 3 fingerbreadths and splenomegaly of 1 fingerbreadth were palpated below the costal margins. Erythematous maculopapular skin rashes without pruritis were observed on both lower extremities. Neurologic examination was normal.", "Initial laboratory exams showed a hemoglobin of 13.1 g/dL, hematocrit 37.0%, white blood cell (WBC) count of 6,310/mm 3 Chest radiography conducted on admission was normal without any lesions in the lung (Fig. 1) . Computed tomography (CT) scans of the abdominal revealed mild hepatomegaly with periportal edema ( Fig. 2A) . Diffuse edematous change of the gallbladder and small amount of ascites was also found on CT images (Fig. 2B) .", "The patient was followed at the outpatient clinic two weeks after discharge. Laboratory exams showed normalization of levels that were above normal range prior to discharge, revealing a CRP of 0.03 mg/dL, AST of 33 IU/L, ALT of 24 IU/L, CK of 87 IU/L, LD of 412 IU/L. Serum antibodies to M. pneumoniae detected by ELISA were 79.6 AU/mL for IgG, and 2.6 index value for IgM, confirming the diagnosis of M. pneumoniae infection." ] },{ "paper_id": "64531e8dca54414b55f67981cd6e67b77fe8c43c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All tissues were fixed in 10% neutral-buffered formalin, routinely processed and embedded in paraffin wax. Tissue sections of 4 \u00b5m-thick were stained with hematoxylin and eosin (HE). Selected brain sections were subjected to immunohistochemical examinations. Normal feline brain tissue was also stained as a control. Deparaffinized and rehydrated sections were treated through the antigen retrieval methods listed in Table 2 . After being immersed in 3% hydrogen peroxide in methanol at room temperature for 5 min, the sections were treated with 8% skim milk at 37\u00b0C for 40 min. The sections were then incubated with the primary antibodies listed in Table 2 at 4\u00b0C overnight, and then incubated with the Dako EnVision + System horseradish peroxidase (HRP)labelled anti-rabbit (Dako-Japan, Tokyo, Japan) or anti-mouse secondary antibodies (Dako-Japan) at 37\u00b0C for 40 min. The antigenantibody reaction was visualized with 0.05% 3.3\u2032-diaminobenzidine and 0.03% hydrogen peroxide in tris-hydrochloric buffer. Counterstaining was performed with hematoxylin." ] },{ "paper_id": "645a3eaa114cc4a4827d02c0ef31b8a19c45b802", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "647f5293613f9be827c37bb609d3248db9889d78", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Anemia-anaemiaimmun* 723", "Anemia-anaemiaimmun*-inclusion 248", "Anemia-anaemiaimmun*-inclusion 181" ] },{ "paper_id": "6485112a971484dfa041b32b35b25707954807db", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The intracellular transport of newly synthe-", "A summary is presented in Tables II and III of Bars, 100 nm.", "Received for publication 19 January 1988, and in revised form 19 October 1988." ] },{ "paper_id": "649b681845a59b87d339917c75ef51c6c55b3a46", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We have used the sedimentation behavior of catalase and thyroglobulin in parallel gradients as markers to get an estimate of the size of M/S complexes. These proteins peaked in fractions 13 and 12, respectively (data not shown). This indicates that most complexes migrated as structures with sedimentation values higher than 20S.", "When the m A b a M was used instead, coprecipitation of labeled S was not observed immediately, but only after 10-20 min of chase. Later, the amount of coprecipitated S, including its cleaved form S/gp90, gradually increased. These observations indicate that S associated with M before its processing to the mature forms S/gpl80 and S/gp90. M and S thus engage in complex formation at different rates: M rapidly associates with S, while S does so only after a considerable lag time. This implies that newly synthesized M molecules associate with S molecules already present.", "Under conditions of analysis, the stability of the envelope glycoprotein complexes is critically dependent on the detergents used for their solubilization. M-S interactions are preserved in a combination of NP-40 and sodium deoxycholate. Several observations indicated that M/S complexes do not form nonspecifically after solubilization. First, other proteins were not significantly coprecipitated with M and S. Second, newly synthesized S started to associate with M only after a lag time of about 20 min. Third, M/S complexes were not formed upon mixing lysates containing M and S that had been separately expressed. Moreover, flotation analysis ruled out the possibility that M and S were coisolated as part of detergent-insoluble membranes (data not shown). Collectively, these data provide evidence for the existence and specificity of M-S interactions.", "If these interpretations were correct, the M and S proteins would be incorporated into virus particles with different kinetics. We therefore performed a pulse-chase labeling of infected cells and monitored the appearance of labeled proteins in extracellular virus. Because MHV is assembled intracellularly, such an analysis provides an indirect measurement of the kinetics of incorporation of newly synthesized proteins into virus particles. Virus was purified by pelleting and analyzed by SDS-PAGE (Fig. 3 A) . The results of the quantifications of the radioactivities in the bands representing M and S (S/gp180 + S/gp90) are shown in Fig. 3 B." ] },{ "paper_id": "64b6854e48706ee2c77c4450292e72d11b7e4252", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Citation Imperiale MJ, Casadevall A. 2015. The importance of virology at a time of great need and great jeopardy. mBio 6(2):e00236-15.", "Despite all this good news, much remains to be done. It was recently estimated that there are 320,000 mammalian viruses (2), many of which may have the potential for human transmission. Even if only a small fraction of these viruses can jump into humans and cause disease, humanity is living under a tremendous threat from viral zoonoses. Less expensive drugs are needed for treating those with viral infections such as hepatitis C. While the HPV vaccine can prevent many infections, there are viral types that are not covered by the vaccine, and many millions of people were infected before the vaccine came on the market. Infections with numerous other viruses are not treatable due to the lack of effective antivirals. Clearly, vaccines against HIV, hepatitis C, and Ebola, to name a few, would save countless lives. New pathogens continue to emerge, and existing nonviral pathogens become resistant to common antibiotics. Hence, we are living at a time of great need for the discipline of virology.", "We think that the field of virology and, by extension, the field of microbiology are at a critical crossroads. Funding for research in the United States and elsewhere is stagnant, if not losing pace with inflation. Working with the most pathogenic organisms requires even higher costs and is heavily regulated. Some senior scientists are rethinking their career choices, and there is growing concern that young scientists will be discouraged from entering the field, especially in areas of controversial research, such as studies of the transmissibility of highly pathogenic influenza viruses (3). While some have argued that virology is a dying field, that assertion has been elegantly refuted by Dan DiMaio (4). Adding to these stresses, scientists and society are struggling with a new antiintellectual movement that challenges scientific conclusions, from anthropomorphically induced climate change to the absence of any link between vaccines and autism. The rise of antivaccine movements is of particular concern to society, for reduced vaccination rates threaten to undermine some of the greatest accomplishments of virology and public health in the 20th century. The combination of reduced funding, increased regulation, experimental controversies, and the emerging antiscience intellectual milieu is a toxic blend that makes this time one of great jeopardy for virology." ] },{ "paper_id": "64d31d4587a86108556e52c45e1ea3750fa7303f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The JEE process in Taiwan in 2016 involved the participation of at least 19 government agencies or institutions.", "The key to success in achieving such large-scale multisectoral collaborations for JEE is the 10-month preparatory work beforehand: advocacy of the One Health concept among stakeholders, sensitization of high-level political leadership across levels and agencies, and the Taiwan government's strong commitment to transparency and accountability.", "At the end of the pilot visit, the 3 experts and Taiwan's JEE working group discussed next steps, jointly planned for work to be completed before the experts' next visit in June 2016, and developed a proposed agenda for the next visit." ] },{ "paper_id": "653ebe846e79113660523aeb3d87942c3890cd05", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "65648f466638ba2c4b63d49a1c46e834719890a5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "656804baa38b83efc3fbbc24cbc19b89e6d778f0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 We also outline the current knowledge of existing IAV proteins and the role of alternative splicing and frameshift in their formation. The potential functions of these proteins, if known, are also discussed.", "The IAVs are among the fastest evolving families of viruses [6] and are notable for their ability to rapidly change from one season to the next or even within seasons [7] . Over the course of a few generations, the virus can change sufficiently to become virulent. Like many emerging infectious diseases such as Ebola virus or severe acute respiratory syndrome (SARS) [8] , IAV depends on animal reservoirs, where they can reside [9] [10] [11] [12] [13] and transfer between species that share the same environment [14] . As one major reservoir involves migratory birds [15] , the potential to rapidly spread an infection throughout the world is of major concern and IAV is under constant watch (http://www.who.int/ csr/don/archive/year/en/). During the past 100 years, there have been three major epidemics with extensive fatalities [16] and one minor one (mostly because of quick action from the WHO and health practitioners) [17, 18] , the Spanish flu (1918, H1N1, 75 million fatalities worldwide), the Asian flu (1957, H2N2, 2 million fatalities), the Hong Kong flu (1968, H3N2, 1 million fatalities) and more recently the swine flu (2009, H1N1, 14 000 fatalities).", "Function unknown but may be an important protein factor for adaptation to new hosts [31] clear how the vRNPs combine in the filamentous virion; however, it seems reasonable that the filamentous-shaped virus also preserves this '7 \u00fe 1' pattern.", "\u2022 In this work, we summarize our current understanding of the structural aspects of transcription and replication." ] },{ "paper_id": "657558034931a24e09f761877fed36cb70f4f6fe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "use, and it is a powerful tool for the control of PED. However, virus variability and co-infections of PEDV with other enteric viruses are unpredictable. These factors make it difficult to understand and control PEDV infections. Therefore, future work should continue to trace the variability of PEDV strains and co-infections of other enteric viruses, improve PEDV vaccines using variant strains as candidates and elucidate the pathogenicity of PEDV variant strains.", "Porcine epidemic diarrhea (PED) is a highly contagious, intestinal infectious disease caused by porcine epidemic diarrhea virus (PEDV). The disease is characterized by severe diarrhea, vomiting and dehydration. PEDV infections can occur in pigs of all ages, and infections are most serious in piglets, with morbidity and mortality often reaching 100% [9, 40] . Pigs that tolerate PEDV infections usually exhibit growth retardation, reduced food conversion rates, increased feeding costs and the co-occurrence of other diseases. Furthermore, PEDV infections result in reduced pig slaughter rates, insufficient pork supplies and pork price instability, because of a large number of piglet deaths.", "Recently, a large number of studies of PEDV have provided an in-depth understanding of PEDV infections in the pig population in China. In particular, a trivalent live vaccine for viral diarrheal diseases of swine has been authorized for (b) Fast neighbor-joining (NJ) tree (1,000 replicates, Kimura two-parameter distance) constructed using the recombinant region of each potential recombinant event; (c) Fast neighbor-joining (NJ) tree (1,000 replicates, Kimura two-parameter distance) constructed using the non-recombinant region of each potential recombinant event.", "Genetically engineered vaccines: Mucosal immunity plays an important role in the immune mechanism of viral diarrheal diseases. Immunoglobulin A (IgA) antibodies secreted by the intestinal mucosa can defend against invading pathogens. Oral vaccines can stimulate mucosal immunity and produce protective mucosal and serum IgA antibodies, and they are an effective method for prevention of intestinal infectious diseases. For PEDV oral vaccines, Hou et al. reported that lactic acid bacteria expressing the PEDV N protein could activate the production of mucosal IgA and circulating IgG antibodies against the PEDV N protein [16] . Ge et al. reported that recombinant lactobacilli expressing * Group was defined based on the phylogenetic tree of S1 gene of the selected PEDV strains in our study (see Fig. 2 )." ] },{ "paper_id": "65a29504e9fb777dea5b6642112095999a8892ec", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Initial phases were improved by mutation of the sequence to poly-Ala followed by \"atoms update and refinement\" mode of ARP/wARP (Perrakis et al., 2001) . Symmetry operators were applied to the first monomer to create the two trimers. The structure was refined with iterative cycles of manual model-building using COOT (Emsley and Cowtan, 2004) , restrained refinement with REFMAC5 (Murshudov et al., 1997) and density improvement with ARP/wARP as the correct sequence was gradually built into the improving electron density maps. Data collection and final refinement statistics are summarised in Table 1 .", "N-CEACAM1 was manually docked into its putative binding site (the hydrophobic patch identified from the crystal structure) on UspA1 (527-665) using guidance from the mutational data of both components and visual inspection of shape complementarity. This model complex was then soaked with a 5 \u00c5 layer of water and relaxed with 2000 steps of conjugate gradient energy minimisation and the CVFF forcefield. Multiple 0.1 ns molecular dynamics simulations of UspA1 -with none, one and two N-CEACAM1s bound -were performed at 300 K under 12 different initial random velocities to investigate possible bending of the coiled-coil. A representative example of each is shown in Supplementary data 6. InsightII 2005/ Discover 2.98 (Accelrys) were used to view, manipulate molecules and for the molecular mechanics calculations.", "Bacterial cells were disrupted with 0.5mm glass beads at 48000 oscillations per minute for 30 sec in a mini-bead beater\u2122 (Biospec Products Inc. OK, USA). Unruptured bacteria were removed by centrifugation (2500g, 5 min), bacterial membranes were collected by ultracentrifugation (30,000g, 30 min at 4 o C) and suspended in PBS. Samples (5 \u00b5l) of envelopes, either native or pre-incubated with N-CEACAM1 (2.5 ng/ml) were applied to glow-discharged collodion coated copper grids. The grids were then washed by placing face down on two consecutive drops of sterile filtered water and negatively stained using 1% methylamine tungstate. The grids were viewed using an FEI CM10 EM operated at 80KV. Images were recorded at 39,000 x magnification on Kodak 4489 film with the first zero of the contrast transfer function in the range 20 -25\u00c5." ] },{ "paper_id": "65d508add328dceec3427a9bc54cff552b6a2271", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "662b7fe72aeb5beee387582742e087253b27201c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "663f66630b5b3b7914dcbcaed555d5865da925dd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Here, we report our experience in EQA carried out during this MERS-CoV outbreak." ] },{ "paper_id": "66b67940ae16f657fd93fad230081d20d98c55f7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(i) A respiration rate greater than 30 breaths per minute, dyspnea;", "(ii) Treatment recommendations for patients in severe or critical conditions:", "\u2022 Noninvasive ventilation for 2 hours first, withdrawn gradually when the patient shows better signs." ] },{ "paper_id": "6708dd7c675e9a967e9f5487cd3f3b6bc225775a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "2.", "3.", ", ," ] },{ "paper_id": "671e9e8a89727d0b94d1798c56f5120c63c83617", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. Descriptive statistics were performed, with continuous variables summarized as median and range, and categorical variables summarized as frequencies and proportions. The statistical significance between various groups was tested using the x 2 -test or Fisher exact test for categorical variables and independent t test or nonparametric test for continuous variables. A two-sided P value of less than 0.05 was considered to be statistically significant. Analyses were performed using SPSS version 11.5 (SPSS).", "SAFV strains accession numbers. The sequences obtained from the study were submitted to NCBI with the GenBank Accession Numbers KJ944637-KJ944718. The genomic sequences were assembled using Lasergene's DNA SeqMan software (version 7.1.0, DNA Star Inc. Madison, WI, USA). The MEGA program (version 6.0, Sudhir Kumar, Arizona State University) was used for alignments and phylogenetic tree construction by maximum likelihood method using 1000 bootstrap pseudo replicates. Nucleotide identities among strains were calculated using BioEdit (version 7.13, www.mbio.ncsu.edu/bioedit/bioedit.html).", "myocardium of a previously healthy child who experienced sudden death, suggesting that the virus might cause serious invasive infection in children 25 ." ] },{ "paper_id": "671f008a0c8884f741c6500eb243db4d06391004", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Relative rescue activity was calculated as described (Chang and Gould, 1998) .", "The yeast strain BY3168 (Vidal et al., 1996) was used for all dihybrid assays. Pairs of plasmids, one encoding the appropriate binding domain (BD) fusion, the other encoding the appropriate AD fusion, were used to transform the yeast to leucine and tryptophan prototrophy. After selection, the modified strains were incubated at 30 \u040a C for 2 d, transferred to BA-85 membranes (Schleicher and Schuell), grown for an additional 2 d, and assayed for \u2424 -galactosidase activity.", "For blot overlay assays, all in vitro transcription/translation reactions were performed using TNT rabbit reticulocyte lysates (Promega). 5 g of 6xHis-PEX19 and a nonspecific control protein (XECI, a nuclear enoyl-CoA isomerase) were resolved by SDS-PAGE electrophoresis and transferred to PVDF membrane. The membrane was blocked for 2 h at room temperature in buffer A (500 mM Tris-HCl, pH 7.5, 50 mM NaCl, 100 mM sodium acetate, 100 mM KCl, 1 mM DTT, 5 mM MgCl 2 , 1 mM EDTA, 0.3% Tween 20, 0.1 mM ZnCl 2 , 5% milk, 0.1 M methionine). The membrane was incubated for 2 h at room temperature with 5 ml of buffer A containing 35 S-labeled PMPs that had been synthesized in vitro, washed, and exposed to film. For far Western analysis, membranes containing 5 g of each protein were blocked as before, incubated with 10 ml of buffer A containing 2 g of purified 6xHis-PEX14, washed, and probed with affinity-purified anti-PEX14 antibodies.", "Preparation of rat liver postnuclear supernatant, separation of the peripheral nervous system by Nycodenz centrifugation and assay of marker enzymes were performed as described previously using a 15-45% Nycodenz gradient (Mihalik, 1992) . For differential centrifugation analysis, a rat liver was homogenized, a postnuclear supernatant was generated, and then spun at 25,000 g for 30 min. This supernatant was removed and subjected to further centrifugation at 200,000 g for 1 h. Equal proportions of the resulting homogenate, supernatants, and pellets were processed for immunoblot with anti-PEX19 antibodies. For the differential release assay, GM5756-T fibroblasts were harvested by trypsinization, washed, and divided into seven equal fractions. The cells were gently resuspended in 100 l of STE (10 mM Tris, 1 mM EDTA, 250 mM sucrose) that was adjusted to various concentrations of digitonin (0, 50, 100, 200, 300, and 400 g/ml) or 400 g/ml digitonin and 1% Triton X-100. After a 10-min incubation on ice, clarified supernatants were generated by centrifugation and analyzed by immunoblot. All immunoblots were performed using HRPconjugated secondary antibodies and chemiluminescent detection (Amersham)." ] },{ "paper_id": "674e4b0b5ce420b596a783bf0d9d7fccc5a76403", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The data was analyzed using descriptive statistics and analyzed using Statistical Package for Social Science Software version 22.0 (SPSS Inc, Chicago, IL, USA).", "Yes n (%)" ] },{ "paper_id": "6755e8b9e6792097d1be5bdf0041c3df1980ec60", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Brefeldin-A was either the generous gift of Dr. R. Klausner (National Institutes of Health) or purchased from Epicenter Bioteclmolngy (Madison, WI). RCA-I agarose, 3-[(3-cholamidopmpyl)dimethylammonio]-l-propanesulfonate (CHAPS), galactosyltransferase, ~-galactosidase, and deoxymannojirimycin (dMM) were from Sigma Chemical Co. (St. Louis, MO). Pentamannosyl phospbate-Sepharose and L/maxflovus slug lectin-Aifigel were prepared as described (17, 34) .", "Protein was determined according to the method of Bradford (5) using BSA as standard. Autoradiograms were quantified using a densitometer (model 300A; Molecular Dynamics, Sunnyvale, CA). Neuraminidase treatment of man6P receptors was carried out using Arthrobacter ureafaciens neuraminidase as described (17) .", "Cells were labeled with [35S]methionine and cysteine (Translabel; Amersham Corp., Arlington Heights, IL) at 0.1 mCi/ml in aMEM lacking cysteine and methionine but containing 10% dialyzed FCS. Chase periods were initiated by washing cells twice in TD (25 mM \"Iris C1, pH 7.4, 5.4 mM KC1, 137 mM NaC1, 0.3 mM NazHPO4), followed by addition of complete media. After the times indicated, cells were washed once in ice-cold TD and lysed with 1.0 ml RIPA buffer (50 mM Tris HCI pH 7.2, 0.15 M NaCI, 1% Triton X-100, 1% deoxyeholate, 0,1% SDS, and 0.1% gelatin). Lysates were centrifuged at 330000 g for 10 rain in a centrifuge (model TL-100; Beckman Instruments, Fullerton, CA). Suspension cells were labeled at a density of ~2 x l(P/ml." ] },{ "paper_id": "67595d2304315ae4af47ec96fbd42c55bd6855e2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "c According to RDP II database, release 9.60.", "ORMA scripts were developed under Matlab 6.1 (Mathworks, Natick, MA, USA) environment (Release 12.1). No additional toolboxes are required. All statistical analyses and representations were made by the same software. Probe designs and simulations were run onto a hp Workstation xw4100, with a Dual-core 3.2 GHz. Intel Processor and 2.5 GB RAM. ORMA functions and m-code are available for free upon request.", "a Clonal DNA from environmental sample." ] },{ "paper_id": "67629939944591734aa3934d4a2c9aadf49ccedf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Militaries and nonstate actors alike are using health interventions to serve their political aims in conflict situations.", "Tropical Medicine, University of London, London, United Kingdom (Kelley Lee).", "Conflict of interest: none declared." ] },{ "paper_id": "679aafff5a2403fb48ab7bf416b6d5d97c02b798", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors report no conflicts of interest in this work.", "The initial cases of MERS-CoV were detected among patients admitted with severe community-acquired pneumonia and the ", "People working with camels such as farm workers, slaughterhouse workers, and veterinarians may be at higher risk of MERS-CoV infection than other people. 39 Goats, cows, sheep, water buffalo, and birds were negative for antibodies to MERS-CoV. 16, 31, 39 Thus, so far no other animal link has been identified apart from camels and bats. 40, 41 " ] },{ "paper_id": "67a52569919632f4bf58782538ff24838ac7f26c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Pre-DCm019", "Pre-DCm009", "Pre-DCm020" ] },{ "paper_id": "67a530bb1b7075edffe904df66644b0a1da97d1f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "67c79979c388cfcad87bb12d0ea644699500d736", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "67db14be4e5b68f4d42496330429a1d86266a161", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "avian influenza / epidemiology / poultry farming / spatial analysis / Thailand", "All data were integrated into a geographical database and geoprocessing was carried out with the Spatial Analyst extension of ArcGIS software v. 9 " ] },{ "paper_id": "67f40427adfd7f712e114a8f5da4a33158fc9f37", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We thank David I. Meyer and Christian Zwieb for helpful discussion and comments. We also thank Annie Steiner for typing this manuscript." ] },{ "paper_id": "6803ffb755ca44defc371b10e0ad52ccdbb67108", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A recent case report in Saudi Arabia has led to the discovery of a sixth new coronavirus. The patient had pneumonia and acute respiratory distress syndrome with multi-organ dysfunction syndrome and died 11 days after admission [7] . This has also been recently referred to as the Middle East respiratory syndrome coronavirus.", "All guidelines recommend severity scoring tools in conjunction with clinical assessment in adult communityacquired pneumonia management, although controversy remains about which scoring system to use and when to use it.", "Abbreviations ATS-IDSA, American Thoracic Society-Infectious Diseases Society of America; BTS, British Thoracic Society; COPD, chronic obstructive pulmonary disease; HCoV-EMC, Human Coronavirus-Erasmus Medical Center; ICU, intensive care unit; LBP, lipopolysaccharide-binding protein; proADM, pro-adrenomedullin; PSI, pneumonia severity index." ] },{ "paper_id": "680adbe0c280f4774383793afb8b70fd9ab3d5d0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All clinical samples from suspected patients were cultured on plates of Sabouraud glucose agar (Merck, Darmstadt, Germany), with chloramphenicol and cycloheximide (SCC). The plates were incubated for 4 -6 weeks at 28\u00b0C. All colonies were examined macroscopically and microscopically in Lactophenol Cotton Blue. The Trichophyton species were identified based on microscopic morphology and in vitro tests including urease and hair perforating tests, as required.", "Purified PCR products (1 \u00b5L) were mixed with 2 U Pfu (1 \u00b5L) DNA ligase (Bioneer ISO 13485, Alameda, CA, USA) and 1 \u00b5L of padlock probe in 500 mM Tris-HCl (pH 7.5), 50 mM KCl, 100 mM MgCl2, 2.5 \u00b5L/mL bovine serum albumin (pH 7.5), 10 mM ATP, and 50 mM DTT with a total reaction volume of 10 \u03bcL. Multiple cycle ligations were conducted with one cycle of denaturation at 94\u00b0C of 5 min, followed by five cycles at 94\u00b0C for 30 s and 4 min of ligation at 62\u00b0C. ", "RCA reactions were performed in a 25-\u03bcL volume containing 8 U of Bst DNA Polymerase (New England BioLabs, Ipswich, MA, USA), 200 \u00b5M deoxynucleoside triphosphate mix, 1 \u00b5L of each RCA primer, and 2 \u00b5L of ligation product. Probe signals were amplified by incubation at 65\u00b0C for 60 min and 85\u00b0C for 2 min, and the accumulation of doublestranded DNA products was detected by electrophoresis on 1% agarose containing ethidium bromide (Sigma, St. Louis, MO, USA). Ladder-like patterns were interpreted as positive reactions, while negative reactions showed no illumination." ] },{ "paper_id": "687611906b82bcee9941de1cf6543e8e7871da06", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "68ad2dd709c43428a872d1d91ff37534082da3f7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "68c6921af95469f234a2405a9234d5c5e9695bb8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "68e2c47647afe4bf0237d9f17bb7787738fc8663", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "BHZC36972_Beihai_picobirna-like_virus_10", "BHJJX25356_Beihai_picobirna-like_virus_1", "Lysoka_picobirna-like_virus_P16-366*" ] },{ "paper_id": "68f9d17b3481fc9b2466a48716d7e977ca9bbfad", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This method is an isothermal template amplification technique that can be used to detect trace amounts of DNA or RNA of a particular sequence (Becton Dickinson and Company, Sparks, MD). In its current format, strand displacement amplification occurs in two phases, target generation and exponential target amplification [22] .", "For more information, it can see the article entitled \"Human papillomavirus (HPV) genotyping: automation and application in routine laboratory testing\".", "The author declares that they have no competing interests.", "These techniques use enzyme-mediated processes, in which the enzymes synthesize several copies of target nucleic acid. The amplification products are detected by two oligonucleotide primers that bind to complementary sequences. The final result is the production of millions of copies of the targeted sequence. There is possibility of contamination, so false positive results must be reduced through special laboratory design, practices and workflow." ] },{ "paper_id": "6909d7db535645308e0b2e726b5dea3b854a1aa5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.00884-14/-/DCSupplemental. ", "Arabia, where the index case and the majority of cases of MERS have been reported. Citation Alagaili AN, Briese T, Mishra N, Kapoor V, Sameroff SC, de Wit E, Munster VJ, Hensley LE, Zalmout IS, Kapoor A, Epstein JH, Karesh WB, Daszak P, Mohammed OB, Lipkin WI. 2014. Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia. mBio 5(2):e00884-14." ] },{ "paper_id": "6931b5e9ff438fd47df998904ce32f6f027514e8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6979d40067c7917b6b92917ff8c3db8a440f5f4c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "I am indebted to the Canadian Institutes of Health Research (grant # MOP82921) for funding our proteomics research. I also wish to thank Kerstin Radtke for excellent suggestions and Daniel Henaff for critical reading of the manuscript.", "Moreover, ICP0 interacts with the host cyclin D3 (Kawaguchi et al., 1997) . However, it was recently reported that stress, rather than the cell cycle per se, may be a critical feature (Bringhurst and Schaffer, 2006) . Clearly, the interaction of herpesviruses with the cell proliferation apparatus is complex and likely involves several host and viral proteins. Identifying novel players that might be incorporated into mature virions may thus be very useful to clarify this process.", "Interestingly, HSV-1 does not require cells to be in the S-phase and even arrests the cell cycle at the G1/S transition step (Shadan et al., 1994; Song et al., 2000) , which partly explains why it can grow in non-dividing neurons. While the precise mechanism of this arrest is unclear, it is known that the viral ICP0 protein and the VP16 cellular partner HCF modulate the cell cycle (Hobbs and DeLuca, 1999; Lomonte and Everett, 1999; Piluso et al., 2002) .", "An interesting scenario is the possible regulation of apoptosis by host proteins loaded onto viral particles. Apoptosis is regulated both negatively and positively by several viruses (Teodoro and Branton, 1997; Goodkin et al., 2004) , presumably to insure their survival at the early stages of the infection but their efficient release later on. Conceptually, the presence of anti-apoptotic proteins in herpes particles might thus provide a mean to quickly evade death upon entry, while the presence of pro-apoptotic proteins on newly assembled/enveloped viral particles may trigger or stimulate their extracellular release. Only further work will resolve this open question." ] },{ "paper_id": "69ca8c0a79935fbe985f02fc53c1a9da5c42acd3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The protocol of the current study was reviewed and approved by the Institutional Review Board (IRB No 2015-11-134) of each institution and was conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from all participants. " ] },{ "paper_id": "69ec8583af7713749c3c85d5a3eb5e506196150b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6a14ff1798aa6ca90d45bab127740593ab37fac3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Grip strength is measured non-invasively by taking advantage of the mouse's instinctive tendency to grab as they are gently pulled backward. This method can be used to test for limb grip using a horizontal bar with small diameter 0.1 cm which is attached to a force transducer. The advantages are that the grip strength is reproducible and can be measured repeatedly in rodents to detect progressive motor deficits, value of therapy and genetic modifications [16] . Mean latency to fall was determined with a maximum cut-off at 60 s.", "This task is used to assess sensorimotor function and balance in rodents.", "Protein extracts from cortex brain were mixed with equal volumes of SDS buffer (0.125 M Tris-HCl, pH 6.8, 2% SDS, 0.5% (v/v) 2-mercaptoethanol, 1% bromophenol blue and 19% glycerol) and then boiled for 5 min. Protein concentration was determined using a modified Lowry method [17] . Proteins were separated by SDS-PAGE gels and transferred to nitrocellulose membranes using standard techniques." ] },{ "paper_id": "6a2d45016115d187120a5c232f671df30422870b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Descriptive statistics were used to explore and analyse the association between host and environmental factors and viruses with nasal microbiota. Assuming non-normal distribution, Kruskal-Wallis and Wilcoxon-signed rank sum tests were used. Fisher's exact tests, Chi-squared tests and enrichment analyses [22] were employed where appropriate. Associations between clusters and symptoms were evaluated using logistic regression analyses and adjusted for season and age. A p-value of <0.05 was considered statistically significant. Statistical analyses were performed using Stata 11 software (StataCorp. 2009. Stata Statistical Software: Release 11; StataCorp LP, College Station, TX, USA) and Matlab 2015b (The MathWorks, Inc., Natick, MA, USA)." ] },{ "paper_id": "6a3c7595bc8fa30e3f74fd3d350d7cb7e3a1668b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In conclusion, we propose a novel model to describe -1 PRF, in which three tRNAs are involved. A detailed understanding of -1 PRF mechanism should contribute to the development of novel anti-frameshift agents that affect the replication capacity of viruses, such as HIV-1.", "Frameshift assays in eukaryotes were monitored by transient transfection of the dual-luciferase plasmids (pDual-HIV derivatives) into human embryonic kidney 293T cells (HEK293T) maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% (v/v) FBS (Wisent), with 2 \u00c2 10 5 cells/well seeded in 6-well plates. Two mg of plasmids were diluted in 3% of the initial culture volume in fresh serum-free medium and mixed with an equivalent volume containing 5 mg of PEI (polyethylenimine, Polysciences Inc.). The mixture was incubated for 15 min at room temperature prior to the addition to cell culture. Cells were cultured for 48 h before being washed twice with 2 ml of PBS, and lysed with 450 ml of the Cell Passive Lysis Buffer 1X (Promega). Fluc versus Rluc activities of each construct were measured for 10 s as relative light units (RLU) with an EG&G Berthold Lumat LB 9507 luminometer, using a non-commercial dualluciferase enzyme assay system (48) .", "Present address: Dominic Dulude, Centre de recherche, Ho\u02c6pital Ste-Justine, 3175, chemin de la Co\u02c6te-Ste-Catherine," ] },{ "paper_id": "6a8fc2a90c03d2ade186c1a30777f5e56dc174a0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A single attribute a has L a levels. A single set of policy/ outcome options contains A attributes in all, and so the information about the set is contained in the object (l 1 , l 2 , . . . , l A ). To facilitate analysis, the information is reformulated as a vector of dummy variables,", "Contributors Conceived the study: ARC, MICC, EAF. Oversaw data collection: EAF. Performed analyses: ARC, XZ. Wrote the paper: ARC, XZ, MICC, EAF.", "Each pair contains the same attributes but different levels of each attribute; the attributes and levels used are found in table 2.", "The average utility \u00b5 b over individuals in the population presented with a set of options b is modelled as a linear combination of utility components" ] },{ "paper_id": "6aa4476feb03bb59ab1cd8452bb48c77c9816a73", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis was performed using one-way analysis of variance (ANOVA) with GraphPad Prism software. The p-value of <0.05 was considered statistically significant.", "Western blot was performed according to the protocols described in Molecular Cloning: A Laboratory Manual (Sambrook and Russell, 2001). Each sample was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) on a 12% acrylamide gel and transferred electrophoretically to a PVDF membrane. The primary antibodies used were anti-Flag (Sigma), anti-HIV-1 p24 (Santacruz), anti-Fluc (Cal Biochem, USA), anti-glyceraldehyde 3-phosphate dehydrogenase (GAPDH), anti-beta-actin (abcam), anti-RFP polyclonal, and anti-GFP monoclonal (Clontech/Takara Bio Co, USA). The secondary antibodies used were HRP-goat anti-mouse IgG conjugate and HRP-goat anti-rabbit IgG conjugate (Zymed, USA). Specific protein bands were developed using LAS-4000 (Fujifilm, Japan). The density of each band was analyzed using the software Image J (32).", "The amounts of p24 in each sample were determined using an HIV-1 p24 ELISA kit following the manufacturer's protocol (Xpressbio). Coated monoclonal antibodies against p24 epitopes were used in this kit to detect p24." ] },{ "paper_id": "6aaf920479e8c440f99cd8a14a3e9ebd9250d15f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 Influenza pseudotypes can be employed to determine which proteases are involved in haemagglutinin activation of individual subtypes.", "\u2022 TMPRSS2 functions in effecting the activation, presumably by cleavage, of Group-2 influenza A virus haemagglutinins to produce high-titre influenza pseudotypes.", "\u2022 Group-2 influenza pseudotype particles are neutralized by matched or related reference antisera.", "In the present study we have shown that:" ] },{ "paper_id": "6ae4586f198b9710e0285939e265149fbdb3bdab", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6b881730788724e674806854f0c20fec32ee9d96", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We see several barriers to realizing the goal of active, on-theground surveillance and early detection of viruses with epidemic potential.", "These authors contributed equally to this work." ] },{ "paper_id": "6bb0038a55ff68a2f47a36e8c845126da7fea61b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. The viability and cytokine assay results are presented as the mean \u00b1 standard deviation (n=3). All CdCl 2 -treated cell data are presented as a percentage value compared with the untreated control cells (100%). The data were analyzed for significance by Dunnet's multiple comparison test, using GraphPad Prism software version 3.0 (GraphPad Software Inc., San Diego, CA, USA). P<0.05 was considered to indicate a statistically significant difference.", "Protein estimation. The protein concentration of the cell lysates were determined using a Bicinchoninic Acid Protein Assay kit (Pierce Biotechnology, Inc., Rockford, IL, USA) with bovine serum albumin as a standard protein. The protein standards and working reagents were prepared, according to the manufacturer's instructions. In triplicate eppendorf tubes, 25 \u00b5l standard or lysate sample were added. The working reagent (500 \u00b5l) was added to each tube, incubated at 37\u02daC for 30 min and was subsequently measured at 562 nm in a Beckman spectrophotometer (Beckman Coulter, Inc., Fullerton, CA, USA). The concentration of the lysate samples were determined using the standard curve.", "Chemicals. The F12 K medium, penicillin/streptomycin antibiotic solution (100X), fetal bovine serum (FBS), trypsin-EDTA solution (1X), amphotericin B (1,000X), phosphate-buffered saline without calcium and magnesium, CdCl 2 , 25% glutaraldehyde and crystal violet were purchased from Sigma-Aldrich (St. Louis, MO, USA). The human IL-10 (cat. no. ELH-IL10-001) and human IL-1\u03b1 (cat. no. ELH-IL1alpha-001) enzyme-linked immunosorbent assay (ELISA) kits were purchased from Ray Biotech, Inc. (Norcross, GA, USA)." ] },{ "paper_id": "6bb631f4a1c7c8c53d07c971b5e52a2563c66106", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "No other viruses were isolated from specimens, and PCR was also negative for all specimens from cases 1 and 2 when tested for bovine viral diarrhea virus [27] , bovine coronavirus [26] , rotavirus [3, 10, 25] , bovine torovirus [11] , bovine enterovirus [12] , paramyxoviruses [24] , bovine adenovirus [14] and bovine herpesvirus 4 [1] .", "Neutralization test for paired sera of case 2: A significant increase in antibody against 24-100 strain was confirmed by neutralizing tests using paired sera. Neutralizing titers in sera collected during the acute phase of infection were less than 1:2, but increased to 1:4 during the convalescent phase.", "Although the standard method for detecting antibodies to Chlamydiaceae spp. in animals is still the complement fixation test [18] , our study showed that a neutralization test was also a useful method for diagnosis of C. pecorum infections." ] },{ "paper_id": "6bbd4c83266579a2afbe995cf64f3200d4d4cb7b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Newly identified sequences were aligned with kobuvirus reference sequences from NCBI database using ClustalW (Larkin et al. 2007 ). We used SSE V1.3 software to calculate uncorrected distance of new sequences against reference sequences (Simmonds 2012 ", "Supplementary data are available at Virus Evolution online. ", "Conflict of interest: None declared." ] },{ "paper_id": "6bc66c3abc451b39ae1bba08b1f1ff3f7e7f5b95", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6bc8969058239852857384c5a87a7e75f41193b6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6bd2dac1db0e974c27b6b7b5a17aaab35fc8d36c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6bd9a619434c6c57efe77c253b97c31d98369b02", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Subsequently, the patient could feed orally without complications. The patient was hospitalized for two weeks to recover.", "There is limited evidence for other therapies like intravenous immunoglobulin and cyclophosphamide. [1] [2] [3] Rehabilitation and physical therapy role are essential in the management. Children generally have a better outcome than adults with 50% of pediatric cases making a complete recovery by 2 years. 1-3 Yet it is important to remember that M. pneumoniae induced transverse myelitis can result in significant neurological sequalae despite appropriate treatment. 8 Infants tend to have a worse outcome possibly due to inability of their immature nervous system to recover and higher incidence of LETM in this age group. 1 Mortality is associated with respiratory failure and high cervical cord lesions. Risk factors for relapse are female gender and abnormal brain MRI. 1" ] },{ "paper_id": "6bdb41aa63efed5063efbecbb615896b8ea4ae5e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Whole genome sequences were downloaded for all viruses available from the NCBI FTP site ftp://ftp.ncbi.nlm.nih.gov/ genomes/Viruses. Of the 5757 viral genomes, 2548 were RNA viruses with linear genomes, and these were selected for analysis. All 6408 coding regions (annotated with a CDS in Genbank) were analyzed, excluding 291 regions annotated with a \"join\" indicating some form of midsequence frameshift in the established gene such as a ribosomal slippage (leaving 6117 coding regions analyzed).", "This analysis was performed using R (version 3.3.2; R_Core_Team 2016) and required the packages seqinr ", "Supplementary data are available at Molecular Biology and Evolution online." ] },{ "paper_id": "6c3132687a4cd25b59f39f851b6b924c99afe345", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "[CST], Shanghai, China), phosphorylated FAK Tyr576/577 (CST), \u2424-actin (Sigma-Aldrich), and \u2424-tubulin (Sigma-Aldrich) were used. The intensity of the bands was measured using ImageJ software (43) .", "IMPORTANCE", "We are greatly indebted to our colleagues who shared valuable reagents with us, and we are grateful to" ] },{ "paper_id": "6c51eafc88ddf46d27452c1a1b7a009c5341e848", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The PCR product was purified using HiBind DNA spin-column of the E.Z.N.A DNA probe purification kit (Omega) and eluted in ultrapure water. A total amount of 500 ng of each purified PCR product was used for in vitro transcription using the MEGAshortscript T7 kit (Ambion) or the HiScribe TM T7 High Yield RNA Synthesis Kit (NEB). The reactions were performed according to the manufacturer's instructions (1x T7-polymerase buffer, 7.5 mM ATP, 7.5 mM CTP, 7.5 mM GTP, 7.5 mM UTP, 25 U T7-enzyme mix) for at least 5 h at 37 \u2022 C. The DNA template was removed by digestion with 1 l TURBO-DNase for 1 h at 37 \u2022 C. The in vitro transcript was phenol-extracted, ethanol-precipitated and analyzed by electrophoresis in a 10% polyacrylamide-urea gel and subsequent staining with ethidium bromide.", "As one of the rare examples of 5 -UTR-derived sRNAs, the trans-acting attenuator RNA rnTrpL characterized in this study highlights the regulatory potential and the versatility of bacterial mRNA leaders.", "Plasmid constructs were transferred to S. meliloti, A. tumefaciens or B. japonicum by diparental conjugation with E. coli S17-1 as the donor (46) . Bacteria were mixed, washed in saline and spotted onto a sterile membrane filter, which was placed onto a TY plate without antibiotics. After incubation for at least 4 h at 30 \u2022 C, serial dilutions were plated on TY agar with selective antibiotics.", "The deletion mutants 2011\u0394trpL, 2011\u0394trpC and 2011\u0394trpL\u0394trpC were constructed as described (47) , using TY solid media. For in-frame deletion of trpC, it was necessary to supplement the TY medium with 20 g/ml L-tryptophan. Deletion mutant candidates were confirmed by PCR analysis of cell lysates using primers which correspond to sequences located outside the chromosomal region that was cloned in the pK18mobsacB-trpL and pK18mobsacB-trpC, respectively. The \u0394trpL deletion was additionally confirmed by Northern blot analysis in comparison to the parental strain." ] },{ "paper_id": "6c6b13bdca7f70d6afec7257e4769bb5c10b1a19", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Citation Banerjee S, Chakrabarti A, Jha BK, Weiss SR, Silverman RH. 2014. Cell-type-specific effects of RNase L on viral induction of beta interferon. mBio 5(2):e00856-14.", "Our studies suggest that during viral infections, the OAS/RNase L pathway can either enhance or suppress IFN production, depending on the cell type. IFN regulation by RNase L is suggested to contribute to tissue protection and survival during viral infections.", "The interferon (IFN)-inducible antiviral state is mediated in part by the 2=,5=-oligoadenylate (2-5A) synthetase (OAS)/ RNase L system. 2-5A, produced from ATP by OAS proteins in response to viral double-stranded RNA, binds to and activates RNase L. RNase L restricts viral infections by degrading viral and cellular RNA, inducing autophagy and apoptosis, and producing RNA degradation products that amplify production of type I interferons (IFNs) through RIG-I-like receptors. However, the effects of the OAS/RNase L pathway on IFN induction in different cell types that vary in basal levels of these proteins have not been previously reported. Here we report higher basal expression of both RNase L and OAS in mouse macrophages in compari-" ] },{ "paper_id": "6c7341f17bfd790cdc05b6d1010c63f4f8eb5890", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6ce22e4f892e54b0f6317315b113f3fd46ed7245", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Virchow's classical triad of abnormalities including blood stasis, hypercoagulability and vessel damage has been regarded as the authentic theory for explaining pathogenesis of VTE since 19's century (13) , however, the triad does not fit all clinical profiles.", "Similar to GO analysis, Fisher's exact test was employed for the study of over-representation of selected genes.", "In 2010, we reported a patient who died of SARS developed VTE in multiple organs, which implies the viral infection induced systemic VTE and there is correlation between viral infection and occurrence and VTE (28) ." ] },{ "paper_id": "6d04e85d2c994d73c9a7e2692af91470f407ddeb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Disclosure of potential conflicts of interest James A. Williams has an equity interest in Nature Technology Corporation. Due to this relationship with Nature Technology Corporation, the author acknowledges that there is a potential conflict of interest inherent in the publication of this manuscript and assert that an effort to reduce or eliminate that conflict has been made where possible.", "systems can increase gene expression, as well as, DNA vaccine immunogenicity. Although many of the earliest carrier formulations did not show a significant clinical benefit, more recent studies highlighted herein yielded promising clinical data. As microparticles can be prepared with significant structural diversity (size, surface charge, lipid content), they offer considerable flexibility of vaccine formulation. This allows for optimization of the vaccine based on the specific needs of the clinician.", "The constant emergence, and re-emergence, of known and novel pathogens challenges researchers to develop new vaccination technologies that allow for the rapid development of safe and effective vaccines. Nucleic acid (DNA and RNA) vaccines have characteristics that meet these challenges, including ease of production, scalability, consistency between lots, storage, and safety. DNA vaccine technology usually is based on bacterial plasmids that encode the polypeptide sequence of candidate antigens. The encoded antigen is expressed under a strong eukaryotic promoter, yielding high levels of transgene expression. 1 Inclusion of transcriptional enhancers, such as Intron A, enhance the rate of polyadenylation and nuclear transport of messenger RNA (mRNA). 2 The vaccine plasmids are generally produced in bacterial culture, purified, and then used to inoculate the host." ] },{ "paper_id": "6d16e166279a7d116a78a21d4bd4c00b505a617e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6d28097d6542b0b34f34ca4d2359856cc461b5f5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The median duration of ILI episodes was 15 days. No clear patterns were seen in terms of episode duration according to virus type, although the numbers were small (data not shown).", "rhinovirus/enterovirus (40%). Dyspnea and wheezing were most frequent in RSV infections (51% and 46%, respectively). Cough was present in >90% for all virus types.", "Supplementary materials are available at The Journal of Infectious Diseases online (http://jid.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.", "Informed consent was given to participate in INFLUENCE65. Samples from US subjects were not included in the present study as ethics approval for additional virologic studies would have been required, leaving a study population of 36 132 subjects." ] },{ "paper_id": "6d479d399ca496281c8dccc3198cb86d965deb1e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6d53690848c0b900e6d766993d9fefd2c4c27c48", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6d6294ef224683962e08a1059ea4b027b769e5ed", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Total RNA was isolated from each group using the QIAamp viral RNA Mini Kit (Qiagen, Hilden, Germany). Reverse transcription was performed using RNase Inhibitor, M-MLV RT 5\u00d7 Buffer, M-MLV Reverse Transcriptase, Oligo(dT)15 primer, and dNTP mixture manufactured by Promega (Madison, WI, USA), and quantitative real-time PCR was performed using the THUNDERBIRD TM SYBR qPCR Mix (Toyobo, Osaka, Japan) on the CFX96 TM Optics Module (Bio-Rad, Hercules, CA, USA), with the following primers: HRV5\u2032-NCR-up: 5\u2032-TCC TCC GGC CCC TGA ATG-3\u2032, HRV5\u2032-NCR-down: 5\u2032-GAA ACA CGG ACA CCC AAA G-3\u2032, CCL2-up: 5\u2032-TTA AAA ACC TGG ATC GGA ACC AA-3\u2032, CCL2-down: 5\u2032-GCA TTA GCT TCA GAT TTA CGG GT-3\u2032, IL-6 up: 5\u2032-CTG GAG TCA CAG AAG GAG TGG-3\u2032, IL-6 down: 5\u2032-GGT TTG CCG AGT AGA TCT CAA- ", "We used Student's t-test to compare differences between two groups. To compare multiple groups, we carried out oneway ANOVA followed by the Newman-Keuls test. Values of p<0.05 were considered significant at a 95% confidence interval.", "Original Article" ] },{ "paper_id": "6daf14d0342bca1c7e6c9f52a65ba4fa3fe618ba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Five commercially available hand antiseptics, which were based on propanol and ethanol, were chosen to study the virucidal effects against HBV. These included Sterillium classic pure (100 g contain: 45 g 2-propanol; 30 g 1-propanol; 0.2 g mecetronium ethylsulfate), Manorapid Synergy (100 g contain: 57.6 g ethanol 96%; 10 g 1-propanol), Poly-Alcohol Hand Antisepticum (100 mL contain: 70 mL 2-propanol), Sterillium med (100 g contain: 85 g ethanol) and desderman pure (100 g contain: 78.2 g ethanol 96%; 0.1 g 2-biphenylol).", "Supplementary material and methods" ] },{ "paper_id": "6db877f61327ae24341591d620abda3793639462", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Many laboratories (75%, 30/40) used phosphate-buffered saline for pretreatment of sputum specimens. All reagents for the detection of MERS-CoV were components of ready-made kits, and the PowerChek MERS Real-time PCR Kit (KogeneBiotech, Seoul, Korea) was the most commonly used kit (72.5%, 29/40). Most laboratories used CFX96 (Bio-Rad Laboratories, Hercules, CA, USA) or ABI7500 or 7800 systems (Life Technologies, Carlsbad, CA, USA) for rRT-PCR (85.0%, 34/40) ( Table 4 )." ] },{ "paper_id": "6dfe2e77c8175b3eb38d6fc3ccc440fb81a0e2f0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All HRCT images were reviewed by two chest radiologists with over 10-year working experience (Yang ZG and Li Y) blindly to the clinical information.", "All the patients were kept in supine position and imaged with a 256-detector CT scanner (Revolution CT, GE Healthcare, Milwaukee, Wis) during full expiration and without injection of any contrast. The scanning parameters were as follows: 120 kilovolt peak, 146 mA, 0.28 s gantry rotation, 80-mm collimation, a 360-mm field of view and 512-mm matrix. Images were reconstructed with a high-spatial-resolution algorithm for parenchymal analysis.", "We also recorded the presence of nodules, masses, cavitation or calcification, pleural effusion, lymphadenopathy, and any other abnormalities of the chest images." ] },{ "paper_id": "6e1cd91f28e6a422438a943b5ef37b9911ddad2c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Refer to Web version on PubMed Central for supplementary material.", "Results are from one of two independent experiments, acquiring 2,500 cells per sample each time (**p < 0.01, *** p < 0.005). ", "This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)." ] },{ "paper_id": "6e33bf088cfbcde318f35f3be8dea6810b0b96ce", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6e4cdb85e0a4e9f66a92f231bba4bb3b91f9f822", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Infectious diseases have caused great catastrophes in human history, as in the example of the plague, which wiped out half of the population in Europe in the 14th century. Ebola virus and H7N9 avian influenza virus are 2 lethal pathogens that we have encountered in the second decade of the 21st century. Ebola infection is currently being seen in West Africa, and H7N9 avian flu appears to have settled in Southeast Asia. This article focuses on the current situation and the future prospects of these potential infectious threats to mankind.", "Three (H7N9, H6N1, and H10N8) avian influenza viruses broke the animal-human barrier in Asia in 2013. 31 One avian influenza case was detected in Taiwan due to H6N1 subtype, whereas 2 of 3 H10N8 human infections observed in China were lethal. 31 However, human infections due to H7N9 have been progressively increasing since its first identification in 2013, and approximately one-third of the H7N9-infected patients died. 31-33 Avian flu had the potential to spread \"silently\" among poultry and H7N9 infections did not cause severe disease in poultry, accordingly. 34 Viral characteristics. Influenza is an infection of birds and mammals caused by RNA viruses from the family of Orthomyxoviridae. There are 2 main types of influenza virus, type A and type B. Type A viruses are the most virulent human pathogens among the other influenza types and cause the most severe disease. Influenza A viruses are divided into subtypes based on the hemagglutinin (H) and the neuraminidase (N) localized on the virus surface. So far, 18 hemagglutinin and 11 neuraminidase subtypes were documented. 35 Influenza B almost exclusively infects humans and is less common than influenza A. 36", "O utbreak is an epidemiological definition to describe an unexpected occurrence of an infection at a certain time and place. It may affect a small and a localized group, or impact on millions of people across continents. Two cases of a linked rare infection can be defined as an outbreak. A revisit through the history discloses that outbreaks were vast, deadly, and basically changed the course of human history. 1 As an example, the plague reshaped the landscape of Europe and the world between 1347 and 1351. During this period, the global population was estimated to be 450 million, and 75 million at a minimum are believed to have perished. Consequently, half of Europe died in a period of 4 years. 2 In the pre-antibiotic era, bacterial outbreaks caused much more mass destruction compared with other outbreaks with different infectious agents. 1 But, this trend changed with the advent of antibiotics and viral outbreaks emerged. We believed that Ebola virus and H7N9 avian influenza virus are the most potential pathogens to cause mass destruction in the world. Thus, in this paper, we will focus on the current outbreaks of these 2 viral infections with the potential to cause mass destruction, and to greatly impact the international travelers." ] },{ "paper_id": "6e4d9a7b61701ca9620df0205d89b7fb8c22f265", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A randomized controlled trial might also be undertaken, although with 1:1 randomization, a statistically significant reduction in mortality from 50% to 25% would require 210 patients, and only half would receive active treatment. Given the known high mortality rate of untreated patients, investigators might instead choose an adaptive trial design. This would minimize the number of untreated placebo subjects and allow different treatment regimens to be tested simultaneously for efficacy and safety.", "It must be emphasized that treating the host response would not prevent or cure Ebola virus infection itself, but it might allow individual patients to survive long enough to develop an immune response that eliminates the virus. These agents could be used in combination with antivirals if they are available.", "Unfortunately, supervising physicians and health officials in Sierra Leone have not released reports of the treatment results, although they exchanged letters and memoranda describing their experience, with one letter noting \"remarkable improvement\" on treatment (O.M.R., unpublished observation). It will be up to others to rigorously review and validate these findings. (22) . Perhaps atorvastatin and irbesartan treatment of some of these patients helps explain the decrease in the Ebola case fatality rate observed at the Hastings Center." ] },{ "paper_id": "6e6e7f0218c6b5affa20bb27bb263517a113f7b1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6e99aa3d7287b2e04d3c2a975ba94212158ac45c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6edbfac15ca59eb0e18859543190088f7a52112e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6f1014ef2ef3a31e4e58cad28dc625df3701ac42", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Finally, it should also be noted here that, owing to the constraints of this study, namely, the paucity of healthy, normal human brain tissue samples and respective available data, the F 1 super variable needs to be further validated with a larger, independent cohort.", "Computer software. All analyses in this study were carried out with custom software written in MATLAB R2012b. All computer programs in connection with the model were also created using MATLAB R2012b.", "Mathematical modeling of aging. Given the aforementioned biovariability in connection with hippocampal gene expression, I wanted to explore whether, via mathematical modeling, I could generate a function that could" ] },{ "paper_id": "6f5c8e7b610ecc3b139756ce244a25c699d33946", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6f64870ea0f8f51525b16926dc6dbb42911f850f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6fa649c67f566b9bcd0450e3a9614cbd6fddf74c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u00f0\u00c0 log p\u00de k k!", "The candidate taxa are then ranked by this combined P-value.", "sharing the same state for a given probe, and applying Bayes' rule:" ] },{ "paper_id": "6fe5c74868af62cfacb629af957915de0b094af9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Immunofluorescence Assay. Immunofluorescence assays were performed as described previously (46), using primary antibody mouse-\u03b1-G3BP1 (611126, 1:1,000; BD Biosciences), and secondary antibody donkey-\u03b1-mouse-Alexa488 (A-21202, 1:200; Thermo Fisher Scientific).", "Western Blot Analysis. Western blot assays were performed as described previously (46) , using primary antibodies rabbit-\u03b1-puromycin (MABE343, 1:1,000; Merck Millipore), rabbit-\u03b1-eIF2\u03b1 (9722, 1:2,000; Cell Signaling), rabbit-\u03b1-eIF2\u03b1-P (ab32157, 1:1,000; Abcam), or mouse-\u03b1-tubulin (T9026, 1:5,000; Sigma-Aldrich), and secondary antibodies goat-\u03b1-mouse-IRDye680 (1:15,000; LI-COR) or goat-\u03b1-rabbit-IRDye800 (1:15,000; LI-COR)." ] },{ "paper_id": "6ff336c5f099acbe84cf7cfe5f68bd5ba672d6b8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To the best of our knowledge, this is the first report of the direct effects of a PED outbreak on the subsequent numbers of pigs marketed. We are continuously recording the production parameters of these herds with our data-recording system PigINFO and plan to investigate the potential risk factors for PED outbreaks. Sporadic PED continues to occur in 2015, and the strict biosecurity measures against PED must be strengthened because PED outbreaks cause serious economic losses.", "Although many case reports have described PED outbreaks and compared PED viruses genetically, very little information is available regarding the effects of PED outbreaks on swine productivity and economic factors. The objective of this study was to summarize the characteristics of the PED infections in the second epidemic in Japan using data from herds belonging to the clients of consulting veterinarians. We also investigated the effects of the herd-level PED status on productivity using a data recording system (PigINFO) recently developed for Japanese swine producers [17] .", "In Japan, PED was first confirmed at one swine farm in 1982 [14] . In 1996, a large PED epidemic occurred in 102 affected herds, and 39,539 pigs died [10] . From 1997 to 2006, only sporadic cases of PED were reported (1-3 cases/ year), and no cases were reported from 2007 to 2012 [10] . On 1 October 2013, a new case of PED was reported in a herd located in Okinawa Prefecture. From December 2013 to February 2014, the first PED epidemic (0-25 cases/week) was reported, primarily involving herds located on the southern island of Japan. From March to June 2014, a more severe PED epidemic (5-100 cases/week) was reported among herds throughout Japan [10] . By the end of August, these two PED epidemics had affected 817 herds, detected in 38 prefectures [9] and caused serious economic damage to the swine industry, as in the United States." ] },{ "paper_id": "6ff8826ca04c185f3a88ab4b0d5a912aea4ab1a6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We have shown that these TNT-PNA probes hybridize quantitatively and specifically to their targets and that the probes perform reliably over a wide dynamic range providing a new platform for multiplexed and quantitative genomic analysis.", "Biotinylated, fully complementary target 50-mer oligodeoxyribonucleotides for the hybridization experiments were synthesized by Yorkshire Bioscience (York, UK) on a 1-mmol scale. Target sequences are shown in Table 3 .", "FMOC-protected peptides were custom synthesized by PepSyn Ltd (Liverpool, UK) using commercially available FMOC-protected amino acids on a Beckman synthesizer." ] },{ "paper_id": "7037460cc980744603573744bf370ee8f49a4ffe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sciences, Foster City, CA, USA, and hold stock interests in the company.", "Drug preparation GS-441524 was provided by Gilead Sciences as a pure and highly stable powder and diluted to a concentration of 10 or 15 mg/ml in 5% ethanol, 30% propylene glycol, 45% PEG 400, 20% water (pH 1.5 with HCI). The mixture was placed in sterile 50 ml glass injection bottles, agitated until in suspension, and then placed in a sonicated water bath for 5-20 mins until clear. The diluted drug was refrigerated and used within 3-4 weeks.", "ORCID iD Niels C Pedersen https://orcid.org/0000-0001-6269-929X", "Drugs that inhibit virus replication have become mainstays in the treatment of acute and chronic RNA and DNA virus infections of people. 1 However, interest in antiviral drugs for infections of animals has been much slower to develop. This is especially true for cats, which suffer from several chronic viral infections resembling those in people. The infectious agents include feline leukemia and immunodeficiency viruses (FeLV and FIV, respectively), 2 " ] },{ "paper_id": "7048d2fc8e7a1daab3747ea6d2257a874a9723b0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CONFLICT OF INTEREST. The authors declare no conflicts of interest directly relevant to the content of this article. ", "Furthermore, we examined four infectious diseases including Toxoplasma gondii (T. gondii), Feline coronavirus (FCoV), feline leukemia virus (FeLV) and feline immuno-deficiency virus (FIV) that are major diseases of the cat and compared the seroprevalence in feral cats and domesticated cats.", "Testing for antibodies against E. cuniculi was performed using an enzyme-linked immunosorbent assay (ELISA) with glutathione S-transferase fusion polar tube protein 2 as the antigen [16] . Individual cat serum samples diluted to 1:400 and horseradish peroxidase-conjugated goat anti-feline immunoglobulin G antibody (MP Biomedicals, Santa Ana, CA, U.S.A.) diluted to 1:10,000 were used as the first and second antibodies, respectively." ] },{ "paper_id": "707804d48dc9d8ebd7016536cf785c6c0be25bf8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "70785546b2ab863782992d42183b0df0a1916ddb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7089e8b9423d428a8e1539366978157492f89f19", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To examine the TL1/PK2 tertiary interaction (13, 16) , antisense-interfered SHAPE (aiSHAPE) strategy has been applied (37) . In this method, displacement of one strand of an RNA duplex by hybridizing an antisense oligonucleotide would disrupt long-distance interactions and would be characterized by enhanced NMIA sensitivity of the displaced nucleotides ( Figure 3A) .", "Locked nucleic acid (LNA)/DNA chimeras were ordered from Exiqon, the sequences of which are provided in Supplementary Table S1. Chimeras were added at 10-fold excess after folding. Samples were subsequently incubated at 37 C for 15 min before NMIA treatment (see earlier in the text). To quantify alterations induced by ai-oligonucleotides, raw data were processed as described earlier in the text. Tertiary interactions were introduced manually into RNAstructure version 5.3 generated models (22) .", "Unlike cellular mRNAs, which only contain translational regulatory motifs, viral RNA genomes have evolved functional regions, which act at different stages of their life cycle. These specific structures, their interactions and association with host proteins and ligands, together orchestrate the multifunctionality of viral RNA genomes. Often, RNA-RNA interactions spanning significant distances (1,2) bring regulatory motifs into proximity, changing our view of a functional viral RNA genome from that of a linear molecule to one whose 3D structure is an important contributor during the life cycle (3, 4) .", "In addition, the apex of the rightmost hairpin showed lowered cleavage intensity as compared with DENV-MINI RNA (Supplementary Figure S2) .", "Before Pb 2+ ion-induced cleavage, RNA transcripts (10 pmol) were subjected to refolding as described earlier in the text. A freshly prepared solution of Pb(OAc) 2 was added to a final concentration of 0.5 mM, and the reaction mixtures were incubated for 10 min at room temperature (23) . Reactions were quenched by adding an equal volume of 20 mM EDTA followed by ethanol precipitation. Cleavage sites were detected by primer extension as described earlier in the text (19) ." ] },{ "paper_id": "7096c575274ae29d1398ec04938f568e5187c9a1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Student's t test was used for data analysis. P < 0.05 was considered to be statistically significant.", "we tested the infectivity of MERS-CoV after exposure to fed-state simulated gastric fluid (FeSSGF) or fed-state simulated intestinal fluid (FeSSIF), which contains a high concentration of bile salts that solubilize the lipid membrane of enveloped viruses. The results showed that MERS-CoV survived FeSSGF while being less tolerant to FeSSIF. Nevertheless, a small proportion of the virus can survive FeSSIF after treatment for 2 hours. As a control, EV71, a prototype human enterovirus, was generally resistant to all the tested gastrointestinal fluids." ] },{ "paper_id": "709c30173f5cfdd55b8636f71cf76d3788a0553d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Diagnoses: He was diagnosed with PCP, and further evaluations revealed underlying X-linked hyper-IgM syndrome.", "Interventions: He was treated with trimethoprim/sulfamethoxazole for PCP, and eventually received allogeneic hematopoietic cell transplantation for hyper-IgM syndrome.", "Outcomes: Twenty months have passed after transplantation without severe complications." ] },{ "paper_id": "70fd2c4e38970a59c42925daef90f674d7b21302", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "There are a handful of case reports on MERS outcomes in other vulnerable populations, including three cases in pregnant women and one in an HIV-positive individual.", "Kinetics of response may also be important. An antibody kinetics study with 17 patients in South Korea (from the same research group that later reported waning antibody titers in patients over a 1-year follow-up) found that most patients produced a robust neutralizing IgG antibody response beginning at about 2 weeks and peaking by about 3 weeks; delayed response was generally correlated with a less favorable prognosis .", "Currently, the main treatment strategy is symptomatic supportive care; mechanical ventilation and ICU admission are usually required for severe cases." ] },{ "paper_id": "71195817c4cfe2c8b7bc13418d2062226a71d0e9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "*Correspondence to: Tabitha Kimani, PO Box 1510-00200 Nairobi, Kenya, Email: mugethikimani@yahoo.com I nfectious diseases are likely to continue emerging and re-emerging in the foreseeable future, with profound negative impacts on multiple sectors and global economies (1) . Zoonoses account for 70% of emerging infectious diseases (EIDs) and 60% of human pathogens/ diseases (2\u00c14). About 80% of human infectious disease pathogens could be used for bioterrorism (5) . Major zoonotic EIDs that have occurred over the last 20 years include bovine spongiform encephalopathy, highly pathogenic avian influenza (HPAI), severe acute respiratory syndrome (6) , Hendra virus disease (7), Nipah virus encephalitis (8) , West Nile fever (9) , pandemic H1N1 influenza (10) , Middle East respiratory syndrome (11) and Ebola (12) . Apart from the EIDs, endemic zoonoses such as Rift Valley fever (RVF) are also of great concern.", "To mitigate the worrying trend of EIDs, the One Health (OH) strategy is expected to gain momentum as a tool to address both associated multisectoral impacts and environmental, animal and human health drivers for their emergence and spread. Major drivers for (re-)emergence of pathogens include increased movements and contacts of people, wildlife and livestock; intensification of livestock production; and low biosecurity in farms and live animal or wet markets (13\u00c115). A main driver of RVF is climate change where El Nino events influence the frequency of outbreaks.", "To generate sociograms or visual diagrams of the network, the interval data were binarised where scores 0 and 1\u00c18 were coded as absent '0' and present '1', respectively." ] },{ "paper_id": "711ffbd9492fb8100b4c89fea6842c38682e4410", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Before reverse transcription reaction, all RNA samples were individually treated by Genomic DNA elimination reaction gene was normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The primer and probe sequences are shown in Table 1 ", "Total RNA was extracted from 12 individual chicken organs (12 kidneys) per group by homogenization in TranZol reagent (TransGen Biotech, China) using a homogenizer under low temperature according to the manufacturer's protocols. RNA was diluted in nuclease-free water, then quantified based on UV spectrophotometry at 260 nm. The integrity of the extracted RNA was confirmed by 0.8% agarose gel electrophoresis.", "All data were analyzed by SPSS (ver. 17.0; SPSS, USA). Data were determined to be normally distributed by the Shapiro-Wilk test. Differences between the control and the affected group were identified by one-way analysis of variance (ANOVA). The results were expressed as the means \u00b1 the standard deviation (SD). Data were considered statistically significant at p \uff1c 0.05." ] },{ "paper_id": "715842fa536064980818ad7e31ce511272a4b6bc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "715fec9052e391ea2d2bd055e7fea736b2882bc7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "71a02ec5050593d346595f2af85aa3ce3b403bdc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "71b1e5b3dcbccd130699fbbdbc537a66a24598bc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "rMERS-CoV-\u232cE could also be used as the starting point to generate an inactivated vaccine in case of an urgent need to control the disease. In order to guarantee the absence of virulent viruses after an incomplete chemical inactivation due to clump formation, potential noninactivated viruses would be propagation defective and, therefore, attenuated.", "The assembled infectious cDNA clone was stable during its propagation in Escherichia coli DH10B cells for more than 200 generations, as determined by restriction endonuclease analysis (data not shown).", "likely have not required hospital assistance. In fact, recent data suggest that mild respiratory illness might also be part of the clinical spectrum of MERS-CoV infection (3) . In addition to mild or acute respiratory illness, other reported clinical symptoms are abdominal pain and diarrhea, fever, and in some cases, renal failure (9) . Many hospitalized cases occurred in persons with chronic underlying medical conditions or immunosuppression (3, 13) . The virus loads are highest in lower respiratory tract samples, although low concentrations of viral RNA can also be found in stool, urine, and blood samples (12) .", "rMERS-CoV-\u232cE, in which one of the nonessential accessory proteins was deleted, could be considered a marker vaccine, as it will allow the sera of field-infected patients to be distinguished from sera of vaccinated patients, based on the lack of antibodies specific for nonessential viral proteins (60) ." ] },{ "paper_id": "71b5ffbc04fa339eed42ead8bb5dd1bf0e471b8f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Three bovine RVA strains (IS1 (G6P [5] ), NCDV (G6P [1] ) and KK3 (G10P [11] )) were subjected to study of sensitivity of detection. An established fetal rhesus monkey cell line (MA-104) was used for virus propagation, and culture fluids were used for tests. The titers of each virus stocks were 10 7.0 TCID 50 /ml. Thirteen fecal samples were taken twice daily from seven beef farms located in Ishikawa Prefecture, Japan, that had an epidemic history of RVA. These specimens were collected between 2012 and 2013 from calves (aged<1 year) that showed watery or sticky diarrhea that was white, yellow or greenish brown.", "Thirteen fecal samples, which were negative for the Dipstick and RT-PCR, were subjected to next-generation DNA sequencing. Bovine RVA reads were recovered from all samples ( Table 2 ). The two of them yielded 155 and 828 reads covering 11 segments (24 and 59 VP1, 17 and 19 VP2, 29 and 94 VP3, 20 and 30 VP4, 13 and 76 VP6, 21 and 73 VP7, 3 and 60 NSP1, 7 and 117 NSP2, 10 and 191 NSP3, 5 and 38 NSP4 and 6 and 72 NSP5 sequences). Mapping the 50-mer short reads of two samples to the reference VP4 and VP7 sequences allowed genotyping of G and P. Almost all of the reads of No. 3 and No. 8 were aligned with G10P [11] and G6P [5] reference sequences, respectively (Fig. 1) .", "We investigated the sensitivity of human rotavirus rapid antigen detection (RAD) kits, RT-PCR and next-generation DNA sequencing (NGS) for detection of bovine group A rotavirus (RVA). The Dipstick 'Eiken' Rota (Dipstick) showed the highest sensitivity out of the seven RAD kits against all selected strains in limited dilution analyses, which was consistent with the results for equine rotavirus previously reported. RT-PCR had 10 0 -10 3 -fold higher sensitivity than the Dipstick. NGS using thirteen RT-PCR-negative fecal samples revealed that all samples yielded RVA reads and especially that two of them covered all 11 genome segments. Moreover, mapping reads to reference sequences allowed genotyping. The NGS would be sensitive and useful for analysis of less dependent on specific primers and screening of genotypes." ] },{ "paper_id": "71b8c50ee0e1f4e79e6618301b768befbf943a5d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cite this article as: Patel S, Shah NM, Malhotra AM, et al. Inflammatory and microbiological associations with near-fatal asthma requiring extracorporeal membrane oxygenation. ERJ Open Res", "We performed a retrospective review of all adult asthmatics requiring mechanical ventilatior and/or ECMO for near-fatal asthma admitted to our single large tertiary hospital between 2011 and 2016. Clinical and demographic data including ventilator parameters, biochemical and immunological indices, and microbiology isolates were recorded. We compared patients requiring ECMO with patients requiring conventional mechanical ventilation only, to identify any factors that were significantly associated with the need for ECMO.", "Extracorporeal membrane oxygenation (ECMO) has developed as a critical tool permitting lung protection in severe respiratory failure. Its use was largely confined to acute respiratory distress syndrome [1]; however, as technology has advanced, it is now used in a range of respiratory diseases, including asthma. In the context of near-fatal asthma exacerbations, ECMO provides a management strategy for difficult-to-ventilate patients who would otherwise be unlikely to survive. Importantly, in asthma, traditional mechanical ventilation strategies can be associated with volutrauma and barotrauma due to the high pressures required in the presence of severe bronchospasm [2] . To date, there is a paucity of data for ECMO use in acute asthma and it is unknown whether specific clinical or inflammatory characteristics are associated with the need for ECMO." ] },{ "paper_id": "71cb2319da3251ef1b4bc99ce5c4ca633b2cb1b9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Enforce laws and regulations that protect health and ensure safety.", "Development of policies and institutional capacity for health planning and management.", "**Skills development and maintenance." ] },{ "paper_id": "71edbd57cdd9af956a12054932e0cbdb87ce1fea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Men (n=273) Women (n=384)" ] },{ "paper_id": "721b3e6ae8af24a4f625540bbb6e2c02fb77b491", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Escherichia coli strain MAS90 [E. coli K-12, recA1 D(pro-lac) thi ara F 0 : lacI q1 lacZ::Tn5 proAB + ]. Liquid cultures were grown in minimal MOPS media (32) using glycerol as carbon source. Cultures were incubated with shaking at 37 C for at least 10 generations in the log phase prior to being used in frameshift assays.", "All pseudoknots investigated stalled some fraction of the frameshifted ribosomes, however, significantly more ribosomes stalled in the artificial pseudoknots than in those resembling naturally occurring pseudoknots (PK400 and PK401).", "structures more similar to naturally occurring pseudoknots (Figure 1 insert), inspired from structures in the infectious bronchitis virus (22, 28, 30) . The pseudoknot structures in this type of virus are selected for their effects on vertebrate ribosomes, but the stem1 length variations were found to yield approximately the same relative stimulatory effect in E. coli (25) and suggest that stem1 strength is equally important for stimulating bacterial ribosomes to frameshift.", "The in vivo frameshift assays were performed as described previously (25) . Briefly, 1 ml of an exponentially growing culture was induced with Isopropyl b-D-Thiogalactopyranoside (IPTG) to a final concentration of 1 mM at an optical density of 0.4-0.7 measured at 436 nm (OD 436 ). After induction for 15 min, the culture was pulse-labelled with $10 mCi L-[ 35 S]-methionine for 20 s and chased with 100 mg L-methionine for 2 min before being transferred to 25 ml of chloramphenicol (100 mg/ml) on ice. The cells were harvested by centrifugation and proteins were boiled in SDS buffer and separated by 9% SDS-PAGE. The gel was dried and placed on a phosphor imager screen (Molecular Dynamics) and left to expose for 1-3 days. Relative amount of protein of the relevant polypeptides was quantified using ImageQuant software and the frameshift efficiency (e) was determined as follows:" ] },{ "paper_id": "7220982ea4592afc5109160c63d728f1fdaa8373", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Our study provides an opportunity to consider how this strategy might be established.", "diseases. However, the allocation of R&D funding for neoplasms was more than nine times that of musculoskeletal disorders. Neurological disorders, which include Alzheimer's dementia, were ranked second after neoplasm in the MOHW R&D funds.", "The recognition of the importance of non-communicable diseases is growing worldwide, 13,14 including in Korea. In a previous study by Prince, 15 Studies for behavioral risks Behavioral risks \u00b7 Tobacco smoking \u00b7 Alcohol use \u00b7 Diet high in red meat \u00b7 Diet high in processed meat \u00b7 Diet high in sodium \u00b7 Diet low in calcium \u00b7 Diet low in fiber \u00b7 Physical inactivity and low physical activity Socio-economic risks \u00b7 Childhood sexual abuse \u00b7 Intimate partner violence Climate & environmental risks \u00b7 Unimproved water and sanitation \u00b7 Ambient particulate matter pollution \u00b7 Household air pollution from solid fuels \u00b7 Ambient ozone pollution \u00b7 Residential radon \u00b7 Lead exposure" ] },{ "paper_id": "722738d238370488034852a1867cfa04b564d331", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "There was no interference by any of following substances: hu-man blood (1:20 dilution), barium sulfate (0.25 mg/mL), loperamide (0.25 mg/mL), metronidazole (0.25 mg/mL), hemoglobin (0.25 mg/mL), bilirubin (0.25 mg/mL), or triglyceride mix (0.25 mg/mL)." ] },{ "paper_id": "723d2ca57cbcc702c68347fb8183376d16d80f1a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "the glucose concentration in the incubation medium was increased from 3.3 to 16.7 mmol/l (Fig. 1) .", "Insulin release. The quantity of insulin released from the INS-1 cells was significantly increased, as expected, when ", "Statistical analysis. Statistical analyses were performed using GraphPad Prism 5 (http://www.graphpad.com/), and data are expressed as means \u00b1 standard error of the mean. One-way analysis of variance followed by Tukey's or Dunnett's tests were used to compare all groups or selected groups to the control and P<0.05 was considered to indicate a statistically significant difference." ] },{ "paper_id": "7248a954a71c38b84dcc81be1105e231728286fc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "www.e-trd.org of the manuscript, or decision to publish.", "Supplementary material can be found in the journal homepage (http://www.e-trd.org)." ] },{ "paper_id": "724a937a58d4217e5d5cc6d1d1e438a5b5b35d6e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "725f0a6590f20c15be0ae719463c0624a34ee1af", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Blood (0.5 mL) was taken from mice of each group through eyeball extraction, and serum was separated by centrifugation at 4000 rpm for 10 min at 4\u00b0C and stored at -80\u00b0C. An ELISA kit Shanghai Jianglai Biotechnology Co., Shanghai, China) was used to measure CXCL5 expression and IL-1b, IL-6, TNF-a, and IL-10 expressions (Shanghai Enzyme-Linked Biotech Co., Shanghai, China) following the manufacturer's protocol. The 96well microplates were read using a microplate reader (Thermo, Waltham, MA) at 450 nm.", "Abbreviations: ARDS -acute respiratory distress syndrome; CXCL5 -Cxc chemokine ligand 5; CXCR2 -Cxc chemokine receptor 2; MMP2 -matrix metalloproteinases 2; MMP9 -matrix metalloproteinases 9; LPS -lipopolysaccharide; UCC -uterine cervix cancer; H&E staining -hematoxylin-eosin staining; W/D -wet-to-dry; ELISA assay -enzyme-linked immunosorbent assay; SDS-PAGE -sulfate polyacrylamide gel electrophoresis; PVDF -polyvinylidene fluoride; TBST -tris-buffered saline plus 0.1% Tween 20", "Full-text PDF: https://www.medscimonit.com/abstract/index/idArt/915835" ] },{ "paper_id": "72903336c1c94d9acc0491f7aadc93d7365a6934", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "72bf8d8fff5a84e84e219df26f0d4cbdfa0bb15c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Keywords: germanium biotite, immune enhancement, porcine reproductive and respiratory syndrome virus 136 Bock-Gie Jung et al.", "The mice were fed the control or experimental diets for 2 weeks. The animals were then sacrificed and the spleen was collected. The spleens were aseptically removed with scissors and forceps, placed in cold phosphate-buffered saline (PBS), and single-cell suspensions were prepared by pushing the tissue through a 40-\u03bcm nylon mesh (BD Biosciences, USA). Erythrocytes in the cell mixture were destroyed by incubation with Tris-NH 4 Cl. The lymphocytes were washed with PBS twice prior to resuspension in complete medium consisting of RPMI-1640 medium (Lonza, Switzerland) containing 10% (v/v) fetal bovine serum (FBS; Gibco, USA) and 2% (v/v) antibiotic-antimycotic solution (Lonza, Switzerland). Live cells were detected by staining with trypan blue.", "Source and composition of the GB feed supplement GB used in this study as a feed supplement was provided by Seobong Biobestech (Korea). The supplement was composed of silicon dioxide (SiO 2 , 61.90%), aluminum oxide (Al 2 O 3 , 23.19%), iron oxide (Fe 2 O 3 , 3.97%), sodium oxide (Na 2 O, 3.36%), and 36 ppm germanium." ] },{ "paper_id": "72e25d8530d2d778392e2ca2a1ec1b7e13e24a30", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "One set of five mice from control and treated groups were lavaged as described in Poulsen et al. (27) . In brief, a total of 2 mL of 0.9% sterile saline was injected in lungs and was recovered. The BALF was immediately put on ice until further processing. BALF was centrifuged at 4\u00b0C and 400 g for 10 min to collect cells, which were resuspended in 0.5 mL PBS.", "Genes showing expression changes of at least 1.5-fold in either direction compared with their matched controls and showing FDR P \u2264 0.05 were considered as significantly differentially expressed genes (DEGs) and were used in all downstream analyses. All microarray data have been deposited in the NCBI gene expression omnibus database and can be accessed via the accession number GSE81570.", "Supplementary Tables 1 to 7 and Supplementary Figures 1 to 8 ", "Five-to-seven-week-old female C57BL/6 mice (Jackson Laboratory, Bar Harbor, ME, USA) were housed in autoclaved cages with a 12-h light-dark cycle. All mice were given food and water ad libitum throughout the experiment. Animals were weighed before beginning the exposure and once every week during the course of the experiment. Mice were housed in pairs. All animal procedures were conducted in accordance with the guidelines of the Canadian Council for Animal Care and approved by Health Canada's Animal Care Committee." ] },{ "paper_id": "7307753da247144e66cc91b8f48c33e5a9ceff2b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CONFLICT OF INTEREST. The authors declare no conflicts of interest." ] },{ "paper_id": "731ee91af20f34fccc9866d85a18b787c16bbe1e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(Medicine 95(14):e3014)", "Abbreviations: CAP = community-acquired pneumonia, PBS = phosphate-buffered saline, PCR = polymerase chain reaction, RSV = respiratory syncytial virus.", "Editor: Roman Leischik." ] },{ "paper_id": "7321a41ee2054c07a18ede4e04a420621cb33087", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "734f6b97fbdf729498fe7077f74f49db8311d2b9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "73706c27f129eddf80395baf777ba70dd9432e8e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Labeling with charged topographical markers and affinity studies revealed that S-layers from several Bacillus strains do not possess a net negative charge as demonstrated for the underlying peptidoglycan-containing layer or other bacterial surface structures (S ara & Sleytr, 1987a; Gruber & Sleytr, 1991; S ara et al., 1992) . In native S-layers, carboxyl groups are neutralized by an equal number of amino groups, leading to a charge neutral outer surface (Weigert & S ara, 1995) .", "To summarize, S-layer carrier conjugates are superior vaccine carriers because (1) they elicit DTH and immuno-protective antibody responses without the use of extraneous adjuvants, (2) they can be administered by several different immunization routes (intramuscular, subcutaneous, nasal/oral), and they are immunological unique, which means that antibody and delayed-type hypersensitivity responses to each S-layer are specific and not cross-reactive (Malcolm et al., 1993b) .", "[The copyright line for this article was changed on 7 October 2014 after original online publication]", "Self-assembly products are formed in solution during the dialysis of the disrupting agent against selected buffer solutions (ionic strength and pH). Monitoring the time course of self-assembly by light scattering yielded multiphasic kinetics with a rapid initial phase and slow consecutive processes of higher than second order (Jaenicke et al., 1985) . The rapid phase may be attributed to the formation of oligomeric precursors. Concentrationdependent light scattering measurements gave evidence for a 'critical concentration' of association, suggesting that patches of 12-16 proteins are formed and recrystallize into the final (native) S-layer structure.", "In a recently carried out detailed study using in situ AFM, it was shown that the reassembly of SbpA S-layer proteins from Lysinibacillus sphaericus CCM2177 on mica does not necessarily follow the classical pathway of crystal growth. Instead, a kinetic trap keeping the system at a higher-energy, long-lived transient state may hinder the reassembly into extended matrices . Over time, finally the trapped state transforms into a stable, low energy state. Careful analysis of the time and temperature dependence of formation and transformation yielded an energy difference by only 1.6 kJ mol \u00c01 (or 0.7 kT). But the energy barrier to transform into the final low energy state is 38 times higher (61 kJ mol \u00c01 )." ] },{ "paper_id": "737650f6ab6664da7582430d4b45ff9dd2e76866", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Two review authors independently extracted data and assessed study risk of bias and confidence in effect estimates (certainty of evidence) for each outcome using GRADE (Grades of Recommendation, Assessment, Development and Evaluation). We described results and presented them in GRADE tables.", "Absolute effect* (95% CI) Relative effect (95% CI) " ] },{ "paper_id": "7377d7ad2d731e3fbd3ed4fa15ed541b06e3587c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.", "HLH can also be secondary to other conditions, such as autoimmune disorders (adult-onset of Still's disease) (7), malignancies (particularly T cell lymphomas) (8) , viral, bacterial, fungal, or parasitic infections (4), or immunosuppression (9) .", "Patients with X-linked lymphoproliferative syndrome, a rare disorder that affects males, can develop HLH after infection by the Epstein-Barr virus (10) ." ] },{ "paper_id": "73aa8683fd7c4fd68b73f231b6bc3e609d4e9af9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study", "This study RNA half-life analysis mRNA half-lives were determined in yeast strains containing the rpb1-1 temperature-sensitive mutation and tetO7 promotor substitutions using methods described previously (19) . MF2 and ACT1 band intensities were normalized against SCR1 band intensity (a pol III transcript).", "Cell cultures of cells expressing C-terminally TAP-tagged Dhh1 were centrifuged and 10-ml cell pellet volumes of exponentially growing (OD 600 = 0.5) or post-diauxic shift (OD 600 = 2.0) cells were processed as detailed previously (20) . After elution proteins were then concentrated by TCA precipitation and resolved by SDS-PAGE and stained with Sypro Ruby protein stain. Following excision of Sypro Ruby stained (or control) bands, the gel slices were subjected to in-gel proteolysis with trypsin and peptides were analysed by LC-ESI-MS using a Bruker AmaZon ETD system Data were processed using DataAnalysis (4.3) and searched against SwissProt v57_15 using MASCOT (21) . Figure S8 )." ] },{ "paper_id": "73f48a992c779f349ff5e305afe2f0538699ec33", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "746804f73409212ee4161597d1ebb4fd5e8cd296", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To facilitate efficient infections, viruses have evolved a wide range of evasion strategies, targeting host DNA sensors, adaptor proteins and transcription factors. In this review, the current literature on virus-induced activation of the STING pathway is presented and we discuss recently identified viral evasion mechanisms targeting different steps in this antiviral pathway.", "Cellular sensing of virus-derived nucleic acids is essential for early defenses against virus infections. In recent years, the discovery of DNA sensing proteins, including cyclic GMP-AMP synthase (cGAS) and gamma-interferoninducible protein (IFI16), has led to understanding of how cells evoke strong innate immune responses against incoming pathogens carrying DNA genomes. The signaling stimulated by DNA sensors depends on the adaptor protein STING (stimulator of interferon genes), to enable expression of antiviral proteins, including type I interferon.", "With the accumulating insight into the mechanisms of viral evasion of DNA sensing, there is now a need to understand the importance of these mechanisms in vivo. Further knowledge on the cellular targets and mechanisms of action of viral strategies to evade the DNA sensing machinery will lead to better understanding of the pathogenesis of viral diseases, and could also uncover potential targets for future immunomodulatory drugs." ] },{ "paper_id": "748d4c57fe1acc8d9d97cf574f7dea5296f9386c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Mean measurements (\u03ee standard deviations [SD]) were derived from three separate experiments, unless otherwise indicated. Statistical significance was established by Student's t test or by one-way analysis of variance (ANOVA) with a post hoc Dunnett's test (**, P \u03fd 0.01; ***, P \u03fd 0.001; ****, P \u03fd 0.0001).", "Text S1, DOCX file, 0.01 MB. Figure S1 , TIF file, 0.1 MB. Figure S2 , TIF file, 0.1 MB. Figure S3, " ] },{ "paper_id": "74b7e481670a3a785ee8f82702d4be3b5488eb88", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ginseng is divided into fresh ginseng, white ginseng, and red ginseng depending on the processing method.", "Patients receiving glucosamine sulfate showed improvement in symptoms of pain and stiffness and radiographic findings showed reduced joint space narrowing. 38 After these two long-term studies presented favorable results, glucosamine has attracted much attention in managing osteoarthritis.", "Moreover, they addressed that red ginseng has no favorable effect on DM." ] },{ "paper_id": "74bc0b72bd1e1984f0428c90223d5f9cceda5f22", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Growth inhibition Piboonpocanun et al. (2005) ", "Stimulation of immature DCs by SP-A also inhibits the allostimulation of T cells, enhances dextran endocytosis, and alters DCs chemotaxis toward RANTES (Brinker et al., 2003) .", "Does not enhance phagocytosis Rosseau et al. (1997) Coccidioides posadasii + nd Disrupts levels of pulmonary surfactant Awasthi et al. (2004) Cryptococcus neoformans + Mannose, glucose (requires capsule)" ] },{ "paper_id": "750eb3af6059e879b20beac9fb982f85332dd552", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In order to visualize the clustering, a principal component analysis (PCA) was applied to project the RSCF vectors to a plane spanned by their first two principal components. In order to visualize the separation between clusters a maximum margin separation line-a line for which the distance between it and the nearest point from either of the groups is maximized, was calculated and plotted.", "Supplementary data are available at DNARES Online." ] },{ "paper_id": "751591a95a9673f692d3a0189ca5a9b0c7e8781c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Since the age of 5 mo, the patient had a history of recurrent fevers (3-5 d/mo) associated with digestive features including diarrhea, abdominal pain without any vomiting, transient cutaneous rash, and intermittent urticaria, initially suggestive of an auto-inflammatory syndrome since no infectious agent was identified. Prior to any supportive treatment, IL-1\u03b2 and TNF\u03b1 were positive, respectively, at 17.9 pg/ml (0-15) and 25.1 pg/ml (0-20), whereas IL-6 and IL-10 were normal and negative. MEFV, MVK, CIAS1, and TRA PS were sequenced and found without any deleterious variation. Anti c1q antibodies were consistently positive, but sequencing of DNA SE1L3 was normal.", "Intravenous Igs at 0.4 g/kg/3 wk were begun at 2 yr 8 mo of age because of recurrent viral infections, resulting in an improvement of her recurrent fever profile, digestive symptoms, and susceptibility to viral infection.", "For viral replication, the Prism 7 software (GraphPad) was used to calculate P values using one-way ANO VA with Dunnett's multiple comparisons, Kruskal-Wallis test with Dunn's multiple comparisons.", "Standard immunological tests were performed. Serum levels of IgG, IgA, and IgM were unremarkable. T and natural killer lymphocyte count were conserved, whereas a modest B lymphocytosis was measured (Table S1 ). Lymphocyte proliferation was normal for PHA, tuberculin, and candidin (n > 50), but low in the presence of tetanus, CMV, and HSV antigens (n > 10; Table S2 ). T and B cell counts were within normal ranges. The patient was IgG seropositive for tetanus, diphtheria, haemophilus, measles, mumps, rubella, and HBV (Ag HBs negative, anti-HBs positive, anti-HBc negative) following routine vaccination. She remained seronegative for HIV1/2, HAV, HCV, VZV, Parvovirus B19, EBV, CMV, and pneumococcus despite proper vaccination for the latter." ] },{ "paper_id": "751764ca73c84e497075d172d6417ea95c1a7e09", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "75251cc3d312b0d2c63117458c68dba563715155", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "St. John's Rehabilitation Centre (SJR) is a 154-bed rehabilitation facility located in Toronto, Ontario, Canada and is a tertiary care teaching hospital affiliated with University of Toronto. The patient population includes cardiac, amputee, stroke, trauma, medical debility, burn and musculoskeletal patients. The average length of stay is approximately 21 days and there are about 2500 admissions per year.", "Interventions Based on comprehensive analysis of prior outbreaks, the following changes were implemented:" ] },{ "paper_id": "75275e1adbc2a3dcb78893dd1cf92d7fcf2915cc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "756dbc931627ce595e70224e084e8cb89d38287c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The computations of RR, RD and WMD were given by the following standard formulas:", "The Table 1 , where anti-SARS formulae were evaluated in ten studies, herb extracts were evaluated in three studies, and other combinations of herbal medicines were evaluated in eleven studies." ] },{ "paper_id": "75fbdec55c05102f8337e48dda0c8b6cf27dac52", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All experiments were approved by the Committees on the Ethics of Animal Experiments of Kitasato University and the University of Tokyo. For immunohistochemistry, 48 samples of canine mammary gland tissue embedded in paraffin blocks were obtained from the histopathological files in the Veterinary Pathology Laboratory, Kitasato University. Although the classification method about simple carcinoma is under controversy [18] , the diagnosis of all specimens was based on the WHO classification [11] . Immunohistochemical staining was performed using the rabbit polyclonal antibodies against human SSTR2 (1:300 dilution, bs-1138R, Bioss, Boston, MA, U.S.A.). Peroxidase-conjugated anti-rabbit immunoglobulin G (Histofine Simple Stain MAX-PO (R), Nichirei, Tokyo, Japan) was used as the secondary antibody. After immunoreaction, sections were colorized with diaminobenzidine and counterstained with hematoxylin. Canine pancreas tissues were used as positive controls. Negative controls were carried out by replacing the primary antibodies with antibody diluents.", "Somatostatin (SST) is a peptide hormone produced in the hypothalamus, pancreas and intestine; it regulates both endocrine and exocrine gland function [17] , and downregulates cell proliferation in various tissues of many species including dogs [1, 3, 4, 10, 14] . Among the SST receptor (SSTR) superfamily, SSTR2 is the most dominant receptor, with the highest affinity to the ligand and the strongest antiproliferative effect [3] . In human breast cancer, tumor tissues that express SSTRs are less aggressive and more differentiated than tumors with little SSTRs expression, which are massive and highly malignant [5] . These findings lead to the speculation that SSTR signal transduction is closely related to the malignancy of human breast cancer.", "In dogs, all subtypes of SSTRs, except SSTR4, have been already identified, and their expression was confirmed in just several tissues, such as pituitary and pancreas [2, 16] . Although SSTRs are predicted to be a molecular target of breast cancer therapy, there is little information about SSTRs in dogs. Hence, in this study, we examined and compared the distribution and expression of SSTR2 in normal canine mammary tissues, benign mammary gland tumor (MGT) and malignant MGT. Immunohistochemistry and Western blotting methods were utilized." ] },{ "paper_id": "760fa9225c5f571c77674f53a1f2d9648eb2adb0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study was conducted as a prospective longitudinal observational study." ] },{ "paper_id": "7627a1c7020be9b495eb7345fb3867484d618d78", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "766b9c02fdb5aaeee2c3a399ae9a6d5e179eca8f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Citation Lipkin WI. 2012. Biocontainment in gain-of-function infectious disease research. mBio 3(5):e00290-12.", "The discussion of H5N1 influenza virus gain-of-function research has focused chiefly on its risk-to-benefit ratio. Another key component of risk is the level of containment employed. Work is more expensive and less efficient when pursued at biosafety level 4 (BSL-4) than at BSL-3 or at BSL-3 as modified for work with agricultural pathogens (BSL-3-Ag). However, here too a risk-to-benefit ratio analysis is applicable. BSL-4 procedures mandate daily inspection of facilities and equipment, monitoring of personnel for signs and symptoms of disease, and logs of dates and times that personnel, equipment, supplies, and samples enter and exit containment. These measures are not required at BSL-3 or BSL-3-Ag. Given the implications of inadvertent or deliberate release of high-threat pathogens with pandemic potential, it is imperative that the World Health Organization establish strict criteria for biocontainment that can be fairly applied in the developing world, as well as in more economically developed countries.", "In lieu of a shift to BSL-4, it may be feasible to introduce specific requirements for research at BSL-3-Ag for agents with pandemic potential, particularly research concerned with a gain of function that enhances virulence or transmissibility. Such requirements could be developed by the World Health Organization as an extension of the International Health Regulations circular Laboratory Biorisk Management: Strategic Framework for Management 2012-2016 (6) . Given the implications for humankind, whatever course we pursue must be developed with global consultation and oversight." ] },{ "paper_id": "7680374114c808d702b43749801a6418bc371f42", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "from 0.1 to 20 \u03bcM. All reactions were performed in triplicate and in parallel. The change in FP was measured in the linear range over a period of 0-7 min, with readings recorded every 5 s. The FP measurements were plotted over time, and initial velocities of ISG15-TAMRA cleavage were determined. Michaelis-Menten parameters were calculated using Prism 6 GraphPad Software.", "Swatek et al. www.pnas.org/cgi/content/short/1710617115" ] },{ "paper_id": "7688b1a7662e60226e0011fe6262f6d9114e1906", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Biosensing is an important activity due to myriads of cell signaling pathways and circuits in cells. It is an important component of two-way communication between implanted engineered cells and natural cells of the body. Examples of synthetic biosensing are [9] : (1) Transcriptional biosensors are built by linking environment-responsive promoters to engineered gene circuits for programmed transcription. (2) Translational biosensors are typically built by linking RNA aptamer domains to RNA regulatory domains. (3) Posttranslational biosensors consist of membrane-bound protein receptors that trigger signal transduction cascades.", "In conventional one-way biosensing, a therapeutic substance is released from an implanted device or a genetically engineered cell in response to a programmed mechanism, e.g. release of insulin according to rise of blood glucose level. A two-way communication between the host, enabled by construction of synthetic circuits, can enable more personalized control of adjustment of therapy from implanted cells.", "The ability to control expression in target areas within a genome is important for synthetic biologists who are developing chemical-producing organisms for commercial applications. In Transcription Activator-Like (TAL) Effector Technology, two hypervariable amino acid residues in each repeat recognize 1 bp in the target DNA [10] . Recognition sequences of TAL effectors are predictable. The TAL code is similar to a navigation system for the genome, allowing pinpoint delivery of functional control elements to any specified sequence. The modular protein architecture has enabled the construction of artificial effectors with new specificities. ", "To apply this method to other types of cells, researchers will have to design and synthesize the DNA of choice and develop a system to boot up the genome. These two tasks will have to be accomplished in parallel for every new species. Accuracy in the genetic code is important for engineering of synthetic genes. The J. Craig Venter Institute is currently working on a project with the National Institutes of Health of the USA and Novartis on vaccine production using this technology." ] },{ "paper_id": "76bbd67d210cfbd619123b103b0aa1966857b75a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Frequency of tuberculosis among diabetic patients in the PRC infection and an increased prevalence of latent TB infection. Therefore, improvements in the diagnosis and treatment of MDR-TB are needed. In addition, the incidence of TB is increasing with the increase in DM, chronic diseases such as AIDS, and increased drug resistance. Although over the last 20 years the People's Republic of China has successfully reduced its TB burden with its excellent free China National Tuberculosis Program (incorporating the \"DOTS\" [directly observed treatment + short-course chemotherapy] model for TB control), the disease is still a considerable problem. 22", "We conducted another investigation of DM and TB from January 2003 to December 2012 in our DM clinic at the Chinese PLA General Hospital, Beijing, People's Republic of China (Table 3) , which identified 15,302 ward patients with DM and 758 (4.95%) ward patients with DM + TB in the past 10 years. The number of ward patients with DM increased yearly and the number of ward patients with DM + TB also increased yearly. Our data are in line with a previous report. 20 We also strictly ruled out other risk factors for TB including HIV, steroid use, and immunocompromised states that may coexist in patients with DM and TB. ", "The frequency of TB among patients with DM in the People's Republic of China is about 958 per 100,000 people, which is much higher than that of the general population (78 per 100,000), as reported by the WHO in 2011. 18 Active TB screening in patients with DM may increase earlier detection, facilitating better treatment of TB. It also may improve clinical outcomes with anti-TB treatment and DM routine care. Moreover, early diagnosis of TB in DM patients will reduce the risk of TB transmission. The introduction of active TB screening in DM patients may lead to better use of the well-established DOTS system to monitor, record, and report information about TB patients. Bidirectional screening for DM and TB should be of significant benefit in the People's Republic of China." ] },{ "paper_id": "76cbada4dbb0c067cbffac6a1f1cede25aec708b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We conducted this study in compliance with the principles of the Declaration of Helsinki.", "A pediatric patient was defined as a patient who was younger than 18 years of age. We subdivided the pediatric patients into 3 groups: younger than 1 year of age (infants), 1 to 4 years of age (young children), and 5 to 17 years of age (school-aged children).", "The protocol of this study was reviewed and approved by the Institutional Review Board of Seoul National University Hospital (IRB No. 1511-015-715). The informed consent was waived." ] },{ "paper_id": "76d2990a2663635e195b8a9818f9664872b6d3af", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.01714-14/-/DCSupplemental. Table S1 , DOCX file, 0.1 MB.", "Citation Baldwin DA, Feldman M, Alwine JC, Robertson ES. 2014. Metagenomic assay for identification of microbial pathogens in tumor tissues. mBio 5(5):e01714-14." ] },{ "paper_id": "778e12208f719a2e26d1387a5a489cdc93c612f4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Word Counts: 299 words (abstract); 2658 words (text);", "The global population is ageing as a combined result of the demographic transition from high to low levels of fertility and mortality. 1 Population ageing increases the total global disease burden, with approximately 23% attributable to disorders in people aged \u226560", "were only TPPA positive, and 1136 (43.7%) were false positive (Figure 1) ", "The authors declare no competing interest." ] },{ "paper_id": "77cdb9f7f5451fd710304093391bca2637411c85", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A d C 7 -i n l a n d E V 7 1 -i n l a n d Antibody responses to enterovirus and adenovirus X Wang et al 3", "Antibody responses to enterovirus and adenovirus X Wang et al 5", "Human rhabdomyosarcoma (RD) and human embryonic kidney (HEK293) cells were maintained in complete Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum (Gibco BRL, Grand Island, NY, USA), 2% penicillin and streptomycin (HyClone, Logan, UT, USA). EV71 strain G082 (genogroup C4) and CA16 strain SZ05 (GenBank accession NO EU262658), kindly provided by Dr Zhong Huang (Institute Pasteur of Shanghai, Shanghai, China), were amplified in RD cells and purified by sucrose density gradient centrifugation. Recombinant replication-defective adenoviruses AdHu5 and AdC7 expressing green fluorescent protein were constructed in our laboratory using published protocols. 17 The recombinant adenoviruses were amplified in HEK293 cells to generate high-titer viral stocks and then purified by cesium chloride density gradient centrifugation. All four viruses were dissolved in phosphate buffered saline with 10% glycerol and stored at 280 6 C for use in all tests in this study." ] },{ "paper_id": "77dd0ff052179336391f3256d7a4afb57a71a6b2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "77fcb3d2473e9f9c05c8f0bce3f4ebecdd5252ca", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7818d1ffe60f6ea1d6b44e73402132ce41453ab2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "- - - - N N - - - CH-STC-12-2014 N - - - N N - - - CH-TPC-12-2014 N - - - N N - - - CH-CLC-01-2015 N - - - N N - - - CH-GGC-01-2015 N - - N N N - - - CH-GLC-02-2015 N - - - N N - - - CH-HFEC-01-2015 - - - - N N - - - CH-HGC-01-2015 N - - - N N - - - CH-HSYKFC-01-2015 N - - - N N - - - CH-JPYC-02-2015 N - - - N N - - - CH-QTC-01-2015 N - - N N N - - - CH-SBC-03-2015 N - - - N N - - - CH-WTC-02-2015 N - - - N N - - - CH-XBC-01-2015 - - - - N N - - - CH-YGC-01-2015 - - - - N N - - - CH-ZSC-01-2015 N - N N N N - - - CH-ZWBZa-01-2015 - - - - N N - - - CH-ZWBZb-01-2015 N - - - N N - - - CH-ZWC-01-2015 - - - N - N - - - South", "Previous research has shown that the Severe Acute Respiratory Syndromes (SARS) corona virus (CoV) originated from Guangdong Province in southern China and has a recombinant history with lineages of type I coronavirus such as PEDV [21] . Moreover, the high frequency of recombination events in CoVs may result in the generation of novel viruses with high genetic diversity, and it could invoke unpredictable changes in virulence during human infections [23] . As such, the information we have gathered about the mutation of S genes could be informative for monitoring and predicting the potential emergence of a recombinant CoV from animals.", "Phylogenetic analysis of S gene showed that all PEDV strain sequences could be divided into four groups ( (MB-021). Forty-five of the fifty-five South China PEDV strains belonged to G2b.", "High morbidity and mortality were observed in pigs that were immunized with inactivated or attenuated PED vaccines based on CV777 [19] , suggesting that the CV777 vaccine is unable to provide full protection in swine. We have reported on further investigations into the S gene mutations responsible for the failure or otherwise of the existing CV777 vaccine [28] ." ] },{ "paper_id": "782f0ba982d2370ea1a79af73ac66052cd4ad504", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cellular \u00c01 RF signals are mRNA destabilizing elements", "Full length EST2 expression vectors (pJD641), EST2 mutant vectors (pJD796) and null plasmids (pJD315) were transformed into WT (JD1281), EST2 deletion (JD1287), UPF2 (JD1288) and EST2/UPF2 (JD1276) deletion strains. Total RNA was extracted with acid phenol/chloroform (pH = 4.5) from mid-logarithmic cell cultures. In parallel, total RNAs were extracted from isogenic rpl3D strains expressing wild-type RPL3 (JD1228), the down-frameshifting rpl3-R247A allele (AM-L3R247A), or the up-frameshifting rpl3-W255C/ P257S allele (JD1229). To prevent amplification from contaminating cellular DNA, RNA was treated with DNase I before reverse transcription using Turbo DNase (Ambion). cDNA was generated using the Bio-Rad iScript cDNA synthesis kit and used in the LightCycler real-time PCR system. PCR reactions were performed with 2 ml of cDNA in 20-ml reaction mixtures containing $10 nM each sense and antisense primer, and 1x LightCycler 480 SYBR Green I Master Mix (Roche). PCR cycles were run as follows: 1 cycle of 95 C for 10 min; 40 cycles of 95 C for 10 s, 54 C for 20 s and 72 C for 20 s. U3 snoRNA was chosen as a reference gene.", "It is now clear that PRF is employed by organisms representing every branch in the tree of life, suggesting an ancient and possibly universal mechanism for controlling the expression of actively translated mRNAs (8) . The past few years have witnessed several reports describing in silico identification of recoding signals using a variety of computational approaches (9) (10) (11) (12) (13) (14) (15) (16) . While the methodologies of each study covered a broad range of bioinformatics techniques, the general goal with the exceptions of (9, 15) was to first find out-of-frame ORFs followed by the identification of PRF signals in the overlapping region between them. While this can identify new classes of PRF signals, it is based on the assumption that PRF outcomes should mimic those observed in viral genomes and thus cannot identify new operational outcomes of frameshifting." ] },{ "paper_id": "786282089d03a2eaed7139f503755faa30dd741f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Relapsing fever C0038992", "Sweating fever C0085594", "Fever with chills C0149993" ] },{ "paper_id": "789ca66c03e2a2aaf30da4cf0df1d25b6b37b9d5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "78dc2abf39a665aec9b4a48738a2b4b838bfe72e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.", "Recently, a lot of effort has been made to discover biologically active components from marine plants. Ecklonia cava is", "Abstract" ] },{ "paper_id": "7910f7d2d13423c6eecb4ac66c0349e7830a57aa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All experiments were performed in triplicates, and the results are expressed as mean \u00b1 standard deviation (SD). Statistical analysis was analyzed by One-Way ANOVA analysis and LSD test using SPSS 17.0 software (SPSS, Inc., Chicago, IL, USA). Differences with a probability value (P) <0.05 were considered to be statistically significant.", "These results indicate that emodin may induce apoptosis in HepaRG cells via the mitochondrial caspase-dependent pathway. ", "Emodin (1,3,8-trihydroxy-6-methylanthraquinone) (Fig. 1) is a naturally occurring anthraquinone derivative, which is found in a variety of tradition Chinese herbs including Rheum palmatum (9) , Polygonum cuspidatum (10) , Polygonum multiflorum (11) and Cassia occidentalis (12) . Modern pharmacological studies have revealed that emodin possesses anti-proliferative effects on various cancer cells, such as pancreatic cancer (13) , breast cancer (14) , hepatocellular carcinoma (15) , lung carcinoma (16) , gastric carcinoma (17) and prostate cancer (18) . Furthermore, this drug has also been reported to exhibit antiviral (19) , antibacterial (20) , anti-allergic (21) , anti-osteoporotic (22) , anti-diabetic (23) , immunosuppressive (24) and neuroprotective (25) activities. Nevertheless, an increasing number of recently published studies have reported the deleterious effects of emodin in in vivo and in vitro investigations (26, 27) . Panigrahi et al reported that emodin isolated from the methanol extracts of Cassia occidentalis might be one of its main hepatotoxic ingredients (28) . Furthermore, an in vivo study demonstrated that emodin may be one of the primary chemical components in Rheum palmatum L. that causes hepatic and renal toxicity (29) ." ] },{ "paper_id": "7925057cfe0cb75ae6079879cb2d22d23e42dfa5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "792b2b2b74f58b9a32b31b57c7930dbfea9895c5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "There have been many reports of long-term sequelae of severe acute respiratory syndrome (SARS), 5-10 but to the best of our knowledge no report has addressed long-term sequelae in", "In summary, patients with more severe MERS-CoV pneumonia may have more impaired pulmonary function at 1 year, which is compatible with the radiological sequelae.", "The previous study found that SARS survivors who required intensive care unit admission had lower predicted FVC and DLCO than those who did not, but there were no differences in the 6-minute walking test. 5,12 These findings were also compatible with our results, which showed that severe pneumonia requiring oxygen therapy is associated with more impaired lung function, but there was no difference in exercise capacity." ] },{ "paper_id": "793bb8ec176e4a5df8323e0bd2276e134b958b5f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ciliary beating plays an essential role in human airway biology and pathology, and 50-80% of airway epithelial cells are ciliated (17) . However, immunostaining (Fig. 1A ) and flow cytometry indicated that ciliated cells were apparently underrepresented in these AOs. Therefore, despite the discernible multilineage differentiation and the ability to support replication of IAVs, further improvements in morphology and differentiation appeared required.", "Plaque Assay. A plaque assay was performed to determine titers of the virus stocks and supernatant samples as described elsewhere (26) , with minor modifications. Briefly, MDCK cells were seeded in 12-well plates. Confluent monolayers were inoculated with 400 \u03bcL of 10-fold serial dilutions of samples and were incubated for 1 h at 37\u00b0C. After the inoculum was removed, the monolayers were overlaid with 1% low melting point agarose (Invitrogen) supplemented with Eagle's minimal essential medium (MEM) and 1 \u03bcg/\u03bcL TPCK-treated trypsin and were further incubated for 2-3 d. The monolayers were fixed with 4% paraformaldehyde (PFA) and were stained with 1% crystal violet to visualize the plaque after the agarose plugs were removed. Virus titers were calculated as plaque-forming units per milliliter.", "Statistical Analysis. Student's t test was used for data analysis. P < 0.05 was considered statistically significant. *P < 0.05; **P < 0.01. ***P < 0.005." ] },{ "paper_id": "79697e89c89116547c539a46e2041bd81d52d5d0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(Medicine 95 (15):e3090) Abbreviations: ICU = intensive care unit, LRTI = lower respiratory tract infection, NPA = nasopharyngeal aspirate, RSV = respiratory syncytial virus.", "Meteorological data for each city were obtained from the National Institute of Meteorology database and included the average monthly temperature (8C), relative humidity (%), solar radiation (kJ/m 2 ), and precipitation (mm).", "Editor: Susanna Esposito." ] },{ "paper_id": "79c0f8dbc31024ca3901227a97df7d35341d5229", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.00862-13/-/DCSupplemental. Table S1 , PDF file, 0.1 MB. Figure S1 , PDF file, 0.4 MB. Figure S2 , PDF file, 0.2 MB. Figure S3 , PDF file, 0.1 MB. Figure S4 , PDF file, 0.1 MB. Figure S5 , PDF file, 0.1 MB. Figure S6 , PDF file, 0.1 MB. Figure S7 , PDF file, 0.1 MB. Figure S8 , PDF file, 0.1 MB. Text S1, DOC file, 0.1 MB.", "In these experiments, transfection of a TIM-1-expressing plasmid served as a transduction control, since TIM-1-dependent entry into endosomes is GP independent and should be independent of the GP glycosylation status (16, 30) . Consistent with this, the entry of all pseudovirions was similarly enhanced by transfection of TIM-1 (Fig. 4A) .", "Lennemann et al." ] },{ "paper_id": "79e75fc82b515edcb68d6c8a6b83d630e3b21193", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 Owners should be questioned about specific environmental exposures and identified mineral dusts should be avoided.", "Authors declare no conflict of interest.", "Authors declare no off-label use of antimicrobials." ] },{ "paper_id": "79f2edaa6e757d6032bd265f4735512738f51797", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Anti-FCoV antibody-negative seven specific pathogen free (SPF) cats aged 5-6 months were used. The cats were maintained in a temperature-controlled isolated facility. All experiments were approved by the President of Kitasato University through the judgment of the Institutional Animal Care and Use Committee of Kitasato University (2004, and 18-050), and performed in accordance with the Guidelines for Animal Experiments of Kitasato University. Sample sizes were determined based on the previous study, and the minimum number of cats was used. ", "RNA was isolated from rectal swab samples by a method reported previously [8] . To synthesize cDNA from FIPV genomic RNA, 1 \u00b5l RNA extract and 0.02 mol sense primer for the FIPV nucleocapsid (N) gene (positions 876-895, 5\u2032-CAACTGGGGAGATGAACCTT-3\u2032) were added to Ready-to-Go RT-PCR beads (GE Healthcare Life Sciences) and the volume was adjusted to 50 \u00b5l with water. The resulting solution was incubated at 42\u00b0C for 1 hr to synthesize cDNA. cDNA was amplified by PCR using primers specific for the FCoV N gene (sense primer, positions 876-895, 5\u2032-CAACTGGGGAGATGAACCTT-3\u2032; antisense primer, positions 1644-1663, 5\u2032-GGTAGCATTTGGCAGCGTTA-3\u2032). PCR was performed as reported previously [8] . ", "ACKNOWLEDGMENT. This work was in part supported by MEXT/JSPS KAKENHI Grant Number JP16K08027." ] },{ "paper_id": "7a0d4f63df57cc9873f41c16e27b5ec3d2b76f88", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "and the probability of observing a reference allele is:", "Because each y i is in fact a Bernoulli variable, we can write down the log of the likelihood function as a sum of log-likelihood functions:", "A P-value can be similarly derived using Wilks' theorem:", "where F X 2 1 is the cumulative distribution function of the chi-square distribution with one degree of freedom.", "The region-wide variation rate is the averaged variation rate across all covered positions in the region (denoted n)." ] },{ "paper_id": "7a11ebc3954fa5d2d95ad487b8540bc73feb68f1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7a3b1df462ac5224e195a12287ee156064910bf0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "acknowledgements The authors would like to thank Mr. Joshua Steele for graphic design.", "Competing interests None declared.", "Patient consent Not required.", "funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors." ] },{ "paper_id": "7a5d731cd59597da7bcef171af936c0af4d7528c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Guests who stayed on the same floor of the same lodging facility underwent active monitoring as well.", "2) Self-quarantine and active surveillance and monitoring of the contacts Lodging and restaurant staffs who were confirmed to be close contacts through travel channel determination underwent selfquarantine. Meanwhile, the general contacts who were confirmed based on CCTV recordings underwent active monitoring.", "Although it was fortunate that none of the Jeju citizens was diagnosed with MERS, this incidence was reported to have caused Jeju Island a loss of 150 billion won in June [5] . Considering the industrial economic structure and geographic environment of Jeju Island, the depicted MERS incidence shows that operation of a center that can proactively and preemptively monitor external infectious diseases is urgently needed [6] ." ] },{ "paper_id": "7a819c63e6e9a3c1979c34b11e3866d23dbed476", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "ADAM33 is a transmembrane protein which contains ADAM. 9 Based on the ADAM protein structure, it is presumed that ADAM protein family members play a critical role in cell adhesion, proliferation, differentiation, signaling, apoptosis and inflammatory responses.", "The importance of the 17q21 gene locus to asthma was initially suggested from a GWAS study which identified the 17q21 region as an important asthma susceptibility locus for childhood onset asthma. 38 This 17q21 locus harbors a cluster of genes including ORMDL3, and GSDMB. 39 The association between 17q21 gene polymorphisms and childhood-onset asthma has been demonstrated in many studies. [40] [41] [42] ", "Periostin is a member of the matricellular family of proteins that are highly expressed at the site of injury or inflammation. Periostin can potentially interact with other extracellular matrix proteins in asthma to mediate airway remodeling in particular fibrosis. Th2 cytokines, such as IL-13, are potent inducers of periostin, and periostin has thus been utilized as a Th2 biomarker. Periostin has the potential to mediate peribronchial fibrosis as it activates TGF-\u03b21, 51 up-regulates type I collagen, 51 induces differentiation of fibroblasts to myofibroblasts, 52 and promotes epithelial-mesenchymal transition. Overexpressed periostin in epithelial cells upregulates collagen fibrils." ] },{ "paper_id": "7a920d6b53c292f53323cb6c5109732a9575e33c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "LGPVKLSAEGPT, TAAKTHTVRGFKV, SYFAADRLVP SAG1, GRA2, GRA7 [41] KLFETTDMY, VRQEAIARALARAAA", "ARTICLE HISTORY" ] },{ "paper_id": "7aa307b2fa1b8d8aa3fa0a19abc0bd86c1c139cd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. Values were expressed as percentages for discrete variables, or as mean and standard deviation for continuous variables. Clinical characteristics and laboratory variables were compared using the chi-square or the Student t-test or Fisher's exact test, as appropriate. Statistical significance was defined as a p-value less than 0.05. All analyses were performed with the Statistical Package for the Social Sciences (SPSS), version 15.0 (SPSS Inc., Chicago, IL, USA).", "Demographic data and clinical presentation of patients were compared to general pathogens identified ( Table 2 ) and the individual viral pathogens (Table 3) ." ] },{ "paper_id": "7aaaac381f47fcb8d47d69b810efd23a0db7bf15", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "That is, within a run, each abundance value for peptide j is compared with the median peptide abundance values of the run i.", "2.1.5 Metric 5: kurtosis The peakedness, or 'heavy-tailedness', of a distribution is described by kurtosis. The same parameters are used as skew.", "Kurtosis is calculated as," ] },{ "paper_id": "7ab7699be02b690053288d296a55d2cead606c40", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Varying concentrations of ATP were then added to initiate the reaction and the OD 340 nm value of NADH was measured using the Perkin-Elmer Envision. The K m value was calculated using GraphPad Prism.", "The protein solution was collected and concentrated to 6.7 mg/ml and then incubated with 25 thymine single-stranded DNA(dT25) at a molar ratio of 1:1.2 and then incubated with 2 mM AMPPNP at 4 \u2022 C for 3 h. The hanging-drop vapor-diffusion method was used to grow the Nsp13 crystals. The conditions for optimal crystal growth were 12% (w/v) polyethylene glycol 20 000, 2 M ammonium sulfate and 0.1 M MES monohydrate pH 6.5 at 16 \u2022 C. The protein and this crystallization buffer were mixed in equal volumes.", "Data collection and processing statistics are summarized in Table 1 .", "H/DX MS is an established method for protein-protein and protein-DNA interaction detection on peptide level (20) . The exchange of amide backbone hydrogens for deuterons is monitored by mass spectrometry, and can be localized to specific peptides within the primary structure, upon proteolytic digestion. It can report on interaction related regions with backbone amide groups involved in interactions or sequestration of regions of a protein in a solvent-inaccessible hydrophobic core, as deuteration will require both exposure of the region to solvent and fluctuations in hydrogen bonding (21) .", "How does the \u242419-\u242420 loop participate in the unwinding process?" ] },{ "paper_id": "7acb13da2225f2c681714a69df8d7787d3312203", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "www.e-shaw.org at predicting the risk of an epidemic or at least at detecting early signs of its onset.", "Environmental pollution may expose wildlife species to infectious agents that can be disseminated. Open-air landfill sites, manure dispersal and, more recently, the attitude of some breeders of wasting in the environment without costs, the carcasses of the animals sacrificed in as preventive measure against bovine spongiform encephalopathy diffusion, represented very good opportunities for foxes, stray dogs, prey birds as well as marauders, especially seagulls, to pick up and disperse pathogenic agents, such as enterobacteria, mycobacteria, brucelles and other biological agents [17] .", "In developing countries, as reported by Kock et al. [9] in Africa, the close contact between human and livestock populations have led to major health problems, and in particular to the creation of a cycle of degradation and disease affecting especially traditional pastoral systems with a close physical association between people, livestock, and wild animals. An example is the recent outbreaks of M. bovis in wildlife in Kruger National Park, whose onset originated from an infected cattle herd [10] .", "In some cases, at the basis of the disease's emergence, there are increases in the density of animal or wildlife populations associated with intensive breeding methods for domestic animals, and proximity with human and animal populations caused by growth of the human settlements [8] . Examples diseases are Mycobacterium bovis (M. Bovis), Brucella spp. or Francisella tularensis' infection in cattle breeders.", "In this light, the concept, defined as the \"One Medicine\" by Schwabe [23] , has seen an unprecedented revival in the last decade and has evolved towards \"One Health\" conceptual thinking, emphasizing epidemiology and public health [24] ." ] },{ "paper_id": "7af72db19cf1096560e19d5265dc5783ea8dc2cc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All sampling techniques and the study protocol were revised by the local ethical committee and permitted under experimental license number EC2014-164.", "The random herd effect was significant in all models." ] },{ "paper_id": "7afb40ff1e8710f31b4805249e6e6fcce6467e96", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The experimental protocol was reviewed and approved by the Animal Care and Use Committee at WSU (ASAF# 04793-001). Owner consent was obtained prior to sampling.", "Macarena G. Sanz https://orcid.org/0000-0001-6565-9947", "Although this approach is complete, it is costly and may not always be achievable." ] },{ "paper_id": "7b0abf2414de3794e54ed37050884f636333972f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7b1dd68a2de5fb4b3902e834ecc2fb6bd12f28f2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The anti-malaria drug chloroquine is well known as autophagy inhibitor. The compound is also known as drug with ", "The authors declare no conflict of interest." ] },{ "paper_id": "7b3a1e17837723ff83422617fef30925bab713a4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Electron microscopy. Infected and healthy P. equestris leaves were investigated for virus particles by both negative staining and thin sections under H-7650 Hitachi transmission electron microscope (Tokyo, Japan) at 80 kV as described (Lan et al., 2016) .", "Reverse transcription polymerase chain reaction (RT-PCR). Total RNA was extracted from 0.1 g symptomatic leaves of P. equestris with Trizol reagent (Invitrogen, Carlsbad, CA, USA) as instruction. RT-PCR was performed with the primers to amplify the coat protein (CP) gene of CymMV and ORSV with Invitrogen SuperScript IV VILOTM kit (ThermoFisher, Waltham, MA, USA) as instruction.", "sRNA-seq and analyzing. The RNA extracted from infected and healthy P. equestris (n = 3) was used for library construction and sequencing for three times by Novogene Technology Co. Ltd. (Beijing, China) as described previously (Lan et al., 2015) . To identify siRNAs, using the software Bowtie v.0.12.7 with 0 mismatch, we aligned all the cleaned reads to the viral genome sequences and calculated the average depths and the genome coverages. The average depth is calculated as the total number of nucleotides of the aligned reads divided by the read-covered positions on the reference genome. The genome coverage represents the proportion of read-covered positions against the genome length. Reads obtained above were analyzed using Excel. Single-base resolution maps along with virus genomes were created using Bowtie tools and in-house Perl scripts. sRNAs from each sample were assembled de novo using Velvet. Assembled contigs were used to search the Gen-Bank/EMBL/DDBJ database using BLASTn or BLASTx. Coverage and distribution of virus-specific contigs by siRNAs were determined using the program MAQ under default parameters, and results were exported to Microsoft Excel for further analysis. Primers were designed for amplification and Sanger sequencing based on the identified viral contigs using Vector NTI (Invitrogen). Phylogenetic tree analysis was performed using MEGA 5.0.", "In this study, we analyzed the characterizations of the siRNAs in CymMV-and ORSV-coinfected P. equestris plants, and explored their potential roles in targeting a series of P. equestris genes which are related to host stress response, RNAi antiviral immunity defense, cytoskeleton, metabolic processes (chloroplast photosynthesis and mitochondria energy supply pathways, fatty acid biosynthetic process and protein phosphorylation), pathogenesis and symptomology. We also found that siRNAs derived from CymMV and ORSV could decrease the expression levels of all target genes in P. equestris. All results in this study provide an understanding of the RNAi mechanism and an insight into the function and implication of RNAi pathway in viruses-P. equestris interactions." ] },{ "paper_id": "7b9f9339ac1f541b560e1c3c0ce6697cb8c8cc3b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(a/a+b)", "values >38 excluded (n=7,856)." ] },{ "paper_id": "7be16a5fe61f446de54e71a73b7686d629f24059", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7c5c81226bc5cf7d5506fb44115d566dfc3fa1db", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "controlled studies to investigate the relationship between IMHA and Borrelia infection may be warranted.", "Three studies were identified and evaluated. [5] [6] [7] One prospective case-control study asking if D.", "caninum. 19 IMHA resolved in all 3 dogs when treated concurrently with fenbendazole and a 4" ] },{ "paper_id": "7c8829abbf6087d8a19a616952acf92bb76dc38d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "D E statistically significant." ] },{ "paper_id": "7c9b0de06457ee197e904b3bc7f312ccb888baa7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Koatech Laboratory Animal Center (Pyeongtaek, Korea). Experimental procedures involving laboratory animals were approved by the Institutional Animal Care and Use Committee of Chonbuk National University (approval numbers: CBU 2011-0061 and CBU 2015-0004) and carried out in accordance with the guidelines suggested by the committee.", "Statistical analyses were performed using Prism 7 (GraphPad Software, La Jolla, CA, USA). Data are presented as means\u00b1standard error of repeated experiments unless otherwise specified. Differences in the means of multiple independent variables were compared between the control and treatment groups using 1-way analysis of variance, followed by Tukey's post hoc test. Differences were considered significant at p<0.05.", "For western blot analysis, the protein lysate was treated with or without isopropyl \u03b2-D-1-thiogalactopyranoside, subjected to 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis, and transferred to polyvinylidene fluoride membranes. Immunoblotting was performed using an anti-GST Ab (Santa Cruz Biotechnology, Dallas, TX, USA). For visualization, a horseradish peroxidase (HRP)-conjugated secondary Ab was added, and bands were detected using an enhanced chemiluminescence detection kit (GE Healthcare Life Sciences)." ] },{ "paper_id": "7ca300b9a142c9df5da9d660610782ace344a412", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7d1b56a1da849ab1a3e0ee57807511ebac91de24", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7d23656771268d325fc276045ff002b7d0184e7b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Citation Totura AL, Baric RS. 2015. Reply to \"Statins may decrease the fatality rate of MERS infection.\" mBio 6(5):e01303-15.", "Our study and others indicate that, in animal models of highly pathogenic coronavirus infection, the aberrant signaling stemming from a lack of either Toll-like receptor (TLR) adaptor TRIF or MyD88 leads to severe lung disease or death (7, 13, 14) . If", "MyD88 signaling was largely repressed by the use of statins in MERS patients, this could lead to exacerbated compensatory signaling by other innate immune factors, resulting in a poor disease outcome in coronavirus patients. Of critical importance is that the absence of these central TLR adaptor molecules results in increased viral loads that persist for longer periods of time than in wild-type mice following SARS-CoV or MERS-CoV infection (7, 13, 14) . Currently, high viral titers during the acute phase of infection are thought to be a potential factor that increases the likelihood of person-to-person transmission of highly pathogenic coronaviruses. Caution must be used when weighing potential therapeutic options that may increase the likelihood of the spread of these viruses." ] },{ "paper_id": "7d2c839823df05875ad1170a68a88c981bf0e859", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7d3facc82a83039b3871ebb8a299bcdb9700156f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "of the ZnF of USP9X, we mutated residues chelating the zinc ion, C1727A, or H1729A, and measured their activities.", "Generation of ABPs and Assays Using the ABPs. The monoUb-based probe was synthesized by reacting the Ub 1-75 -MESNA with PA or Gly-VME for 40 min followed by HiTrap SP HP cation exchange (GE Healthcare) column purification.", "Ubiquitination is an important posttranslational modification that regulates almost every aspect of cellular functions. Ubiquitin can form chains of different topology; each has a distinctive role in dictating the function and fate of the modified proteins. Deubiquitinases (DUBs) reverse ubiquitination. How DUBs recognize ubiquitin chains is a topic of immense interest due to the therapeutic potentials of human DUBs. We obtained the atomic details of the USP9X catalytic core, a DUB involved in cancers and developmental disorders, and revealed its unusual mechanisms of action using a set of activity-based ubiquitin probes. These probes will propel future investigation of how DUBs recognize and process ubiquitin chains and identify potential new sites on DUBs for drug discovery.", "Crystallization. A surface entropy reduction (43) mutation (K 1637 E 1638 to two alanines) was introduced to crystalize USP9X CD. Crystal used for X-ray data collection was grown at room temperature using the sitting-drop vapor diffusion method by mixing 0.5-\u03bcL protein (20 mg/mL) with 0.5-\u03bcL reservoir solution containing 20% PEG3350 and 0.2 M diammonium tartrate. Crystal was cryoprotected by first immersion in the well solution supplemented with 10% ethylene glycol, then in Paratone-N (Hampton Research) before being flash frozen." ] },{ "paper_id": "7d780290822a5408a54dfdf2ae32139cf1a2892c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee of Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun. All patient data were analyzed in anonymity. As neither individual data were published nor any intervention was performed on patients, patient consent was waived by the ethics committee.", "ACV, aciclovir; ADV, adenovirus; a/cGVHD, acute/chronic graft versus host disease; ALL, acute lymphoblastic leukemia; allo-, allogeneic; AML, acute myeloblastic leukemia; ANC, absolute neutrophil count; ARAC, cytarabine; auto-, autologous; BCNU, carmustine; BKV, polyoma BK virus; BM, bone marrow; CARV, community-acquired respiratory virus; CI, confidence intervals; CIBMTR, Center for International Blood and Marrow Transplant Research; CMV, cytomegalovirus; D, days;", "The study was designed as multicenter nationwide cohort analysis performed on behalf of the Polish Society of Pediatric Oncology and Hematology. Viral infections diagnosed during a six-year period (between January 1, 2012 and December 31, 2017), were reported by all Polish pediatric HCT centers (Bydgoszcz, Krakow, Lublin, Poznan, Wroclaw) and data were analyzed centrally by two independent researchers. Data from the first 2-year period were collected retrospectively, then prospectively afterwards." ] },{ "paper_id": "7d7bab4809a66048899e1e95227eb5d72e46818f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7d9c27d988dd4ca25668f573e610145140d2266e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Coronavirus, and Severe Acute Respiratory Syndrome Coronoavirus to", "Supplementary materials are available at The Journal of 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.", "One part by volume of the test virus suspension and 1 part by volume of the organic load were mixed with 8 parts by volume of 1 of the 2 WHO formulations at different concentrations. Additional information is provided in the Supplementary Data." ] },{ "paper_id": "7da1a3651e1aba73bc607cf4aaa93105af0c2bf7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "PIL in eight non-affected adjacent provinces (region 3) were also calculated as potential economic losses. The direct PIL of 27 prefectures for the H7N9 cases are described in detail in table 4." ] },{ "paper_id": "7db910e35a0a22ccef05b0a5b4c9789acfef2daa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Little or no effect Suppression of PB1-F2 neither affected viral replication nor virus loads in the lungs of mice (McAuley et al. 2010 ).", "3", "Supplementary information and figures S1-S7 are available at Molecular Biology and Evolution online (http://www.mbe .oxfordjournals.org/).", "Moderate effect Suppression of L* decreases the ability of Theiler's virus to induce a chronic infection of the central nervous system (Stavrou et al. 2010 )." ] },{ "paper_id": "7db9b801730d8b60d1fc331ba3389460e9ea3794", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We configured the platform to the static state, and the patients underwent posture maintenance training and center of gravity transferring postural training in eight directions after initially aligning the center of gravity with the middle line of the monitor. We did not restrict any of the groups' activities to balance training, and we advised the subjects to perform their same daily activities as before (Fig. 2B ).", "A decrease in balance control can be caused by various factors, including central nervous system diseases (such as stroke and traumatic brain injury), musculoskeletal disorders (such as back pain or arthritis), and vestibular diseases. Loss of balance control decreases the ability and speed of patients' gait, especially in those with hemiplegia caused by brain damage. Fear of falling in these patients reduces their activity level and makes daily activities of living difficult for these patients. Therefore, improvements in balance control and mechanical movements are important treatment goals [1] .", "The Berg Balance Scale (BBS), 10-m walking test (10mWT), Timed Up and Go (TUG) and Functional Reach Tests (FRT), and trunk strength evaluated using Spine Balance 3D system's evaluation program were used as clinical indicators to evaluate the level of function before the exercise. The Korean version of the Fall Efficacy Scale-International (KFES-I) was recorded using the information from the survey. The patients performed 30-minute exercises, three times a week for 7 weeks (Fig. 1) .", "We performed the statistical analyses using SPSS ver. 18.0 (SPSS Inc., Chicago, IL, USA), and analyzed the demographics of the two groups and pre-treatment evaluations by using an independent t-test. We compared the pre-treatment evaluations with post-treatment evaluations in both groups to determine whether statistical changes were present. We analyzed the measured values before and after the treatment in each group by using Wilcoxon signed-rank tests, and considered only p-values less than 0.05 to be statistically significant." ] },{ "paper_id": "7e1d33cf80c62e4e7de67f8beb280c86266b887f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The Gini coefficients of these four conditions are presented in Table 1 . In the first two conditions (C1 and C2, without temporal variability), the Gini coefficients were both very close to zero, indicating all individuals had almost equal contribution to the new infection, despite C1 having no degree order change and higher prevalence. In the latter two conditions (C3 and C4, with temporal variability), C3 had a larger Gini coefficient, indicating the individuals with constantly high degree order contributed to more new infections than the lower order ones.", "In our simulation of disease dynamics, we assume that the disease does not substantially change the individual's behavior. This implicit assumption is appropriate for non-clinical conditions and for demonstrating the importance of dynamic networks on disease dynamics. Nevertheless, in realistic systems modeling clinical diseases, animals may change their behavior during the infected stage, resulting in a different contact pattern [37] [38] [39] [40] . Furthermore we have assumed frequency-dependent transmission through contact to simplify the model. To model more realistic directly transmitted disease systems and design effective controlling strategies, it is important to make the correct assumptions about transmission mode (frequencydependent or density-dependent, or a combination of both), observe the actual contact network for all the individuals over time, and understand both temporal and individual heterogeneity in the contact network [41] [42] [43] .", "The time series of hourly number of contacts is shown in Fig. 1 for all three pens. The analysis of variance (ANOVA) was carried to investigate temporal and individual variability. ANOVA results revealed highly significant hourly variability nested in day (P 5 0.003), individual variability nested in pen (P 5 0.001), and at pen level (P 5 0.003) but marginal insignificance between day variability (P 5 0.06). Further spectrum analysis confirmed a peak frequency correlated to an approximate 6.25-h period in number of contacts. Thus there was a clear pattern of diurnal cycle in network degree distribution.", "An analysis of variance (ANOVA) was performed to further test whether the degree distribution of the networks varied among different individuals in different pens and/or in different hours on different days. The hour factor was nested in the day and the individuals were nested in the pen. Furthermore, spectrum analysis was performed with timeSeries package in R to explore the periodic (within-day) change of the time series of aggregated degrees (number of total contacts of all calves in each pen) in the networks." ] },{ "paper_id": "7e2390fbb36e75e858fe46a1c81266144ab176de", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7e3f8778b0ccf9aa5fe2a4e0ee2740f01691bca5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In 1996 Clarke et al. [13] recognised that whilst GIS had been in development for over 30 years, it was only then that such systems had become readily usable for those not extensively trained in their use. Their review article 'On epidemiology and geographic information systems: a review and discussion of future directions [13] ' specifically addressed the disciplinary crossover between GIS and public health and epidemiology.", "She stated that at that time, GIS-based research on service performance and effectiveness was in its infancy and that whilst efforts were underway to integrate GIS with spatial decision support systems they were still in the stages of early evolution. www.e-hir.org", "In 2011, Nykiforuk and Flaman [3] continued the debate by reviewing once again GIS for health promotion and public health. They identified four predominant themes from a systematic review which was comprised of 621 journal articles and book chapters: 1) disease surveillance, a) disease mapping, b) disease modeling; 2) risk analysis; 3) health access and planning; and 4) community health profiling.", "Current examples include supporting Hispanic community transitions [68] , assessing community primary care needs [69] , community development [70] , community pharmacy populations [71] , and developing an understanding of the spiritual dimension of health for communities [72] .", "Disease surveillance is an epidemiological practice that monitors the spread of disease in order to establish patterns of progression. A key component of modern disease surveillance is disease case reporting. Interestingly in these days of advanced technologies disease progression can sometimes be tracked by individuals' internet search engine usage more quickly than through traditional reporting mechanisms [16] . By tracking the location of individuals seeking information about the flu Google was able to estimate flu activity by region in the USA about two weeks later than traditional methods of Centre for Disease Control & Prevention (CDC) flu outbreak reporting.", "Bizarrely, despite GIS technologies being freely available on the internet, the Canadian outbreak of severe acute respiratory syndrome (SARS) in Canada in 2003 was managed by paper charts and color-coded post-it notes. It is one thing for a developing country, such as India, to state that \"without computers and the Internet, we are fighting 21st century health problems with 19th century tools [6] , \" but it is quite another for Toronto's Chief Medical Officer to observe the same thing [7] in a country as developed and technology literate as Canada within the last decade! Astonishingly, it was only nine years ago (2003) that the term 'Geographical Information Systems (GIS)' was added to Medical Subject Headings (MeSH) reflecting the growing interest in the application of cartography (mapping) functions to healthcare." ] },{ "paper_id": "7e54f67d82b8e54609d3029b20d765865895928d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7e757d19351d6680088ee7343c19873de2e1bcfa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "S2 Contents S1.", ".", "General information \u2026S3" ] },{ "paper_id": "7e7c6670854897412ce9930eefc95f348ae432a2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7e92581ed1b5f05b3002790d3cd71974982f7a3f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "These disadvantages have made it essential to explore alternative novel approaches for future vaccine development. Preference will be given to those vaccines that are capable of stimulating broad neutralizing antibody responses and cross-protective immunity against divergent IAVs, including the pandemic strains of 2009 H1N1 and highly pathogenic strains of H5N1.", "The latest influenza pandemic caused by 2009 swine-origin IAV H1N1, coupled with the continuing threat of the highly pathogenic avian influenza A virus H5N1, makes it essential to develop efficacious vaccines to prevent future influenza pandemics and epidemics.", "RBD vaccine could elicit strong neutralizing antibody responses and protection against SARS-CoV challenge. [15] [16] [17] These findings suggest that this RBD-based vaccine has considerable potential for development into a safe and effective SARS vaccine to prevent future SARS epidemics.", "To design vaccines with the ability to induce highly potent and cross-reactive neutralizing antibodies with high binding affinity, we recommend the following strategies: (i) construct an immunogen containing the discontinuous sequences of bonding set and/or induced epitopes; (ii) induce conformational changes by mutation or glycan shield of the non-neutralizing immunodominant epitopes from the immunogen in order to reduce the immunogenicity of these epitopes; and (iii) add an immunopotentiation motif to the immunogen in order to enhance the immunogenicity of the RBDbased vaccine." ] },{ "paper_id": "7ec5f725610673671e1703613932224d6494e880", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The best laboratories maintain careful training and testing of operators, tracking and testing of pathogen samples, and rigorous safety protocols. Notwithstanding these efforts, lapses of protocol occur, as recently documented at the CDC high-containment laboratory (http://www.usatoday.com/news/nation/story/2012-06 -13/cdc-bioterror-lab/55557704/1). Infections of laboratory workers occur, as most recently emphasized by the tragic death of a technician working on Neisseria meningitidis B in a BSL-2 laboratory in San Francisco, CA (6) , and other events before that. Standards of laboratory safety vary by institution (given the strong reliance on institutions and even individual investigators to enforce the details of biosafety between government inspections) and by country, with tremendous heterogeneity in the precautions required for working on a particular pathogen (7).", "Recommended measures. While the current moratorium is operative, we have an opportunity to define a set of conditions that will minimize the risks of laboratory-released infections or epidemics. Clearly we must continue to emphasize the importance of learning about the pathogenesis of high-risk infectious agents and recognize the likelihood that the greatest infectious risks come from nature, like H5N1 influenza. Hence, there is a continuing need for research on a wide variety of pathogens, including those that are not currently fashionable; we note that study of coronaviruses would never have been considered \"pandemic preparedness\" before SARS, but it was. Only a very limited number of experiments need to be done with potential pandemic pathogens themselves. We urge consideration of the following policies.", "While these figures may sound low, the key problem is that they increase as more laboratories undertake work on PPPs and as they do so over a longer period. Even at the NIAID, the intramural estimated rate of 2 exposures per 100,000 operator-hours, a remarkably low rate that likely reflects very careful practices, one would expect 1 out of every 50 technicians working half-time (1,000 h) in such a laboratory to be exposed each year and 1 of every 600 to become infected. Over a 10-year period, with 100 such laboratories each employing 5 such technicians, one would expect 100 exposures and about 8 infections. Klotz and Sylvester estimate that with 42 laboratories working on PPP and a 0.3% risk of an escape per laboratory-year, there is an 80% risk of an escape of a PPP every 13 years (5) ." ] },{ "paper_id": "7ed89e5691a56b6757c21984c3bbb733b5a2dfdc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7f070cac1f9fd46107d2a521e65b385e87efea85", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7f37181b66f15b8ca2d62b6943d9a6f92e843a66", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "His eye-opening research findings were published in the Customs Gazette and later the Journal of Linnean Society of London, Zoology in 1878. 6 While his paper was read out in the society's meeting, one critic remarked that`what they had heard represented either the work of a genius or more likely the emanations of a drunken Scots doctor in faroff China, where everyone was aware, they drank far too much whisky'. With time, his experiments were reproduced and his mosquito hypothesis was widely accepted.", "We are very grateful to Dr Samson S Y Wong (the University of Hong Kong, Hong Kong, China) who proofread this review and supplied three of the figures. Emerging Microbes and Infections", "KKW To and KY Yuen 4 Memorial Hospital. In Manson's presidential address to the Society, he indicated the lack of education and research on tropical medicine which rendered doctors unable to differentiate malaria from typhoid fever. Due to such gaps in training, there was often wastage of quinine for non-malarial fever. His philosophy towards the judicious use of antimicrobials is even more important in the present era of rising antimicrobial resistance. Though newly recognized clinical entities such as tropical (fatty) liver could be easily be treated by heavy exercise and dietary (food and alcoholic beverages) discretion, there was no portal of sharing on such important knowledge between doctors till the founding of this medical society.", "Amoy was known as just another white man's grave in the tropics which is hot and humid. The streets were narrow, irregular and filthy with excreta and litters. In those days, the only machinery for sanitation at Amoy was the pigs and dogs which ate up the excreta and litters. The inhabitants were in extreme poverty who subsisted on rice and sweet potatoes occasionally flavoured with vegetable pickles and salted fish. The area was highly endemic for malaria, typhoid fever, dengue fever and leprosy. His estimation by survey showed that about 1 in 450 inhabitants were infected by leprosy. In the 1877 cholera outbreak in Amoy, 95% of the population was affected and 2% died. Unfortunately, his younger brother David Manson also died in Amoy in 1878." ] },{ "paper_id": "7f69a764a32e9fefc971d79582da33db151cdeb5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cell culture and transfection BFP-CLC RPE cells were grown in 1:1 F12: DMEM supplemented with 10% FBS, 20 mM Hepes, Pen/Strep/l-glutamine (100 U/ml, 100 \u00b5g/ml, and 300 \u00b5g/ml, respectively) and incubated at 37\u00b0C with 5% CO 2 . Cells were seeded onto acid-washed coverslips at a density of 5 \u00d7 10 4 cells per coverslip for 24 h before transfection with 1-2 \u00b5g of plasmid DNA using 3 \u00b5l Fugene transfection reagent per microgram of DNA (Promega). Cells were imaged 16-20 h after transfection. Two independent transfections were performed for each plasmid construct, and data were pooled from both transfections.", "A spinning disc confocal microscope (Zeiss Axio Observer Z1 with Yokagawa CSU-X1M) was used to image GUVs, tethered vesicles, and live RPE cells. Laser wavelengths of 488 and 561 nm were used for excitation. Emission filters were centered at 525 nm with a 50-nm width, and 629 nm with a 62-nm width. A triple-pass dichroic mirror was used: 405/488/561 nm. The microscope objective was a Plan-Apochromat 100\u00d7, 1.4 numerical aperture oil immersion objective. Images were collected on a cooled (\u221270\u00b0C) EMC CD iXon3 897 camera (Andor Technology).", "In cell experiments, Fig. 4 C displays data from n > 90 cells per condition from two independent transfections. Fig. 4 D displays a subset of the data in Fig. 4 C that is within the specified protein expression range, with n > 20 cells per condition. Bars represent mean \u00b1 SEM. Fig. 4 E displays the lengths of individual tubes from cells within the specified protein expression range, where n > 80 tubes per condition. Fig. 4 F displays the lifetimes of individual tubes measured from TIRF videos, where n > 40 tubes per condition. Black lines in Fig. 4 , E and F, indicate means. The indicated P values were calculated using unpaired, two-tailed Student's t tests." ] },{ "paper_id": "8016c07acf423bde29ea3e2742fb37286a9b013a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The following recommendations are based on the information available at the time of this writing. For clarity, the consensus panel subdivided pathogens into the following categories for the dog and cat:", "1.", "Initial clinicopathologic screening of potential donors is advised (eg, CBC, serum biochemistry, urinalysis, fecal examination). Determination of the PCV is advised before each collection.", "Blood Collection Procedure Recommendations" ] },{ "paper_id": "801bdee04f820908695b58d1d23a04d3ecbf103f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "801d5411eaa50cb50b03e37bf199b1636341c5c2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "PVA-co-PE (ethylene content of 27 mol %), BA, 3,3\u2032,4,4\u2032-benzophenone tetracarboxylic dianhydride (BPTCD), CDI, tetrahydrofuran (THF), dioxane, acetone, chloroform, isopropanol, CDI, polyphosphoric acid (PPA), 25 weight % (wt %) glutaraldehyde solution, 37% formaldehyde solution, 4 wt % osmium tetroxide (OsO 4 ), potassium iodide, sodium hydroxide, ammonium molybdate tetrahydrate, potassium hydrogen phthalate, PI, and SG dye were purchased from Sigma-Aldrich. p-Nitrosodimethylaniline (p-NDA), CA, Luria-Bertani (LB) broth, LB agar, Tryptic soy broth, and Tryptic soy agar (TSA) were purchased from Thermo Fisher Scientific. Phosphate-buffered saline (PBS) and tris-buffered saline were obtained from USB Co. Ltd.", "All calculations were performed using computational chemistry software package Gaussian 09 ver. 08. Initial geometries at ground state were optimized at unrestricted DFT-B3LYP/6-31+G(d,p) level of theory in conductor-like polarizable continuum model (CPCM)-H 2 O solvent. Using these geometries, the nature of singlet and triplet excited energy calculations was performed using the TDDFT-B3LYP/6-31+G (d,p) level of theory in CPCM-H 2 O solvent. The Gibbs free energies of all compounds were obtained by frequency calculations at unrestricted DFT-B3LYP/6-311+G(d,p) level of theory in CPCM-H 2 O solvent using geometries optimized at unrestricted DFT-B3LYP/6-31+G(d,p) level of theory in CPCM-H 2 O solvent. The ESP calculation was performed by single-point energy calculations with CHELPG 5 ESP population analysis at unrestricted DFT-B3LYP/6-31+G(d,p) level of theory in CPCM-H 2 O solvent. Total electron density was first plotted and then mapped with ESP-derived charges to show a distribution of charges on the molecular structure.", "Characterization SEM images were examined by a Philips FEI XL30. UV-vis absorption spectra were collected with an Evolution 600 spectrophotometer (Thermo Fisher Scientific), and the diffuse reflection spectra were collected with a DRA-EV-600 diffuse reflectance accessory (Labsphere). 1 H NMR spectra were recorded on a 400-MHz Bruker Avance HD spectrometer, and DMSO-d 6 was used as a solvent. A TSI Model 8130 automated filter tester (TSI Inc.) was used to measure the filtration efficiency and pressure drop, and NaCl monodisperse aerosols with a size of 0.3 to 0.5 mm and an SD less than 1.86 were used as the model particles. The filtration QF values were defined by the formula: QF = \u2212ln(1 \u2212 h)/Dp, in which the h was the filtration efficiency and the Dp was the pressure drop." ] },{ "paper_id": "801e028d1c0aa75910dbe03019538ed0dc28b905", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Foot-and-mouth disease (FMD) is an extremely contagious disease that affects more than 33 species of cloven-hoofed animals including This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted use, distribution, and reproduction in any noncommercial medium, provided the original work is properly cited.", "foot-and-mouth disease virus / RNA interference / Salmonella choleraesuis / conserved sequence / swine" ] },{ "paper_id": "80228934cbb48467699deb5d9ea5826c635939a9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Citation Klotz LC. 2015. Danger of potential-pandemic-pathogen research enterprises. mBio 6(3):e00815-15.", "Solving equation 1 for y gives", "log(1 \u03ea E) \u03ed log(1 \u03ea P 1 ) yxn \u03ed y \u03eb n \u03eb log(1 \u03ea P 1 ),", "Fouchier mentions vaccination and antivirals (5) as factors that reduce onward transmission. Antivirals would not be prescribed for undetected LAIs. Vaccines may reduce viral replication in the index case, but active virus may still be present when the infected person leaves the laboratory, potentially infecting unvaccinated persons. The annual flu vaccine is sometimes less than 50% effective, so it is unclear if vaccinated laboratory workers are protected by the laboratory vaccine strain." ] },{ "paper_id": "802c4e9e532b2a48928179795754847a229252ec", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Bornavirus nucleic acid detection by polymerase chain reaction (PCR)", "ARTICLE HISTORY" ] },{ "paper_id": "80522e9ca5c69f759fcb3da6fcfdf3523891594e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "80786183397e485664fd049d086f6e3e38ba210f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Autophagy inhibitors are considered as potent chemosensitizers and might therefore be introduced into combination regimens for optimal anticancer therapies. Methods to measure autophagy include electron microscopy for quantifying autophagosomes, immunoblotting for detecting the lipidation of microtubules-associated protein 1 light chain 3 (also known as LC3), or immunofluorescence microscopy for monitoring the redistribution of LC3 from a diffuse pattern to a punctate one. 41 Complementary techniques are necessary as the autophagosomal accumulation of LC3 can be influenced by lysosomal acidification. For instance, another way is to assess the autophagic flux, thanks to several methods: pulse-chase, immunoblotting, or luciferase-based methods for monitoring the degradation of autophagic substrates. A luciferase coupled with LC3 has recently been used to develop a real-time HTScompatible assay for monitoring the autophagic flux. Moreover, firefly luciferase has been shown to constitute a preferential autophagic substrate and is hence a trustful marker of autophagic degradation that may be applicable to HTS studies. In addition, recent developed assays allow determining the phosphorylation status of substrates from critical autophagy regulator kinases, such as mTORC1 and UNC51-like kinase 1. Besides, several of these assays have been recently adapted for HTS. Finally, these methods should be used to identify the underlying molecular mechanisms of autophagy more than quantifying its levels. [42] [43] [44] [45] Detection of necrosis, ferroptosis, and immunogenic cell death", "The assessment of new potential chemotherapeutics and drug screening involve cell viability and cytotoxicity assays to identify and define safety thresholds for subsequent clinical use. Such assays rely on several cell functions, including enzyme activity, cell membrane activity, cell adherence, adenosine triphosphate (ATP) production, coenzyme production, and nucleotide uptake activity. If a compound interferes with cellular attachment, causes dramatic morphologic changes, affects cell growth rate, or leads to a reduction in overall viability, it is considered to be cytotoxic. 19 However, cytotoxicity reflects the cell-killing property of a chemical compound and is not associated with a specific cell death pathway. Cell viability can be defined as the number of healthy cells in a sample, without any distinction between cells which are actively dividing or quiescent ones, whereas cell proliferation is the measurement of the M\u00e9ry et al 3 number of cells that are dividing in a culture. Viability assays aim to measure cellular maintenance and survival parameters. Thereby, a myriad of assays have been designed and used so as to measure viability or cytotoxicity in vitro, including, in particular, classical dye inclusion or exclusion and colony formation assays. 20", "Cell death plays a crucial role for a myriad of physiological processes, and several human diseases such as cancer are characterized by its deregulation. There are many methods available for both quantifying and qualifying the accurate process of cell death which occurs. Choosing the right assay tool is essential to generate meaningful data, provide sufficient information for clinical applications, and understand cell death processes. In vitro cell death assays are important steps in the search for new therapies against cancer as the ultimate goal remains the elaboration of drugs that interfere with specific cell death mechanisms. However, choosing a cell viability or cytotoxicity assay among the many available options is a daunting task. Indeed, cell death can be approached by several viewpoints and require a more holistic approach. This review provides an overview of cell death assays usually used in vitro for assessing cell death so as to elaborate new potential chemotherapeutics and discusses considerations for using each assay." ] },{ "paper_id": "808ed8eb35c9674d24e464888c76c898ea979691", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "808f6be54af8e7c20446dc1ebdeeb68af2c28fba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "80a789fb3ed3279911f241585e315718b54c9a91", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "& $ %" ] },{ "paper_id": "80cdffc26a496e89e2d94c7478749adbabafe180", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The objectives are to introduce a provincial level surveillance system, which has been initiated in response to the MERS-CoV outbreak of South Korea, and describe findings from systematic investigation of individual admissions attributed to acute febrile illness for the first year.", "Gyeonggi-do province was the most affected region in the 2015 MERS-CoV outbreak, 67 of 185 cases were residents of this province. GAFINet Initiative is a meaningful step for rapid detection of emerging or overseas imported infectious diseases at the provincial level. To validate data and co-analysis with pre-existing surveillance data, we need a more long-term of continuous operation of GAFINet. As a next step, we are preparing the additional lab-based surveillance system to detect new or re-emerging pathogens. ", "Between 30 September and 3 December 2016, about 6,000 of patients visited ED of ten hospitals a week, and 10% of them were AFI cases. The proportion of AFRI was the largest, 33.64 to 71.96 per 1000 visits/week, and the second-largest was the other infectious AFI. The proportion of AFRI showed the highest rate at the age 1-9 years, while those of AFGI and AFEI were the highest at the age under 19 year and 70-79 years, respectively. 31 cases with international travel history were reported, and the majority of them traveled China and South East Asian counties. Some of them were suspected cases of Zika viral infection, MERS-CoV, or viral hemorrhagic fever. 3 cases undiagnosed until discharge were also reported." ] },{ "paper_id": "80dc6a5a5b823d6e1fb9802becae1575ddb8dd89", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "However, even if contaminations were underestimated, the number of reported incidents is still alarming.", "Recommendations for decontamination mainly emphasize hand washing. However, despite hand washing, healthcare workers could touch other parts of their bodies or clothing that has not been properly decontaminated and consequently infect themselves. 18 More intensive education and training is required for safe doffing. Evaluation of the effectiveness of training is also required." ] },{ "paper_id": "80f0bc76680d66fa78c6665807bedcf74b190751", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Among viral pathogen species known to cause human diseases, 76.0% also infect other vertebrate animals [18, 19] . Moreover, a 41.8% seropositive rate against SFTSV has been reported in domestic animals in China, strongly suggesting that animals are major reservoirs of tick-mediated SFTSV transmission [1, 3, 4] . In addition, seropositive shrews and rodents were recently implicated as potential animal hosts susceptible to SFTSV [9] . A study in Korea showed that SFTSV-positive ticks are widespread throughout most provinces, particularly during summer [13] . Moreover, recent evidence has shown that SFTSV acts as a zoonotic pathogen, and further studies of serological prevalence in farming or wild animal species are necessary.", "SFTSV isolated from a human patient in Korea in 2013 was kindly provided by the Korea Centers for Disease Control and Prevention (KCDC) [25] . The SFTSV was grown in Vero E6 cells (American Type Culture Collection, USA) according to a previously described method [23] .", "Bovine field serum samples (n = 416) were collected from breeding cattle in the southern part of Korea (Gyeongsang province) from September 2013 to August 2014." ] },{ "paper_id": "810e609cbc20ab7c1543f7131f18b7fd0a3e2ca8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Finally, DPO can be used for any PCR approach which makes use of the ability of primers to specifically hybridize to complementary sequences except for the case of long and accurate PCR (LA-PCR) which is achieved by DNA polymerases having proofreading activity (e.g. Pfu). It was found that such DNA polymerases have a tendency to completely drop off the DNA when they encounter inosine in a PCR primer (20) .", "Since the development of the polymerase chain reaction (PCR), a variety of modifications in primer design and reaction conditions have been proposed to enhance and optimize specificity (1-3), but a fundamental solution for eliminating non-specific priming still remains a challenge and limits the versatility of PCR in nucleic-acid-based tests (NATs). Achieving a high level of specificity in priming currently requires very rigid primer search parameters and optimization of PCR conditions. Even when these requirements are satisfied, a high risk of nonspecific priming is inevitable.", "fragments, and no false positives. In addition, DPO primers detected the influenza A virus in patient 1 (lane 6), which was not detected using the conventional primer system (lane 1). The presence of respiratory viruses in each patient was further validated by sequencing the fragment. These results indicate that a DPO-based multiplex PCR approach is a reliable tool for detecting multiple pathogens." ] },{ "paper_id": "817a885e9613363e08ef920a9e5826a4cb9e1c1e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "818b42cf815357fc1ee73a17caa5dfef24c55027", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.", "PEDV specific IgG titer was increased gradually until 32 dpi PEDV specific IgA titer was increased until 21 dpi Duodenum" ] },{ "paper_id": "818d12fd5ffa6680a7624f66305538221c85300e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A full ophthalmological examination, including slit lamp biomicroscopy (portable Keeler PSL \u00ae , Keeler Ltd., Windsor, U.K.) and indirect ophthalmoscopy (Vantage Indirect Ophthalmoscope \u00ae , Keeler Ltd.), was performed. Based on the history and the ophthalmic findings, a tentative diagnosis of hypovitaminosis A was made. Blood samples were collected, transferred into lightblocking containers, and sent to the laboratory for serum vitamin A measurement using liquid chromatography.", "No clinical response was identified in the affected calves. However, no further ocular problems were observed in this herd. The affected calves were planned to be brought to market weight and presented for slaughter.", "Vitamin A levels in the animal body depend on dietary sources of \u03b2-carotene as de novo synthesis of this micronutrient does not occur in vertebrates [5] . Therefore, it has been reported that vitamin A deficiency could occur more often in winter or spring, when the animal diet might lack green plants, an important source of \u03b2-carotene. It is well-known that hypovitaminosis A occurs in young cattle [3, 6] . However, hypovitaminosis A accompanied by blindness has been uncommonly reported in Hanwoo calves [10] . The purpose of this case report is to present two bovine patients of hypovitaminosis A and to discuss its cause and the ways to prevent it.", "A standard physical examination was performed on all cattle in the herd. No abnormalities were observed, except for complete blindness noted in the two calves from among 11 cattle, a morbidity rate of 18%. The calves exhibited bilaterally dilated pupils on slit lamp biomicroscopy, with no menace response or pupillary light reflex. The fundus examination using the indirect ophthalmoscope and a portable fundus camera (Genesis \u00ae , Kowa, Tokyo, Japan) revealed swollen optic discs with indistinct margins bilaterally in both calves. No retinal changes, except for papilledema and an enlargement of the retinal veins, were observed ( Fig. 1) ." ] },{ "paper_id": "8198fbb4175a2f90bcb43dafc0a365677c916d77", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Primer A 5'-GTTTCCCAGTCACGATA-(N 9 )-3' Primer B 5'-GTTTCCCAGTCACGATA-3' ", "The video component of this article can be found at http://www.jove.com/video/2536/", "The steps of the Virochip assay include (1) nucleic acid extraction from clinical samples, (2) reverse transcription of extracted RNA and 2 nd strand cDNA synthesis, (3) PCR amplification of randomly primed cDNA, (3) Cy3 fluorescent dye incorporation, (4) hybridization of labeled material to the Virochip microarray, and (5) scanning and analysis ( Figure 1 ). The protocol shown below will demonstrate the use of the Virochip assay on a nasal swab sample from a child with an influenza-like illness." ] },{ "paper_id": "81a11c6680ce725535704809655d945cd1d4a088", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "smFRET measurements were performed using a homebuilt total internal reflection fluorescence (TIRF) microscope (IX71, Olympus) equipped with a 100\u00d7 objective (UAPON 100XOTIRF, Olympus), a 532-nm laser (CL532-075-L, CrystaLaer) and an EMCCD (iXon DU-897D, Andor). Details of the microscope setup are described in Supplementary Methods.", "Dye-labeled RNA complexes were immobilized on a slide surface, in a buffer containing 40 mM HEPES-KOH (pH 7.5), 70 mM NH 4 Cl, 7 mM Mg(OAc) 2 and 1.7 mM Trolox (Sigma-Aldrich). To improve dye stability, the following oxygen scavenging system (43) was also included in the buffer: 2.6 mM protocatechuic acid (PCA; Sigma-Aldrich) and 48 nM protocatechuate 3,4-dioxygenase (PCD; Sigma-Aldrich). Fluorescence movies were recorded at 20 Hz using SMET, a LabView-based program package (44), and processed by the IDL (Exelis) scripts released from Taekjip Ha's lab (https://cplc.illinois.edu/software). Time-evolved smFRET traces were analyzed by custom-written MAT-LAB programs. The first 10 data points from each trace were averaged and reported for FRET distribution.", "Dye-labeled RNA oligomers were synthesized by Dharmacon, with Dy647 (acceptor) and Dy547 (donor) covalently linked to the 5 and 3 ends, respectively. Singlestranded DNAs (dna9-dna16) were synthesized (Life Technologies) with a (dC) 21 linker and a biotin tag on the 5 end for immobilization." ] },{ "paper_id": "81b22a5b5989dfc8f57c6d05fd29d3c735785887", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Middle East respiratory syndrome coronavirus (MERS-CoV) continues to cause outbreaks in humans as a result of spillover events from dromedaries. In contrast to humans, MERS-CoV-exposed dromedaries develop only very mild infections and exceptionally potent virus-neutralizing antibody responses. These strong antibody responses may be caused by affinity maturation as a result of repeated exposure to the virus or by the fact that dromedariesapart from conventional antibodies-have relatively unique, heavy chain-only antibodies (HCAbs). These HCAbs are devoid of light chains and have long complementarity-determining regions with unique epitope binding properties, allowing them to recognize and bind with high affinity to epitopes not recognized by conventional", "To sequence the inserts, colony PCR was performed using PfuUltra II Fusion HS DNA Polymerase (Agilent Technologies) and primers (29) 5\u2032-TTATGCTTCCGGCTCGTATG-3\u2032 (MP57) and 5\u2032-CCA-CAGACAGCCCTCATAG-3\u2032 (GIII) under the following conditions: initial denaturation at 95\u00b0C for 3 min, followed by 39 cycles of (95\u00b0C for 20 s, 55\u00b0C for 30 s, and 72\u00b0C for 40 s), and a final extension at 72\u00b0C for 5 min. The amplicons were gel-purified and sequenced in both directions using the BigDye Terminator v3.1 Cycle Sequencing Kit and an ABI PRISM 3100 genetic analyzer (Applied Biosystems). The obtained sequences were assembled and aligned using CLC Genomics Workbench (CLC Bio 4.9)." ] },{ "paper_id": "81c92759c804f01629de5c8499535a5b300b5f16", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "81cfdc6601a05ba9db405a714d3372ea328a2186", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The study included 6138 FRI episodes among 5677 participants (enrolled over approximately 5 years; " ] },{ "paper_id": "82256b182006e2f9abcd1475c906b290a8daad13", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "824e4aebd39a0531625542fb7328917bb061e5a4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "MERS-CoV has caused sporadic infections, along with several local outbreaks throughout the Middle East since its discovery in 2012 [25, 26] . Although much remains unknown, closely related viruses have been isolated from camels [27] and highly homologous MERS-like bat CoVs have been identified in African Neoromicia capensis bats [28] . Local surveillance efforts have detected high levels of antibodies that recognize MERS-CoV in dromedary camels [29] ; furthermore, sampling of archived camel serum samples has revealed MERS antibodies from as early as 1992 [30] . These data suggest that bat to camel to human transmission routes may have seeded the 2012 outbreak in human populations, perhaps associated with the expanding camel trade that has emerged between equatorial Africa and Saudi Arabia over the past 20 years.", "In this review we focus solely on hCoV interactions within the context of the respiratory system and infection of relevant cell types. More specifically, we review some CoV-host interactions that alter cell-intrinsic antiviral defence programmes and other host pathways that contribute to pathological findings of ARDS, with its associated exudative and organizing phase diffuse alveolar damage and pulmonary fibrosis.", "Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), can arise after many types of injury to the lung, including sepsis, mechanical and chemical injury and bacterial and viral infections [1] . In ALI, the mortality rate is in the range 20-30%, with about 55% of the cases progressing to ARDS within a few days. ARDS causes significant morbidity and approximately 40% mortality, resulting in \u223c75 000 deaths/year in the USA alone [2] . In the past two decades, five emerging viruses have been known to cause significant ARDS-related mortality, including influenza H1N1 2009 and, in particular, the highly pathogenic avian influenza H5N1 and H7N9 viruses and the SARS and MERS coronaviruses. In this review we focus on mechanisms of coronavirus-induced lung pathogenesis and ARDS." ] },{ "paper_id": "8263c153cb3159c41641227ad129b668e9bc2d76", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "82742db34be3eee4be2483c14909b1e62e3912ae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Serum samples collected from RVFV G-protein-immunized mice were used to generate 2-fold serial dilutions. Next ", "A polyclonal antibody against the RVFV G-protein (1:4,000 dilution; IBT Bioservices) was diluted 20-fold and 40-fold.", "To enhance expression, codon optimization was performed on the G-protein gene sequence of the RVFV ZH501 strain. The cloning primers were designed based on optimized sequences, and Not I and Kpn I restriction sites were introduced at the 5\u00b4 ends of the upstream (5\u00b4-CGGGGTACCATGGCTGGTATC GCTATGAC-3\u00b4) and downstream (5\u00b4-ATTTGCGGCCGCTT AAGAGGCTTTCTTTGTGGC-3\u00b4) primers. The primers were synthesized by Sangon Biotech (China).", "After 48 to 72 h of transfection, the cell culture supernatant was collected, placed into a 50 mL centrifuge tube, and centrifuged at 4 o C and 5,000 \u00d7 g for 10 min. The supernatant was then collected, filtered through a 0.45 \u03bcm filter, and transferred into a new 50 mL centrifuge tube. Finally, the filtrate was transferred into centrifugal filter devices and centrifuged at 4 o C and 5,000 \u00d7 g for 10 min. The liquid in the bottom layer was discarded, and the filtrate further centrifuged at 4 o C and 5,000 \u00d7 g for 30 min. The solution in the top layer of the filter device was the virus concentrate. The viruses were aliquoted and stored at \u221280 o C." ] },{ "paper_id": "82994e41869e2ada2685ca424ac757c20e6c88c3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A definite mechanism for SILI is not yet known. However, some authors proposed that the potential toxicity mechanism might be mediated by intracellular lipid metabolism, mitochondrial metabolism, and immunologic response, as well as some genetic or other predisposing factors 7 . Diagnosis of SILI generally depends on the relationship between causative agents and clinical symptoms, as well as radiologic findings and the exclusion of infectious diseases, because of its unclear mechanism.", "Statins, hydroxymethylglutaryl CoA reductase inhibitors, are known to lower the plasma low-density lipoprotein (LDL) cholesterol level and reduce the incidence of cardiovascular events and mortality 1, 2 . Currently available statins include lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin, Tuberc Respir Dis 2015;78:281-285", "Although the histopathological findings are also non-diagnostic, based on prior reports and studies, the possibility of diagnosis is significantly increased if the alveolar macrophages have a foamy appearance, as confirmed by cytology, along with the patient' s clinical history 8 . Furthermore, some reports suggested that the most prominent feature of DILD on BAL fluid was a lymphocytic alveolitis either pure or associated with neutrophil and/or eosinophilic alveolitis along with an imbalance in T lymphocyte phenotype 9 ." ] },{ "paper_id": "829ce386c84e17559ca6a06ee9aee0475e473343", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Parents were trained to recognise respiratory symptoms and provided with diary cards designed in a tick-box format and listed with predefined respiratory symptoms or diagnoses to be completed daily and returned by regular mail monthly. The diary cards were modified from a prior study 16 and used successfully elsewhere. 17", "What is the key question?", "Of 891 potential participants approached, 165 (18.5%) eligible singleton infants from 163 families were enrolled (two families enrolled two siblings) (figure 1). Seven were excluded subsequently; one from ineligibility (born <36 weeks) and six for failing to provide any swabs. " ] },{ "paper_id": "82b0cd320ba1e619c08fee764bec158f166fab55", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "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.", "Ribonucleic acid was extracted using QIAamp Viral RNA Mini Kit (QIAGEN, Hilden, Germany) following the manufacturer's protocol. Complementary deoxyribonucleic acid (cDNA) was synthesized using ReverTra Ace qPCR RT kit (Toyobo, Osaka, Japan). Ribonucleic acid was quantified using real-time polymerase chain reaction (PCR) with an Applied Biosystems 7300 real-time PCR system. Real-time PCR was performed using 2 \u03bcL of cDNA with specific primers targeting the genes of interest (\u03b2-actin, forward, AGTGTGACGTGGACATCCGCAAAG and reverse, ATCCACATCTGCTGGAAGGTGGAC; ZIKV, forward, CAACTACTGCAAGTGGAAGGGT and reverse, AAGTGGTCCATATGATCGGTTGA) and 5 \u03bcL of quantitative PCR SYBR Green real-time PCR Master Mix (Toyobo) in a final reaction volume of 10 \u03bcL. The cycling conditions were 45 cycles of 95\u00b0C for 15 seconds, 60\u00b0C for 15 seconds, and 72\u00b0C for 30 seconds. Messenger RNA (mRNA) expression (fold induction) was quantified by calculating the 2 \u2212\u0394CT value, with \u03b2-actin mRNA as an endogenous control.", "Various concentrations of compounds were added to Vero cells for 3 days, and the cell viability was determined using CellTiter-Glo luminescent cell viability kit (Promega, Madison, WI) according to the manufacturer's instructions." ] },{ "paper_id": "82dcb53e236df1adb5c3c9f5291dc4e8eabb354a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To assess the goodness of fit of the logistic regression model, the Demographic and clinical data are summarized in Table 1 . The patients (32 boys and 25 girls) ranged in age from 1 month to 9 years (median, 9 months) and 44 (77%) children were less than 1 year old.", "Klebsiella pneumoniae 4", "Pseudomonas aeruginosa 2", "Stenotrophomonas maltophillia 1" ] },{ "paper_id": "82f9d88193226177c20342d42a29a26ebba90fa1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A random group of 105 camels that presented for slaughter in February (n053) and March (n052) 2014 were sampled for MERS-CoV analysis (Table 1) . Animals either had come directly from within Qatar or KSA, or had been sold through the central animal market (CM).", "Two of the earliest Middle East respiratory syndrome (MERS) cases were men who had visited the Doha central animal market and adjoining slaughterhouse in Qatar. We show that a high proportion of camels presenting for slaughter in Qatar show evidence for nasal MERS-CoV shedding (62/105). Sequence analysis showed the circulation of at least five different virus strains at these premises, suggesting that this location is a driver of MERS-CoV circulation and a high-risk area for human exposure. No correlation between RNA loads and levels of neutralizing antibodies was observed, suggesting limited immune protection and potential for reinfection despite previous exposure.", "To obtain further insight in the diversity of the viruses that circulated in dromedary camels at the slaughterhouse, MERS-CoV strains were sequenced according to a recently developed technique that enables the identification of divergent MERS-CoV types [sequences and technique in (8)]. In total, five different sequence types were identified with three different types found at both sampling moments (Table 2) . Camels either came from the large Al-Shahaniya international racing complex (ASH) or from different sources elsewhere in Qatar (indicated by the initial arrow for animals 6\u00c18 and 10\u00c112 in (Table 2) . Subsequently, they were either brought to a showing area (Al Mazad, AM), to the barns at the CM for a holding period, or immediately sent to the slaughterhouse (SH). Therefore, the sampling for animals 1\u00c15 and 9\u00c113 reflects MERS-CoV sequence diversity as a result of import from other regions in Qatar, whereas virus circulation at the CM more likely explains the virus diversity for animals 6\u00c18." ] },{ "paper_id": "8301fef06e9bbbde5f145096ba75e82f3e0ec160", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Flow cytometric analysis. cancer cell apoptosis was calculated via flow cytometry. cells were harvested and washed three times with PBS, after which they were stained with Annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (Pi) in binding buffer. apoptosis was assessed using a FACSCalibur flow cytometer (BD Biosciences, Franklin Lakes, nj, uSa) after 15 min incubation at room temperature in the dark. fluorescence was detected at an excitation wavelength of 480 nm via FL-1 (530 nm) and FL-2 filters (585 nm). The number of apoptotic cells was then analyzed using Win-mdi software (version 2.9; http://facs.scripps.edu/wm29w98.exe).", "Fluorescence imaging. tissue samples were washed twice with PBS and fixed with 3.7% (v/v) formaldehyde in PBS for 15 min. cells were permeabilized for 5 min with 0.1% triton X-100. for immunofluorescence, phosphorylated (p)-nf-\u03baB and 50 \u00b5g/ml mouse anti-caspase-3 antibodies were employed, followed by incubation with 2 \u00b5g/ml alexa fluor 488-goat anti-mouse secondary antibodies. daPi (Sigma-aldrich; merck KGaa, darmstadt, Germany) was also used to stain cells. images were acquired by confocal laser scanning using epifluorescence microscopy (nikon te2000-e; Shanghai Sunny Biotech co., ltd., Shanghai, china).", "Cell culture and treatment. B16f10 murine melanoma cells and Hs68 human foreskin fibroblast cells were purchased from american type culture collection (manassas, Va, uSa). the cells were maintained in a monolayer culture in dulbecco's modified Eagle's medium (dmem; Gibco, Grand island, nY, uSa) supplemented with 10% fetal bovine serum (fBS; Gibco), 0.012% penicillin G, 0.027% streptomycin, 0.022% sodium pyruvate and 0.26% sodium bicarbonate at 37\u030ac in an atmosphere containing 95% air and 5% co 2 . juglanin stock solution was prepared in dimethyl sulfoxide (dmSo) and was diluted to the desired final concentration (10 and 20 \u00b5M) in culture medium 24 h prior to use. The final concentration of DMSO did not exceed 0.1% (v/v)." ] },{ "paper_id": "830267d850fecba497f80f0c51331a397a734a94", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8318896fad2acf22ac94d15d6d571dd2f7cf121d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "83303635687128ac583152565ba1d7e29540f2af", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In support of this, the WHO has produced guidelines to promote hand-washing practices among member countries.", "The topic of HCAIs is a very broad issue, and it has therefore not been possible to cover all aspects of HCAIs in one paper; hence, we have been selective in selecting key aspects of the current debate. " ] },{ "paper_id": "8387ba520ac3172c8b428e5c95b6aad52d23d509", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "839df627ece5b5fc7bb1ce3b4f96127677fd0494", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "83bb5fda8d9d959fe92af64a2f154c9dcbe38bc0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Unlike animal-based toxicology testing, there are clearer definitions and greater agreement for what constitutes cytotoxicity in vitro. Classically speaking, a compound or treatment is considered to be cytotoxic if it prevents cellular attachment, causes dramatic morphological changes, adversely affects replication rate, or leads to a reduction in overall viability [2] . It should be noted that the manifestation of these effects is greatly dependent on length of compound exposure and mechanism of cytotoxicity [3] .", "Well Number signal from serum sources of LDH found in supplemented growth media [47, 48] . Exogenous sources of LDH greatly elevate background values and negatively impact the overall signal window. This experimental detriment can be largely mitigated by careful pre-screening of serum sources for cell culture prior to LDH assay. LDH assays are also subject to assay artifacts by compounds that inhibit the LDH activity and by standard fluorescence and color quenching interferences [49] [50] [51] .", "Reagent compatibility is a major consideration in samewell multiplexing. There is an absolute requirement that individual signal readouts are distinct and can be parsed for meaningful data set analysis. Also, reagent formulations must not compromise functional aspects of the chemistries. For instance, lytic assays for ATP measurement or caspase activation must be conducted in a sequence-specific order after first measuring experimental cytotoxicity.", "All commercial ATP quantification reagents contain luciferase enzyme and luciferin substrate supplied with a lytic buffer. Cell lysis is necessary to liberate cellular ATP and is typically facilitated by detergents in the buffer. The most useful formulations for HTS applications also contain thermostable recombinant luciferase and ATPase inhibitors which allow for \"glow-type\" luminescence that produces a sustained signal with a half-life on the order of 5 hr [34, 35] . Prolonged maintenance of the luminescent signal allows for batch processing of plates and obviates any inter-plate kinetic variability." ] },{ "paper_id": "83dee742692ed551c9fcdc5d76742f44acce2057", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Refer to Web version on PubMed Central for supplementary material.", "Variants from the reference sequence comprising at least 5% of reads were identified by the quality-based variant detection algorithm in CLC Genomics Workbench, using a neighbourhood radius of 5, minimum neighbourhood quality score of 25 and a minimum central quality score of 29.", "Next-generation sequencing data were analysed using a custom workflow in CLC Genomics Workbench 8.5 (Qiagen, Hilden, Germany). Adapters, and an additional 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, and a consensus sequence was called based on regions that had 10\u00d7 or greater coverage." ] },{ "paper_id": "83e5553035f500f4bcc4aeeaa41aa74ebf578567", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nasopharyngeal samples were collected using nylonflocked nasal swabs. The swabs were immersed in 3 mL of 1\u00d7 phosphate buffered saline and kept at \u221270\u00b0C until further use (see below). Relevant clinical information as well as demographic data, including age, gender, and epidemiological data, were collected with a standardized questionnaire and from medical files of patients included in this study.", "The study protocol was reviewed and approved by the research ethics committee of the College of Medicine, Hawler Medical University, and the collection and use of clinical samples and data from patients at the Raparin Pediatric Teaching Hospital was approved by the Erbil Director of Health. Informed consent was obtained from the parents of all the participating children.", "Statistical analyses were performed using SPSS (version 18) and unpaired Student's t test, considering a P < .05 as significant." ] },{ "paper_id": "845be0716daab542bf27a9d735e03f86a8f3ea85", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Marcia Slater and Elen Ortenberg are employees of Thermo Fisher Scientific Inc. that produces reagents and instruments used in this article.", "NOTE: Keep all reagents and samples used in the preamp reaction on ice at all times. Following preamp, keep all reagents at room temperature.", "The Center for Disease Control (CDC) influenza matrix assay described by Shu et al. 7 ). The significance of adapting these tests to a high-throughput platform with a species-independent internal control is that they can be incorporated into a OneHealth surveillance approach. Having both of these assays on a high-throughput testing platform will facilitate emergency preparedness for clinical facilities, shelters, and performance events.", "With the demand for rapid and comprehensive detection of multiple agents in clinical diagnostics for humans and animals, single-organism molecular diagnostic methods for pathogen detection are burdensome unless used for large numbers of samples being tested for a single disease. In the veterinary context, high-throughput diagnostic methodologies are particularly important due to the additional need for covering pathogens from a wide variety of species. OneHealth approaches for management of food-borne disease and emerging pathogen surveillance are examples of testing needs that include a number of bacteria, viruses (DNA or RNA based), parasites, and fungi. The challenge to combining tests for multiple analytes together (multiplexing) in order to improve testing efficiency is a possible loss of sensitivity and a large burden for optimization and validation of assays." ] },{ "paper_id": "84d00088f2124eac73c0e79cb15fbe4924109178", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "84d3fe51518523e73a65e73756e4496587e4f2f4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The affinity-purified protein sample was concentrated by tangential flow filtration using Amicon Ultra centrifugal filters (Merck) to 1 mg/ml for further analysis. For size exclusion chromatography, concentrated protein sample was mixed with BSA control and loaded onto a Superdex 200 increase 10/300 GL column (GE Healthcare) after pre-equilibration with buffer containing 50 mM HEPES-KOH (pH 8.0). Chromatography was taken with BioLogic Nucleic Acids Research, 2019, Vol. 47, No. 11 5839 DuoFlow system (Bio-Rad) at a flow rate of 1 ml/min. Peak analysis was performed using the ASTRA software package (BioLogic Chromatography Systems).", "A BioLux Gaussia luciferase assay kit (New England Bio-Labs, Ipswich, MA, USA) was used to measure the GLuc activity. Culture supernatants were harvested and centrifuged at 10 000 g for 3 min. A 20-l volume of supernatant was added into a 96-well white plate, and 50 l of GLuc assay solution was added and mixed with culture supernatant immediately before measurement of the luminescence by the use of a VarioSkan Flash reader (Thermo Fisher Scientific).", "Total cellular RNA was isolated using TRIzol reagent (Tiangen, Beijing, China). RT was performed using a Re-verTra Ace qPCR RT kit following the protocol of the manufacturer (Toyobo, Kyoto, Japan). Quantitative PCR was carried out utilizing SYBR green real-time PCR master mix (Toyobo). The RT and qPCR primers were described previously (41) .", "Supplementary Data are available at NAR Online." ] },{ "paper_id": "84da44d2366d3f082d0ec30cbaff70807ca732c7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/3.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.", "A new strain of influenza A virus, H1N1 subtype as \"Pandemic H1N1 influenza\", proved by the Institutional Review Board of Dongguk University Gyeongju Hospital." ] },{ "paper_id": "84dc4e9ee5f8dd324d2d436d7c07c7d0044a58a4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "84ef152ba76ced39a6ab7f082895541c1b3ea9ec", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Patient consent for publication Not required.", "Provenance and peer review Not commissioned; externally peer reviewed." ] },{ "paper_id": "84f8946f903a07243c54bde0a3e6d5ccecf9c5b9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study showed that a BCoV vaccine provides horses with antibodies against ECoV to some extent. It is unclear whether the antibodies provided by the BCoV vaccine are sufficient to be effective against ECoV, and therefore ECoV challenge studies in horses are needed to evaluate the efficacy of the vaccine in the future.", "Statistical analysis was carried out using Ekuseru-Toukei 2012 (SSRI, Tokyo, Japan). Logarithmic transformations of the reciprocal antibody titers were made to stabilize variances. Antibody titers after logarithmic transformation were analyzed by one-way ANOVA with Dunnett's multiple comparison post hoc test using the antibody titers at 0 dpi as control. A P-value of <0.05 was considered statistically significant.", "doi: 10 .1292/jvms. first isolated in the United States in 1999 [4, 17] . Two-fold serial dilutions of serum were mixed with an equal volume of viral suspensions containing two hundred 50% tissue culture infective doses per 0.1 ml and incubated for 60 min at 37\u00b0C. Then, 0.1 ml of each mixture was applied to HRT-18G cells on 96-well plates and incubated for 6 to 7 days. Virus-neutralizing antibody titers were expressed as the reciprocal of the highest serum dilution that inhibited viral cytopathic effects." ] },{ "paper_id": "8509342038d6b5c6a8a9d980bf207a83f37cd970", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "They were asked open-ended questions about their ongoing participation in increased consultation time, to ascertain the chances of institutionalizing the protocol and to obtain their suggestions for improving the project.", "The study protocol was reviewed and approved by the Institutional Review Board (IRB) in Seoul National University Hospital (IRB No.H-1707-139-871) and written informed consents were collected from all subjects.", "Data for baseline characteristics were presented as mean \u00b1 standard deviation, number, and percentage. Differences in perceived and preferred consultation time were tested using the Student's t test. The control group was selected after adjusting for the effects of gender and age. All analyses were conducted using SPSS (version 23.0; SPSS, Inc., Chicago, IL, USA) and GraphPad Prism (version 8.0; Graphpad Software, Inc., San Diego, CA, USA) software. Statistical significance was indicated when P values were < 0.05.", "Patients visiting the tertiary hospital for the first time could only be enrolled if they fit the protocol of the 13 participating departments, and possessed a referral letter from their primary care physician explaining why the referral was recommended and what medical services were anticipated (Supplementary Fig. 1) . We defined serious and non-curable disease as four serious diseases-cancer, stroke, coronary artery disease, and rare and intractable disorders-by regulations." ] },{ "paper_id": "854545208a6bc7cafa8744604899e32237ff2047", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. In the cell viability assays and MMP experiments, all data were expressed as the mean \u00b1 standard deviation. Statistical significance among groups was assessed using one-way analysis of variance and the Tukey test. P<0.05 was considered to indicate a statistically significant difference. Finally, statistical analyses were performed using GraphPad Prism 5.0 (GraphPad Software, Inc., La Jolla, CA, USA).", "Determination of mitochondrial membrane potential (MMP). At 24 h following transfection, the culture medium of the NCI-H292 cells was replaced with DMEM that did not include phenol red and was supplemented with 5 mg/l JC-1 dye (Beyotime Institute of Biotechnology) in the dark for 20 min at 37\u02daC. Subsequently, the cells were washed twice with PBS and placed in fresh medium without serum. Finally, MMP was analyzed by calculating the ratio of fluorescence intensity at 555-488 nm in triplicate.", "Avian influenza A (H5N1) virus is a highly pathogenic contagious agent that causes severe impairment in poultry and humans, particularly limited person-to-person transmission (1) . The cumulative number of confirmed human cases of H5N1 from 14 countries between November 2003 and July 2014 reached 667, 393 of which were fatal according to a report issued by the World Health Organization (2). In total, 47 individuals infected with H5N1 were identified in China and 30 (63.8%) succumbed to the H5N1 infection (2). H5N1 causes primary viral pneumonia with rapid progression to lung failure following invasion of epithelial cells in the upper and lower respiratory tracts (3) . However, the exact mechanism for elucidating the severity of human H5N1 infection remains unclear. Previously, apoptosis was not only observed in the alveolar epithelial cells of 2 patients who succumbed to H5N1 infection, but was also induced by H5N1 in numerous cell types in vivo and in vitro (4) (5) (6) . These results indicated that apoptosis may be important in H5N1 pathogenesis in the human body." ] },{ "paper_id": "8582184d3d2e497088f716ad0fa5bd49976f0dd3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Because of the difficulties encountered when applying the postulates of causality, it is accepted that not all criteria listed by authors need to be fulfilled. 7, [9] [10] [11] 19 In case it is impossible to fulfill all the criteria, the evidence accumulated over time and the common sense of researchers will be important to identify the causal agent of a certain disease. 9,13,19", "In the end of the 19 th century, Koch 11 defended the fundamental principles that helped establish the causal association between microorganisms and infectious diseases according to a set of criteria laid out by him. According to this author, a proof of causality requires the agent to be present in every case of a particular disease, to be absent in other diseases, and after isolation and culture, be sufficient to reproduce the disease by inoculation of a susceptible host.", "Teresa Keico Nagasse-Sugahara RESUMO A abordagem metagen\u00f4mica tem sido ferramenta muito importante atualmente na descoberta de novos v\u00edrus em amostras ambientais e biol\u00f3gicas. Aqui discutimos a maneira como essas descobertas podem ajudar a elucidar a etiologia de doen\u00e7as e os crit\u00e9rios necess\u00e1rios para que a associa\u00e7\u00e3o causal entre um v\u00edrus e uma doen\u00e7a seja estabelecida." ] },{ "paper_id": "85b24dcdfc025236507fb1a3bdbb8eb816bbef92", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "85c04886b69b27eeddd4a72c74e2e1727a80598f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Coronaviruses are found in a wide variety of animals and are associated with respiratory, enteric, hepatic and neurological diseases of varying severity. Based on genotypic and serological characterization, coronaviruses were divided into three distinct groups (1) (2) (3) . As a result of the unique mechanism of viral replication, coronaviruses have a high frequency of recombination (2, 4) .", "CoVDB is constructed by the Department of Microbiology, the University of Hong Kong. It is available at no charge at http://covdb.microbiology.hku.hk. ", "MyBlast. 'MyBlast' employs the same blast program as the Blast page mentioned above. However, instead of selecting a predefined nucleotide or amino acid sequence database, multiple sequences can be pasted into the second sequence input box to generate a temporary sequence database. One or more query sequences can be pasted into the first sequence input box for blastn or blastp search against the temporary sequence database." ] },{ "paper_id": "85dfb59af4c4ec824f1f62c645e5b91a6e3cc814", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "85e8b1143c1869125270527aa26d4e48ad63fb5b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Seasonal influenza is a significant problem for travellers that should be routinely addressed in pre-travel counselling and in the differential diagnosis of any returning traveller with fever.", "There are several ways to decrease the risk of catching influenza. First of all hygienic measures, including active ventilation of crowded places, hand sanitation and (possibly) wearing a facemask can reduce the risk of spreading influenza. Influenza prevention by vaccination and specific problems associated with vaccinating travellers against influenza, are discussed in more in detail below. As an adjunct to vaccination, the value of early antiviral therapy or prophylactic antiviral usage is also discussed.", "Conflict of interest: None declared." ] },{ "paper_id": "85f0fe06df221d355fc228db1495a4f940e7c9b7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "85f4ff3ff33bcc47e9826ee3bd468626fba5870d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "85f7430c807f1334c2b9c5621304e9e7fa8ad64a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "19", "Upload your completed checklist as an extra file when you submit to a journal.", "In your methods section, say that you used the SPIRIT reporting guidelines, and cite them as: " ] },{ "paper_id": "860ffcab2771f1935ac5a59e986d416a603b3de3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The study protocol was reviewed and approved by the Animal Ethical Experimentation Committee ", "ARTICLE HISTORY" ] },{ "paper_id": "8682e080613d625a9f6955e5eb0fe80bbbaefda9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Plasmids and transfection. All plasmids used were created as previously described using a Gateway expression system (Invitrogen) (56) . Briefly, all constructs had a modified pCAGGs backbone containing a Woodchuck hepatitis virus posttranscriptional regulatory element (WPRE) and were C-terminally tagged with either an HA tag sequence followed by a tobacco etch virus (TEV) cleavage site and a biotinylation signal sequence (HA-Bio) or an HA tag sequence followed by a 3\u03eb FLAG tag sequence (HA-3\u03ebFLAG). Transfections were conducted using Lipofectamine 2000 (Invitrogen) per the manufacturer's protocol." ] },{ "paper_id": "869a5a7ca9cf0fc9a2f5cd0332ac7c6b8e8e2ab9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Furthermore, our results show that Irf8 depletion does not promote pDC differentiation into tDC-like cells.", "Wu, X., Satpathy, A.T., Kc, W., Liu, P., Murphy, T.L., and Murphy, K.M. (2013) . Bcl11a controls Flt3 expression in early hematopoietic progenitors and is required for pDC development in vivo. PLoS ONE 8, e64800.", "Wu, X., Brise\u00f1 o, C.G., Durai, V., Albring, J.C., Haldar, M., Bagadia, P., Kim, K.-W., Randolph, G.J., Murphy, T.L., and Murphy, K.M. (2016) . Mafb lineage tracing to distinguish macrophages from other immune lineages reveals dual identity of Langerhans cells. J. Exp. Med. 213, 2553 -2565 . Zhang, H., Gregorio, J.D., Iwahori, T., Zhang, X., Choi, O., Tolentino, L.L., Prestwood, T., Carmi, Y., and Engleman, E.G. (2017 . A distinct subset of plasmacytoid dendritic cells induces activation and differentiation of B and T lymphocytes. Proc. Natl. Acad. Sci. USA 114, 1988 USA 114, -1993 " ] },{ "paper_id": "86afebc58ebd3a14ab6d730d4c5fc32dc56ec3c5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Anti-Ly6G (1A8) antibody (UCSF Monoclonal Antibody Core, San Francisco, CA) or total rat immunoglobulin G (Sigma-Aldrich) as control were given to mice. A total of 50 \u03bcg of the antibodies were administered once i.n. 4 hours before bacterial infection.", "Levels of cytokines and chemokines in BAL fluids were quantified using Luminex multianalyte technology (Luminex Molecular Diagnostics, Toronto, Ontario), according to the manufacturer's protocols. Levels of IFN-\u03b1 were measured in BAL, serum, and culture supernatants using the VeriKine Mouse Interferon Alpha ELISA Kit (PBL Interferon Source, Piscataway, NJ).", "Flow cytometry was performed on BAL and lung cells. Cells were incubated for 15 minutes with the CD16/CD32 Fc block antibody and then stained with extracellular antibodies (BD Biosciences unless otherwise stated) for antigen-presenting cells (APC-Cy7-anti-CD45, Alexa Fluor 700-anti-MHCII (eBioscience, San Diego, CA), Pacific Orange-anti-Gr1 (Life Technologies, Burlington, Ontario), APC-anti-CD11c, PECy7-anti-CD11b), NK cells (V450anti-CD3, PE-anti-NK1.1), and T cells (V450-anti-CD3, APC-Cy7-anti-CD4). Stained cells were analyzed on the LSRII flow cytometer (BD Biosciences) and analyzed using FlowJo software (Tree Star, Ashland, OR). Neutrophils (CD45 + CD11b + Gr1 + ), macrophages (CD45 + Gr1-AF + CD11c + ), NK cells (CD3-NK1.1 + ), and CD4 + T cells (CD3 + CD4 + ) were assessed as total number of cells per tissue compartment by multiplying the \"frequency of total\" of the population by total cell number in the tissue." ] },{ "paper_id": "86f8e5cdfe075d029d603b36ce6f43a5ed86a8a5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8793343683237029bac548225ba51f403489cd35", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Competing interests JV has received research grants from Maquet. RMK is a consultant for Covidien and has received honorarium from Maquet for lecturing.", "Provenance and peer review Not commissioned; externally peer reviewed.", "Data sharing statement No additional data are available." ] },{ "paper_id": "879df084e06fcce1980e3f73c36748068b39f049", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "87b8b85391605bcd1b6c7ddaf1189b3229db4e06", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "and p 1 , p 2 , q 1 , q 2 are non-negative parameters. The standard SIR model can then be modified as S'~L{mS{P S SI{n S SzlS q , I'~P I SI{ d I zazmzd I \u00f0 \u00de I, S' q~QS SI{ lzn Sq zm \u00c0 \u00c1 S q , I' q~QI SIzd I I{ d Iq zazm \u00c0 \u00c1 I q , R'~n S Szn S q S q zd I Izd I q I q {mR,", "with", ":" ] },{ "paper_id": "87dcbcb15da36050308aca4284d842193d99cd6c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Until now, little or no resistance to zanamivir has been observed [13] , and only a small percentage of A(H1N1)pdm09 viruses had highly reduced peramivir inhibition [19] . Although oseltamivir resistance was found in virtually all former seasonal A(H1N1) viruses, the frequency of oseltamivir resistance in A(H1N1)pdm09 viruses has remained low on a global scale. However, with the appearance of permissive mutations in A(H1N1)pdm09 viruses, the risk that oseltamivir-resistant viruses may spread globally is increasing [13] . With the appearance of permissive mutations in A(H1N1)pdm09 viruses, the risk that oseltamivir-resistant or even multidrug-resistant viruses may spread globally is increasing [13, 20] , and there is a need for new antivirals with other mechanisms of action." ] },{ "paper_id": "885674f9e88e504ac2fed625ec9c64fdc3ad71f0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The immunocomplex on Sepharose beads was resuspended in 300 Al of 0.1 M sodium citrate, pH 5.5, 0.1% Triton X-100, 0.1% 0-mercaptoethanol, 100 mg/ml aprotinin, and 1 mM CaC12. 10 mU of endo H was then added. After overnight incubation at 37\u00b0C, the beads were recovered and lysed in 80 Al SDS sample buffer followed by SDS-PAGE.", "The Journal .of Cell Biology, Volume 117, 1992 S46D. Chimeric cDNA coding for S46D was similarly constructed by using oligonucleotides 1 and 5 .", "Immunoprecipitated proteins were eluted from beads by boiling in 80 Al SDS sample buffer (without \u00df-mercaptoethanol) followed by dilution in several milliliters of lectin buffer (40 mM Tris-HCI, pH 7.5, 150 mM NaCl, 1 mM CaC12, 1 mM MgC12, and 1 MM MnC12). An aliquot of this was incubated withthe various lectin-agaroses (120 Al slurry) for 60-120 min. After extensive washing, the bound materials were eluted by boiling in SDS sample buffer and analyzed by SDS-PAGE." ] },{ "paper_id": "887264fa70bfd2130e5ef9089f058332364d6313", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Because of the severity and complexity of STIs, feasible and effective screening approaches are essential for timely implementation of effective infection control measures to prevent further transmission. Additionally, increases in antimicrobial drug resistance in N. gonorrhoeae and M. genitalium remain an important concern. 1 Large-scale epidemiological studies and surveillance programs are needed to determine optimal prevention strategies and to reduce the global burden of STIs." ] },{ "paper_id": "8894efb9895e24c82697cf864b69e9a2eb0751c2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The fractionation of membranes in the presence of high pH sodium carbonate was performed as described (Roberts et al., 1989) .", "The Fusl-LacZp expression plasmid pCJRll4 as follows: a 6-kb NheI-HindllI fragment, encoding the 254 NH2-terminal amino acids of the FUS1 protein fused to ~-galactosidase, under the GALl promoter (isolated from pCJRll3, a derivative of pSB231 (Trueheart and Fink, 1989) ) was cloned into the Xbal-Hindlll sites of pVT105U, a 2# plasmid (Vernet et al., 1987) , creating pCJR114.", "Oligonucleotides for mutagenesis were prepared by the University of Oregon Biotechnology Laboratory on an Applied Biosystems 380B DNA synthesizer (Foster City, CA) as described (Ito et al., 1982) . Tran35S-label and Zymolyase 100T were from ICN Biomedicals (Irvine, CA), Endo H was from Boehringer Marmheim (Indianapolis, IN), ultra-pure SDS was from BDH Biochemicals (San Francisco, CA), glusulase was from Dupont Pharmaceuticals (Wilmington, DE), and all antibodies (except anti-DPAP B, anti-DPAP A, anti-ALP, and anti-Vat2p antibodies) used for indirect immunofluorescence were from Jackson ImmunoResearch (West Grove, PA), Cappel Products (Malvern, PA), or Promega Biotech (Madison, WI). All other reagents were from Sigma Chemical Co. (St. Louis, MO). DPAP and invertase assays were performed as previously described (Gildstein and Lampen, 1975; Roberts et al., 1991) .", "For the simultaneous induction of the GAL/ promoter and the secl4 secretion defect, ceils were grown to log phase in minimal media plus raltinose and then harvested and resuspended in YEP-raitinose. After a 1-h incubation at 25~ galactose was added directly to the cultures and at the same time the cultures were shifted to 34~ After 2 h, the cells were fixed immediately and prepared for indirect immunofluorescence as described below." ] },{ "paper_id": "89122ac5b68dcc5252569b3be17c47f66385b7fb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8931fabdc25094445ab2450c3a5117dab632e868", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CFTR. This could be explained by incomplete inhibition of proteasome activity and/or the involvement of other, presently unidentified proteolytic mechanisms.", "dence time at the cell surface. These in turn are responsible, at least in part, for the phenotypic manifestation of CF. We propose that the proteasome-ubiquitin pathway may be involved in the peripheral quality control of other, partially unfolded membrane proteins as well.", "We thank R. Haguenauer-Tsapis (Jacques Monod, University of Paris VII, Paris, France), J. Bonifacino (National Institutes of Health, Bethesda, MD), and M. Fukuda (The Burnham Institute, La Jolla, CA) for their generous gifts of cDNA. The authors are indebted to J. Brodsky ", "The influenza hemagglutinin (HA) epitope was attached to the NH 2 terminus ubiquitin using PCR mutagenesis and the cDNA of the yeast ubiquitin as template (provided by Dr. R. Haguenauer-Tsapis, Jacques Monod, University of Paris VII, Paris, France). To generate the Tac-Lamp1 chimera, the extracellular and transmembrane segment of the interleukin 2 receptor (Tac) was fused to the cytoplasmic tail of Lamp-1. The constructs were sequenced to verify that no errors had been introduced. The cDNA, encoding for the Tac and Tac-TCR \u2423 , were provided by Dr. J. Bonifacino (National Institutes of Health, Bethesda, MD). Tac, Tac-TCR \u2423 , and Tac-Lamp1 were stably transfected in BHK-21 cells using the pNUT expression cassette (Haardt et al., 1999) ." ] },{ "paper_id": "8946e4b778ae5312b4db84cd75b68848c39a3a93", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Of the 85 patients, 17 (20%) had contagious diseases and 37 (44%) were male. Most patients had fever (n = 64, 75%) and/or dyspnea (n = 66, 78%). Twenty-seven patients (32%) had septic shock, 33 (38%) had respiratory failure, 10 (12%) had heart failure, and 15 (18%) had an illness with an unknown cause.", "Samsung Medical Center is a modern 1,989-bed universityaffiliated tertiary hospital providing referral care in Korea and about 200 patients are seen in the ED each day. In ED for adult, there are 58 beds were spaced roughly 1.5-2.0 m apart with curtains or wall in between and ambulatory zone with 24 chairs for stable patients.", "The Institutional Review Board of the Samsung Medical Center approved this study and permitted the review and publication of patient records (IRB registration number 2016-08-166). The requirement for informed consent by individual patients was waived due to the retrospective design of the study.", "Acute respiratory illnesses are the leading cause of death from infectious diseases around the world, and occasional outbreaks of particularly virulent strains are potential public health disasters. In 2002, a few cases of a life-threatening respiratory disease caused by corona virus in China (3, 4) , ultimately resulted in a global epidemic of severe acute respiratory syndrome. Recently, a large outbreak of fatal Middle East respiratory syndrome-coronavirus (MERS-CoV) occurred following a single patient exposure in the emergency department (ED) of our institution, a tertiary-care hospital in Korea, which resulted in significant public health and economic burden (5, 6) ." ] },{ "paper_id": "894e9a681490af51667a059d727a9cce8dddbf7f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The views expressed are those of the authors and should not be construed as representing the positions of the U.S. Army or DoD.", "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.00276-11/-/DCSupplemental. Figure S1 , TIF file, 0.3 MB. Figure S2 , TIF file, 0.4 MB. Figure S3 , TIF file, 0.6 MB." ] },{ "paper_id": "89767ba998659a73d2be1534cfaacdff2fbc0488", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For all experiments, statistical analysis was performed using GraphPad Prism version 6.0.c (GraphPad Software, La Jolla, CA, USA). For all data obtained, we used the unpaired t-test to infer significance.", "All cells used in this study were maintained in RPMI-1640 medium (Invitrogen) supplemented with 10% fetal bovine serum (FBS) (Biochrom). Primary B cells were isolated from human blood buffy coats by Ficoll (GE healthcare) density gradient centrifugation and positive selection using CD19 PanB Dynabeads (Life technologies) with corresponding DETACHaBEADs (Life Technologies). Primary B cells were cultured in medium supplemented with 20% FBS until LCLs were established. HEK 293 cells are human embryonic kidney cells generated by transformation with adenovirus (ATCC: CRL-1573). The HEK293-B240 are HEK 293 cells stably transfected with the recombinant M81 BACMID and have been described previously (9) . The HEK293-2089 producer cell lines have also been described previously (22) .", "All sequencing data are available under the following NCBI accession number: GSE81802.", "All human primary B cells used in the experiments were isolated from anonymous buffy-coats purchased from the Blood Bank of the University of Heidelberg for which no ethical approval is required." ] },{ "paper_id": "8977825a7fbaa1e4d672a361e7122b48785f93dd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Bispecific and chemically-conjugated antibody reagents provide an alternative strategy to target multiple HIV-1 epitopes to control viral escape and engineer avidity." ] },{ "paper_id": "89cc80396595df1ebb851e602666945754ab0257", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To the best of the author's knowledge, this is the first clinical description of MM associated with a suspected phaeochromocytoma in a cat. Simultaneous neoplasms tend to be rare in feline patients, 13 and the information reported herein should alert veterinarians to being vigilant for multiple neoplastic processes in cats.", "This paper was handled and processed by the European Editorial Office (ISFM) for publication in JFMS Open Reports Case description A 12- year-old, male neutered domestic shorthair cat was admitted for polyuria and polydipsia of 2 months' duration, in addition to progressive blindness, weight loss, weakness and several episodes of open-mouth breathing. Initial physical examination findings included a temperature of 38.7\u00b0C, pale mucous membranes and a body condition score of 3/9 (according to World Small Animal Veterinary Association Global Nutrition Committee criteria).", "The patient was initially treated (day 0) with a combination of prednisolone (2 mg/kg q24h) and melphalan (0.1 mg/kg q48h) by mouth, plus amlodipine (0.18 mg/ kg) and spironolactone (2 mg/kg) by mouth for management of MM and systemic hypertension, respectively, but no improvement in clinical and biological condition was observed at days 10, 30 and 45. Therefore, a chemotherapy protocol with cyclophosphamide (200 mg/m\u00b2 every week) by mouth plus prednisolone (2 mg/kg q24h) was undertaken, but once again no improvement was observed at days 55, 85 and 90. The cat was euthanased 6 months later owing to persistent poor general condition. Autopsy was declined by the owner. " ] },{ "paper_id": "89d4bbbaafc5df5274e5ca4f2b21b3f27b50b216", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "89f214be6e76049510daa238a9182f8302cfdbbb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Qualitative variables are expressed as counts and percentages and quantitative variables are expressed as means and standard deviations. The Student's t test for independent samples was used to perform comparisons between means whereas the Man-Whitney test was used in case variables did not meet the criteria of normality. The chisquare or Fisher's exact test were used for comparisons of proportions. A p value of less than 0.05 was considered significant. Data were analyzed using statistical software (SPSS, version 15.0; SPSS; Chicago, IL).", "Methods: Patients with chronic obstructive pulmonary disease (COPD) exacerbation were recruited and classified as elderly (>65 years) and non-elderly (\u2264 65 years). Sputum and oropharyngeal samples were assessed, PCR for respiratory viruses and cultures for common pathogens were performed." ] },{ "paper_id": "8a6809df45d5f80a822d68d3c305f7640e10234a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This article describes the development of the various genetic analysis components, and their validation using clinical samples. Accession numbers for 84 complete H1N1(2009) genomes generated are listed in Supplementary Data File 1.", "In addition, we evaluate the robustness and reproducibility of EvolSTAR by employing six pairs of replicate experiments consisting of one pair nasal swab and five pairs of cell culture isolates, belonging to the same patient sample 305 (Supplementary Data File 4) .", "Supplementary Data are available at NAR Online." ] },{ "paper_id": "8a8d2206e8fa15801497ee0d24618adb7e34b693", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Yu Liu https://orcid.org/0000-0002-5246-0290", "Commentary" ] },{ "paper_id": "8ab9e9b90aa057cdd59acac5cce30ec1a6784e71", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All animal protocols for this study were reviewed and approved by the Animal Ethics Committee of the University of Miyazaki's Faculty of Agriculture. During the study, animal health was monitored by licensed veterinarians and the animals were not manipulated beyond what is required for diagnostic purposes." ] },{ "paper_id": "8ac886d6b20755b99f0d627f55536e4cc0d6107c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Likewise, the idea that physicians acting as clinical investigators should set aside their primary medical duty and their own therapeutic preferences is particularly daunting when Ebola infected patients die in high numbers. While clinicians would generally accept the idea to test an unproven intervention within the frame of a monitored trial, randomised designs make this situation even more problematic. Unless dictated by scarcity, randomisation was often perceived as a tragic choice for humanitarian workers who could not readily forfeit their therapeutic obligations and wished to maintain patients' trust in such difficult circumstances. The clustering of EVD inside households illustrates this kind of dilemma. When several members of a family attended an isolation facility, their random allocation to different regimens was emotionally difficult and felt as morally problematic [Annick Antierens, personal communication]. In addition, randomisation adds unnecessary burdens to the management of EVD patients, and additional risks of nosocomial accidents. 34 ", "One could deplore that none of the promising treatments used in Ebola field trials could so far be convincingly confirmed as curative. 52 Regardless, with their variable merits and shortcomings, those emergency clinical trials conducted in the course of a major epidemic could collectively contribute to building pragmatic foundations of disaster research ethics. This exercise would be more meaningful if ethicists and social scientists seized the opportunity to bring the voice of victims, investigators, clinicians and survivors into ethical debates that have too often been disembodied and rhetorical." ] },{ "paper_id": "8acd6f32fca98b572ad9c5cce743dd21d26b115e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Processed connexin polypeptides that were possibly generated under normal expression conditions in wild-type cells most likely escaped detection because of their low abundance (Fig. 3) .", "Construction of eucaryotic connexin expression vectors will be described in more detail in separate reports. Briefly, human/3t GJ protein was expressed in yeast cells (Saccharomyces cerevisiae) after the human/~1 GJ eDNA was cloned into the BamHI site of the yeast expression vector YEP G2 containing a polyadenylation signal, a 2-/~ plasmid origin of replication, and a galactose regulatable promoter.", "Microsome Sedimentation. Microsome sedimentation assays were principally performed as described by Gilmore and Blobel (1985) using the Beckman Airfuge (Beckman Instruments, Inc., Palo Alto, CA). After trans-lation, 15-/xl aliquots were adjusted to 50/~1 volume with buffer 1 consisting of 150 mM KOAc, 50 mM triethanolamine-acetic acid (pH 7.0), and 2.5 mM MgOAc. For alkali extractions, aliquots were adjusted to pH 11.5 with 1 M NaOH, and adjusted to 50 #1 volume. Samples were incubated on ice for 10 rain, overlayed onto a 100-/~1 cushion of 0.5 M sucrose in buffer 1 or a 100-/~1 cushion of 0.2 M sucrose in 30 mM Hepes adjusted to pH 11.5, 150 mM KOAc, 2.5 mM MgOAc, and fractionated into a supernatant (S) and pellet (P) fraction. Proteins in the superuatant fractions were then precipitated with \"I'CA and neutralized with saturated Tris base before processing for SDS-PAGE." ] },{ "paper_id": "8adc81255b4ba0eb48cbd7ddfe86f13959f39c7d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The obtained MSAs were converted into Hidden Markov Model (HMM) profiles or position-specific scoring matrices (PSSM) and used as queries to search for homologs in three different types of databases composed of: individual sequences (nr database, including GenBank CDS translations, RefSeq proteins, SwissProt, PIR and PRF (67)), profiles (PFAM A (68)), and protein 3D structures (PDB (69)). For GenBank scanning, HMMER 3.1 software (57) was used with the E-value cutoff of 10. To search for homologs among protein profiles and 3D structures, HHsearch of HH-suite 2.0.15 software (62,63) and pGenTHREADER 8.9 software (70-72) were used, respectively.", "To assess the chemical nature of the nucleotide-protein bond, the pH was temporarily shifted after product formation. To this end, 1 l HCl or NaOH (both 1 M) was added before incubation at 95 \u2022 C for 4 min. Afterward the original pH was restored by addition of the complementary base or acid, and samples were separated and analyzed as described.", "Nucleotidylation assays were performed in a total volume of 10 l containing, unless specified otherwise, 50 mM Tris, pH 8.5, 6 mM MnCl 2 , 5 mM DTT, up to 2.5 M nsp9 and 0.17 M [\u2423-32 P]NTP (Perkin Elmer, 3000 Ci/mmol). Furthermore, 12.5% glycerol (v/v), 25 mM NaCl, 5 mM HEPES, pH 7.5, and 0.5 mM DTT were carried over from the protein storage buffer. In preliminary experiments magnesium (1-20 mM) did not support nucleotidylation activity and was consequently not pursued further. Samples were incubated for 30 min at 30 \u2022 C. Reactions were stopped by addition of 5 l gel loading buffer (62.5 mM Tris, pH 6.8, 100 mM dithiothreitol (DTT), 2.5% sodium dodecyl sulphate (SDS), 10% glycerol, 0.005% bromophenol blue) and denaturing of the proteins by heating at 95 \u2022 C for 5 min. 12% sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) gels were run, stained with Coomassie G-250, and destained overnight. After drying, phosphorimager screens were exposed to gels for 5 h and scanned on a Typhoon variable mode scanner (GE healthcare), after which band intensities were analyzed with ImageQuant TL software (GE healthcare). The buffers used to find the pH optimum of the nu-cleotidylation reaction were MES (pH 5.5-6.5), MOPS (pH 7.0), Tris (pH 7.5-8.5) and CHES (pH 9.0-9.5) (20 mM)." ] },{ "paper_id": "8b39433dd865c0f71c7b2f333e1f506b73d722f1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8b3f1411a204bf1cd829342b87e5fa88bb9f12ed", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Meningococcal vaccination is a visa requirement for international pilgrims, so the vaccine coverage is essentially 100% [36, 37] , however domestic pilgrims and " ] },{ "paper_id": "8b78861684f93b6c17ed9e9d18027cfc12c41644", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "No competing interests declared." ] },{ "paper_id": "8b965ccb656960174a81c75effed2a6f2315f0e7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Our study has several limitations including the retrospective nature of data collection and small population. The results of well-designed and randomized, controlled ongoing clinical trials will prove the value of our findings.", "All patients with neurological symptoms were routinely evaluated by neurosurgeons and admitted to our neurointensive care unit or neurosurgical unit. This series of patients did not include those with hemorrhage due to intracranial aneurysms, arteriovenous malformation, arteriovenous fistula, cavernous malformation, moyamoya disease, or tumor bleeding. Most of these diseases could be excluded by taking CT angiography or enhanced CT at the same time during their first CT. When tumor bleeding was suspected, the patient's cancer history was confirmed and magnetic resonance images (MRI) were taken after 2 to 4 weeks. Cavernous malformation was excluded via MRI after the hematoma was absorbed.", "The target systolic BP was lower than 140 mmHg. This value was determined according to several ICH guidelines. 3, 14, 15, 30) BP was monitored continuously through the arterial line. Initial high BP was controlled by a diltiazem or nicardipine bolus intravenous injection, and to maintain systolic BP under 140 mmHg, continuous intravenous administration of nicardipine was used in the neurosurgical intensive care unit during the first 48 hours after admission. For better BP control, we made great efforts to reduce pain by using non-steroidal anti-inflammatory drugs and various analgesics (e.g., narcotic or patch type analgesics). The visual analog scale was utilized to quantify pain. Analgesics were used when the patient complained of pain, including headache. In unconscious patients, analgesics were used when BP was controlled but not controlled." ] },{ "paper_id": "8b9992937c24368f15eb03e7009ba85beadab1e2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "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": "8ba51fdaf2a9dc9a0b4defc7c07d360e0f9a3984", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Restriction endonucleases, T4 DNA polymerase, T4 DNA ligase, and Klenow fragment were purchased from either Bethesda Research Laboratories, (Gaithersburg, MD) or New England Biolabs (Beverly, MA), and were used as recommended by the suppliers. Unless otherwise stated, reagents used in these experiments were obtained from Sigma Chem. Co., St. Louis, MO.", "The various truncation mutations of KEX/were placed downstream from the GAL/promotor in plasmid pMB258 to create the following plasmids: pKX1-25WT, pKX1-25Hpa, pKX1-25Bcl, and pKX1-25Hinc." ] },{ "paper_id": "8bc2d0429d1c8168ddb3869ad0a81cebfe5fd8ac", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8bf17efaaca3885956b262ec027b83e86cc1711f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CONFLICT OF INTEREST. The authors declare that they have no conflicts of interest." ] },{ "paper_id": "8c4233100da83790ea6544851b543977da15a4ca", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "c-myc is an immediate early gene that is expressed as cells gain competence to exit Go and progress into Gt (12) (13) (14) .", "CTL Assa?s. Mouse target ceils (L-929, BALB/c NIH 3T3, P815, YAC-1, and A20) were labded either with sodium Slchromate for a cytoplasmic label or with [SH]thymidine or [mI]iododeoxyuridine (12sI-IUDR.) for a DNA label and examined for the release of labels as specified in the figure legends. Where indicated, DNA was purified by guanidine HC1 denaturation in the absence of detergent and dectrophoresed in 1.5% agarose gels, as described (5).", "Effector Cells. In this investigation we used purified primary CD8 + spleen CTLs, induced by acute infection of adult C3H/ HeSnJ x C57BL/6J)F1 mice for 8 d with lymphocytic choriomeningitis virus (LCMV), strain Armstrong (5). The use of these primary CTL (LCMV-CTL) precludes artifactual problems associated with CTL lines. These LCMV-CTL contain azurophilic granules and specifically induce the lysis and DNA fragraentation of LCMV-infected targets in an MHC class I-restricted fashion (7). A Con A lectin-dependent killing assay was used to bypass the requirements for specific antigen, in order to compare the susceptibility of various target cells to CTL-induced apoptosis (5) ." ] },{ "paper_id": "8c8c5fb760997ded36fe4ae8fc77103ec66f9d14", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8c96d28abcf7aa309ce804e40c11c9caf88a7a62", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8cb5954efbc7ab4a0d43db196b9b58b3838945b0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8cb96ebaf1320867609839df21072f96631e9015", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Korean J Pediatr 2016;59 (7):308-311", "In clinical practice where virology testing is not easily accessible, clinical features like palmar-plantar erythema and/or hyperferritinemia might be helpful to diagnose HPeV-3 infection. We recommend testing for ferritin in febrile neonatal patients with palmar-plantar erythema. However, additional studies will be necessary to demonstrate the diagnostic value of these features in HPeV-3 infection. If these findings are unique to HPeV-3 infection, pathogenic mechanisms should be studied.", "Human parechoviruses (HPeVs) are newly recognized single-stranded RNA viruses that were formerly classified in the Enterovirus genus 1) . Among 16 HPeV serotypes, HPeV-3 infection occurs most frequently among infants below the age of 3 months 2) . Since HPeV-3 was first isolated in Japan in 1999 1) , the HPeV serotype has been increasingly identified as an important pathogen of sepsis-like illness and central nervous system infections in neonates and young infants 3) . Life-threatening illnesses such as hemophagocytic lymphohistiocytosis have been reported in neonatal HPeV-3 infection 4) . However, the major clinical features displayed by patients with HPeV-3 infection are also common in those suffering from severe infectious diseases caused by other pathogens 5) . Thus, the diagnosis of HPeV-3 infection is difficult based only on clinical signs.", "Here, we report HPeV-3 infection in 2 neonates who had prolonged fever with palmar-plantar erythema. Elevated AST, LDH, and ferritin levels were characteristic laboratory findings in both cases, suggesting tissue damage caused by hypercytokinemia. IVIG was administered in case 1 because severe systemic inflammatory responses were considered in the patient. Case 2 displayed a milder clinical presentation, and the patient recovered spontaneously." ] },{ "paper_id": "8cd6d7c2eeb732eeecb6b7618d02eafe82aa62a4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Immunofluorescence staining for confocal microscopy was performed on similarly prepared, cut, and fixed cryostat brain sections. Sections were blocked with Superblock (ScyTek, Logan, UT) and stained with primary antibodies; rat anti-mouse CD8, rat anti-mouse F4/80, and mouse anti-rat myelin basic protein (Boehringer Mannheim, Indianapolis, IN). Secondary fluorescent antibodies used were Texas red-labeled horse anti-mouse IgG and FITC-labeled rabbit anti-rat IgG (Vector Laboratories) and the slides were mounted in Vectashield (Vector Laboratories). Double-immunolabeled sections were examined with a BioRad (MRC 600) laser scanning confocal microscope equipped with an argon/krypton mixed gas laser.", "These results indicate that infection of mice by a virus that shares immune determinants with a protein expressed in oligodendrocytes can induce a chronic inflammatory disease of the CNS associated with clinical abnormalities.", "MBP-NP and -GP mice from all lines were observed for up to 1 yr of age. None of the mice studied showed any signs of clinical disease due to the consequences of brainspecific expression of these viral genes. Additionally, histological examinations of CNS tissue taken at various ages did not detect any abnormalities." ] },{ "paper_id": "8cfe567d42fa459cb4364e240ddfe29629d03f85", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The study was approved by the local Bioethics Committee, and all study subjects provided their informed consent." ] },{ "paper_id": "8cfedfcfe692d38a55444702e704325ad1163277", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In this study, we document a case of phenobarbital-induced anticonvulsant hypersensitivity syndrome (AHS), which has been rarely reported in veterinary medicine. A 2-yearold, 5.4 kg, neutered male Russian Blue cat was diagnosed with idiopathic epilepsy and started on phenobarbital treatment. Eight days after initiation of phenobarbital treatment, the cat showed tachypnea and hyperthermia. CBC and serum biochemistry were unremarkable. However, the patient showed high serum amyloid A (SAA). On abdominal ultrasonography, generalized enlargement of abdominal lymph nodes and splenic multiple hypo-echoic nodules, which were consistent with reactive lymphadenopathy were found. The cat was diagnosed with AHS, and phenobarbital was discontinued. After 10 days of cessation, the patient had normal SAA, and clinical signs were resolved.", "Case reports of AHS in cats have been previously published. Baho et al. reported that a 4-year-old female shorthair cat had lymph node enlargement after four days of phenobarbital administration. Subsequently, the medication was changed from phenobarbital to levetiracetam, and the size of the lymph nodes were decreased after 10 days [1] . In another report, lymph node enlargement was observed after four weeks of phenobarbital administration in a 2-year-old female shorthair cat. Phenobarbital was replaced with levetiracetam, and no lymph node enlargement was observed after 10 days [8] . Although mild symptoms of AHS can be self-limiting, AHS in dogs or cats should be monitored carefully [1, 7] .", "After 8 days of phenobarbital use, no seizure symptoms were observed. Nevertheless, the patient was admitted into hospital due to high fever and lethargy. The body temperature at the time of admission was 40.1\u00b0C (reference range, 37.4-39.2\u00b0C). There was no specific finding on CBC, and no abnormal findings were found in serum chemistry analysis. SAA reached a high of 179 mg/l (reference range, 0-5 mg/l) and a small number of D\u00f6hle bodies in the white blood cells were observed on blood smear evaluation. Abdominal ultrasonography showed splenomegaly and enlargement of the abdominal (colic; 1.14 \u00d7 0.69 mm, ileocecal; 0.85 \u00d7 0.47 mm, pancreaticoduodenal; 11.37 \u00d7 6.98 mm) lymph nodes. Fine needle aspiration (FNA) was performed under ultrasound guidance, and a provisional diagnosis of reactive lymphadenopathy was made (Fig. 1) . Also, we could not find any evidence of infection or tumor by history taking, physical examination, blood analysis, and imaging. Although the serum concentration of phenobarbital was not measured at this time, through an evaluation of the clinical course, a diagnosis was made of hypersensitivity due to phenobarbital, the prescribed anticonvulsant drug." ] },{ "paper_id": "8d21989761b3a358d565559bade36a9b8654dd78", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Finally, several properties of LNA, including its good aqueous solubility, low toxicity, highly efficient binding to complementary nucleic acids, high biostability, and, improved mismatch discrimination relative to natural nucleic acid (47) make LNA a promising candidate for in vivo applications of antisense-induced frameshifting.", "RNA6: GCGCGC, RNA9: CCAGCGCGC, RNA12: C CUCCAGCGCGC, RNA15: UGGCCUCCAGCGCGC, RNA18: CCAUGGCCUCCAGCGCGC, 18RNA: GCG CGCUGGAGGCCAUGG, and RNA13: CCAAGGGG UUGAGG.", "Funding for open access charge: Leiden Institute of Chemistry, Leiden university.", "Determination of the melting temperature of oligonucleotide duplexes RNA oligonucleotide 18RNA (5 0 GCGCGCUGGAGGC CAUGG3 0 , Dharmacon, USA) was mixed in a 1:1 molar ratio with RNA18, DNA18 or one of the various DNA/ LNA mix-mers, in UV-melting buffer (100 mM NaCl, 10 mM Cacodylate acid, pH 6.8). The analysis was performed on a Varian Cary 300 spectrophotometer using temperature ramps of 0.25 C /min during heating and cooling. The absorbance at 260 nm was recorded and normalized to the blank control." ] },{ "paper_id": "8d487139eb8085addba9850f90597f206531f3c9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The number of vacuoles containing one, two, four, or eight parasites was visualized under a fluorescence microscope (100\u00d7). Means \u00b1 SD combined from three independent experiments, each performed in triplicate, were analyzed by two-way ANOVA. No significant difference was found among these three groups, hence these data clearly demonstrated that vimentin expression levels did not affect the proliferation of T. gondii.", "Mouse ( " ] },{ "paper_id": "8d4a2fb48616bae57771c62a5bcbaf86e08b8276", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Movement Reconstruction. After each flight, the movement observations were collated from the separate observation zones. Research assistants then aggregated, cleaned, and prepared the data for analysis of behaviors, movements, and ultimately time-delimited contact networks.", "Then how can we explain case reports documenting the over 40% of transmission of influenza and SARS to nontribe passengers? Some transmissions may have occurred while waiting in the airport, while boarding, or while deplaning. Alternatively, some passengers may have been infected by other sources before or after the flight. Three of the five flights in these case reports range from 9.5 to 14 h, providing many more opportunities for transmission. Other transmissions may have occurred via fomites. Flyers can protect themselves from fomite transmission by exercising careful hand hygiene. Finally, our model assumes that droplets are the main transmission route for influenza and SARS. This assumption is based on general public health agency guidance to health care providers, but it may not be true: significant transmission may also occur via smaller virus-laden particles (the smallest being aerosols), which have larger dispersion distances.", "Thus, there was no obvious virus shedding into the cabin. Furthermore, the airline's cabin-cleaning policy is to disinfect all hard surfaces whenever the plane \"overnights,\" and all surface samples were taken from hard surfaces. Not all flights were the first of the day for that plane. We chose to sample seat-belt buckles, believing that these would be the most likely items to be touched and the least likely to be thoroughly disinfected." ] },{ "paper_id": "8d5870809b9534c49bb0a3544de6a356b63d9a5a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8d612e0c4433db428f3e06657888d5296a43b653", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8d732d6fc180c5be5a7c49cd8d8cf49332d24b39", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To account for intragroup correlation with children presenting multiple times, we used the clustered sandwich estimator. 21 Data cleaning was completed using IBM SPSS Statistics, V.24, with statistical analyses conducted in STATA V.14 and EpiBasic V. 3. 22 Patient and public involvement This is a total population-based study examining patient records retrospectively. A community reference group of parents and other members of the general public were consulted prior to project commencement to ensure broad project outcomes were a priority to the community.", "There are other limitations to our study and these data. Although the risk factor analysis was restricted to children aged less than 5 years, birth-level information, such as maternal postcode of residence at the time of her child's birth used to determine the socioeconomic index score, may not be relevant to children from older age groups. A further limitation is a lack of comorbidity information in the ED data to enable identification of children at higher risk of respiratory infections, such as those with immunocompromising conditions, chronic lung disease or neurological diseases who may experience different frequencies of ED presentations for ARI.", "The respiratory disease category had the highest presentation rates for Aboriginal children in each age group, far higher than any other category (185/1000 child-years overall; table 1). The highest rates overall were observed in children <12 months old. For most infections or symptoms affecting the lower respiratory system including pneumonia, bronchiolitis, pertussis, unspecified ALRI, bronchitis and wheeze/cough/crackles, rates in Aboriginal children were 2-3 times higher than in non-Aboriginal children under 12 months but similar in the older age groups.", "ED presentation for ARIs is common and has an enormous impact on the healthcare system. We have provided a comprehensive analysis of the ED burden across WA using population-based data linkage. These data from EDs across geographical areas provide essential information for ED planning, both within season and by site and to use when exploring the impact of specific interventions (eg, vaccination) or modifications to community health services (eg, establishing general practitioner after-hours clinics). Notwithstanding the limitations of clinical diagnostic accuracy, these data provide a more community-based level of the ARI burden of disease to complement previous studies assessing only hospitalisation and death at the tip of the burden of disease pyramid. There is a lack of primary healthcare data with diagnostic information in the community in general, and these ED data will be important for understanding where to target prevention strategies and form the baseline for evaluating policies. " ] },{ "paper_id": "8d811ab0308d0b39edc268e8b0dd87bd4c3eca26", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "There are many reports showing that virus infection can alter the cellular microRNAs (miRNAs) to affect virus replication, some of them oppose the function of host restriction factors to enhance virus proliferation [2, 3] . Nowadays, researchers are trying to design miRNAs against virus proteins to control virus replication.", "Although heavily mutagenic and responsible for deleterious gene disruptions, retroelements may have provided some beneficial genomic functions with potential evolutionary advantages.", "It is generally believed that cytoplasmic RNA viruses do not encode miRNAs, owing to inaccessible cellular miRNA processing machinery. In a genome-wide analysis and identification of miRNAs originating from hepatitis A virus (HAV), a typical cytoplasmic RNA virus [36] , two novel virally encoded miRNAs, hav-miR-1-5p and hav-miR-2-5p, were identified, generated from viral miRNA precursors (pre-miRNA).", "Incubation of mouse zygotes with 5 -bromodeoxyuridine (BrdU) yields massive incorporation of this nucleoside analogue in newly synthesized DNA; surprisingly, a significant incorporation still occurs in both zygotic pronuclei in the presence of aphidicolin, a specific inhibitor of DNA replication. This aphidicolin-resistant BrdU incorporation is quantitatively abolished when embryos are simultaneously exposed to abacavir, a nucleoside RT inhibitor, thus revealing its RTdependent nature. Moreover, quantitative PCR analysis showed that LINE-1 copies are newly synthesized at the zygote-and two-cell embryo stages and nearly doubled compared to gamete copy number. These findings support the conclusion that RT-dependent amplification of LINE-1 retro-transposons is a distinctive feature of early embryonic genomes [7] ." ] },{ "paper_id": "8dc8c40ee8b61c5660b15c9e81e928eb3dc44ee5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(" ] },{ "paper_id": "8dd1202c8cda0d3a3859c3346cfbc6647317b4f3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ ". Use of highly pathogenic avian influenza A(H5N1) gain-of-function studies for molecular-based surveillance and pandemic preparedness. mBio 5(6):e02431-14.", "The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.", "Ongoing H5N1 circulation has appropriately resulted in a focus on sequencing viral genomes to understand the evolution of these viruses and the significance of observed genetic changes. Expanded laboratory capacity for high-throughput Sanger sequencing and recent technological advances, such as nextgeneration sequencing and parallel computing, have revolutionized the quantity, quality, and availability of gene sequences and our ability to quickly and accurately analyze these data (3) . Consequently, the number of animal and human influenza virus sequences available in publically accessible databases has dramatically increased over the years, as have the bioinformatics tools required for efficient investigation (4, 5) . These advances in laboratory and analytical methods provide strong incentives to utilize molecular data for pandemic risk assessment of zoonotic influenza viruses at the animal-human interface (6) .", "As coordination of international surveillance activities and global sharing of viruses improve (especially in the wake of the 2009 pandemic and emergence of H7N9 viruses in China), molecularly based surveillance has great potential for rapid risk assessment of samples collected as part of active and passive surveillance systems. Real-time feedback to investigators in the field or authorities making policy decisions related to poultry outbreak containment, clinical intervention, and diagnostic methodology, to cite a few examples, will remain critical in the future. In addition, as building laboratory capacity is prioritized in countries impacted the most by endemic H5N1 virus circulation and the higher incidence of human infection, the ability to screen viruses for amino acid markers or lineage-associated molecular determinants by sequencing, pyrosequencing, mass spectrometry, and real-time reverse transcription (RT)-PCR assays will become the reality for more and more laboratories." ] },{ "paper_id": "8de34443c38db9422b06a2f583416660f1dca670", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org/ lookup/suppl/doi:10.1128/mBio.00297-15/-/DCSupplemental. Figure S1 , TIF file, 3.8 MB. Figure S2 , TIF file, 4.4 MB. Figure S3 , TIF file, 1.8 MB." ] },{ "paper_id": "8e101b19cc15410540e85ce7f2e77208e3c411d5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8e51b76492d9bb9fe3f64f80f5bdb3e29a8c5519", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8ee4731a0d1dabf9a61a177aed392c62ca6fb69b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8f05419fedcefa7d7f276b4ddebe1ad2fb363257", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8f0e032bd15bab3c9c9af33305a2578b525e224c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.01450-14/-/DCSupplemental. Figure S1 , PDF file, 1.3 MB. Figure S2 , PDF file, 0.1 MB.", "IMPORTANCE This work clearly highlights the importance of continuous surveillance and infection control measures to control the global public threat of MERS-CoV. While current MERS-CoV transmission appears to be limited, we advise minimal contact with camels, especially for immunocompromised individuals, and the use of appropriate health, safety, and infection prevention and control measures when dealing with infected patients. Also, detailed clinical histories of any MERS-CoV cases with epidemiological and laboratory investigations carried out for any animal exposure must be considered to identify any animal source." ] },{ "paper_id": "8f4348a9455035db6487252e4fb48c65708a1e1f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The ability of saturated fatty acids to induce cell fusion without further treatment may also find application in certain situations.", "Fusion Protocol: PEG used for fusions was obtained from J. T. Baker Chemical Co. Phillipsburg, N J, and autoclaved before use. In this study all fusions were performed using PEG 1000 (average molecular weight 950-1,050). Unless otherwise indicated (as in Fig. 3 ), a 50% solution (wt/vol) was prepared in growth medium without serum. For some experiments, PEG was recrystallized from ethyl ether as described by Honda et al. (16, 17) , or passed over a hydrophobic column and lyophilized before use. In agreement with Smith et al. (39) , no substantial differences in ability to induce fusion were observed between these purified preparations and PEG used directly as supplied from the manufacturer.", "After treatment with PEG and the subsequent incubation period, cells were rinsed in isotonic saline solution, fixed in methanol, and stained in Giemsa stain (Fisher Scientific Co., Fair Lawn, N J). Coverslips from small petri dishes were mounted on glass slides with UVinert Aqueous Mountant (Gum Ltd.; distributed by Bio/medical Specialties, Santa Monica, CA}. For cells grown in larger dishes, a small amount of mountant was added directly to the dish, over which was laid a 50-ram diameter # 1 glass coverslip (Corning Glass Works, Coming, NY). Cells were observed with a Zeiss Photomieroscope III equipped with phase-contrast optics. Observations were recorded on Ilford Pan F film (ASA 50) by locating confluent regions at low power and photographing at higher magnification without further selection of field." ] },{ "paper_id": "8f64ab87b255d034c48a5a7c8a8a82a4ea81e67b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The localization of proteins to late-Golgi", "To date, little direct evidence exists to discriminate between this sort of retrieval mechanism and a static retention mechanism where proteins would be excluded from vesicles leaving Golgi membranes and, consequently, have a longer residency period in the TGN.", "T he secretory pathway of eukaryotic cells is composed of a series of membrane-bound organelles, each with its own unique complement of components. Transport of components between these organelles is achieved by means of vesicular transport, which results in a flow of membrane traffic throughout the pathway (Rothman, 1994) . To maintain its identity, an organelle must ensure that its resident proteins do not get swept with those proteins passing through en route to other destinations in the cell. To achieve this localization, resident proteins can either be retrieved once they have exited the organelle, or they may be prevented from ever leaving that organelle in the first place . These two mechanisms need not be mutually exclusive, since efficient localization of a protein to an organelle could arise through a combination of both mechanisms." ] },{ "paper_id": "8f73d388e9ac6eedc6e60400d1fc7e3809814042", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Vaccination continues to have a major impact on the health of humans and animals. Furthermore, vaccination of animals is proving to be effective in reducing transmission to humans. Understanding linkages between innate and adaptive immunity are improving formulations of new, as well as existing, vaccines, making them more effective.", "Based on the recent advances in understanding immune responses and identifying antigens involved in inducing protection from a number of infectious agents combined with the willingness of regulatory agencies to begin licensing combination, adjuvants gives us confidence that we will be able to develop new vaccines to new agents and also improve existing vaccines that can even be safer than our vaccines used today. In this way, all members of society will benefit.", "Another big challenge to vaccination today is that most vaccines are delivered by needle injection. This often results in local mild reactions and these minor adverse events are being used as a reason to dissuade individuals not to vaccinate their children. Indeed, in our society, all forms of 'preventive medicine' are looked upon less favorably than therapies. Many of our therapeutic drugs cause significantly greater adverse reactions than vaccines. However, they are accepted because they are treatments. Anti-cancer drugs are one of the best examples, which may have many side effects. The reason for this dichotomy is that our society is much less accepting of preventative medicine versus therapeutic approaches to disease management. If the focus continues to favor expensive therapeutics over economic preventative medicine, escalating costs of health care will bankrupt society." ] },{ "paper_id": "8f810a6f1464d6871d6184e04cf3fb1417983abc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The present study has certain limitations. Some samples contained viruses at low titers, hindering statistical analyses for certain viruses, such as PIV1 and PIV4, and could not reflect the entire range of seasonal variations in each viral infection.", "Since rapid reporting of viral diseases is critical, rapid PCR assays have been introduced, but these assays have limited throughput. However, according to our analysis, All16 can be performed twice per day without requiring more workers. Therefore, if many samples need to be run, All16 could be advantageous, especially compared with Any16.", "Detecting pathogens in respiratory infections is crucial for diagnosis, patient management, and to avoid improper antibiotic treatment and unnecessary laboratory testing. However, the goldstandard methods for detecting viral infections, non-molecular methods, have critical limitations such as the requirement of labor-intensive and complex procedures and time-consuming steps [1, 2] . Therefore, in many instances, cell culture is no longer considered the gold-standard method, and molecular assays have become the standard of care for diagnosis [1, 3] . Multiplex real-time PCR is useful for diagnosing respiratory viral infections because the process time is faster than that of viral culture, it detects multiple pathogenic viruses simultaneously, and it is reli-able [3] ." ] },{ "paper_id": "8fe6e12ec1f61c111c3ca33189fcc0ec90c03803", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "MINIREVIEWS", "In multivariate analysis, males (aOR = 1.9, 95%CI: 1.22.9, P < 0.01), heavy smokers (smoking more than 30 cigarettes per day) (aOR = 4.6, 95%CI: 2.68.0, P < 0.01) and postgraduate degree holders (aOR = 2.1,", "Multivariate analysis showed that being male (aOR = 4.8, 95%CI: 2.88.2, P < 0.01), heavy smoker (aOR = 4.5, 95%CI: 2.67.7, P < 0.01) and having a chronic disease (aOR = 4.8, 95%CI: 3.56.6, P < 0.01), especially chronic kidney disease (aOR = 6.3, 95%CI: 1.526.9, P < 0.01) significantly increased the likelihood of being vaccinated against pertussis (Table 4) ." ] },{ "paper_id": "8fec2036fb2e98cbb9d4f955ce1d5198d1a09b3c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8fefbc58375c244a64a82e3f88c4084076838b88", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.00265-10/-/DCSupplemental. Figure S1 , TIF file, 3.902 MB. Figure S2 , TIF file, 5.443 MB. Figure S3 , TIF file, 5.300 MB. Figure S4 , TIF file, 3.468 MB. Table S1 , PDF file, 0.098 MB.", "Statistical analysis. Statistical differences between groups were determined using a two-tailed Student's t test. P values of \u03fd0.05 were considered significant. " ] },{ "paper_id": "8fefe8e70632ffdfd96f701facc6f2dcce16167a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9033adf08248ec28fb49e61abe6c1209d7811843", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dual luciferase assay was performed as described previously (27, 28) . Transfection efficiencies were normalized to a control plasmid expressing Renilla luciferase (pSV-RLuc from Promega).", "Real-time reverse transcription-PCR (RT-PCR) was performed as described (27, 30) . Normalization was made to glycerialdehyde-3-phosphate dehydrogenase (GAPDH) mRNA. Quantitation of target mRNA was achieved with the comparative Ct method. Relative expression level of target mRNA was calculated from 2 \u2212 Ct . Primers were listed in Supplementary Table S1 .", "HepG2 and HepG2.2.15 cells were transfected with 100 nM of siRNA using Lipofectamine 2000 (Invitrogen). RNA interference (RNAi) experiments were performed as described (27, 30) . siRNAs were listed in Supplementary Table S1 .", "Hepatitis B virus (HBV), a member in the family of Hepadnaviridae, has a DNA genome 3.2 kb in size which is partially double stranded. Over 350 million people are chronically infected with HBV worldwide, including \u223c10% of the population in Hong Kong and China, 15-40% of whom will terminally develop severe liver diseases including hepatocellular carcinoma (HCC) (1) . Although multiple factors are involved in the development of HCC in HBV carriers, high level of HBV DNA has been identified as a major risk (2) ." ] },{ "paper_id": "904d886a8a305e2bc1125fccad82741d78690fef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study was approved by the Institutional Review Board (IRB) of Gachon University Gil Medical Center (IRB No. GBIRB2017-361).", "We retrospectively analyzed the medical records of patients with MP pneumonia aged \u2264 18 years old who were hospitalized at Gil Medical Center between January 2015 and April 2017.", "Side effects such as Cushing appearance and peptic ulcer for CST, tooth discoloration for DXC, and tendinopathy, arthritis for LFX were evaluated for one month after medication." ] },{ "paper_id": "905e2b35719215760ebed8f3e93fdf6ea8ec9bcf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As previously mentioned, the detection of efflux will be possible if the light is shining brightly and directly onto the exposed spinal cord during the injection. Efflux is most likely to happen with 30 gauge needles (versus 33 gauge) and if the injection is done too rapidly. Though this protocol has given us good results, others have reported longer waiting periods (up to 5 minutes) before retracting the needle following injection 8, 9 . Also, smaller gauge needles are preferable, but we have observed that some cells are too easily lysed when passed through 33 gauge needles.", "Cell replacement therapies for the treatment of some CNS disorders are currently in clinical trials 10 .", "No conflicts of interest declared." ] },{ "paper_id": "90b31a2542e2275640ec9dc8264cdf1e975d807e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The phylogenetic tree was analyzed using MEGA6 with the neighbor-joining method, maximum composite likelihoodparameter distance matrix, and bootstrap values of 1,000 replicates.", "Infected hosts exhibit different clinical courses, ranging from asymptomatic to severe symptoms in their respiratory, digestive, and genital organs [1, 2] . There are 6 known coronaviruses that typically cause infection in humans. Among these, coronavirus 229E, OC43, NL63, and HKU1 generally cause mild cold-like symptoms, whereas severe acute respiratory syndrome-coronavirus (SARS-CoV) in 2003, and Middle East respiratory syndrome-coronavirus (MERS-CoV) in 2012, caused severe respiratory diseases such as pneumonia and death [5, 6] .", "Gene sequencing was performed using CLC Main Workbench 7.9.1. Alignment was conducted using human and animal coronavirus sequences registered in Global Initiative on Sharing All Influenza Data (GISAID) and NCBI GenBank.", "Coronavirus is an RNA virus consisting of positive-sense single-stranded RNA of approximately 27-32 kb. Coronavirus belong to the family Coronaviridae, which comprises of alpha, beta, delta, and gamma coronaviruses [1, 2] . As the name indicates, the spherical external spike protein displays a characteristic crown shape when observed under an electron microscope [3, 4] . The virus is known to infect a wide range of hosts including humans, other mammals, and birds.", "T h e v i r u s wa s i s o l a te d f ro m n a s o p h a r y n ge a l a n d oropharyngeal samples from putative COVID-19 patients." ] },{ "paper_id": "90cc93e5eac1e836f5cbce50fe92ded531045abf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Analysis of gene-specific mRNA cap structures. Regions corresponding to the first 300 to 500 nucleotides of the target messages were PCR amplified from cDNAs using the following oligonucleotides:", "RNA purification. Total RNA was prepared from mouse (C57BL/6) tissues using Trizol reagent (Invitrogen). The poly(A) RNA was purified twice using oligo(dT) cellulose (Fluka) followed by oligo(dT) magnetic beads (Invitrogen). All samples were quantified and assayed for poly(A) purity using an Agilent Bioanalyser.", "In order to get quick access to the required m 6 Am phosphoramidite building block for solid-phase oligoribonucleotide synthesis, we performed a selective one-step methylation of the commercially available 2'-OMe-Bz-A-CE phosphoramidite. Due to its high reactivity and sensitivity towards acids and bases, Aritomo's relatively mild phase transfer catalysis (PTC) method was used 30 . Under these conditions (iodomethane, sodium hydroxide, tetrabutylammonium bromide) the N 6 -methylated product was obtained as the major product in 56% yield, with the N 1 -methylated isomer being formed as a byproduct in 25% yield. Due to their different Rf values, the N 6 -and N 1 -methylated products were easily separated via column chromatography, and the purified m 6 Am phosphoramidite was used directly for RNA synthesis." ] },{ "paper_id": "9104c8bed3340e783a7a0a820ff269711f39bc8f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors state that they have no Conflict of Interest (COI).", "Nivolumab is an immune checkpoint inhibitor (ICI) that has become a new treatment option for malignant tumors. While initially proven effective for melanoma, the diseases for which this agent is administered have been expanding. However, a number of immune-related adverse events (ir-AEs), which are rarely seen in conventional chemotherapy, have been reported with this drug, and as the frequency of its use increases, there are concerns that the number of side effects will also increase.", "We herein report a case of nivolumab-induced myocarditis that developed one year after its administration. A cardiac muscle biopsy specimen showed T cell-dominant lymphocyte infiltration, which was successfully improved by corticosteroid therapy." ] },{ "paper_id": "913cd784df40966fdfd97281dd38d9c9b421f32e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "915bbf3af94c8bb413b496b0d4d7f88a1ed7d7bb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9171b9ab69fa99aa5528c2173d4bf414c6d8c9cb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Citation Fouchier RAM. 2015. Reply to \"Comments on Fouchier's calculation of risk and elapsed time for escape of a laboratory-acquired infection from his laboratory.\" mBio 6(2):e00407-15.", "Another key aspect is that Dr. Klotz estimates the likelihood of onward transmission from a case of LAI as 0.1 (10%), in contrast to my justification for an adjusted likelihood of \u03fd1 \u03eb 10 -5 , based on the specific conditions under which the research is performed, without providing a rationale for that important deviation (2) .", "Dr. Klotz proposes to multiply the low likelihood of LAIs by 300, based on an estimated 30 laboratories involved in the \"whole research enterprise\" for 10 years, and assumes that part of this research enterprise may lack the rigorous safety practices in place at Erasmus MC. Both assumptions are wrong, to the best of my knowledge; just over a handful of laboratories have worked on airborne transmission of avian influenza viruses, each of which has rigorous safety practices in place (3) (4) (5) (6) (7) ." ] },{ "paper_id": "91abd69ad1b79240b58ffdfbce651e6980dca5bf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "ACKNOWLEDGMENTS. We would like to thank Friedrich-Loeffler-Institut for providing ZZ-R cells (Catalog number CCLV-RIE ", "The Iwate strain of MVV, which was isolated from peripheral blood leukocytes of a seropositive sheep in Japan, was used in the present study [12] . The virus was propagated in a primary culture of fetal goat lung (FGL) cells and used after filtration through a 450-nm Millipore filter. Information pertaining to the isolation of the virus was reported previously [12] .", "Because most retroviruses do not produce obvious CPE and persistently infect cultivated cells in vitro, virus neutralization tests are not easy for their serological tests, and ELISA and AGID are used for the antibody survey. Because lentiviruses are not oncogenic and do not malignantly transform cells as oncoviruses do, an established cell line is required for persistent production of a lentivirus. Because ZZ-R cells were shown to continuously release MVV antigens, this cell line may be used to produce large amounts of a viral antigen for serological tests." ] },{ "paper_id": "91bf77728f819af91ffed7f116dd2da12a1bd2a0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "91bfca3d386f93c5b083464adb93c8d36f773fb0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9200568d5a5c88f0f1b203240e94e90f96546431", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9209041d93cd781cde415406283ebad549610042", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "920ac358de68e48b50b4d65dc500935ade21c997", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "92142e072745fbab996c5861e5974aa03805398a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Given that M\u03c6 play important roles in maintaining tissue homeostasis and fighting disease, polarized M\u03c6 subsets that specifically contribute to the pathogenesis or amelioration of various diseases present themselves as attractive targets for therapeutic intervention. Different therapeutic strategies include either targeting the polarized M\u03c6 themselves or manipulating the signaling pathways involved in the process of M\u03c6 polarization to a desirable outcome.", "IKK\u03b2, a downstream mediator of insulin resistance and activator of the NF-\u03baB pathway (and therefore of M1 polarization), is inhibited by anti-inflammatory salicylates like aspirin, which attenuates hyperglycemia and hyperinsulinemia in obese rodents (Yin et al., 1998; Yuan et al., 2001) . Several small trials in patients with type 2 diabetes have demonstrated that treatment with salicylates results in a marked reduction of diabetic metabolic parameters and improved glycemic control (Tateya et al., 2013) .", "This work was supported by NIH grants R01AI098126 and U19AI066328.", "Macrophages, found in circulating blood as well as integrated into several tissues and organs throughout the body, represent an important first line of defense against disease and a necessary component of healthy tissue homeostasis. Additionally, macrophages that arise from the differentiation of monocytes recruited from the blood to inflamed tissues play a central role in regulating local inflammation. Studies of macrophage activation in the last decade or so have revealed that these cells adopt a staggering range of phenotypes that are finely tuned responses to a variety of different stimuli, and that the resulting subsets of activated macrophages play critical roles in both progression and resolution of disease. This review summarizes the current understanding of the contributions of differentially polarized macrophages to various infectious and inflammatory diseases and the ongoing effort to develop novel therapies that target this key aspect of macrophage biology." ] },{ "paper_id": "921c3701d112c1aeef737e5d395e9996a81b9bff", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "924dc69ab73fbedf0c55ba2f7cd22e76710512ea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Differences between means of continuous variables were calculated using ANOVA for normally distributed data and a Kruskal-Wallis test otherwise. A p-value , 0.05 was considered significant.", "On admission, most patients had bronchiolitis of moderate severity, with a median RDAI score of six, but no significant difference in the severity score was observed between age groups (0-6 months, 6-12 months, and .12 months). An oxygen saturation lower than 95% was observed in 21 patients (28.3%)." ] },{ "paper_id": "927e00e594ec72a344b692093b2f3f77bbd911f4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "92a4cbcc55d992b5fd6f9c77de0fb4f5030a566a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Drawings were made from the Brookhaven database entries (A) 5HMG and (B and C) 1HTM.", "V55P fused slowly and did not appear to form syncytia. V55P/S71P did not mediate fusion.", "Received for publication 7 April 1997 and in revised form 10 April 1998." ] },{ "paper_id": "92a5a662e916fd3d1520764cbfca4ad457dd09d7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "92aca69f518fc394bd00b525898264893d9550af", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The p53 protein family consists of p53, p63, and p73. Different isotypes can be generated from their genes due to the presence of different promoters (Levine et al., 2011) . For example, the p63 gene generates two types of transcripts:", "The activated p53 then binds to p53REs for transcriptional activation of its target genes (e.g., BAX, CDKN1, and PUMA) that mediate cell cycle arrest and/or apoptosis, depending on the degree of stresses (el-Deiry et al., 1994; Miyashita and Reed, 1995; Nakano and Vousden, 2001 ).", "\u0394 \uf061" ] },{ "paper_id": "92ae74cf9e28a780d600c36da4b09591b65c87cd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data analysis and data normalization were performed using the method described by Quackenbush (8) . For background correction, the mean intensities of areas surrounding spots were subtracted from spot intensities (local area background). Data sets were normalized by dividing the mean intensity value of every spot (in duplicate) by sum of all spot intensities within a sample to eliminate experimental or data acquisition variations. Normalized data were used to calculate the gene expression level ratios of different culture stages. A two-fold expression cut-off was applied. For hierarchical gene cluster analysis, expression ratios were calculated for all genes as described by Eisen et al. (9) .", "MSCs were pelleted into micromasses and differentiated in serum-free medium in the presence of TGF-\u03b23 and dexamethasone. Immediately after centrifugation, the cells appeared as flattened pellets at the bottom of tubes. One day later, pellets had a thickened lip, and between days 2 and 3, pellet became spherical without any increase in size. Pellets then grew in size and pellet diameters increased to about 2-fold on days 7 and 14 (Fig. 3A) .", "Total RNA was processed using the Genesys Applied Biosystem Facility (Genesys, Munster, Germany), according to manufacturer's recommendations. Each RNA pool (2 \u03bcg) was labeled with Digoxigenin-UTP using the ABI Chemiluminescent RT-IVT Labeling Kit v 1.0. Double-stranded cDNA was prepared from total RNA. UTP-digoxigenin-labeled complementary RNA (cRNA) was synthesized by in vitro transcription. Labeled cRNA (10 \u03bcg) was hybridized to ABI Human Genome Survey Microarray v 2.0, which was then incubated with alkaline phosphatase-linked digoxigenin antibody. Phosphatase activity was then initiated to produce the chemiluminescent signal. Chemiluminescent (cRNA) and fluorescent (spot background) signals of the cRNA and standard control spots were then scanned. Chemiluminescent detection and image acquisition was performed using an Applied Biosystems 1,700 (AB1,700) Chemiluminescent Microarrays Analyzer, according to the manufacturer's instructions. Using the software supplied with the AB1,700 apparatus, the spot chemiluminescent signal was normalized over the fluorescent signal of the same spot to obtain normalized signal value. For inter-array normalization, global median normalization was ap-plied across all microarrays (7)." ] },{ "paper_id": "92b6e41df821c7c137bfa56339734cee1715df3d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "92ca79afc9f624d2ff6417edfd83e081fcace484", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For 1 year (January 2016 to January 2017), we prospectively enrolled children age 6 months to 18 years who were admitted to the Monroe Carell Jr. Children's Hospital at Vanderbilt (MCJCHV) with acute MSKI undergoing a surgical drainage/ biopsy procedure. Potential study subjects were identified by daily communication with the pediatric orthopedic surgery service.", "The identification of a causative organism in MSKI is critical and allows for optimal targeted antimicrobial therapy. Traditionally, clinicians have relied on bacterial culture for pathogen isolation and antibiotic susceptibility testing, although blood and operative cultures frequently remain negative [1] [2] [3] . Several reasons for this exist, including antibiotic administration before tissue sampling and the fastidious nature of causative pathogens.", "Demographic data were collected from the electronic medical record system at MCJCHV. Sensitivity and negative predictive values were calculated to compare TEM-PCR to culture.", "Blinded clinical samples were submitted to Diatherix-Eurofins for TEM-PCR detection of Kingella kingae, Haemophilus influenzae, Streptococcus pyogenes, Streptococcus pneumoniae, S. aureus, methicillin (mecA) and clindamycin/erythromycin (ermA, ermC) resistance genes, and the Panton-Valentine leukocidin (PVL) locus. Briefly, nucleic acid was extracted from 275 \u00b5L of clinical sample, and 20-\u00b5L PCR reactions were prepared using 2X Platinum Multiplex Master Mix (ThermoFisher Scientific, Waltham, MA), 2.4 \u00b5L of TEM-PCR primer mix, and 4 \u00b5L of template DNA. Amplification was performed in 96-well plates on the GeneAmp PCR System 9700 thermocycler (ThermoFisher Scientific, Waltham, MA). In a single reaction, each target was amplified with nested primers and subsequently amplified with a pair of universal primers containing proprietary sequences to amplify all targets in the single reaction. The reverse universal primer was biotinylated for downstream detection. Biotinylated amplicons were detected by hybridization to a detection probe covalently coupled to a glass microarray substrate, and streptavidin-phycoerythrin conjugate was added. Fluorescent signal emission was measured on a SensoSpot imaging reader (Sensovation AG, Radolfzell, Germany)." ] },{ "paper_id": "92dc5a63d0776632f789e874bb0217c4ac1d021b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "92e14fff3e37477102149550fc8f3ff9d5ffc6f6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "When normality or linearity assumptions were violated, we provide output from both parametric and nonparametric methods. All statistical tests are two tailed and were carried out in SAS (SAS Institute Inc. 1989).", "Despite its poorly adapted codon usage,", "Based on the tRNA data collected and RSCU values calculated, we defined two indices for viral codon usage and tRNA packaging: " ] },{ "paper_id": "9305dcf034dfe834775ad84358b90ae50092b829", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration, and has been approved by the authors' institutional review board or equivalent committee. Informed consent: Written informed consent was obtained from the patient for publication of this manuscript and any accompanying images.", "A 63-year-old man visited an outpatient clinic complaining of cough and dyspnea (Borg scale 4). He was a current smoker of 20 pack-years and denied histories of taking any medications or illness including cardiovascular, allergic, rheumatologic or respiratory diseases. A complete blood count revealed values within normal range, except for a lower value of platelet count, 91,000/mm 3 . Increased haziness on the lower lobe of the right lung was noted on his chest radiography.", "Small-cell lung cancer (SCLC) is a lung cancer histological subtype unusual in its favorable response to cytotoxic chemotherapy. Life-threatening manifestations at presentation are rarely reported and should be an important clinical concern. We report a case of a 63-yearold man presenting with rapid-onset refractory severe thrombocytopenia, development of massive hemoptysis, and death from respiratory failure. This case provides clinicians a reference for this unusual presentation and carries clinical implications for managing SCLC patients." ] },{ "paper_id": "9316c8c673768c7310978f482fcaa1d3bd62d547", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "933b17f79aad3485aa3e1d489a7a89ea0ae94a66", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "934f45d3ce46b7e090b1a3d76a96e2acb705cc91", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "production of a cellular ligand, as in human papillomavirus 16 (44) .", "Supplemental material for this article may be found at http://mbio.asm.org/ lookup/suppl/doi: 10 " ] },{ "paper_id": "9363422a0f9b40cd6bb8f6c7fbbcaadf146f20a6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "StatisticalAnalysis. Statistical analysis was carried out using analysis of variance and the Wilcoxon ranked sum test. A p value of 0.05% or less was considered statistically significant.", "We have recently produced a panel of mAbs to MHVinduced macrophage PCA (8) . The antibodies did not react with purified viral proteins nor did they inhibit viral replication. One of these mAbs (3D4. 3) , an IgG2ak, strongly inhibited PCA expression in a one-stage dotting assay and inhibited conversion of prothrombin to thrombin (8) . This antibody had no reactivity with murine, rabbit, or human tissue factor. The monoclonal bound to a 70-kD protein that is distinct from murine and human tissue factor (42 kD) (9, 10) .", "The purpose of this study was to determine whether treatment with this specific murine antiprothrombinase would modify the morbidity and/or mortality associated with murine hepatitis virus infection." ] },{ "paper_id": "9369b15083026f2929d6eb01a67999d1800e2ec0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "diagnosis in a discrete manner, using the problem oriented veterinary medical record (POVMR) as their diagnostic tool.", "Blood samples were taken from the jugular vein using vacutainer tubes with EDTA as anticoagulant. Complete blood cell counts (CBC) were performed using an automated cell counter (QBC vet-IDEXX Laboratories, Inc., Westbrook, ME, U.S.A.). The blood films were stained with Wright-Giemsa and examined under a photonic microscope. Leukopenia was considered when a total CBC count was less than 6 \u00d7 10 3 /\u00b5l [3] .", "All the amplification products were identified through horizontal electrophoresis in 2% agarose gels stained with 0.5 \u00b5g/ml of ethidium bromide and visualized with a UV transilluminator.", "Frequency of clinical signs showed by these dogs was as follows: 44.4% displayed vomiting and diarrhea; 20% had fever, vomiting and diarrhea (catarrhal or hemorrhagic); 17.7% showed only diarrhea; 8.8% displayed only vomiting; and 4.4% had diarrhea and fever, and 4.4% presented vomiting and fever. Leukopenia was observed in 48.8% of the dogs (Table 1) ." ] },{ "paper_id": "93c68999496870d3c22d197c05645a9bd747c8cc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "93d77f602ff27ef1575dd6f700d3f39033bba576", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All values are expressed as the means \u00b1 standard deviation of the means (SDM). All statistical significances were evaluated by a Student's t-test by using GraphPad Prism software version 5.0 (GraphPad Prism Inc., USA). The p values of less than 0.05 were considered statistically significant.", "Phylogenetic analysis based on the complete S protein clearly classified the PEDV strains into two distinct genogroup clusters, G1 and G2, with two subgroups in each genogroup (Fig. 3A) .", "The Aram strains belonged to subgroup G2b, as it clustered closely with the contemporary domestic and global G2b isolates. Subsequent whole-genome phylogeny showed the same grouping structure as that of an S gene-based phylogenetic tree (Fig. 3B) ." ] },{ "paper_id": "93dae518889d2a93960963fa3e99158f58738eda", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ ". . . , s n \u00bc (21) n a 0 . By using Newton's famous identities 11 :", "As a result, the coefficients of the poly-", ". . . ; n:" ] },{ "paper_id": "93df1925c1aa0cf7e721ebcbaed2d261c032d925", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "93f3546142cf477c77ef113ed4ff98a881a2c8c1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "While this is a technical report, detailed methods covering animal housing, pathogen status, and clinical assessments of sick and moribund mice are pertinent as these variables impact phenotypes and vary between facilities. Reporting of such details is in compliance with the ARRIVE guidelines (10) . Technical necropsy and histopathology methods are briefly covered for completion; the reader is referred to comprehensive reviews for additional information (11\u00c113).", "While maximum lifespan has been the mainstay metric of aging research, it is recognized that longevity alone, while informative, is incomplete as it does not allow for assessment of health. Physiologic, behavior, and pathology assessment coupled with the foundation of lifespan extension offer a more accurate characterization of a gene or intervention's effect on maintenance of functional health. Pathobiology aging studies are now shifting toward characterizing health span and age-related disease onset in mouse models (5\u00c17).", "At necropsy, of all major organ systems and any grossly abnormal tissues were preserved in 10% neutral phosphate-buffered formalin. Fixed tissues were trimmed using a standard protocol developed by the University of Washington Veterinary Diagnostic Laboratory. Boney tissues were decalcified and all tissues were routinely processed and paraffin embedded. Samples were sectioned at 4\u00c15 mm and stained with hematoxylin and eosin." ] },{ "paper_id": "940982caa84b1a49e2fd8b4dd0f12e2e904fc55b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9427765d1870e8f4acfb6556a78f297e19068464", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Provide multiple whole-genome alignments, gene and whole-genome translations for all RNA virus species Identification and taxonomic searching facility Guidance to other web resources.", "Viruses are divided into two similar-sized groups depending on whether the virus particle contains DNA or RNA, and, as causes of human fatality, RNA viruses are by far the more important (1) . New viral diseases continue to appear as a result of several changes in human activity: travel, population growth, interaction with wild habitats etc. Well-known novel, or emergent, RNA diseases include severe acute respiratory syndrome (SARS) (2), human immunodeficiency virus 1 (HIV-1) (3), and may come to include Avian influenza H5N1 virus (4) . These emergent diseases are an important factor behind the increase in the number of genome sequences that NCBI treats as representing new species (Figure 1 ). In 2005, more than 200 new virus species were submitted to GenBank (more recent dates are less reliable because there is typically a delay between submission and public availability). As more emergent viruses appear, it is important to have a site that allows their genomes to be compared to those of known viruses. The origin of most major infectious diseases is unknown because of our ignorance of the diversity of pathogens in wild animals. This restricts our ability to both predict risks and develop treatments (5) .", "We intend to update the database on at least a 6-monthly basis in order to include newly discovered viruses, and are currently working to incorporate biological and epidemiological data. We also intend to release soon a DNA virus database using the same format. As discussed in Introduction, we are keen to collaborate with other groups over further developments of our database. ", "Despite some advances (6, 7) , the evolutionary history of RNA viruses is in general poorly known, especially the deep phylogenetic relationships between virus families (8, 9) . We believe that one of the reasons for this is a lack of easily available translated genes and genomes for all species, and the lack of aligned genome sequences representing different isolates of the same species." ] },{ "paper_id": "9449746a1b41b08251ce0e1cb8fc5654b2faf043", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "945fac2c9ade4e451cc0cb8388cf9de8b2f00a47", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study was reviewed and approved by the Marshfield Clinic Institutional Review Board. During each season, all study participants (or parents) provided informed consent for influenza testing. Multiplex RT-PCR testing to detect additional viruses was subsequently approved by the institutional review board with a waiver of informed consent.", "No. of ED visits in the prior 12 mo, median (min-max) b 0 (0-6) 0 (0-15) .5 0 (0-3) 0 (0-6) .5", "No. of hospital admissions in the prior 12 mo, median (min-max) b 0 (0-6) 0 (0-13) .4 0 (0-3) 0 (0-6) .003", "No. of outpatient visits w/ provider in the prior 12 mo, median (IQR) b 8 (4-13) 8 (4-15) 1.0 8 (4-12) 9 (5-15) .04" ] },{ "paper_id": "949ec05f3fbd741cc6c4a08b2bcffdaa3d479866", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "94af6bf9cae266730bbc0480ab71595c12072891", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "If global temperature increases by 2-3 \u00b0C, as it is expected to, the population at risk for malaria could increase by 3%-5%. 45 " ] },{ "paper_id": "94c1ee6fefd3a09fdf245d6d4a0c2321c9d994de", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Over the past 4 years, EuPathDB has routinely updated existing databases and added two new databases. We added new data, expanded the range of supported data types, enhanced infrastructure and added new analysis tools.", "RNA-sequence analysis workflow updated. Our pipeline for analyzing and loading RNA-sequence data was updated to use standard tools and to accommodate data sets with biological replicates. The new workflow aligns reads with GSNAP and calculates FPKM/RPKM with HT-Seq (33, 34) . DESeq2 is used to determine differential expression for experiments that have appropriate biological replicates (35) .", "As one of four National Institute of Allergy and Infectious Disease (NIAID/NIH) funded Bioinformatics Resource Centers (2-6) EuPathDB provides data, tools and services to scientific communities researching pathogens in the NIAID list of emerging and re-emerging infectious diseases which includes NIAID category A-C priority pathogens and many fungi. Additional EuPathDB support for the kinetoplastid and fungal research communities is funded by The Wellcome Trust in collaboration with GeneDB (7), including support for focused curated annotation. This manuscript describes expanded content, features and tools added since 2013 that increase the data mining and discovery power of EuPathDB.", "Public strategies. Strategies marked as Public when saved to a user's profile will also be shared with the community in the 'Public Strategies' tab of the 'My Strategies' interface. Users control the availability of the strategy and can remove it at any time. The panel also includes example strategies provided by EuPathDB." ] },{ "paper_id": "94d47d45fbe70e69c32aa588b44fbdfc0333751a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "94f679e7bf40010e41952e26e8953a5703be64c0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Influenza A virus hemagglutinin (HA) can be cleaved and primed by a variety of cellular proteases. Even bacterial proteases may promote influenza virus spread by cleaving HA 0 into HA 1 and HA 2.", "The ratio of mature to immature prM depends on a variety of factors, including the producer cell type and the flavivirus species. For example, dengue viruses are known to release high amounts of immature or partially mature viruses, most likely because of a conserved acidic residue within the furin recognition site 78 (Table 2) . Importantly, the content of prM in viral particles also affects antibody recognition and consequently antibody-dependent enhancement of dengue virus infection. 77 Thus, furin-mediated protein processing may once again markedly affect the outcome of infection.", "Although the therapeutic application of furin inhibitors may be full of pitfalls, it is certainly a promising approach that should be further pursued. Future studies will elucidate the role of individual PCSKs and their substrates in disease progression and a better understanding of cellular pathways regulating furin activity may uncover additional targets for therapeutic intervention.", "Furin is a member of the evolutionarily ancient family of proprotein convertases. Their similarity with bacterial subtilisin and yeast kexin proteases has coined the abbreviation PCSK (proprotein convertase subtilisin/kexin type). Humans encode nine members of this protease family (PCSK1-9), with PCSK3 representing furin (Table 1) . PCSKs are well known for their ability to activate other cellular proteins. The proteolytic conversion of inactive precursor proteins into bioactive molecules has already been described in the 1960s. 3 However, it took more than 20 years until furin was identified as the first mammalian proprotein convertase. 4, 5 To date, more than 200 cellular substrates of PCSKs have been described, including hormones, receptors, growth factors and adhesion molecules." ] },{ "paper_id": "9521353cc7ef3d0734d76453622762532f06f777", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "953ce6c11451011ff271b730ac3d2bdadda75830", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "However, the outbreak of Middle East respiratory syndrome ", "Ethical considerations have been embedded in plans made throughout the world for outbreaks and pandemics [1] [2] [3] [4] . Lessons from past epidemics warn that without ethical safeguards, public health measures can inadvertently encroach on human rights and values [5] . The incorporation of relevant ethical principles in pandemic planning can help enhance voluntary cooperation based upon public trust, and reduce the undesirable outcomes of public health measures [1] .", "In Korea, public health ethics is not an established field. Bioethics was introduced to Korea in the 1990s, mostly in the form of clinical ethics and research ethics programs in medical schools and hospitals. From the beginning, the principalism proposed in Beauchamp and Childress's Principles of Biomedical Ethics [6] played a dominant role in biomedical ethics education in Korea. With the four principles of respect for autonomy, nonmaleficence, beneficence, and justice, this liberal indi-vidualistic ethical frame was established for patient-health professional relationships based on the premise that patients are pure autonomous agents. Korea legally codified considerations regarding research ethics within a very short period of time. Enacted in 2005 to regulate genetic and embryo research, the Bioethics and Safety Act of Korea was revised in 2013 to mandate informed consent and ethics review for research on human subjects, including public health research. Enforcement of the Bioethics and Safety Act has promoted the awareness of individual rights and interests in research. Although Korea is a family-oriented, collectively-minded society holding strong communitarian values, the individualist libertarian approach imported from Western societies has been dominant in the field of biomedical ethics." ] },{ "paper_id": "9547b74fb56cd1288d9af6facbd337148cf45895", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We also obtained data regarding each patient's age, sex, and major underlying associated diseases (as determined at autopsy)." ] },{ "paper_id": "954d000b2e7252ffb05812341a6436d3d784494a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9555f44156bc5f2c6ac191dda2fb651501a7bd7b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.", "In a large-scale cell-based screening campaign of alkylated, silylated, or acylated pyrimidine nucleosides, 2 0 ,5 0 di-O-trityluridine and 3 0 ,5 0 di-O-trytiluridine were identified as inhibitors of DENV-2 and YFV replication, showing high antiviral potency and favorable cytotoxicity profiles in Vero cells. 78, 102, 103 Substantial antiviral effect against YFV was observed also in 2 0deoxy-3 0 ,5 0 -di-O-trityluridine and in several 5-halogenated bis-tritylated pyrimidine nucleosides; however, their anti-DENV activity was proven to be weaker. 104 Thymidine or 2 0 -deoxyuridine congeners of 2 0 ,5 0 -and 3 0 ,5 0 -tritylated nucleosides led to the loss of antiflavivirus activity or to increased compound cytotoxicity.", "The mechanisms of action of tritylated nucleosides are not completely understood. Based on the observed inhibition of DENV replication in subgenomic replicon assays, it is assumed that these compounds may be acting as inhibitors of intracellular viral replication events rather than suppressing either early or late processes of viral infection, such as entry or assembly. 103 Although the presence of large, hydrophobic trityl moieties does not make these structures ideal candidates for further drug development, their chemical structures may provide valuable information for advanced mechanistic studies and for further development of related nucleoside scaffolds with improved biological parameters. 104 " ] },{ "paper_id": "955a11ffa21e8ea71e2dd4ed9b59ebc6a8990535", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A disease-associated mutation triggers the ERAD of Kir2.1", "The intracellular residence of Kir2.1 was determined by sedimentation in a sucrose gradient essentially as described (Sullivan", "To analyze experiments performed in HeLa cells (Figure 6 ), statistical analysis was performed using Prism (GraphPad, La Jolla, CA). Statistical significance was determined by one-way analysis of variance (ANOVA) and Tukey's post hoc test in G and two-way ANOVA and Bonferroni post tests in H." ] },{ "paper_id": "956f777cf3a26f2989c840cbb927ac552b95732e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Fisher's and Pearson's \u03c7 2 tests were used to assess the associations. The probability level to determine statistical significance was considered to be 0.05 and the statistical analyses were performed using IBM SPSS Statistics for Windows, version 20.0 (IBM Corp., Armonk, NY, USA).", "Thirty-one patients had multiple (more than one) admissions. All of them except one were associated with rhinovirus detection. The only one reported was due to RSV.", "Viral RNA and DNA were extracted together using the High Pure Viral Nucleic Acid Kit (Roche, Mannheim, Germany) from respiratory samples according to the manufacturer's recommendations, and 100 \u03bcl of nucleic acids was eluted. For RNA viruses, cDNA was synthesized using Superscript III reverse transcriptase (Invitrogen, Carlsbad, CA). The extracted genome elutes and cDNA were stored at \u221220\u00b0C for further studies with conventional and real-time polymerase chain reaction (PCR).", "The study protocol was approved by the ethics committee of the hospital. Legally authorized representatives of the children provided informed consent.", "The typical viruses to cause exacerbations are rhinovirus, RSV, influenza, coronavirus, and parainfluenzavirus [12] . Our previous study on hBoV in children with asthma exacerbation revealed that the detection rate of hBoV was 6% of studied subjects [9] ." ] },{ "paper_id": "9572c5aae9bef12492279374fa1f562a03eafd08", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "95a06052b68c5712d187bd826376e31dbe8ced00", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "tracheal epithelial cell / infectious bronchitis virus / basal cell / primary culture / glycosaminoglycan", "Embryonated egg inoculation is commonly used to amplify avian RNA viruses. Successful viral replication mainly depends upon viral adaption to and replication in the cells of the embryonic and extraembryonic tissues. Growth retardation and malformation of the embryo are the main indicators of viral reproduction in this system and signal the proper period for harvesting the amplified virions from the amniotic or chorioallantoic fluids." ] },{ "paper_id": "95b9bac4d7a86402203e36f44eb826352f406b13", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "95c40fb092ef550e2c0d8316a3af2d6c025df87d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "95cc4248c19a3cc9a54ebcfa09fc7c80518dac5d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Coronaviruses (CoVs) have caused a major outbreak of human fatal pneumonia since the beginning of the 21st century. Severe acute respiratory syndrome coronavirus (SARS-CoV) broke out and spread to five continents in 2003 with a lethal rate of 10% 1, 2 ", "CoVs contain at least four structural proteins: Spike (S) protein, envelope (E) protein, membrane (M) protein, and nucleocapsid (N) protein 10 . Among them, Spike promotes host attachment and virus-cell membrane fusion during virus infection. Therefore, Spike determines to some extent the host range.", "Theoretically, the drugs found through these therapies would exhibit better anti-coronavirus effects, but the research procedure of new drug might cost several years, or even more than 10 years 11 ." ] },{ "paper_id": "95cf6b3c44e05dc3bf6d1e5e3f912af5a7fa8a36", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "vaccine platform for the development of vaccines with protective activity against multiple flaviviruses.", "LNP formulations were prepared by ethanol drop nanoprecipitation on a microfluidic mixer (Precision Nanosystems). Briefly, lipids were dissolved in ethanol at molar ratios of 50:10:38.5:1.5 (ionizable lipid: structural lipid: sterol: PEG-lipid) and mixed with mRNA in 50 mM citrate buffer, pH 4.0, at a ratio of 3:1 (aqueous:ethanol). Formulations were dialyzed against 20 mM Tris-Cl, pH 7.4, containing sucrose (8%) in dialysis cassettes for at least 18 h. Formulations were concentrated using Amicon Ultra Centrifugal Filters (EMD Millipore) and sterile filtered through 0.22-mm filters. All formulations were tested for particle size, RNA encapsulation, and endotoxin and were between 80 to 100 nm in size, with greater than 90% encapsulation and < 10 EU/ml of endotoxin.", "LGTV primers were 5\u2032-GGAACTAGGCCTTGCAGAAT-3\u2032, 5\u2032-TGTT CTCCATTGTCGGGTTAG-3\u2032, and probe 5\u2032-/56-FAM/TGAGGTTAA/Zen/CGTGGCCATGCTCAT/3IABkF-3\u2032.", "Cells-Cell lines were maintained at 37\u00b0 C in the presence of 5% CO2. HEK293T cells were passaged in Dulbecco's Modified Eagle Medium (DMEM) (Invitrogen) supplemented with 10% fetal bovine serum (FBS) (Omega Scientific) and 100 U/mL penicillinstreptomycin (PS) (Invitrogen). Vero cells were passaged in DMEM supplemented with 5% FBS and 100 U/mL P/S. Raji B lymphoblast cells stably expressing the C-type lectin DC-SIGNR (Raji-DCSIGNR) were cultured in RPMI 1640 medium (Invitrogen) supplemented with 7% FBS and 100 U/mL P/S." ] },{ "paper_id": "95ec993129c313d381f4065b6391f0fd40bedab5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "no. 12156792910) from Sigma Aldrich (St. Louis, MO) was performed according to the manufacturer's instructions.", "As fibrosis is an outcome of so many distinct disease states, it is considered a leading cause of death (Tsou et al., 2014) .", "Vimentin has emerged as a critical regulator of the woundhealing process in many distinct tissues and cell types. In studies of skin wound-repair, this protein has been demonstrated to function as a signaling integrator in tissue regeneration and healing" ] },{ "paper_id": "95f7c797080ddb8d466a88443df62ea97f46d932", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nucleic Acids Research, 2019 , Vol. 47, No. 5 2683 ", "NTPase assay. NP868R recombinant protein (0.5 M) was incubated with 0.5 Ci [\u2423-32 P]-GTP or [\u2423-32 P]-ATP in 50 mM Tris-HCl (pH 8.5), 5 mM DTT, 5 mM KCl supplemented or not with 2.5 mM MgCl 2 and incubated at 37 \u2022 C. Reaction was stopped by adding an equal volume of formamide/EDTA gel-loading buffer, and hydrolysis products were separated over a 20% polyacrylamide/8 M urea gel prior to phosphorimaging using FLA3000 instrument (Fuji, Tokyo, Japan).", "MTase assays. MTase activity assays were performed by combining 0.5 M of enzymes with 1 M of GpppAC 4 or mGpppAC 4 The products were spotted onto polyethylenimine cellulose TLC plates (Macherey Nagel, D\u00fcren, Germany), and resolved using 0.65 M LiCl as mobile phase. The radio-labeled caps released by nuclease P1 were visualized using a Fluorescent Image Analyzer FLA3000 phosphorimager." ] },{ "paper_id": "963c0263d2acd998d323aabd13c7c103bb44f6d3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Networks analysed. Model networks and real networks we used are described in Supplementary Note 10 and Table 1 .", ". In close analogy to the SIS dynamics, we have", "where U has the same form as in equation (6), but Y and X are given by", "Compressed sensing. The general problem that CST addresses is to reconstruct a vector XAR N from linear measurements Y about X in the form" ] },{ "paper_id": "9660e4d54d854be62dc2e3ec086d1132a741efd9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "IL-35 is a dimeric protein consisting of p35 of IL12 and Epstein-Barr virus induced 3 (EBI3) subunits which are encoded by P35 and EBI3, respectively [1, [14] [15] [16] . The affinity of two subunits (p-35 and EBI3) to form a heterodiamer was first explained by Devergne et al. in 1997 [17] . Interestingly, two subunits of IL-35 from human and mice can bind to each other, which explain its conservation between species [18] .", "Immune cells consist of multiple checkpoints where distinct types of immune cell(s) are responsible for any unwarranted entry. Like security blankets, immune system cells work in number of layers with each layer responsible for sustainability of respective microenvironment and destruction of unwanted endogenous and exogenous substances [41] . Hence functions of immune system cells is not restricted to killing the foreign substances brazenly, but also to evaluate the antigens, recognize and establish the self tolerance, maintain homeostatic conditions and even regulate the functions of other tissues. Such large scale intelligent modulation by immune system is largely exercised through its regulatory wings namely Tregs and Breg cells [42] [43] [44] [45] .", "Immunosuppressive effects of IL-35 have been linked with progression and amelioration of various diseases. However, the single most vital role that has grabbed attention of scientific community is implication of IL-35 in cancer milieu. The aim of this review is to summarize and analyze important published data on IL-35 effects on cancer progression and tumor microenvironment.", "Although ongoing symphony of IL-35 effects on cancer is still in infancy and are not well understood yet few studies have pointed the possible targets against IL-35. For instance, a group of scientist has showed that IL-15 can help enhance cytotoxicity of CIK cells via suppressing Treg cells and IL-35 concomitantly [108] . Understanding IL-35 and its signal transduction can be helpful in the formulation of vaccines against various inflammatory ailments including particular kind of cancers [109] ." ] },{ "paper_id": "9665e16e8fd0e3198298f64f70cc9180d1cea36a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "There are currently two different types of microarrays commonly in use. The re-sequencing microarrays can identify base changes in an emerging strain by interrogating every base", "Genotyping of large genomes did not take off until the development of in situ probe synthesis and immobilization techniques mentioned above by Maskos and Southern [25] , Pease et al. [26] , and Nuwaysir et al. [27] . In our study, we sought to take advantage of the high resolution power of the tiling array to differentiate among viral subtypes, which is particularly challenging for other traditional methods.", "I strains. In addition, strong hybridization to genogroup IIspecific probes derived from Saitama U17 strain with accession #AB039779 was identified in NoV#186. The phylogenetic tree of the PCR product by genogroup IIspecific primers indicated that NoV#186 amplified by G2SKF and G2SKR was clearly grouped into GII (Fig. 4C) in which it showed highest sequence similarity to Saitama U17 strain. This phylogenetic relationship is also reflected by the microarray hybridization pattern." ] },{ "paper_id": "96a2891a55f0d6076cd89b09e8571d4ce262fbc7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In this study, we investigated the presence of paramyxoviruses in the Eidolon helvum bats captured over a period of 4 years (2008-2011) from KNP (S15:34.688 E28:16.513). During that period, a total of 312 spleen samples were collected from the same number of bats (Table 1) . Appropriate research permits and hunting licenses were obtained from the Zambia Wildlife Authority (ZAWA).", "In conclusion, we report the identification of novel Henipavirus-related (n=5) and unrelated (n=2) viruses in fruit bats from the KNP using RT-PCR. The viruses identified in this study were shown to originate from wide geographical areas, and their presence in fruit bat species might pose a public health risk and as such, continued surveillance of these viruses in fruit bats in essential. The results presented are for the semi-nested RT-PCR-based Paramyxovirinae detection system. Samples shown in this table were collected from the spleens of Eidolon helvum fruit bats. ", "In this study, we describe the detection of novel paramyxoviruses from the Eidolon helvum species of fruit bats. We extracted RNA from 312 spleen samples from bats captured in Zambia over a period of 4 years (2008)(2009)(2010)(2011). Semi-nested RT-PCR detected a total of 25 (8%) positive samples for paramyxoviruses which were then directly sequenced and analyzed using phylogenetic analysis. Among the positive samples, seven novel paramyxoviruses were detected. Five viruses were closely related to the genus Henipavirus, while two viruses were related to the unclassified Bat paramyxoviruses from Ghana and Congo Brazzaville. Our study identified novel Henipavirus-related and unrelated viruses using RT-PCR in fruit bats from Kansaka National Park and indicated the presence of similar Bat paramyxoviruses originating from wide geographic areas, suggesting the ability of bats to harbor and transmit viruses. The presence of these viruses in fruit bats might pose a public health risk." ] },{ "paper_id": "96f65d71931741ea4668f2fbcae54a8d8905abac", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "97040e1e32165ddc6f5ac806f9d970c4141c561e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "97180e8069348d5c8f1db6a79d2dbe4d6a586cf5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Emerging new concepts have recently highlighted the need for a novel approach to our understanding of macrophage response. [34] [35] [36] Similar to T lymphocytes, which feature numerous cellular subtypes, macrophages also differentiate into several phenotypes. 37, 38 Cells belonging to distinct phenotypes are distinguished by expression of groups of markers that define each phenotype. Thorough elucidation of these groups of markers, or panels, has revealed that these phenotypes are distinguished by expression differences in chemokines, chemokine receptors, enzymes, costimulatory molecules, Toll receptors, cytokines, and cytokine receptors. [39] [40] [41] [42] [43] M1 macrophages express inducible nitric oxide synthase (iNOS), the primary marker that confirms the response of these cells in a specific disease (Table 1) . [44] [45] [46] However, a surface marker that defines the identity of M1 macrophages has not yet been identified.", "Response, bacterial killing 48-50,72-78-82 M2 LPS, IL-4, IL-10, IL-13 pSTAT6, pSTAT1, ifr4, Socs2, ccl17, Ccl22, Ccl 24, Arg1 . IRF4, SOCS1, GATA3, CCL4, CCL13, CCL17, CCL18, MRC1, STAB1, MARCO, CD163, FN, TGFB1, MMP1, MMP12, TG, F13A1, TGM2, ADORA3, TGFBR2, IL17RB, ALOX15, ", "Among the phenotypes of M2 macrophages, M2a, M2b, and M2c macrophages are characterized by the presence of arginase (Arg). [47] [48] [49] These subpopulations express a cell-surface scavenger receptor that recognizes haptoglobin-hemoglobin complexes used to identify M2 macrophages and is labeled with CD163. Moreover, a previously unrecognized subpopulation of M2 macrophages, M2d, has been described, but the molecules responsible for the differentiation of M0 macrophages into M2d macrophages remain unknown. However, this population participates in the angiogenesis response, producing interleukin (IL)-10 and vascular endothelial growth factor (Table 1) . [50] [51] [52] Macrophages are capable of differentiating into six additional subpopulations: regulatory (Mreg), hematophage-associated (Mha), oxidative (Mox), M3, M4, and M17 macrophages (Table 1) . [53] [54] [55] [56] Mreg macrophages respond to the stimulation of Treg cells and are responsible for inducing the repair response and inhibiting triggering of mechanisms that produce pro-inflammatory cytokines in tissue lesions. [57] [58] [59] Mox macrophages differ from the other cell types in expressing oxidized 1palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine and producing HO-1 and sulfiredoxin-1. [60] [61] [62] Mox macrophages are also associated with triggering of oxidative responses (Table 1) . [60] [61] [62] Table 1 Macrophage phenotypes, stimulating factors, genes, primary markers, and functions described in the scientific literature Pro-inflammatory" ] },{ "paper_id": "972a4e182f215c25fe41c9e0716a2f14ffd2ed9c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We analyzed 835 635 web pages and 2943 pages associated with our topics. Their distributions are shown in Supplementary Figure S3 and Supplementary Table S1. Shanghai has 922 pages with live poultry trading information. Surveillance of the web sites revealed that live poultry from Shanghai came from Jiangsu, Zhejiang, and Anhui Provinces. The noise of these queries was 45.17% and was determined through the method of excluding words from our search. Thus, we collected a considerable amount of accurate data versus the amount of noise data.", "Through infoepidemiology, high-throughput online data associated with the live bird trade are collected by a distributed focused crawler, and we used these data to estimate the activity of trading links between provinces or cities by analyzing the frequency of their co-occurrences in one web page. We also collected all public online information in which clear trading traces were directly observed as a control for use in further analysis. All queries used in this project can be found on a web site available to the public. The database retains no information about the identity, Internet protocol address, or specific physical location of any user.", "Information-based connection by a distributed focused crawler After CC data were collected, we first analyzed the information online using the distributed focused crawler technology from 244 public news web sites as well as 56 forums and microblogs, including common sites such as ''Sina,'' ''Sohu,'' and ''Yahoo.'' Keywords were used to select online knowledge and entered using the following format: (city name) and (live poultry or poultry or dove or quail or birds or migratory bird or chicken or duck or goose) and (come from or exchange or source or carrier or travel or supply or market or slaughterhouse or production area). The pages that fit our requirements were included in the hash list. A bloom filter was used to adjust and remove repeated information. These pages were clustered with a support vector machine model and categorized into different groups to analyze the orientation of web pages. These confirmed web pages were then downloaded and coordinated by Apache ZooKeeper (The Apache Foundation, Delaware, US)." ] },{ "paper_id": "974de2ddd9575e32633a8038613f4e8f4333a70f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The data are presented as the means \u00b1 standard deviations and number of patients (%). Differences between the two study groups were assessed using an unpaired t test for continuous outcomes and Fisher's exact test for proportions. All p values were two-sided and all analyses were performed with the use of GraphPad Software, version 3.05 (GraphPad Software, San Diego, CA, USA).", "As in many other countries in Latin America, the Brazilian population has been seriously affected by dengue infections. Indeed, approximately 80% of the reported dengue cases in the Americas occur in Brazil and more than one million cases have been reported in all five Brazilian geographic Regions in the last few years (Schatzmayr 2000) .", "online | memorias.ioc.fiocruz.br Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 108(5) : 596-599, August 2013 Dengue is the most important arthropod-borne viral infection of humans and represents an important public health problem in tropical and subtropical areas. The World Health Organization estimates that approximately 2.5 billion people in 100 countries are at risk of infection. It is reported that over 100 million people are infected with dengue viruses (DENV) every year; of these individuals, 500,000 develop a severe form, leading to approximately 20,000 deaths annually (Pinheiro & Corber 1997) .", "This trial is registered with ClinicalTrials.gov (NCT00849602). The study was approved by the Ethical Committee of the Clinical Hospital of the School of Medicine of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, process 12603/2006, and written informed consent was obtained from all participants.", "Side effects were reported by only two patients and consisted of transient blurred vision in one and a loss of consciousness in the other. The latter patient was severely dehydrated and seizure was ruled out based on clinical presentation and follow-up. Both patients were not confirmed to be dengue patients. (63) 0 (0) e a: dengue was confirmed when at least two diagnostic tests (reverse transcription-polymerase chain reaction, IgM antibody capture ELISA and the non structural 1 antigen detection) were positive; b: p > 0.05; c: axillary temperature was considered abnormal (fever) when \u2265 37.8\u00baC; d: clinical variables were obtained active and objectively during a medical consultation by using a research form; e: p = 0.0004; SD: standard deviation." ] },{ "paper_id": "975a8b4abe4cc0181522e859a92c5ddc22f50c29", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Provenance and peer review Not commissioned; externally peer reviewed.", "Participants: All UK cattle farmers were eligible to participate in the study." ] },{ "paper_id": "977370a5432431d0680323ce3f9e67db65f5f7b1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.00737-13/-/DCSupplemental. Figure S1 , PDF file, 1.6 MB. Figure S2 , PDF file, 0.8 MB. ", "Nucleotide sequence accession numbers. The complete genome sequences of the three U.S. PEDV strains have been deposited in GenBank under accession no. KF468752 (MN), KF468753 (IA1), and KF468754 (IA2).", "The significant amino acid changes at the NTD of the S gene differentiate G1 and G2 (Fig. 1C) . Comparison of antigenic index profiles of the NTD between the two genogroups indicated that the second deletion region (DR2) appears to have a higher degree of antigenic change than DR1 and has the distinct N-linked glycosylation site, although DR1 has higher sequence variability (Fig. 1C) . Therefore, the attenuated PEDV vaccines based on the historical CV777-derived G1a strains or DR13-derived G1b strains may be antigenically less related to the newly emergent G2 PEDV strains that have antigenic variations in the NTD." ] },{ "paper_id": "9791d7ab94765e2012facc4084c479cedbdfaf5e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9794fdd25bf5ce08230e7f62838876ca45d05b87", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "97a1bf0cca7e6b48364be99814a22a5440c521f3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.00549-12/-/DCSupplemental. Figure S1 , EPS file, 1.3 MB. Figure S2 , EPS file, 2.8 MB. Figure S3 , EPS file, 2.6 MB. Figure S4 , EPS file, 6.6 MB. Figure S5 , EPS file, 1.3 MB. " ] },{ "paper_id": "97b7ac41d4b2537b9b38666adc27439a808234a5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Bovine respiratory disease complex (BRDC) is one of the most prevalent cattle diseases, causing large economic losses in the cattle industry worldwide. For example, BRDC is estimated to account for 70-80% of all feedlot cattle morbidity and 40-50% of all cattle mortality, resulting in a loss of greater than US $500 million per year in the United States [16, 22] . In Japan, number of illness in the statistics mutual aid for livestock owners in 2014 reported by the Ministry of Agriculture, Forestry and Fisheries indicate that respiratory diseases accounted for 23% of illness in cattle (http://www.maff.go.jp/j/tokei/kouhyou/katiku_kyosai/) (in Japanese). Despite considerable research and attempts to manage hygiene to prevent BRDC, these measures have had a limited effect on reducing the impacts of this disease [29] .", "One of the difficulties in investigation and prevention of BRDC is its multi-factorial etiology, based on host interactions with multiple pathogens, such as virus and bacteria, including mycoplasma. The primary viral infection sometimes results in clinical symptoms, and it was exacerbated by secondary infections with bacterial pathogens [10] . Stressors, such as transportation, and host factors, such as nutritional status, raise the risk and severity of BRDC [17, 28] . Viruses, which are commonly associated with", "BRDC, include bovine viral diarrhea virus (BVDV), bovine coronavirus (BCoV), bovine parainfluenza virus 3 (BPIV-3), bovine respiratory syncytial virus (BRSV), bovine herpesvirus 1 (BHV-1), and bovine adenovirus 3 (BAdV 3) and 7 (BAdV 7) [12, 28] . In addition, a metagenomic approach to BRDC in cattle recently revealed that several other viruses may be involved in BRDC, such as influenza D virus (IDV), bovine rhinitis A virus (BRAV) and bovine rhinitis B virus (BRBV) [13, 23] . Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Trueperella pyogenes and Mycoplasma bovis are bacteria consistently associated with BRDC [1, 11] . Ureaplasma diversum has also been isolated from BRDC cattle [8] . Infection with each single pathogen does not necessarily result in appearance of symptoms, but complex infections with a variety of pathogens, including the indigenous agents, develop severe conditions. Such multiple pathogens infection make it difficult to identify the etiology of BRDC rapidly." ] },{ "paper_id": "98227f184bc6a0b098b4ae6387f97264aaf13654", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Fluorescence imaging was carried out using a laboratorybuilt objective-type, wide-field total internal reflection fluorescence (TIRF) microscope system (30, 38) . It is equipped with a double channel imaging system with a diode-pumped 532 nm laser as an excitation source. An oxygen-scavenging system (300 g/ml glucose oxidase, 40 g/ml catalase and 1% \u2424-D-glucose; Sigma) and 250 nM GTP were supplemented to the Tris\u00b7polymix buffer along with a tripletstate quenching mixture (1 mM 1,3,5,7-cyclooctatetraene (Aldrich), 1 mM p-nitrobenzyl alcohol (Fluka), 1.5 mM Trolox (Sigma)). All the experiments were carried out with time resolution of 35 ms/frame except that the (Cy5)EF-G concentration dependent experiments were carried out with 100 ms/frame. Excitation powers were adjusted to be 4 mW for 100 ms/frame and 6.5 mW for 35 ms/frame to maintain relatively high signal-to-noise ratios. Half-lives of Cy3 until photo-bleached were measured to be \u223c90s and \u223c60s for 100 ms/frame, and 35 ms/frame, respectively.", "Escherichia coli 70S (35) and initiation factor proteins (36) purified as per protocols described in the literature were kindly provided by Harry F. Noller and Laura Lancaster (University of California, Santa Cruz). EF-Tu was purified with a His-tag as described in the published protocol (37) . tRNAs (ChemBlock; Sigma; MP Biomedicals) were aminoacylated with S-100 enzymes and purified by acid-saturated phenol-chloroform extractions (35) . (Cy3)tRNA Lys was prepared by labeling at the natural modification of the 3-(3-amino-3-carboxypropyl) uridine at position 47 (acp3U47) with Cy3 NHS ester and purified with hydrophobic interaction chromatography on FPLC (19) . Purified EF-G was labeled with a Cy5 dye at the C-terminus via the Sfp phosphopantetheinyl transferase reaction according to the published protocols (34) . The pET-SUMO-EFG-peptide plasmid, encoding the peptide-tagged EF-G for the labeling, was kindly provided by S. Blanchard (Cornell University). mRNAs were prepared by in vitro run off transcriptions on synthetic DNA sequences using T7 promoter.", "Tris\u00b7polymix buffer (50 mM Tris\u00b7OAc, pH7.5, 100 mM KCl, 5 mM NH 4 OAc, 0.5 mM Ca(OAc) 2 " ] },{ "paper_id": "9826361eeccaade32208880c9b1907b71bd2cf79", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Reduction of adenoviral infection by more than 95% if administered at 50 \u00b5g/ml with an IC50 15 \u00b5g/ ml (Bastian and Schafer, 2001) .", "Abstract Review", "Irreversible effect on virion infectivity by direct binding to viral particle and downmodulation of the" ] },{ "paper_id": "983df610328c1e73e3c12546d42a14d520844f9b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For S/P ratio ", "ARTICLE HISTORY" ] },{ "paper_id": "98513efd2f4e86626a263f1eb350ed2702ecb8ec", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.00473-12/-/DCSupplemental. Figure S1 , DOC file, 0.1 MB. Table S1 , DOCX file, 0.1 MB.", "Citation van Boheemen S, et al. 2012. Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. mBio 3(6): e00473-12." ] },{ "paper_id": "98788dfeef7084c7c15a66c0f83b521f586bdde0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Immunoblot assay. The cell lysates or extracts were resolved by electrophoresis in polyacrylamide gels and transferred to nitrocellulose membranes. Membranes were blocked for at least 1 h in blocking buffer (PBS containing 5% milk or 2.5% bovine serum albumin [BSA]) and incubated with antisera against Bid (1:1,000), RelA (1:1,000), IB\u2423 (1:500), NS (1:750), cleaved caspase-3 (1:500), PARP (1:1,000), HMGB1 (1:500), tubulin (1:500), or PSTAIR (1:10,000) at 4\u00b0C overnight. Membranes were washed three times for 5 min each with washing buffer (Tris-buffered saline [TBS] containing 0.1% Tween-20) and incubated with a 1:20,000 dilution of Alexa Fluor-conjugated goat anti-rabbit Ig (for RelA, IB\u2423, caspase-3, HMGB1, and PARP), goat anti-mouse Ig (for PSTAIR and tubulin), donkey anti-goat Ig (for Bid), or IRDye-conjugated anti-guinea pig IgG (for NS) in blocking buffer. Following three washes, membranes were scanned and quantified using an Odyssey infrared Imager (LI-COR).", "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.00178-13/-/DCSupplemental. Figure S1 , EPS file, 1.6 MB. Figure S2 , EPS file, 7.2 MB. Figure S3 , EPS file, 5.8 MB. Figure S4 , EPS file, 0.8 MB.", "Thus, our studies reveal that two different events in the reovirus replication cycle can injure host cells by distinct mechanisms." ] },{ "paper_id": "998472a6428c367f65d047147899c5583db27ea2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Liu et al. Meta-analysis of genome-wide association data of bipolar disorder and major depressive disorder. Mol Psychiatry 2011; 16: 2-6 (a)", "Gene Name Immune Function of Gene ATP6V1B2 ATPase, H+ transporting, lysosomal 56/58kDa, V1 subunit B2", "Mice with targeted deletion of mGluR7 show enhanced sensitivity to glucocorticoid inhibitory feedback on the HPA axis, 43 which would be expected to reduce inflammatory signaling. This raises the possibility that mGluR7 signaling may support proinflammatory activity AK294384 similar to Muskelin 1 (MKLN1)" ] },{ "paper_id": "99be48475fc986f16d752a56ceeed588e4f74818", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Serum samples were collected from dromedary camels (n=38; mean age, 4.3 years; range, 1-13 years), goats (n=25; mean age, 3.9 years; range, 1-8 years), sheep (n=25; mean age, 2.7 years; range, 1-4 years), and cattle (n=15; mean age, 6.7 years; range, 1-11 years) from two herds in Bati district, Amhara region, and one herd in Fafen district, Somali region, Ethiopia. All animals appeared healthy, shared the same pasturage during the day, and stayed in barns or small grounds specific for each animal species surrounded by fences at night.", "Transportation of the serum samples to Japan was conducted with the permission of the Japanese government (Animal quarantine inspection number NFIB070602-011) and followed the rules and regulations of the OIE/FAO for biological sample transportation.", "Serum from a rabbit immunized with recombinant MERS-CoV S protein was used as a positive control for neutralization [8] . Sera from animals (5 cattle, 5 sheep and 5 goats) reared on the attached farm of Nihon University were used as negative controls." ] },{ "paper_id": "99da54318cd9e891d43f15d7b96365e2a2e9740d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "99fded56685ed6b4746525a997568696de2befd4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Using the species distribution shape files from the IUCN website (http://www.iucnredlist.org/technical-documents/spatial-data) and the R packages 'sp' and 'rgeos' (Pebesma & Bivand 2005 ), a sympatry matrix was created. Each entry of the matrix was either a 1 if the two species' distributions overlap or a 0 if they do not.", "Generalised least squares (GLS) were used to examine correlates of viral richness per host species, degree and betweenness, while allowing for phylogenetic correlation to be incorporated into the error structure as described below.", "Because many life history traits are correlated, we performed principal components analyses (PCA) on the life history traits: logged body mass, maximum longevity, number of litters per year and litter size (separately for bats and rodents). The variables were rescaled to have unit variance before analysis in R using the 'prcomp' function (R Core Team 2012), and these principal components were then used in subsequent analyses. See Fig. S6 for PCA plots and Table S1 for loading values and variance explained by each principal component." ] },{ "paper_id": "9a0f63b592a07e5823715e548da6f3605faf2bbb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9a27c99f125072894ab9db357b4ff8858a11203d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The clinical data and images are presented under agreement of the patients.", "values of rRT-PCR was converted into RNA copy number of SARS-CoV-2. The detection limit of quantitative PCR reaction was 2,690 copies/mL. Detailed methods and values for the tests are presented in the Supplementary Data 1 and Supplementary Tables 1 to 3.", "In conclusion, we report a unique pattern of SARS-CoV-2 viral kinetics in URT and LRT specimens from first two patients diagnosed in Korea. While two cases were different in disease course, these data will provide valuable insight to understand the nature of this virus." ] },{ "paper_id": "9a494f17a77c5920be077ac59abc8a7546f4ee67", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9a4c0d0a76e1ecd99c5a45fe8ff2a96aeff0fc2b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Another well-studied example of -1PRF is on the dnaX mRNA of E. coli. The slippery site contains the SS motif A 1 AAA 4 AAG 7 encoding two Lys (AAA and AAG) in 0-frame, the downstream SL and an SDlike sequence upstream of the SS (Fig. 1A) [39, 55, 56] .", "The SS1 of HIV-1 was also reported to support -2PRF [16] . Because in those experiments, the frameshifting sequence was placed into an unnatural context followed by an antisense oligonucleotide-binding site, we were prompted to study the extent of alternative slippages on the native gag-pol mRNA frameshifting site [69] . HIV-1 gag-pol SS1 indeed allows -2 and even +1 slippage, but their contribution to the overall frameshifting efficiency becomes significant only when certain aa-tRNAs are omitted. Thus, alternative slippages on SS1 must follow the 'hungry' route of frameshifting.", "Here -1PRF likely proceeds via the one-tRNA (or 'hungry') slippage mechanism, as discussed above for dnaX, HIV-1 gag-pol (FFR) and SFV 6K (FFS). Interestingly, tRNA Gln(CUG) shows tissue-specific expression levels in humans, and the lowest concentration of this tRNA was detected in the brain region called striatum, which is the primary site for Huntington's disease [81] . In summary, the low level of the target tRNA is linked to the increased frameshifting levels and accumulation of the mutated huntingtin protein, thereby contributing to the disease severity in Huntington's patients." ] },{ "paper_id": "9a5d753bbf216af4c354c0aa460a2a127c1da0a8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Our findings illustrate how global health security, which relies on the capacity of all countries to rapidly detect and control public health threats, is critical to the US economy. Our analysis provides data that policymakers can use when deciding on programs to improve the prevention, detection, and response to outbreaks around the world and thereby help enhance global health security.", "For estimates of impact due to larger epidemics, McKibbin and Sidorenko 16 produced a wide range of estimates of economic impact for influenza pandemics of differing severity. These estimates ranged from approximately 1% for a ''mild'' pandemic (1968-like) to an average of approximately 8.3% for a ''severe'' pandemic (1918-like). The country-specific estimates of GDP losses for the latter scenario included 9.2% for Indonesia, 19.3% for the Philippines, and 26.8% for Hong Kong. These country-specific estimates are similar to the Ebola-related impact on GDP measured in West Africa (Table 2 ).", "Obviously, there is a great deal of variability from country to country and, over time, in the correlation between economic growth and trade. Assuming a lower impact of an infectious disease outbreak is, in our model, equivalent to assuming a less than 1-to-1 correlation between GDP and trade (see sensitivity analysis below)." ] },{ "paper_id": "9a6d14471d9c34da1c4f1bf4ef530a35f58ad863", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The RNA oligonucleotides used for gel mobility shift assay were as follows:", "Supplementary Data are available at NAR Online.", "Funding for open access charge: The Heart and Stroke Foundation (NA6164 to R.M.G.)." ] },{ "paper_id": "9a8ffb71928a37a550e689f36fa3196493e036fe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Most lipids and fluorescent probes were from Avanti Polar Lipids, and DiO, DiI, DiD, and octadecyl rhodamine B chloride (R18) were from Invitrogen. MbCD, NEM, and fluorescein isothiocyanate-, Alexa 647-, or Alexa 555-labeled CTxB were purchased from Sigma-Aldrich. Formaldehyde and DTT were purchased from Avantor and RPI, respectively. Alexa 488-labeled CD4 antibody and Alexa 647labeled CCR5 antibody were purchased from Novus Biologicals. HIV entry inhibitors (maraviroc and enfuvirtide), SCDase, and PLA2 were purchased from Sigma-Aldrich. HIV fusion peptide was custom-synthesized by the Yale W.M. Keck Biotechnology Resource Laboratory.", "Finally, this work also showed that GPMVs and a novel procedure to produce supported planar GPMV-derived membranes that we call SPPMs are very useful to study the selected targeting and membrane fusion of HIV virions. We anticipate that these methods will also be useful to study the binding, fusion, and properties of many other particles on cell-derived plasma membranes. The new approaches are versatile and should lead to many new discoveries regarding the role of lipid and protein heterogeneity of cell membranes. They may also serve as novel platforms for screening of viral entry inhibitors. ", "blebbing buffer for 1 hour at 37\u00b0C. Following shaking, solutions containing cell-detached GPMVs were gently decanted into a 50-ml tube. The GPMVs were placed on ice for 30 min to settle relatively large GPMVs (~10 mm in diameter), which were then transferred from the bottom of the tube to coverslips for observation on an epifluorescence microscope.", "The integrity of the SPPMs and the diffusion of the lipids within them were examined by fluorescence recovery after photobleaching (FRAP). Bilayers were bleached in a pattern of parallel stripes, and the data were fit to the model F(t) = F \u221e + (F 0 \u2212 F \u221e )exp(\u2212Da 2 t), where F 0 and F \u221e are the initial and final fluorescence intensities after bleaching, respectively, a = 2p/p, p is the stripe period (12.7 or 3.2 mm), and D is the lateral diffusion coefficient. The mobile fraction (mf), which reflects the percentage of observed fluorescence recovery within the time frame of a FRAP experiment (<1 min), is given by mf \u00bc F\u221e\u00c0F0 F pre \u00c0F 0 \u00c2 200, where F pre is the fluorescence intensity before photobleaching. Ten regions on three independently prepared bilayers were sampled to determine the reported average values." ] },{ "paper_id": "9adb9a55bc7756ff69f23f66796941b73f40f4a1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9afa3940a6e7c461b7b6acfef9de23db0e420462", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9b18c2064a44deefb8f0975a3309d6e5cbf97c36", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9b1db58b45ac9db3de3c103db7e9de544c6c3eea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9b2f83db4c307ae17c146bb6625ddb01474bbd9a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.", ". Therapeutic antibodies are increasingly used for the treatment of infectious diseases as they are well-established and well-tolerated by humans.", ". Therapeutic antibodies targeted against similar antigenic targets may differ in clinical profile, depending on the type of FcgRs that are engaged." ] },{ "paper_id": "9b49622e8c16b0e941616d09e9ccdcfbc5d5ff0c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Patient 19 achieved a chimerism of 60% 6 weeks post-NST but this decreased to 12% by day \u00fe 111. He attained a late PR on day \u00fe 101 with a more than 75% reduction in Table 2 Transplantation-associated adverse events tumor diameter. Chimerism improved from 12 to 62.5%, 18 days after the PR that was related to mild GHVD.", "Pearson w 2 -test or Fisher's exact test was used to test the association between categorical variables, whereas Mann-Whitney U-test was used to test the difference of continuous variables. Best overall tumor response rate was summarized with 95% confidence interval using the Wilson method. 22 Survival and response curves were estimated by the Kaplan-Meier method and comparisons between curves were tested by log-rank test.", "The authors declare no conflict of interest." ] },{ "paper_id": "9b635859a59cb70b756b0768ec74405e226b5568", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Fluorescence-conjugated donkey antibody against sheep IgG and teleostean gelatin (from cold water fish skin) and cycloheximide was purchased from Sigma Chemical Co. (St. Louis, MO). Falcon (Beckton and Dickinson, Lincoln Park, NJ) and Nunc (Roskilde, Denmark) plasticware were used in cell culture. 35S-labeling L-methionine was purchased from Amersham (Braunschweig, Germany). Streptomyces splicatus Endo-/~-N-acetytglucosaminidase H (endoglycosidase H), produced in recombinant E. coli, was purchased from Boehringer-Mannheim (Mannheim, Germany). Brefeldin A (BfA) was purchased from Epicenter Technologies (Madison, WI). Molecular weight markers used in PAGE were the prestained molecular mass marker mixture for range 20-180 kD (Sigma Chemical Co.) and 14CH3molecular mass standards for the range 14.3-200 kD (Amersham),", "Washed immunoprecipitates were suspended in 50/~1 of electrophoresis sample buffer containing 200 mM Tris, pH 8.8, 5 mM EDTA, 1% SDS, 10% (wt/vol) sucrose and 0.1% (vol/vol) bromopbenol blue, with 40 mM DTT (to reduce the disulphide bonds) or without (for nonreduced samples), and incubated at 95~ for 5 rain. It is necessary to use this concentration of IYrT to fully reduce mature HBsAg. After heating the samples were cooled on ice and 10 #1 of iodoacetamide (500 mM) was added to each of the samples to block free thiols by acetylatlon. The samples were immediately mixed well on a vortex, and spun for 3 min at 14,000 rpm in an Eppendorf centrifuge before preparing the supernatant for electrophoresis." ] },{ "paper_id": "9b91bf56210db60e68b22d502496e4b20e80ff3f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Armonk, NY, USA). All statistical tests were two-sided, with a P value of <0.05 indicating statistical significance.", "Nasopharyngeal aspirates were obtained upon admission by gently flushing the children's nostrils with 4 mL of sterile saline solution. All nasopharyngeal aspirates were tested within 24 hours of collection for respiratory syncytial viruses (A and B), human metapneumovirus, human rhinovirus, influenza A and B viruses, parainfluenza (A, B, and C) virus, coronavirus (A and B), and adenovirus. Total viral RNA was extracted from nasopharyngeal aspirates (300 \u03bcL) using Viral Gene-spin Viral DNA/RNA Extraction Kits (iNtRON, Seongnam, Korea) and stored at -80\u00b0C. First-strand cDNA was synthesized using Revert Aid First Strand cDNA Synthesis Kits (Fermentas Inc., Burlington, ON, Canada), followed by polymerase chain reactions using Seeplex Respiratory Viruses Detection Kits-1 (Seegene, Seoul, South Korea) and the GeneAmp PCR system 9700 (Applied Biosystems, Waltham, MA, USA). Each 20 \u03bcL reaction mixture included 3 \u03bcL of cDNA, 4 \u03bcL of 5\u00d7 RV1A or 5\u00d7 RV1B primer, and 10 \u03bcL of 2\u00d7 Multiplex Master Mix. Briefly, 2.5 \u03bcL of extracted RNA was mixed with 5\u00d7 buffer, 0.2mM of each dNTP, 0.5\u03bcM of each primer [13] [14] [15] [16] , 1 \u03bcL of enzyme mix, and DEPC-treated ultrapure water to a final volume of 25 \u03bcL. After incubations at 50\u00b0C for 30 minutes and at 94\u00b0C for 15 minutes, the reactions were subjected to 40 cycles of denaturation for 30 seconds at 94\u00b0C, annealing for 90 seconds at 60\u00b0C, and extension for 90 seconds at 72\u00b0C, followed by a final extension at 72\u00b0C for 10 minutes. The ampli fied products were analyzed on 2% agarose gels containing 0.5 g/mL ethidium bromide.", "Lower respiratory tract infections (LRTIs) are common in early childhood and are mostly caused by respiratory viruses. Wheezing caused by viruses is considered an important risk factor for the development of asthma later in life [1] [2] [3] [4] [5] ." ] },{ "paper_id": "9b992705cb74945a376dfbcf616b8c213b0d6678", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Abbreviations: HIRA = Health Insurance Review and Assessment Service, HSP = Henoch-Sch\u00f6nlein purpura, PCR = polymerase chain reaction, RSV = respiratory syncytial virus.", "The patients diagnosed with HSP were categorized into the 4 age groups according to the classifications developed by the Eunice Kennedy Shriver National Institute of Child Health and Human Development: infant (0-2 years), early childhood (2-5 years), middle childhood (6-11 years), and adolescence (12-18 years). [16] " ] },{ "paper_id": "9bad339dd5a9605d61cc773ecfe0c65d4402f4b7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "R 0 and d were estimated using a Bayesian pseudo-likelihood approach as described by Bolker [12] , with 95% confidence intervals generated assuming a negative binomial distribution [13] . Models were updated each generation as new weekly data became available.", "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.", "In this study, we present a simple, phenomenological model for epidemic growth that we have described previously [10] , but which was not included in the above-mentioned competition. The model we present above has the advantage of being sufficiently simple that it can be constructed in standard statistical spreadsheet software." ] },{ "paper_id": "9c0ebc47e2a6b0592a18266c968e2aa28da9575e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All cell lines used in this study were obtained from the American Type Culture Collection (RoekviUe, MD). Ceils were cultured in DME (Biofluids, Rockville, MD) with 10% FBS, 100 U/mi penicillin, and 100 #g/ml streptomycin (complete medium).", "Protein localization to the TGN was inves-1. Abbreviations used in this paper: CGN, cis-Golgi network; DPAP A, dipeptidyl aminopeptidase A; TGN, trans-Golgi network.", "in these cells could be due to some level of proteolytic activity in intracellular compartments, or to the surface expression of the chimeric proteins in a fraction of the transiently transfected COS-1 cells." ] },{ "paper_id": "9c159594c91b5f2608137dd010930f11a9baf209", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Additional Supporting information may be found in the online version of this article: ", "1160" ] },{ "paper_id": "9c4444ada7a386ec68c8180c998e0b2ec44824d8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. data are presented as the mean \u00b1 Sd. Statistical analyses were performed using SPSS software (version 17.0; SPSS, inc.). differences between groups were analyzed using an unpaired Student's t-test or one-way ANOVA followed by Dunnett's post hoc test. P<0.05 was considered to indicate statistical significance.", "ALP and Alizarin red S (ARS) staining. BMScs were seeded at a density of 1x10 5 cells/well in 6-well plates and incubated with osteogenic medium. According to the manufacturer's instructions, alP staining was assessed using an alP staining kit (nanjing Jiancheng Bioengineering institute) on day 7.", "Flow cytometry was performed to identify BMScs by expression of cd34, cd45, cd73, cd90 and cd105 in the isolated cells. The percentages of cd73-positive cells, cd90-positive cells and cd105-positive cells were 99.8, 99.7 and 99.9%, respectively; while the percentages of cd34-positive cells and cd45-positive cells were 3.66 and 1.2%, respectively, indicating that the isolated cells were BMScs (Fig. 1) . " ] },{ "paper_id": "9c4c3663078fac75ec89955444e1bed1f069e751", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The purpose of our prospective observational clinical study was:", "All computations were done on SAS V.9.1 (Statistical Analysis System; SAS Institute GmbH, Heidelberg, Germany) (proc FREQ and proc LOGISTIC).", "Authors declare no conflicts of interest." ] },{ "paper_id": "9c4f25ca5cba3c28cd396f69bf49454ed15c19d4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Viruses are well-known to counter these defenses and manipulate the regulatory machineries or the modifications themselves (8, 9, 15) . For instance, Crimean Congo hemorrhagic fever virus (CCHFV), severe acute respiratory syndrome coronavirus, and Middle East respiratory syndrome coronavirus all encode proteases with dual deISGylase and DUB activity (16) .", "ubiquitin | ISG15 | viral signaling | FMDV | structure" ] },{ "paper_id": "9c6e96b1ba2b2e3a95621656bbf142cc11eb955a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The family Picornaviridae is highly diverse, currently comprising 17 genera, many of which consist of several species, subspecies and genotypes [1] . Kobuvirus is a newly recognized genus in the family Picornaviridae. Several studies have demonstrated that kobuviruses are transmitted through the fecal-oral route via the consumption of contaminated food or water, and they have a potential role in gastroenteritis in humans and animals [2, 8, 11] . Canine kobuviruses (CaKVs) have been recently discovered in dogs [10] , demonstrating that pets can be infected with members of this genus. At present, epidemiological investigations of CaKVs in dogs are important for understanding their pathogenicity and given the interactions between pets and humans, their zoonotic potential.", "Sampling: In total, 201 rectal swab samples were collected in diarrhoetic dogs from animal hospitals in three districts-Harbin, Daqing and Mudanjiang-of Heilongjiang province in northeast China from May 2014 to April 2015 using 3.5-ml commercial virus sampling tubes (YOCON Biological Technology Co.. Ltd., Beijing, China). Of the 201 samples, 141 were collected from 2 animal hospitals in Harbin, 20 were collected from one animal hospital in Daqing, and 40 were collected from 1 animal hospital in Mudanjiang. All rectal swab samples were stored at \u221280\u00b0C.", "RNA and DNA extraction: 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 (EP) 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. Genomic DNA was extracted from the supernatant using a commercial TIANamp Stool DNA Kit (Tiangen Biotech Co., Ltd.), according to the manufacturer's instructions. The extracted RNA and genomic DNAs were stored at \u221280\u00b0C." ] },{ "paper_id": "9c71b86e38ae06503c1dc05abea7743ef3e7851e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9cc0534fb1e5181fa20aa2891f5614deab6b87f8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9cd8c3706551ab124d7035449350556c72297e2e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The 5 0 -UTR of coronavirus genomic RNA interacts specifically with MADP1", "Cells were fixed at 10 h post-infection with 4% paraformaldehyde for 15 min and permeabilized with 0.2% Triton-X 100 for 10 min. Treated cells were blocked in 10% goat serum, stained with primary antibodies mouse anti-BrdU and rabbit anti-Flag (Sigma Aldrich) and subsequently probed with AlexaFluor 488 anti-rabbit and 594 anti-mouse (Invitrogen) antibodies. Images were captured with Olympus Fluoview Upright Confocal microscope using a sequential laser scanning protocol.", "Biotinylated RNA at 0.1 mM was incubated with cell lysates over-expressing EGFP, Flag-tagged MADP1 or its mutant proteins, respectively, in the presence of 10 mM dithiothreitol (DTT), 100 mg/ml yeast tRNA (Ambion) and 1 U/ml Protector RNase Inhibitor (Roche Applied Science) in a final volume of 200 ml at room temperature for 30 min. The mixtures were incubated with 40 ml (50% slurry) of streptavidin agarose beads (Sigma Aldrich) at room temperature for 30 min. The beads were collected by centrifugation and washed three times with RNase P (RP) buffer (50 mM KCl, 1 mM MgCl 2 , 10 mM HEPES, pH 8.0), suspended in 25 ml of sodium dodecyl sulfate (SDS) sample buffer with 100 mM DTT. Bound proteins were resolved by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and detected with appropriate antibodies.", "Template DNA was amplified from plasmid DNA encoding the 5 0 end of IBV genome with various sets of primers targeting different regions of the 5 0 -UTR (Tables 1 and 2) , with the sense primers containing the T7 promoter sequence (36) . Biotinylated RNAs were in vitro transcribed with T7 RNA polymerase (Roche Applied Science) in the presence of Biotin RNA Labeling Mix (Roche Applied Science) at 37 C for 2 h. Template DNAs were removed by digestion with RNase-free DNase I (Roche Applied Science) and the labeled RNAs purified with UltraPure Phenol:Chloroform:Isoamyl Alcohol (Invitrogen) then solubilized in nuclease-free water." ] },{ "paper_id": "9cda860c97d430aea207a063d13e8612e023320c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In the default setting, none of cattle introduced from outside was assumed to possess sufficient immunity to protect from BVDV infection because none would have been vaccinated. In several scenarios, a certain proportion of cattle in outside were assumed to be vaccinated; thereby they would possess enough immunity to protect from BVDV infection.", "Interestingly, regardless of the target population of compulsory testing, BVD prevalence under the control measure with BTM testing decreased and converged in a shorter period than that without it, though the process that resulted in BVDV prevalence convergence were different among the scenarios. These results would be a base of politic decision for selection of BVD control measures given the estimated cost for implementation, degree of risk reduction as well as terminated BVDV prevalence.", "In the default setting, we estimated that PIs and TIs were detected by clinical manifestation or outbreak investigation of newly infected herds. Herd screening using BTM testing was adopted in several scenarios as an optional diagnosis, but individual tests prior to communal pasture grazing were not adopted in this study. All the parameters related to diagnosis, including probability of clinical manifestation in each age group, test sensitivities of each diagnosis, and probability of outbreak investigation, were same as the previous study [19] .", "When comparing efficacies of compulsory testing of all cattle with those of only heifers, no large differences were observed in the median numbers of detected or missed BVD cattle cases at any level of vaccination coverage. The gaps in the costs between " ] },{ "paper_id": "9ceee77cb6dcbc0a9568b770103698bb7603c97d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Citation Alagaili AN, Briese T, Karesh WB, Daszak P, Lipkin WI. 2014. Reply to \"Concerns about misinterpretation of recent scientific data implicating dromedary camels in epidemiology of Middle East respiratory syndrome (MERS).\" mBio 5(4):e01482-14.", "In short, we stand by the data and conclusions that we have reported in mBio and are pleased that they may have contributed to the adoption of public health policies that will help in the containment of MERS-CoV transmission.", "We agree that the most urgent challenge at present is to investigate the epidemiology of human-to-human transmission. We are also actively pursuing studies focused on the analysis of other animal species for evidence of MERS-CoV infection. Nonetheless, the recent decision of the governments of the Kingdom of Saudi Arabia and Qatar to recommend against consumption of raw DC milk and to exert caution when interacting with DCs is prudent and appropriate. A similar recommendation was issued by the World Health Organization (22) ." ] },{ "paper_id": "9d12f3a201435c9d24dc9b356283edf8bd3a234d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All data were expressed as the average\u00b1standard error, and statistically significant differences between groups were analyzed by unpaired two-tailed Student's t-test for leukocyte population analysis or ANOVA and post-hoc testing for multiple comparisons of the mean. The statistical significance of cytokine gene expression was evaluated by Mann-Whitney test or unpaired two-tailed Student's t-test. A p-value\u22640.05 was considered significant. All data were analyzed using Prism software (GraphPadPrism4, San Diego, CA, USA).", "Mosquito-borne flaviviruses, including Japanese encephalitis (JE), West Nile (WN), and Zika viruses, are major current and emerging threats to millions of people worldwide. Among the neurotropic flaviviruses, JE virus (JEV) is considered the most serious because of its neurotropical impacts, higher fatality rate, and permanent neuropsychiatric sequelae (1) . The expanding geographical range of JEV and potential for outbreaks of JE in nonimmune populations demand an urgent effort to develop effective antiviral therapies or alternate strategies to limit the immunopathology of JE (2) . Indeed, considerable progress in immunopathological studies of JE has been made in both infected patients and murine models (3) (4) (5) (6) (7) (8) . JEV replicates in monocytes/macrophages and dendritic cells (DCs) as primary target cells (9) , and in these cells, the virus travels from the periphery to the central nervous system (CNS), where it causes neurological disorders (10) .", "The authors declare no competing financial interests. " ] },{ "paper_id": "9d36c9a5c87380ec6bb1cee77ced91fd6265d343", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9d651ee3cc003d22f9ffff68394494087112ec45", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "WNV was produced from an infectious cDNA clone according to methods described elsewhere (29) . Briefly, hamster BHK-21 cells (ATCC) were transfected (transMessenger, Qiagen) with RNA transcribed in vitro from pFLWNV (29) , using the mMessage mMachine T7 kit (Life Technologies, Carlsbad, CA). Cells were inspected daily and virus harvested after approximately 3 days of replication. Virus-containing tissue culture supernatant was supplemented with 20% FBS, stored at \u00c080 C in 1 ml aliquots and used without subsequent passage.", "Nasal washes were collected by study team members using similarly quantified-collection method as previously described (30) . The study was conducted with the approval of the University of Tennessee Institutional Review Board and included appropriate informed consent, complying with all relevant federal guidelines and institutional policies.", "All consensus genome assemblies generated as part of this project were submitted to NCBI's GenBank database (Accession numbers JX503071-JX503101). Illumina read data was submitted to NCBI's Short Read Archive under Trace Identifiers SRR513075, SRR513078, SRR513080, SRR513086-87, SRR513092, and SRR527699-726." ] },{ "paper_id": "9d8a94b596784c4280b895452b7f3d0e86b588b4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The incidence rates of cancers (2001-2014), communicable diseases (2003-2016), and noncommunicable diseases were retrieved, classified, and analyzed retrospectively during November 2017, based on data available with the Ministry of Health and were analyzed at the Imam Abdulrahman Bin Faisal University in Dammam, Kingdom of Saudi Arabia.", "The incidence rate of non-communicable diseases increased over the decade and was associated with increased mortality and disability, reduced quality of life, and increased health-care costs, indicating an urgent need to establish prevention and control programs. The rising trend in the incidence of cancers may also become a health care issue in Saudi Arabia in the coming years.", "Methods. Five most common diseases in cancer from cancer registry (2001 to 2014), communicable diseases from Ministry of Health Statistics Year Book (2003 to 2016) and non-communicable diseases from studies published in PubMed (1999 to 2017) were included in the present study. As the existing data from the database/registry were taken, no informed consent and institutional review board (IRB) approval were required for this study." ] },{ "paper_id": "9d9704846cfede2072a22a22c7bfcd99c0470d11", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9ddb63e47ae59fb8d315bfe119d9a1a3426af592", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9ddc6eddec3c91f53a24653e004620fad3a694ec", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "P.P., J.A., J.K., H.R., S.C.W., and A.S. are employees of Genzyme, a Sanofi Company.", "We thank Jennifer Tousignant for valuable comments on the manuscript.", "ATA experiments A 0.5 mmol/l stock of ATA (Sigma-Aldrich, St Louis, MO), generated in 100 mmol/l sodium bicarbonate water solution, was further diluted in DMEM \u00b1 10% FBS into concentration ranges of 12-60 \u00b5mol/l ATA (8.5-21 \u00b5g ATA/ml)." ] },{ "paper_id": "9e7e20f7b3fcd74b3f899215f18e096c30fec048", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9e91991355bc76a376b379387983a5ac08f179ab", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "concentrations, as there is no difference in the other uracil mutation frequencies.", "The quality for each sample/dataset was assessed using FASTQC (Hoffmann et al. 2009 ). The paired-end reads were merged for each sample and then filtered to exclude reads with unknown characters (anything other than A, T, C, G) and low quality (<10 quality score), so that only high quality reads were used during analysis. Additionally, the first 16 bases of each read were trimmed due to nucleotide bias.", "The analysis was performed using VEEV strain TC-83, complete genome (GenBank accession no.: L01443.1) (R. M. Kinney et al. 1989 )." ] },{ "paper_id": "9e9667fc7fcb441ee60a45d5cc2a8550205c9ad3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9e96c7b07f540611fcaccb80520fb7b3432d94b5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A DNA vaccine is currently licensed to immunize horses against West Nile virus [52] and has undergone Phase I clinical trials in humans [53] . DNA vaccines have also been evaluated as candidates against many emerging viruses, including EBOV [54] , RVFV [55] , Dengue virus [56] and CHIKV [57] .", "Immunization is arguably the most appropriate way of preventing infectious disease. The control of many important viral pathogens by vaccination is perhaps one of the outstanding achievements of medical intervention.", "Vaccine-induced immunity that is established in advance of virus infection relies primarily on adaptive immune responses for protective efficacy. Critically, vaccination depends on the properties of antigen recognition, activation, expansion, memory, trafficking and the multitude of specialist functions of lymphocytes. The extent to which vaccine-induced immunity is successful also determines the spread and maintenance of a viral pathogen within a population. Viral vaccines have had profound and enduring consequences for human and animal health; the worldwide eradication of smallpox and rinderpest are testament to their outstanding contribution to modern society.", "In 2014 the unpredicted size, speed and reach of the Ebola virus outbreak in West Africa [6] acted as a wakeup call for researchers, pharmaceutical communities and governments, emphasizing the importance of investment into the study of emerging pathogens. Spurred on by this development and at the request of its 194 Member States in May 2015, the World Health Organization (WHO) convened a broad coalition of experts to develop a research and development (R&D) Blueprint for Action to Prevent Epidemics. Focusing on severe emerging diseases with the potential to generate public health emergencies, and for which no, or insufficient, preventive and curative solutions exist, the R&D Blueprint specifies R&D needs, including vaccine research. Through international governance, the programme aims to define R&D roadmaps for prioritized pathogens and to catalyse funding strategies [7] .", "Surveillance work focusing on epizootics that are, or may become, human pathogens is a useful goal. Currently however, predicting which animal pathogens will become established as globally significant emerging human diseases is guesswork. Nevertheless, in the early stages of a new zoonosis, pathogenic viruses are often poorly adapted to their new human host in terms of sustained human-tohuman transmission [80] . This lag-phase in early zoonosis may, therefore, provide a window of opportunity to control the unrelenting zoonotic pressure of an emerging pathogen before it adapts further to humans. Vaccine targeting of the pathogen within the animal transmission species could therefore bring useful advantages." ] },{ "paper_id": "9ec258353291e981ef7eeb36111794c40b15c752", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9ee72a92dba63a2f7ba385612fa69e180dc8ab09", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nonetheless, the turn of events with the Ebola outbreak and matters arising therefrom raise a number of issues pertinent to our past and ongoing knowledge of global health. ", "Financial Disclosure: None. Funding Support:", "None. Conflicts of Interest: No authors have financial interests that pose a conflict of interest." ] },{ "paper_id": "9f5749af9a7d43c3e5e1ca056c71e5a9c0a0a1ae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9f7ffa3a1bbf4a6ad9e71f2377fb45564589d415", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "After necropsy, representative tissues were fixed in 10% neutral buffered formalin for 24 hr and routinely processed. Processed tissues were embedded in paraffin, then stained with hematoxylin and eosin.", "Genomic DNA was extracted from paraffin-embedded blocks of small intestine using a QIAamp DNA FFPF Tissue kit (Qiagen, Hilden, Germany), following manufacturer protocol. Partial and complete sequences of 5.8 Sribosomal RNA (rRNA) gene, internal transcribed spacer 2 (ITS2), 28S rRNA gene (GenBank accession number: LC025648.1) were PCR amplified using the following primers: 5'-TGTCGATGAAGAG TG-CAGCCA-3' (forward) and 5'-ATCAGTTACATTGCCACATGC-3' (reverse). Thermocycling conditions were as follows: 30 cycles of 1 min at 94\u02daC, 1 min at 55\u02daC, and 1 min at 72\u02daC. The PCR product was purified using a QIA amp Purification kit (Qiagen) and commercially sequenced (Macrogen, Seoul, Korea).", "Histopathological examination of the small intestine revealed severe necrotizing enteritis, with atrophied small intestinal villi and enterocyte exfoliation ( Fig. 2A) . Moreover, intestinal crypt epithelial cells were degenerated or necrotized. In the lamina propria, numerous lymphocytes and a few macrophages were infiltrated. Several trematodes were present within the intestinal lesions, having embedded themselves among the villi and pulling bits of mucosa into the anterior spoonshaped region of their bodies (Fig. 2B) . No other organ presented histopathological lesions." ] },{ "paper_id": "9f82db8107ec9ced3f686b30ccc27645cd6f9643", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9f87d0f127411cb1dc51dbd3041aaecc008d7b8d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Recombination is an important process which expedites selection in many organisms (Muller 1932 ) by unlinking loci. It also leads to different parts of recombining genomes to have different histories which, if not properly accounted for, can interfere with many genetic analyses, of which phylogenetic methods are among the most sensitive. Not accounting for recombination in phylogenetic analyses leads to incorrect (Schierup and Hein 2000) and poorly supported genealogies (Posada and Crandall 2002) and false inference of selection (Anisimova, Nielsen, and Yang 2003; Shriner et al. 2003) .", "\u2022 Excessive homoplasies (Maynard Smith and Smith 1998) . The transfer of genetic material from one genetic background to another will result in apparent repeat mutations in different parts of a phylogenetic tree. However, it is possible for the same locus to undergo mutation independently, especially if the locus in question is under Darwinian selection. Detecting homoplasies alone is not sufficient to infer recombination but should be demonstrated to occur in excess of expectation.", "Recombination leaves several characteristic clues in genomes:", "Additional tests for recombination were also performed, namely the estimation of the pairwise homoplasy index (Bruen, Philippe, and Bryant 2006) and the triplet test implemented in 3Seq (Boni, Posada, and Feldman 2007) ." ] },{ "paper_id": "9f9327703d4203ad1f26dfea48d1a0226e6dd5d4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Beta agonists to facilitate water removal and ion transport have been shown to be promising. These agents may also stimulate secretion of surfactant and have no serious side effects. There were several reports on the pharmacological and molecular actions of beta agonists, surfactant and vascular endothelial growth factor and related molecules as well as angiotensin-converting enzyme (ACE). [107, 125, 126] ", "During the summers from 2001\uf02d2003, we encountered a total of 48 children suffering from hand, foot, and mouth Figure 2 . Isolated and perfused lung in situ preparation. The system consists of a perfusion pump with heat exchanger and a venous reservoir. The rat is artificially ventilated. Pulmonary arterial pressure (PAP) and venous pressure (PVP) are monitored with transducers. The whole rat is placed on a balance platform to record the body weight change. Since the lung is isolated from the whole body, the change in body weight reflects the lung weight change.", "The treatment of ARDS/ALI is difficult and complex. Several review articles and monographs have addressed the issue of possible therapeutic regimen. The modalities include extracorporeal membrane oxygenation, prone position, mechanical ventilation with appropriate tidal volume and respiratory pressure, fluid and hemodynamic management and permissive hypercapnic acidosis. [68, 100, [109] [110] [111] [112] [113] [114] [115] [116] [117] [118] [119] Other pharmacological treatments are anti-inflammatory and/or antimicrobial agents to control infection and to abrogate sepsis, adequate nutrition, surfactant therapy, inhalation of NO and other vasodilators, glucocorticoids and other nonsteroid anti-inflammatory drugs, agents that accelerate lung water resolution and ion transports. [68, 102, [120] [121] [122] [123] [124] Although most animal experimentations on these pharmacological options showed favorable results, the effectiveness and outcomes in clinical studies or trials were conflicting.", "The pathogenesis of ARDS/ALI is complex. Experimental studies and clinical investigations from our and other laboratories have indicated the detrimental role of nitric NO through inducible NO synthase (iNOS). Activation and recruitment of neutrophils that lead to release of neutrophil elastase, myeloperoxidase, malondialdehyde and proinflammatory cytokines may play an initial role in the pathogenesis of ALI/ARDS." ] },{ "paper_id": "9f9984a45e51e8268ed00e6de9ca8b23615fb154", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This confirmatory assay had the same conditions as described above for the upE rRT-PCR, albeit the primer and probe sequences were different. This assay was performed with ORF1b forward primer (TTCGATGTTGAGGGT-GCTCAT) and reverse primer (TCACACCAGTTGAAAATCC-TAATTG), as well as its specific probe (6-carboxyfluorescein [FAM]-CCCGTAATGCATGTGGCACCAATGT-6-carboxy-N, N, N, N' tetramethylrhodamine [TAMRA] ). This target gene did not overlap with those of known pan-CoV assays (2, 6, 7)." ] },{ "paper_id": "9f9de51e9537bc4c203dad26bf1e99d91f2b15e8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Viruses are particulate in nature and usually exist in different morphological forms that generally range in size from 20 to 900 nm [11] [12] [13] . Their intact, mature infectious particles are typically composed of definite units of proteins and nucleic acid that self-assemble to form nanoparticulate structures called virions. The viral proteins are usually arranged in a surface layer called the capsid and sometimes in an outer envelope surrounding an inner core of nucleic acids. This core of viral nucleic acids can be single-or double-stranded (ds), DNA or RNA, one or several molecules, linear or circular in shape, and a few thousands of nucleotides to one million base pairs in size.", "The Coronaviridae family comprises two subfamilies, Coronavirinae and Torovirinae, that were recently expanded to include many viruses. Coronavirinae are classified into four genetically distinct genera (Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus) [112] . Coronaviruses are enveloped RNA viruses that are pleomorphic in shape (spherical and 120-160 nm or bacilliform and 170-200 nm by 75-88 nm). They have a relatively large, positive-sense, ssRNA genome of 27-32 kb that encodes four to five structural proteins (S, the spike glycoprotein; M, the membrane glycoprotein; N, the nucleocapsid interrupt phosphoprotein; E, the envelope protein; and HE, the hemagglutinin-esterase glycoprotein) and 2 nonstructural polyprotein precursors (pp1a, polyprotein 1a; and pp1ab, polyprotein 1ab), which are later processed into several other nonstructural proteins and viral polymerase [113, 114] .", "called hepatitis E, which is widely disseminated in developing countries with poor sanitation conditions and has recently become apparently endemic in some industrialized countries, including the USA [151] ." ] },{ "paper_id": "9f9f59f3137c9871b1a0d7bfe92b9b9f4087b24b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a02f53bba04cb55cd70c09e2299f3ab1556943fb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a03293a6ac86dd01a32f04eeea0f233f367fa742", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Taenia solium (tapeworm)", "Echinococcosis Echinococcus granulosus (tapeworm)", "Wuchereri bancrofti, Brugia malayi, and Brugia timori", "Rapid cellular evolution resulting in the guinea-worm's rapid switch from human to dog as the primary host (Cairncross, 2014) ." ] },{ "paper_id": "a0432d20b18db0900a9074dc773e27bd4b8ad1b8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We identified the set C of all maximal cliques of size at least k in the two groups using a fast depth-first search with pruning-based algorithm (CLIQUES). Next, we calculated its weighted interaction density score (C) as (equation 1):", "Not applicable.", "The rat ovariectomy experiment was approved by the Ethics Committee of Hebei Cangzhou Central Hospital, (Cangzhou, China).", "lower than that in the sham operated group (P<0.05). The result showed that the model was successfully established." ] },{ "paper_id": "a10019330d4147f613949ce0d30e0b0bc66499ea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Immediately before analysis, the mononucleotide mixtures obtained by exonuclease digestion of intact RNA were diluted to 4 ng/l in 150 mM ammonium acetate and 10% isopropanol. All samples were analyzed on a Thermo Scientific LTQ-Orbitrap Velos instrument and a Waters Synapt G2 HDMS ion mobility spectrometry mass spectrometer (IMS-MS), as previously described (49, 50) . Analyses were accomplished by using direct infusion electrospray ionization (ESI) in negative ion mode.", "Infections were undertaken with the following singlestranded positive sense RNA [ss(+) RNA] viruses: ZIKV MR766 Uganda (gift from Brett Lindenbach, Yale University), DENV-2 strain 16681 (infectious clone from Richard Kinney and Claire Huang, CDC) (51), HCV JFH-1 (infectious clone from Takaji Wakita, National Institute of Infectious Diseases, Tokyo) (52) and poliovirus (PV) Mahonney strain (infectious clone from Peter Sarnow, Stanford University).", "Human hepatocarcinoma (Huh7) cells were maintained in Dulbecco's modified Eagle's medium (DMEM) (Life Technologies), 10% fetal bovine serum (FBS) (VWR Life Science Seradigm), 1% non-essential amino acids (Life Technologies) and 1% glutamine (Life Technologies). HeLa and 293T cells were cultured in DMEM, 10% FBS and 1% glutamine. All cell lines were maintained at 37 \u2022 C and 5% CO 2 .", "in which the signal intensity (ai x ) of each PTM was normalized against the sum of the intensities displayed in the same spectrum by the four canonical bases (cr i )." ] },{ "paper_id": "a10f6c3dce3d0abbf575b64df42348446c105b57", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Oany et al specificity. This makes AllerHunter is a very useful program for allergen cross-reactivity prediction. 26, 27 Molecular docking analysis and hla allele interaction Design of the three-dimensional (3D) epitope structure", "To ensure the binding between HLA molecules and our predicted epitope, a docking study was performed using Molegro Virtual Docker, version 6.0 (CLC bio, Aarhus, Denmark). 29 The HLA-B " ] },{ "paper_id": "a14b5655cb13ed64cb8cff7c806a7b58c858b8b7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All code is available as an R package.", "We declare no competing interests." ] },{ "paper_id": "a183646896ed073a4ec4035c5b6c6c77db89f0b3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a1cdea1502a0fd90dbbff6e8a29480d856c03fed", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Background: Neonatal diarrhea accounts for more than 50% of total deaths in dairy calves. Few population-based studies of cattle have investigated how the microbiota is impacted during diarrhea.", "DNA extraction, amplification, and sequencing of bacterial 16S rRNA gene", "Additional Supporting Information may be found online in the supporting information tab for this article:" ] },{ "paper_id": "a209539267a73a6fb2ed9ea4766a50687b9b8cfb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a24b5a764c19d383dbfe795779b18799c6d2f4e9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a25eeb43c5f7e8143b16c6237093f2156b3cef60", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "chondrophila were used as antigens to develop a specific ELISA.", "The obtention of children's sera was done as part of a larger study investigating various agents of lower respiratory tract infection (see below: 'Human sera'). This study was approved by the Geneva University Hospital Ethics Committee (No. CE 04-199). Written consent was systematically obtained from children's parents." ] },{ "paper_id": "a26ffcce0878ea2ebab2a7ed46a9761244fda936", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a2986c7d52f824dd89fc02e5c1fcab46b3f37524", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a2add35b84a53cbad3301093f4191d5edadf1d0e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a2c1a9a13829fc83999db461322319bda6c81530", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a2c2196aecd2142d5881124b7cd8ff252581c784", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To adjust for dilution of BALF in estimating the biomarker concen- ", "The different biomarkers were first analyzed in univariable models and secondly in models adjusted for time after Lntx. All statistical tests were two-sided, and 95% confidence intervals (CIs) that ", "Chi-square, rank sum, Kruskal-Wallis, and Mann-Whitney U tests were Using logistic regression, we calculated odds ratios (ORs) for infection (dichotomized into definite and probable vs no or possible infection and rejection) for each biomarker. We used generalized estimating equation (GEE) models to account for the possibility of dependency due to multiple observations from the same patient." ] },{ "paper_id": "a2d7c5fc05284d7176ae30fd6fe4967cdc111f10", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For each experimental condition, at least three replicates were performed. The results presented in the figures are representatives of these replicates (mean \u00b1 standard deviation (SD), n = 3-6). Two-tailed student t test was used for statistical analysis. A p-value less than 0.05 was considered to be significantly different. For RT-PCR results, any change in gene expression levels that are less than ~2-fold is not considered to be significantly different.", "Visualization of human PF structure was performed by scanning electron microscope (SEM). The tissue samples were fixed with 3% paraformaldehyde and 2% glutaraldehyde in 0.1 M cacodylate buffer containing 1% sucrose for 30 min, followed by 1% osmium tetroxide for an additional 30 min. The fixed samples were dehydrated with 50%, 60%, 70%, 80%, 90%, and 100% ethanol for 15 min each. The samples were treated with a critical point drying instrument and finally coated with gold/palladium using a sputter coater. The structure of PF was examined under a microscope with an accelerating voltage of 3 kV.", "After stretching, media was collected to measure IL-6 and PGE 2 production using their respective enzyme-linked immunosorbent assay (ELISA) kits (Abcam, Cat. No. ab46027, for IL-6, and Cayman Chemical, Cat. No. #514010 (Ann Arbor, MI, USA) for PGE 2 ). In addition, the total RNA of cells in each dish was extracted, and quantitative real-time polymerase chain reaction analysis (qRT-PCR) was performed to evaluate gene expression of stretched and non-stretched cells.", "The characteristics of PF-S and PF-C were further assessed by analyzing cell shape factors of the two types of cells. The cell shape factor is expressed by the cell aspect ratio, which is the cell length along the long axis divided by the cell length along the short axis." ] },{ "paper_id": "a32757c9e2857202acf9b238a2004a533670affc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical probit analysis, a non-linear regression model, was performed to determine the limit of detection at 95% (LOD 95% ); that is, the lowest target concentration that could be detected with 95% confidence interval (CI), by using commercial software SPSS 14.0 (IBM). The 2 \u00d7 2 contingency tables were analysed by kappa (\u03ba) statistic using SPSS, to determine the inter-rater agreement.", "Virus isolation QN10 cells, a clone of feline fibroblasts into which Moloney murine sarcoma provirus had been introduced, 24 were routinely used for FeLV VI at VDS-UG. A sub-confluent layer of QN1O cells in a 12-well plate was in\u00b0Culated with 200 \u00b5l heparinised plasma or serum. The in\u00b0Culum was absorbed for 2 h then replaced with fresh tissue culture medium (Dulbecco's modified Eagle medium containing glutamine, sodium pyruvate and penicillin-streptomycin [Life Technologies]). The cells were examined for characteristic cytopathic effects daily for 4-6 days; negative cells were sub-cultured until day 15. Positive (whole infectious virus) and negative (tissue culture medium) controls were included on each plate.", "A plasmid containing a fragment of the U3 long terminal repeat (LTR) region of FeLV was used to evaluate analytical sensitivity of the assays and to generate the RNA templates by in vitro transcription (IVT) using the MAXIscript T7 kit (Ambion). For IVT RNA, residual DNA was removed using the Ambion Turbo DNA-free kit (Applied Biosystems). Concentration of DNA and RNA was measured using a spectrophotometer (NanoDrop 2000; Thermo Scientific). Single-use aliquots were stored at \u221280\u00b0C. Serial dilutions were made in 40 ng/\u00b5l yeast tRNA." ] },{ "paper_id": "a34f8d05e44966a5fa2a8bdcf553d3533f1851d8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "College students in a course about leadership prison [3, 4] 67 182 Social networks of positive sentiment (prison inmates) dolphin [5] 62 159 social network of dolphins polbooks [6] 105 441 A network of books about US politics football [2] 115 613", "The largest component of netscience.", "where j denotes the column, x" ] },{ "paper_id": "a397f653ecd65b3cd26cf587207f2eec48b0e954", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a3abdec780d11a40fb6740ebaa730dfd313a1106", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a3b5e995f19fca615af9084f08e562b563a74085", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\uf0b7 It is not known if any effects are temporary or how long they last.", "This review suggests that infectious isolation has a number of negative effects on patients. Because this evidence is comprised of cohort and case-control studies, a claim for a causal relationship cannot be made on this evidence, although the strong and consistent effects across the studies may increase the confidence in this relationship. There are some qualitative data, although more in-depth mixed-methods data where those reporting negative effects are questioned about them would strengthen the evidence on this. In some cases large effect sizes were accompanied by very wide confidence intervals, suggesting that studies were underpowered, thus studies with larger sample sizes would be useful.", "Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators." ] },{ "paper_id": "a3cf3a5dc7b63848aef753bf664fc8c7815de577", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a3e2f4a9e9c1bc50381ef0161f062bb6f925b7be", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Informed consent was obtained from parents of all children, and the study protocol was approved by the Eulji University Hospital Institutional Review Board (IRB, No. 2015-03-014-002). Informed consent was confirmed by the IRB.", "Two milliliters of blood were obtained and put in a tube containing 0.019 M (3.2%) citrate anticoagulant. The samples were centrifuged at 1,500-13,000 \u00d7 g to obtain platelet-poor plasma. All procedures were performed at room temperature. The samples were stored in a deep freezer (\u221280\u00b0C) until analysis. The PDMP level was measured using an enzyme-linked immunosorbent assay (ELISA) kit (Zymuphen MP-activity; Medicago, Uppsala, Sweden) and expressed as phosphatidylserine equivalents (nmol). The assay performance and characteristics were as follows: 1) detection threshold, not more than 0.05 nmol; 2) intraassay coefficient of variation (CV), 3% to 8%; and 3) interassay CV, 5% to 10%.", "In the present study, we used the Zymuphen MP-activity (Medicago) ELISA to measure prothrombinase activity with an ELISA https://doi.org/10.3346/jkms.2017.32.7.1147 reader (Bio-Rad, Hercules, CA, USA), measuring samples at a wavelength of 405 nm (18, 19) . The diluted assayed plasma sample, supplemented with calcium, factor Xa, and thrombin inhibitors were introduced into 1 of the microplate wells coated with streptavidin and biotinylated annexin V, and then incubated. The phospholipid concentration is the limiting factor in this ELISA test. Even if flow cytometry is considered the \"gold standard\" of microparticle detection, there are still technical limitations concerning detection of small microparticles (100 nm to 500 nm). Therefore, microparticle activity can be analyzed by prothrombinase assay (ELISA), which is easily performed and shows a significant correlation of results (20) ." ] },{ "paper_id": "a3e8cfc509af101c522d4193c8917d6e8f68b37b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sputum and throat swab specimens collected from all patients at admission were tested by real time polymerase chain reaction for SARS-Cov-2 RNA within three hours. Laboratory confirmation of the virus was performed using real time reverse transcription polymerase chain reaction. 9 Virus detection was repeated twice every 24 hours.", "Ethical approval: This study was approved by the Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine (2020IIT A0001).", "Contributors: X-WX and X-XW contributed equally to this article. XWX and LJL conceptualised the paper. XXW analysed the data, with input from JFS, KJX, XGJ, LJY, CLM, SBL, HYW, SZ, HNG, HLC, and YQQ. XWX and XXW wrote the initial draft with all authors providing critical feedback and edits to subsequent revisions. All authors approved the final draft of the manuscript. L-LJ is the guarantor. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.", "This was a retrospective case series study and no patients were involved in the study design, setting the research questions, or the outcome measures directly. No patients were asked to advise on interpretation or writing up of results.", "Funding: No funding.", "Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work." ] },{ "paper_id": "a40363fa5527e9b6dbf6930b247a4608027e7983", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In our experiments described above [57] , we obtained the interesting result that 0.1 \u03bcM of indomethacin slightly, but significantly increased the production of LTC 4 , and LTE 4 . We also tested indomethacin from another source to avoid the influence of contamination by other factors, and the same result was observed.", "As mentioned above, AERD is not thought to be a type I allergic disease, so we also tested non-allergic stimulation of RBL-2H3 cells with calcium ionophore A23187 and obtained the similar results.", "The author confirm that this article content has no conflict of interest.", "According to the asthma guideline of the US National Heart, Lung and Blood Institute, 21% of adult asthma patients and 5% of pediatric asthma patients have AERD [8] , while the Japanese asthma guideline [9] states that 5-10% of adult asthma patients and 3.6-7.8% of pediatric asthma patients have AERD. According to both guidelines, the majority of AERD patients are adults." ] },{ "paper_id": "a41e8928ee5cb212550be0620946d6e62c34b001", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Objectives and design: Developing an effective HIV-1 vaccine that elicits broadly neutralizing HIV-1 human antibodies (bnAbs) remains a challenging goal. Extensive studies on HIV-1 have revealed various strategies employed by the virus to escape host immune surveillance. Here, we investigated the human antibody gene repertoires of uninfected and HIV-1-infected individuals at genomic DNA (gDNA) and cDNA levels by deep sequencing followed by high-throughput sequence analysis to determine the frequencies of putative germline antibody genes of known HIV-1 monoclonal bnAbs (bnmAbs).", "Methods: Combinatorial gDNA and cDNA antibody libraries were constructed using the gDNAs and mRNAs isolated from uninfected and HIV-1-infected human peripheral blood mononuclear cells (PBMCs). All libraries were deep sequenced and sequences analysed using IMGT/HighV-QUEST software (http://imgt.org/HighV-QUEST/index. action). The frequencies of putative germline antibodies of known bnmAbs in the gDNA and cDNA libraries were determined.", "Preparation of human peripheral blood mononuclear cells The PBMCs of healthy volunteers were obtained from The University of Hong Kong (Hong Kong, China). PBMCs from patient one (pt1) were obtained from Aaron Diamond AIDS Research Center, Rockefeller University (New York, USA). PBMCs from patients 2 and 3 (pt2 and pt3) were obtained from National Center for AIDS/ STD Control and Prevention, China CDC (Beijing, China). All these experiments were approved by ethical committees of the respective institutes, and conducted according to local guidelines and regulations. All three patients were elite controllers. Pt1 was infected with clade B virus whose serum exhibited high titres of broadly neutralizing activity, and a panel of bnmAbs were isolated from pt1 PBMCs by single memory B-cell sorting using gp120 C-C core protein as a bait (pt1 in [18, 28] ). Pt2 and pt3 were infected with clade B' virus and naive to antiretroviral therapy [30] . The sera of pt2 and pt3 also exhibited cross-clade neutralization activity (data not shown). Heparinized whole blood samples were used to isolate human PBMCs by Ficoll density gradient separation." ] },{ "paper_id": "a4490fc5ca8fea133b9a5beb9258df89cf4945b6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The inducible shPRSS1 encodes the same sequence as shPRSS1-c. Lentiviral preparation and infections were performed. Cells transduced with shRNA were grown in medium supplemented with 10% FBS in the presence of puromycin (2 \uf06dg/ml).", "forward, 5\u2032-AGGCACACTCTACCACCATGA-3\u2032; reverse, 5\u2032-ATGTTGTGCTCTCCCAGTCTCA-3\u2032. The SPINK1 primer sequences were as follows: forward, 5\u2032-AACAGGCATCTTTCTTCTCAGTG-3\u2032; reverse, 5\u2032-TTGGGATAAGTATTTCCATCAGTC-3\u2032. The GAPDH primer sequences were as follows: forward, 5\u2032-TGAAGGTCG-GAGTCAACGGAT-3\u2032; reverse, 5\u2032-CTGGAAGATGGTGATGGGATT-3\u2032.", "Human SPINK1 coding regions were PCR-amplified from a human mammary retroviral complementary DNA library and cloned into the prokaryotic expression vector pET22b. The primers used were as follows: forward, 5\u2032-GAATTCTAATGGACTCCCTGGGAAGA-GAGGCC-3\u2032; reverse, 5\u2032-CTCGAGGCAAGGCCCAGATTTTTGAA-3\u2032. The fusion protein SPINK1 was expressed in Escherichia coli and purified by nickel affinity and size exclusion chromatography. Isopropyl-\uf062-d-thiogalactopyranoside (0.2 mM/liter) induction at 16\u00b0C for 16 hours was estimated to be an optimal expression strategy. The expression of the fusion proteins was detected by Western blotting and Coomassie Brilliant Blue G-250 staining.", "View/request a protocol for this paper from Bio-protocol." ] },{ "paper_id": "a45c1bbbc8f619491ce0c5ddc26fadbe7d69c975", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study received NZ Health & Disability Ethics Committee Approval: CEN/10/12/057.", "Difference in logarithm cytokines IL-6 and TNF-\u03b1. The exponent of the logarithm is interpreted as the ratio of mean values." ] },{ "paper_id": "a46ec82f209bf008fd96e99c212ef8f0d4ae33b5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The Great Leap Forward from 1958 to 1961, an effort to induce small-scale industrial activity and collectivization, backfired and ensuing havoc in agriculture resulted in devastating famine. Soon after came the Cultural Revolution, with emphasis on purging social class. 11 It also shattered economic activity resulting in serious setbacks. The more pragmatic Deng Xiaoping set a different course for China once he consolidated power in the late 1970s. 12", "Multivariate analyses use ordinary least squares analysis in SPSS version 16.0 and Excel for Windows 7 to study determinants of household savings. Urban and rural data are analyzed separately consistent with Chinese statistical accouting practice.", "China, like other developing countries, benefits from the integration of a backlog of technologies readily available from the developed world. This approach inevitably exhausts itself as the rural population diminishes, higher wages and prices render manufactured exports less competitive, and higher productivity technologies become widely disseminated." ] },{ "paper_id": "a497dea73b329a11331c9835fabff84a7e5eedcd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The CRP level in VTE patients was detected by scintillation turbidimetry.", "Agilent G4112A Whole Human Genome Oligo Microarrays were purchased from Agilent (USA). A microarray is composed of 44,290 spots including 41675 genes or transcripts, 314 negative control spots, 1924 positive control spots and 359 blank spots. The functions of more than 70% of genes in the microarray have been known. All patients of both groups were subjected to microarray analysis.", "Indirect approach was applied to mark samples. About 1 \u03bcg of total RNA was reversely transcribed into double strand cDNA. After purification, in vitro amplification was performed with Agilent Low RNA Input Linear Amplification Kit (Agilent, Pal alto, USA) and modified UTP [aaUTP, 5-(3-aminoally1)-UTP] was used to replace UTP. The integrated aaUTP can interact with Cy3 NHS ester forming fluorescent products which are then used for hybridization. The integration rate of fluorescence can be determined with a NanodropND-1000 spectrophotometer. Then, hybridization mixture was prepared with Agilent oligonucleotide microarray in situ hybridization plus kit. About 750 ng of fluorescent products were fragmented at 60\u2103 and hybridization was conducted in Human Whole-Genome 60-mer oligo-chips (G4112F, Agilent Technologies) at 60\u2103 for 17 h at 10 rpm. After hybridization, the chips were washed with Agilent Gene Expression Wash Buffer according to manufacturer's instructions. Original signals were obtained Agilent scanner and Feature Extraction software. The standardization of original signals was carried out with RMA standardized method and standardized signal values were used for screening of differentially expressed genes.", "Gene Ontology organizes gene function into hierarchical categories based on biological process, molecular function and cellular component. Fisher's exact test was applied for over representation of selected genes in GO biological categories. In order to assess the significance of a particular category by random chance, false discovery rate (FDR) was estimated for all of categories. After 5,000 re-samplings, FDR was defined as FDR=1-Nk/T, where Nk refers to the subtracted number which was from Fisher's test in random samples. We specified the threshold of significant GO as p-value<0.05, FDR<0.05 and enrichment parameters. Enrichment represents the degree of gene expression significance. The equation of enrichment is as following: Re=(nf/n)/(Nf/N) (14) , where nf is the number of significant genes within the particular category, n is the total number of genes within the same category, Nf is the number of significant genes in the entire microarray, N is the number of all genes tested." ] },{ "paper_id": "a4e3ea0a718f906e5f879917d26384c2c0c49d09", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a4edf4ce073f52028af8e88621a26288d9af4c02", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The positive BSE animal detected on this farm in 2002 was disposed of through incineration, following detection as a fallen animal at a knackery.", "There Feed was stored in a single multipurpose shed in bulk or bagged form. This shed was also used to house calves. The bay containing feed and the bay containing calves were separated by a gate.", "Animal movement records were available for the herd from 2002 to the present. All fallen animals had been sent to the local knackery. Oneadult bovine animal was buried in a paddock beside the farmyard around the period 1999/2000. The burial site was not disturbed during a subsequent extension of the farmyard." ] },{ "paper_id": "a4f39fce76a00087b57733d4da58e67b49966eae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Of course, further studies of electron microscopy focused on CCP are needed to confirm our preliminary impressions.", "In conclusion, the current study precisely describes the three phases of CCP by nasal cytology and confirms that CCP represents a sign of suffering nasal epithelial cell. ", "Acute upper airways inflammation is usually caused by viruses, even though after the viral infection a bacterial overlapped infection may occur, partly favored by the cytopathic effect of the virus itself on the mucosa. Ciliated cells are the most differentiated cells of the nasal mucosa and therefore they are more prone to attack by infections. The most common viruses are Rhinovirus, Myxovirus (Influenza virus), Paramyxovirus (Parainfluenza virus), Coronavirus, Adenovirus and Respiratory Syncytial Virus (RSV)." ] },{ "paper_id": "a559e323cc2f1aaa14ae90f386f079163e2401aa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a5f08604ffadbbd3a3759ba8c3b647913bc1c4b6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "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." ] },{ "paper_id": "a5fddb00475627b88f2761218d9e6a572d14f90d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org/ lookup/suppl/doi:10.1128/mBio.02445-14/-/DCSupplemental.", "Text S1, PDF file, 0.3 MB. Figure S1 , PDF file, 0.6 MB. Figure S2 , PDF file, 0.3 MB. Figure S3 , PDF file, 0.3 MB. Figure S4 , PDF file, 0.2 MB. Figure S5 , PDF file, 1.3 MB. " ] },{ "paper_id": "a60e292d31e4bb27e20f3ace17fc295ad60990c8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To accurately evaluate the trip duration and activities, only travelers with one purpose of travel and one itinerary were included. Travelers younger than 18 years were excluded from all analyses because they are less likely to travel for business or other occupational reasons, and legally do not make the primary decisions regarding their health care.", "GTEN is a consortium of US medical practices that includes academic institutions, health maintenance organizations, pharmacybased clinics, and public health clinics that provide pre-travel health consultations to international travelers; it is described in detail elsewhere. 8 In brief, GTEN collects data from pre-travel consultations of international travelers visiting consortium sites. This data collection began in January 2009 and is ongoing; data collected from 18 clinics from January 2009 through December 2012 were used for this analysis. Human Subjects Advisors at each participating site reviewed and approved or exempted the collection and subsequent analyses of the de-identified data.", "India was the top destination both for business (24%) and research/education (9%) travelers. China (7%) and South Africa (4%) were the other two most commonly visited destinations for business travelers. Although Haiti was selected by most of those providing medical care (20%) and missionaries (15%), Honduras was most common for non-medical service workers (14%). (It should be noted that a large earthquake occurred in Haiti in 2010 during the data collection period of this current study.)" ] },{ "paper_id": "a621b8667d221681dda8e3291d8b2c99a3636868", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "TRITC-and FITC-conjugated secondary antibodies to rabbit or mouse IgG were purchased from Dako A/S, Glostrup, Denmark and peroxidaseconjugated Fab fragments to rabbit IgG were purchased from Biosys, Compiegne, France.", "Immunoprecipitations and endoglycosidase H (Endo H) analysis were carried out as described earlier . The samples were analyzed under reducing conditions in a 10% SDS-PAGE according to Laemmli (1970) . The gels were prepared for fluorography using Amplify TM (Amersham, Aylesbury, UK). The film used for autoradiography was Fuji RX 100 (Fuji Photo Co. Ltd., Tokyo, Japan).", "In conventional electron microscopy the cells were fixed for 1 h at room temperature with a fixative containing 2 % glutaraldehyde and 3 % paraformaldehyde in 100 mM cacodylate buffer, pH 7.4, and postfixed with reduced 1% OsO4 for 1 h on ice. All samples were embedded in LX-112 (Ladd Research Industries Inc., Burlington, VT) and were viewed with a Jeol JEM-1200EX transmission electron microscope operated at an acceleration voltage of 60 kV." ] },{ "paper_id": "a654354060fcce82810e2c8842195d7e16995d11", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a6604f5c880a6a511053e91df3800780cdc3a876", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a6637a61fc42c734211f7df5089e88f859d0da5a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For TEM observation, cells were fixed in 0.1 M PBS (pH7.4) containing 1% glutaraldehyde and 2% PFA at 4 \u00b0C for 2 h and post fixed in 0.1% PBS with 1% osmiumtetroxide. After dehydration through gradient ethanol solutions, the specimens were embedded in Araldite-Epon (Embed-812, Electron Microscopy Sciences, USA). Ultrathin sections were prepared with an ultramicrotome (Leica, Germany). Pale-gold sections were collected on 200-mesh copper grids. Ultrathin sections were stained with uranyl acetate and lead citrate (Electron Microscopy Sciences) and examined with transmission electron microscope (Hitachi, JP).", "Total RNA was extracted from cells and reverse transcribed into cDNA (Invitrogen). PCR was performed by using specific primers targeting BALF5, BZLF1 and EBNA1 as listed below. Actin was used as an internal control.", "BALF5 forward: 5\u2032-CGTCTCATTCCCAAGTGTTTC-3\u2032 reverse: 5\u2032-GCCCTTTCCATCCTCGTC-3\u2032 BZLF1 forward: 5\u2032-TTCAACTGGGCTGTCTATT-3\u2032 reverse: 5\u2032-ACCTGTCTAACATCTCCC-3\u2032 EBNA1 forward: 5\u2032-ATGCCACCGAGGTTCTTG-3\u2032 reverse: 5\u2032-TGACACCACCACCCTTCTA-3\u2032 Actin forward: 5\u2032-GACAGGATGCAGAAGGAGAT-3\u2032 reverse: 5\u2032-TGTGTGGACTTGGGAGAGGACT-3\u2032" ] },{ "paper_id": "a67012609fad77c2a1dc55f139b044c546cd13a8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A substantial proportion of all sequencing reads mapped to the newly reported CoV genome (BWA mem, version: 0.7.12), [16] ranging from 71,883 (0.27% among all reads) in Patient 4 to 37,247,818 (85%) in Patient 5. In addition, very few reads mapped to known bacterial pathogens, including Streptococcus, Acinetobacter baumannii, and Pseudomonas [ Figure 1A -E].", "CPE were observed in 30% of Vero cells inoculated with the new CoV after two passages [ Figure 3A ]. The cells showed a round, refractive, and syncytium appearance.", "This study was conducted in accordance with the Declaration of Helsinki and was approved by the National Health Commission of China and Ethics Commission of the Jin Yin-tan Hospital of Wuhan (No. KY-2020-01.01). The requirement for written informed consent was waived given the context of emerging infectious diseases.", "The Vero cells with CPE were further examined using negative-staining electron microscopy, demonstrating characteristic CoV particles with surface projections [ Figure 3B ]. Immunofluorescent assays of the culture of Vero cells showing CPE with the convalescent serum from patients showed green signals in the cytoplasm, with no signals detected in wells containing control serum, indicating the presence of viral particles in the cells [ Figure 3C ]." ] },{ "paper_id": "a68da0099e002cdce53a89a826b412f7f8bb15d6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Glomerular and vascular lesions are associated with periglomerular fibrosis, glomerular lesions, including ischaemic, microcystic, obsolescent glomeruli, occasional thrombotic microangiopathy-like lesions and focal segmental sclerosis-like lesions. Vascular lesions include arteriolar hyalinosis, intimal fibrous hyperplasia, occasional mucoid arterial intimal fibrosis and multifocal thickening and splitting of peritubular capillary basement membranes detected by electron microscopy [21, 22] .", "All hypotheses related to BEN can be classified into three main groups (Table 1) .", "Cosyns first raised awareness of the unique renal histopathology of CHN with its striking similarity to BEN [56] .", "The pathology of BEN is characterized by a progressive atrophy and sclerosis of all structures of the kidney, and it shares similarities with tubulointerstitial kidney diseases ( Figure 2 )." ] },{ "paper_id": "a6ea21d8e8f97c41b9f69ee6c5d82f5c1a11107b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "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.", "The HEV mNGS results prompted immediate follow-up clinical testing demonstrating serum HEV immunoglobulin M (IgM) positivity, negative immunoglobulin G (IgG), and plasma HEV viremia (5 960 000 international units [IU]/mL) ( Table 1 , Supplementary Figure 2C ), and treatment with ribavirin and low-dose diuretics. Hepatitis E virus RNA declined, transaminases normalized, and ascites, edema, and mentation improved, but the patient subsequently had 2 readmissions for headache, nausea, and vomiting attributed to tacrolimus toxicity or side effects from ribavirin, necessitating multiple ribavirin treatment interruptions.", "The patient is a resident of Orange County, California. She denied sick contacts, pets or other animal exposure, insect bites, and eating shellfish or game meats. She reported travel to the mountains in Utah in August 2016, the Caribbean in 2010, and throughout Europe decades before admission. Her outpatient medications included immunosuppressive medications (tacrolimus, mycophenolate mofetil, and prednisone for lung transplant; teriflunomide for MS), antimicrobial prophylaxis (trimethoprim/sulfamethoxazole and acyclovir), anticoagulation, and pain medications, including an intrathecal morphine pump." ] },{ "paper_id": "a6eb398b44cfa0686f072f5cdbd07372587f0ed0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a6f40ea4a3c00f065ee24e7be886e3cc48a3a6bd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "recognition. 51 Here, we focus on those bacteria that affect mitochondrial morphology, and speculate as to how this may influence inflammation.", "L. pneumophila indirectly activates NLRP3 through the caspase-11 and absent in melanoma 2 (AIM2) inflammasomes. 57, 58 Bacterially-induced metabolic changes may also indirectly affect NLRP3 activation and innate immune function more broadly.", "Another intracellular bacterial parasite, Legionella pneumophila, secretes the toxin MitF to upregulate the fission agent DRP1 at the mitochondrial outer membrane. 56 MitF thereby induces mitochondrial fragmentation, which appears to be a strategy to reprogramme host macrophage metabolism 56 to limit oxidative phosphorylation (OXPHOS) and create the glycolytic environment favored by L. pneumophila." ] },{ "paper_id": "a70f7904950bba73ba43df71226c57344b28aa33", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a78e31beaf8becf35eacaa356661ea99c97e8652", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a7a5f2d3cff5287f3c65c24cb77de1caf5872687", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cells were viewed and photographed using a Zeiss Axioplan Photomicroscope (equipped for epifluorescence at excitation wavelengths appropriate for DAPI and FITC fluorescence) and film and developer (TMAX-400; Eastman Kodak Co.). Photomicrographs are shown at a magnification of 1,000.", "We deduced the primary structure of DPAP B by sequencing DAF2. Fig. 1 shows the restriction map of DAP2 and the sequencing strategy for the 3,135-bp Barn HI-Acc I fragment.", "Restriction endonucleases and other enzymes used for cloning and sequencing were from New England Biolabs ( ", "No significant sequence similarity has been found between DPAP B and any other vacuolar or tysosomal protein for which sequence information is available. However, strong homology has been found between DPAP B and DPAP A, the product of the STE/3 gene (Flanagan, C., and J. Thorner, personal communication; see below).", "Plasmid pC JR6, a multicopy 2-#m yeast vector containing the DPAP B coding region fused to the GAL/promoter, was constructed by inserting a 400-bp Eco RI-Hind III GAL/ promoter fragment (Johnston and Davis, 1984) into the Eco RI and Hind III sites of pSEYS, and subsequently subcloning into the Hind III site of this plasmid (pCJR5) the 2.9 kbp Hind IIl fragment of DAP2 (Fig. 1) , resulting in the fusion of the GAL/ promoter at position -90 of DAP2." ] },{ "paper_id": "a7aaf2c3f905813cd23b5ac719d49e662063edb9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Extracted viral RNA was tested for coronavirus by RT-PCR using the SuperScript III One-Step RT-PCR System with Platinum Taq DNA Polymerase (Thermo Fisher Scientific, Inc.) and pan-coronavirus universal primers that target the polymerase gene [13] ." ] },{ "paper_id": "a7dea443868b1327fef754465f3792ea33a224ca", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a8002f42a29667524fe9cae0a0a94f60fbbf6079", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a802010092ba72fa679f88467ea9b53ac6725577", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Article Focus:" ] },{ "paper_id": "a81c646c5838cf678fd22a7527e88f964bcbb862", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a83f14464310d40fdac66e2b2a00355dcf0b4737", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a841a20b663330228ca243c8c25753fff73cfa4e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a8dd4ad790014376cbea595be02bc5cade42104f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a8fb010702e647142d24caeeb5572e1e67c9fbd5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. The results are expressed as the mean \u00b1 standard deviation. Statistical analyses were performed using the paired Student's t-test, with paired comparisons being made where relevant using GraphPad Prism 5 (GraphPad Software, Inc., La Jolla, CA, USA). P<0.05 was considered to indicate a statistically significant difference.", "Serum HMGB1 levels are reported to be raised in patients with acute organ injuries, including trauma, stroke, acute myocardial infarction, acute respiratory distress, acute pancreatitis and ischemia-reperfusion injury (6) . Additionally, the increases observed in circulating levels of the HMGB1 protein were positively correlated with the severity of the disease in human and animal models. Complete inhibition or neutralization of HMGB1 may attenuate the severity of these diseases, decrease the incidence of organ dysfunction and improve survival, and consequently there is a burgeoning interest in HMGB1 as a therapeutic target. Among the strategies investigated, agents which bind to HMGB1 and neutralize its activity, including antibodies raised against HMGB1 and molecules which inhibit HMGB1 activation or its interaction with specific receptors, are gathering attention.", "Following IPTG induction, the cells were collected by centrifugation, and the cell pellets were resuspended in Ni 2+ -IDA binding buffer and lysed by sonication. The results of the SDS-PAGE experiment revealed that the " ] },{ "paper_id": "a93ae58385828b5de96f52d447e0305af7dbfe80", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "iii) Polymerised Haemoglobin (Polyheme, Hemopure, Hemolink): Here, the surface amino acid groups are linked by reagents like glutaraldehyde. Negligible side effects have been noted with this compound. This product has been transfused several times on compassionate use basis [16] . Administration of polymerized haemoglobin in patients undergoing infrarenal aortic reconstruction have shown an avoidance of allogenic blood transfusion in 27% of the patients [17] .", "Artificial blood substitutes are not devoid of their share of complications. Commonly observed side effects include increase in systemic and pulmonary arterial resistance, decreased cardiac output, jaundice, increased activities of enzymes like amylase, lipase or transaminases [32] [33] [34] [35] . The increased levels reflect clinical pancreatitis or is an error of interference with the photoelectric detector is still speculative.", "None." ] },{ "paper_id": "a94fd30a8dfce024118696e454bbe0f0e41840d9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In addition, aerosol inhalation is the main clinical route of infection for viral respiratory illnesses. There are different clinical presentations in animal models established by different infection routes.", "Total viral RNA was extracted from tissues (lungs, brain, kidneys, spleen, liver, heart, and intestine) homogenized using the RNeasy control. 23 A standard curve was generated for PCR using 10-10 7 copies of a qualified standard plasmid to calculate copy numbers for each reaction.", "Formalin-fixed lung, brain, and kidney samples were embedded in paraffin wax and sectioned at an approximately 5-\u03bcm thickness. Deparaffinized and hydrated tissue sections were routinely stained with H&E to examine histopathological changes." ] },{ "paper_id": "a9a33f1d0a7dee1c6fb63346baa0d6565fc79c00", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study introduces a novel concept that a noncoding RNA shuttles an RNA-binding protein to its functional binding site on a large molecular complex thereby regulating its activity. It is conceivable that this concept is not restricted to translational control but is applicable to a multitude of cellular processes and more examples of RNAmediated protein delivery might be discovered in the future.", "43S and 48S complexes assembled with [ 35 S]-Met-tRNA i Met and [ 32 P]-MVHL-stop mRNA were subjected to centrifugation through 5-25% sucrose gradient containing 20 mM Tris-HCl pH 7.5, 100 mM potassium acetate, 5 mM MgCl 2 , 2 mM DTT in a Beckman SW60 rotor at 60000 rpm for 2 h. Fractions were analyzed by scintillation counting.", "HEK293T cells were transfected with pDL7enh, pDLscAlu or pDL4.5S and 24 h later infected with VSV-PeGFP (50) at a multiplicity of infection of 10 PFU/cell in Dulbecco's modified Eagle's medium (DMEM) 2% fetal bovine serum (FBS). Six hours post-infection, the media was changed and cells were pulse labeled with [ 35 S]-methionine/cysteine for 15 min, proteins were precipitated in 10% TCA, resolved by SDS-PAGE and quantified by phosphorimager analysis.", "Plasmid construction, in vitro transcription, purification of the proteins, RNPs and ribosomal subunits, aminoacylation of tRNA, ribosome binding assay, cell culture and northern blot are described in the 'Extended Methods' section." ] },{ "paper_id": "a9e9e47667e6630156203fe938e7afb876583934", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Proteases-Elastase-1 (from porcine pancreas, E0258) was obtained from Sigma-Aldrich. Tosylphenylalanyl chloromethyl ketone-treated trypsin (from bovine pancreas) was obtained from Pierce." ] },{ "paper_id": "a9ed744baa5ce70adff087cb1ce4e77afc969822", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "and Hes5 (Nye, Kopan, & Axel, 1994; Zhou & Armstrong, 2007) . The ", "All images were acquired with a Spot 2 digital camera mounted to an IX-70 microscope (Olympus), with the exception of the node of Ranvier, which was imaged as fluorescent image stacks acquired using a ", "Associate Editor: Ernesto Bongarzone" ] },{ "paper_id": "a9eec435999ab4cd18d878153a834c72521ad604", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Patient consent for publication Not required. ", "Ethics and dissemination Ethical approval has been obtained from the institutional review board (no 69HCL17_0769). Results will be communicated at scientific meetings and submitted for publication in peerreviewed journals. trial registration number NCT03659773; Pre-results.", "Fungal Aspergillus spp diseases 19 Candida spp diseases 20 Mucormycosis 21 Hyalohyphomycosis-related diseases 22 Pneumocystis jirovecii pneumonia 23 Viral Were excluded: directly treated low viral load (<3 log 10 copies/ mL for CMV/HHV-6, <4 log 10 ", "Peripheral blood B-lymphocyte subset counts \u25ba CD19+. \u25ba CD20+. \u25ba CD21+. Natural killer counts Open access inclusion of 10 patients per estimated parameter in the model. 44 For this reason, at least 50 patients are required." ] },{ "paper_id": "aa029dc2c3ba585c0f6a05b6a1cf54e5aa66073b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "aa09cbc24e8aa582a402d4542656f0a5b49963bb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Technology, Tsukuba, Ibaraki, Japan), respectively. The preparation of antiserum to CPY has been previously described . Secondary antibodies were from Jackson Immunoreseareh (West Grove, PA).", "To prepare a bacterially expressed Mnnlp antigen, E. coli harboring pATH2-MNN1 were induced to synthesize the trpE-Mnnl fusion protein as described by Kleid et al. (27) and the fusion protein was purified as described by Paravicini et al. (42) . Approximately 0.25 nag of get-purified fusion protein was emulsified with Freund's complete adjuvant and injected intramuscularly into a male New Zealand white rabbit. The rabbit was boosted subcutaneously every three weeks with 0.05 nag of fusion protein in Freund's incomplete adjuvant. Bleeds were collected one week after each boost.", "Standard rich (YPD) and synthetic minimal (SD) media for yeast was used (55) . The SD medium was supplemented with 0.2 % yeast extract (SD-YE) and other supplements as needed for growing cells in liquid culture before labeling experiments. Standard rich medium for Escherichia coil (33) was used." ] },{ "paper_id": "aa51356108ada576b1b3a23b26c006b4e8d6cd4a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We wish to thank Michael Lai for the recombinant virus strains and Steve Stohlman, Michael Lai, and Minnie McMiUan for helpful critiques of the data and manuscript. We are also grateful for help with the manuscript provided by Sonia Garcia.", "J. Exp. Med. 9 The Rockefeller University Press" ] },{ "paper_id": "aa56d0f7345de56d6faa6791733fac0863fb1137", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "aa8a0b3cfa95daea83c1fc448904d6627593bb59", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The study was approved by the research ethics committee of King Abdullah International Medical Research Center, Riyadh, Saudi Arabia protocol number (SP18/168/R)." ] },{ "paper_id": "aad0a6df3e62a8279846dd17a8d09675f2b14397", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Abbreviations: CESD-11 = Center for Epidemiologic Studies-Depression Scale 11, KIHASA = Korea Institute for Health and Social Affairs, MERSC = Middle East Respiratory Syndrome Coronavirus, OECD = Organization for Economic Co-operation and Development, SARS = severe acute respiratory syndrome.", "The fit of the measurement model was good: Chi-square (26, N = 7000) = 187.07, P < .001, GFI = 0.995, TLI = 0.985, CFI = 0.991, RMSEA = 0.030 (95% CI 0.026-0.034). This result showed that all indicators adequately measured their latent construct.", "2.2.5. Suicidality. Two questions were used to assess suicidal ideation and suicide attempt. \"Have you ever thought about death in the last year? (yes or no)\". \"Have you ever actually attempted suicide? (yes or no)\". For the analysis, yes was coded as \"1\" and, no was coded as \"0.\" These questions were widely used in previous studies. [10, 25, 32] " ] },{ "paper_id": "aad248c894ac1b35e2adad9e23c9cf40dc3c20aa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "facilitating the development of therapeutic interventions against bacterial infections and other diseases.", "Monitoring Editor" ] },{ "paper_id": "aae7a1522ae3ab5cb39cf204ab3d8ca7f9ac8ef8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "aaeb1b254b13be853e9401cacbf8d18a6b5b3236", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ab312eb3286e189488707ea7ac8551401a178940", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "a pseudopositive-sense orientation, while the L protein and the NP are expressed in a negative-sense orientation, giving the arenaviruses an ambisense gene expression strategy (9) .", "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.02063-14/-/DCSupplemental. Figure S1 , EPS file, 2.8 MB. Figure S2 , EPS file, 1.3 MB." ] },{ "paper_id": "ab58c54193c5257b96d0d8e098fb18d7e2d8d081", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ethical issues (Including plagiarism, Informed Consent, misconduct, data fabrication and/or falsification, double publication and/or submission, redundancy, etc) have been completely observed by the authors.", "In general, prenatal diagnosis rate of BD was increased, such as CHD, as its rate was increased to 82.95% in 2008 from 20% in 2001. (Fig.3) ", "Overall BD prevalence 69,408 infants were covered in 52 surveillance hospitals in 2008 and 961 infants were found to have BDs, making the prevalence 13.85\u2030, which exceeded the last 7 years'. Besides, the prevalence of the first 4 years (2005-2008) was much higher than the latter four (2001-2004) (\u03c7 2 =77.64, P <0.05)." ] },{ "paper_id": "abb4c06114edb9aa57132be9201478ac965a56ba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Briefly, the RNA-retaining mats were washed twice with 10 mM ammonium formate pH 8, twice with water and once with ethanol. They were then soaked with liquid scintillation fluid (Perkin Elmer), allowing the measurement of 3 ", "Codon-optimized SUDV MTase+CTD synthetic genes (Biomers) were cloned into a pET14b vector for expression in bacteria. Mutations were introduced by PCR-amplifying the wild-type sequence using primers carrying the mutations, using the Turbo DNase (Ambion). PCR-products were purified using the Wizard SV PCR Clean-Up System (Promega). Transformed Escherichia coli T7 bacteria (NEB) were cultured at 30 \u2022 C until an O.D. of 0.6 was reached, after which the temperature was changed to 17 \u2022 C and IPTG (Sigma) was added to 20 M. The next day, bacteria were spun down (8000 \u00d7 g for 10 min at 4 \u2022 C) using a Sorval Lynx 6000 centrifuge (Thermo), and pellets were stored at -80 \u2022 C.", "Supplementary Data are available at NAR Online." ] },{ "paper_id": "abd53dcf1f9552913a4e99b759c0df469577d5b5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "It also includes active case management, infection control and decontamination, the importance of which were demonstrated during the MERS-CoV and Ebola outbreaks in 2012 and 2014, respectively (Siedner, Gostin, Cranmer, & Kraemer, 2015; Zaki, Boheemen, Bestebroer, Osterhaus, & Fouchier, 2012) .", "We would like to thank Dr. Piotr Kramarz (ECDC) and two anonymous reviewers for critical feedback on our manuscript. 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.", "No conflict of interest." ] },{ "paper_id": "abd5833ba0f868ce51622b090b9121b3be9c08dc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Low profitability is one of the reasons for the lack of vaccine and treatment research and development in developing countries. However, recent DENV research developments in Southeast Asia and India have led to remarkable economic growth and increased efforts to combat infectious diseases. Thus, the demand for vaccine development has increased, and more research is now in progress. The DENV vaccine market is expected to reach a combined $398.6 million in Brazil, India, Mexico, Singapore, and Thailand in 2020 [36] , and if optimal vaccines are developed using appropriate disease models, there will be a significant economic impact that could be extended to Zika virus and West Nile virus in the future.", "mosquitoes were found in Jeju Island, South Korea. Based on their genome sequence, these mosquitos were identified as a strain of A. albopictus, a species which is known to transmit DENV, from Vietnam [5] . Until now, all cases of DENV infection in Korea have been shown to be imported, and >95% of patients had returned to Korea after being infected in Southeast Asia or South Asia. However, as the domestic climate becomes more subtropical, these subtropical insects can survive much longer, and the possible occurrence of subtropical mosquitoes may result in an influx of DENV in South Korea.", "DENV-susceptible mouse models have been developed by genetically modifying the immune system to maintain the infected state. However, this model has limitations related to the immune response, and it is not applicable to all DENV serotypes. At present, there are no experimental models that reflect the pathological characteristics and clinical symptoms in humans, in part because DENV only infects apes and people. The use of primate species as experimental models also has limitations, including the high cost and challenges of managing them, and such models are not appropriate in certain situations, since they present viremia without clinical symptoms." ] },{ "paper_id": "ac209c3960cd2a4996e560dfefb2bfdc924b6cdb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Before use, conditioned media from virus-infected cells (18 hpi, MOI of 0.5) were UV-irradiated for 5 minutes to inactivate virus. UV-irradiated conditioned media were tested in IMR-5 cells to monitor virus inactivation.", "TET-21N cell line (derived from SH-EP) harbors a repressible control system to regulate the expression of exogenous N-myc at will. 26 N-myc overexpression was induced by doxycycline withdrawal from culture medium for 48 hours. TET-21 control cells (TET-21C) harbor the same repressible system except that exogenous N-myc gene is not present. N-myc expression was assessed by RT-PCR and western blot.", "Molecular Therapy -Oncolytics (2016) 16005 Official journal of the American Society of Gene & Cell Therapy 24 hours. Supernatants were harvested, centrifuged and either four times concentrated or not. FBS was added (5% final concentration) and supernatants were used as conditioned media. For protection assays, SK-N-AS was cultured in conditioned media or regular DMEM medium (10% FBS) overnight followed by infection (MOI of 5 for 48 hours) and viability assays with Alamar blue (Life Technologies).", "Global gene expression analysis by microarray assays Microarray assays using Affymetrix GeneChip Human Prime View was carried out. Cells either treated or not with doxycycline were infected at an MOI of 0.5 for 18 hours, time by which around 50-60% of cells expressed GFP encoded by VSV\u0394M51. RNA was extracted with RNeasy Plus Mini Kit (Qiagen). To assess RNA quality, RNA Integrity Number (RIN) was measured with Agilent RNA 6000 NanoChip on 2100 Bioanalyzer (Agilent Technologies, Santa Clara, CA). The quantity was measured using NanoDrop 1000 (NanoDrop Technologies, Wilmington, DE). A total of 100 ng of RNA for each sample with a RIN higher than 9 was labeled with 3' IVT Express Kit (Ambion) and hybridized to Affymetrix GeneChip Human PrimeView Arrays at 45 \u00b0C for 16 hours. Arrays were stained and washed using Affymetrix GeneChip Fluidics_450 following manufacturer's protocol and scanned using the Affymetrix GeneChip Scanner 3000 7G System. For data analysis, Affymetrix GeneChip array data files were generated using GeneChip Command Console Software (AGCC) and statistical analysis was carried out using Partek Genomics Suite 6.0 (Partek Incorporated). Analysis of variance, P < 0.05, was applied as statistically significant. Fold changes of \u2265 1.5 and \u2264\u22121.5 with P < 0.05 were included in the analysis." ] },{ "paper_id": "ac29d39e0b59cf2d1469af974756f5efbf3c26dd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "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).", "Cells, short interfering RNAs, short hairpin RNAs and plasmids HEK293, 293T and MCF7 cells were obtained from American Type Culture Collection. The short interfering RNAs (siRNAs) targeting PCAF (siPCAF-6: 5 0 -CGGAG TGTACTCCGCCTGCAA-3 0 and siPCAF-7: 5 0 -CAGCA AATAATTGTCAGTCTA-3 0 ) and p300 (sip300-7 siRNA: 5 0 -TTGGACTACCCTATCAAGTAA-3 0 and sip300-10: 5 0 -CCCGGTGAACTCTCCTATAAT-3 0 ) were purchased from Qiagen, and the short hairpin RNAs (shRNA) against PCAF (shPCAF: 5 0 -TAGATGAGGT GCTTTGAGCAGTTCTGAAA-3 0 ) was obtained from Origene. Human XBP-1S and XBP-1U expression plasmids were previously described (26) . The plasmids for expression of human PCAF and p300 were obtained from Open Biosystems. The plasmids containing a series of hemagglutinin (HA) tagged XBP-1 deletions were generous gifts from Dr Hiderou Yoshida (27) . The firefly luciferase reporter plasmids, HTLV-Luc and BiP-Luc [including wild-type and ER stress response (ERSE) mutant BiP-Luc plasmids], were kindly provided by Dr Arnold Rabson and Dr Kazutoshi Mori, respectively (28, 29) .", "Recent studies show that cellular UPR can be induced by infection of various viruses, including Kaposi's sarcoma-associated herpesvirus (13) , West Nile virus (14) , Japanese encephalitis virus (JEV) (15) , hepatitis C virus (16, 17) , human cytomegalovirus (HCMV) (18, 19) , dengue virus serotype 2 (DEN-2) (20) , severe acute respiratory syndrome coronavirus (21) , coronavirus (22) , Epstein-Barr virus (23) and Semliki Forest virus (24) . Some viruses, such as JEV and DEN-2, use the ER of host cells as the primary site of glycoprotein synthesis, genomic RNA replication and virus particle maturation, and thus trigger ER stress as well as UPR (15, 20) . In the other case, some viral proteins, such as HCMV US11, traffic to the ER of host cells and induce UPR (18) . The transactivator of human T-lymphotropic virus type 1 (HTLV-1), Tax, has been shown to be localized in the organelles associated with protein secretion including ER and Golgi complex (25) , raising the possibility that HTLV-1 may affect cellular UPR as well. We previously discovered that XBP-1S stimulates basal and Tax-activated transcription of HTLV-1. Infection of HTLV-1 was found to induce UPR and up-regulation the expression of several UPR genes, including XBP-1. Furthermore, XBP-1 was identified as one of the Tax target genes in cells (26) . Our results not only revealed a positive feedback loop between HTLV-1 and the host cells, but also suggested an important role for XBP-1 in transcriptional regulation of HTLV-1." ] },{ "paper_id": "ac8fb04ef901727de6945ff40313cd94423d1da3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "acb8da60c4ee0bcc69d4c1da2786a429e7a374ee", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All densitometric data obtained from the SQRT-PCR were analysed using SPSS 9.0 (Statistical Package for the Social Sciences, SPSS Inc., Chicago, IL, USA). All data assembled in this study were tested for normal distribution using the Kolmogoroff-Smirnov test. Expression profiles of each chemokine were analysed among each group using simple block variance analysis and Kruskal-Wallis test for normally and non-normally distributed data, respectively. A p-value < 0.05 was considered significant, and a p-value < 0.01 was considered highly significant.", "We used the following oligonucleotides for high-stringency PCR reaction as listed below. Glutaraldehyde-3-phosphate-dehydrogenase (G3PDH) was used to compare expression of the genes mentioned below: " ] },{ "paper_id": "acbe63db4d9bb13ebde8af3b75b797cb29bbd5cb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Subsequently, the erythrocytes were washed with PBS and used in HA tests conducted with the trypsin (5 \u03bcg/mL) pre-treated PDCoV.", "Hemagglutinin, an envelope glycoprotein of some enveloped viruses, can adsorb to erythrocytes. In the presence of virus particles, erythrocytes clump together as a result of the interaction between hemagglutinin and erythrocytes, leading to a lattice formation [5] . Hemagglutination (HA) assessment has been widely used for detecting and quantifying viruses that cause red blood agglutination, such as orthomyxoviruses, paramyxoviruses, and encephalomyocarditis virus [6] . Some viruses of the family Coronaviridae, such as bovine coronavirus (BCoV), human coronavirus OC43 (HCoV-OC43), hemagglutinating encephalomyelitis virus (HEV), avian infectious bronchitis virus (IBV), and PEDV, have been shown to possess the ability to hemagglutinate erythrocytes [7] .", "Porcine deltacoronavirus (PDCoV), a member of the Deltacoronavirus genus, causes diarrhea and vomiting in pigs of any age [1] . The clinical symptoms of PDCoV are similar to those of porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV), but the mortality rates are lower in PDCoV-affected nursing pigs [2] . PDCoV was first identified in pigs in Hong Kong in 2012, while the first PDCoV outbreak in swine herds was reported in the United States in 2014 [3] . Subsequently, PDCoV was detected in Canada, South Korea, mainland China, Thailand, Laos, and Vietnam, indicating that it is widespread among the world's pig populations; moreover, PDCoV can have devastating effects on the swine industry [4] . However, no treatments or vaccines are available for PDCoV." ] },{ "paper_id": "acec6ab753cc4f3bdc2dd1e9b63d3ae8e32a3bae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The affected lungs showed severe consolidation with tissue consistency approximating that of the liver (Fig. 1 A) . The SARS lungs were, on average, three to four times heavier than normal lungs. Conventional light microscopy (LM) demonstrated widespread damage of the lung parenchyma, with extensive fibrin exudate, edema, interstitial thickening, and extensive hyaline membrane formation (Fig. 1 B) . There was extensive alveolar collapse, and the remaining alveoli were filled with fluid and desquamated alveolar and bronchial epithelial cells. Alveolar epithelial hyperplasia was evident. Large syncytial cells with multiple nuclei were present. Small vessel vasculitis was seen. However, cellular infiltrate was rare and conspicuously absent in most cases, and lymphocytic infiltration was sparse. Overall, the diffuse alveolar damage resembled that seen in adult respiratory distress syndrome, but with a paucity of inflammatory infiltrate.", "Infection of neurons seemed to occur in only selected areas of the brain in all eight cases. The scattered red degeneration of the neurons is a sign of neuronal hypoxia/ischemia. The observation of virus in neurons may provide an explanation for the higher than usual incidence of neuronal and psychologic abnormalities that are seen in patients who have late-stage SARS (22, 23) . These neurologic symptoms previously were attributed to negative social pressure during the epidemic.", "Previously, there were reports that immune overreaction played a role in the immune injury and pathogenesis of SARS. However, there has been no concrete evidence to support this notion. The data on lymphokine production in SARS was not conclusive, and there was no report of a uniform and consistent increase of lymphocytes in those patients. The release of respiratory symptoms following steroid treatment (19) could be attributed to the antiinflammatory effect of the therapies, rather than immune suppression. Although the role of immune hyperreaction, particularly in the early phase of the diseases, could not be ruled out completely, the evidence that we obtained points more to a direct immune injury as an important component in SARS pathology and pathogenesis." ] },{ "paper_id": "ad3eea30652fd3de7debecd8a1c4723018a0a465", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ribosomes produce proteins by translating the sequence of an mRNA into the amino acid sequence of a protein.", "phenomenon that produces a single protein from a discontinuous reading frame. Bypassing is a post-decoding event that requires multiple signals in the mRNA. In the following, we will discuss the mechanisms of each of these recoding events in light of the recent progress of biochemical, kinetic and structural studies.", "5 -CUG-3 in S. cerevisiae explains why glutamine is preferentially incorporated at UAA compared to UAG, despite the same non-conventional G-U base pairing that forms upon decoding. The modification of the tRNA bases within the anticodon or in its vicinity affects its ability to read stop codons (34, 55) . The prevalence of readthrough varies between organisms. Analysis of the stop codon contexts of 12 Drosophila species and ribosome profiling studies suggested potential readthrough in several hundred Drosophila genes (44, 56) . However, similar genomic analyses and profiling studies of human genes have so far found only a few candidate genes (44, 56, 57) . Computational analysis of readthrough protein isoforms suggests that these are mostly long, modular proteins with intrinsically disordered C-termini of low sequence complexity (58, 59) . The lack of a structurally ordered C-terminus might provide conformational flexibility that allows the readthrough extensions to perform functions without distorting the native protein. The majority of readthrough genes identified in D. melanogaster have regulatory roles, and appending a functional C-terminal extension may confer conditional advantage to protein function." ] },{ "paper_id": "ad7e256a901378cfdb314e11ab3504eda659df42", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Although the growth of the public sequence databases has been rapid, sequence diversity has not grown as quickly.", "Motif-based probe design provides higher coverage than virus genome tiling", "Supplementary Data are available at NAR Online. ", "Probe sequence composition is a major determinant of hybridization signal and is responsible for much of the variance between probes that target the same nucleic acid strand. Probe-target thermodynamics have been successfully modeled to predict fluorescence (41, 42) , control for variance (43) and even estimate concentrations of target detected in samples (44) . Observing that some probes with more than five mismatches to their targets showed strong fluorescent signal, we concluded that sequence composition is a major factor in our array platform." ] },{ "paper_id": "ad8c7c22faa32a928133bfeb767353400262040c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors do, however, believe strongly that healthcare is a public good, not a private 443 commodity.", "The authors do, however, believe strongly that healthcare is a public good, not a private 477 commodity.", "Objectives 40 This qualitative study attempts to understand the perspectives and experiences of United 41 States-based global health physicians and program leaders on how their experiences abroad 42 influence their healthcare practices in the United States. 43 44 Design 45 We administered online questionnaires and open-ended, semi-structured interviews with 46 global health physicians and program leaders affiliated with United States-based academic 47 medical centers. We utilized open coding procedures and content analysis to derive relevant 48 themes from the data." ] },{ "paper_id": "ad98979eada6e333a276d39efdce21779d538625", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Compound 4 was evaluated against several TK and DNA polymerase mutants derived from the reference Kos strain by CPE reduction assay using as reference drugs ACV, GCV, BVDU, foscavir, CDV and adefovir (ADV).", "For the synthesis of other target ANPs, compounds 5-9 (Scheme 2), previously reported 26,30-34 guanine containing ANPs 11-15, have been exploited as a starting material. Standard diazotization of compounds 11-15 followed by 2-hydroxy-dediazoniation afforded the desired xanthine-based ANPs 5-9 in moderate to good yields (36-82%).", "The synthesis of 9-[2-(phosphonomethoxy)ethyl]xanthine (PMEX, 4, Scheme 1), a xanthine analogue of the well-known antiviral agent adefovir (PMEA), 28 has been reported by our group earlier. 27 The microwave-assisted hydrolysis of 2,6-dichloropurine derivative 10 29 in aqueous HCl afforded the desired xanthine compound 4 in a 85% yield.", "The concentration and ratio of purine nucleotides and deoxynucleotides in the nucleotide pool is highly regulated in order to maintain the proper function and genetic stability of mammalian cells. 1 Imbalances in (deoxy)nucleotide pool may have mutagenic consequences 2 and may lead to various diseases, such as combined immunodeficiency (loss of purine nucleoside phosphorylase (PNP) function), 3 hyperuricemia (loss of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) function) 4 or cancer (uncontrollable activity of inosine-5 0 -monophosphate dehydrogenase, IMPDH). 5 Xanthosine monophosphate (XMP, 1, Figure 1 ) is an important intermediate in the de novo synthesis of guanine nucleotides and its concentration is essential for the maintenance of guanine nucleotide pool, 6 where XMP serves as a substrate for guanosine monophosphate synthase, 7 that produces guanosine monophosphate (GMP). XMP is formed either from inosine monophosphate (IMP) by IMPDH or via salvage pathway using hypoxanthine or xanthine phosphoribosyltransferase. The XMP level is regulated by 5 0 -nucleotidase that hydrolyzes XMP to xanthosine." ] },{ "paper_id": "ad9ac0ac5e7da097253fd545b56e2b15ee9de34f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "through MDs simulations (41) . This water-mediated hydrogen bond with y is believed to restrict y motion and stabilize A-y base pairs (41, 69, 70) , which are most prevalently found at positions 31-39 (14) .", "Supplementary Data are available at NAR Online. National Science Foundation (DUE-0431664 and CHE-0521063) and Truman State University. Funding to pay the Open Access publication charges for this article was provided by the Petroleum Research Fund.", "Conflict of interest statement. None declared.", "MD trajectories were propagated with a 2.0 fs time step, employing the SHAKE algorithm (37) on all hydrogen atoms, with a nonbonded cutoff of 9.0 s. The pairlist was updated every 25 steps. Constant pressure (1 atm) and temperature (300 K) were maintained according to the Berendsen coupling algorithm (38) . The equilibration protocol of Cheatham was followed (39) similar to previous simulations of nucleic acids (40) (41) (42) (43) (44) (45) . Simulations were allowed to equilibrate under production-run conditions for at least 2.0 ns before collection of statistics over 4.0 ns." ] },{ "paper_id": "addfc08009d7a0975783d6208103e9c3c2a41d27", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "adf7da31a81303705ded170f6f60ba708834d024", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "adfc269121799067d9f6d6f7894f12cceb116059", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supported, in part, by grants from the National Nature Science Foundation of China (81571983 and 81371805), the Program of National Ministry of Science and Technology (2014ZX09J14105-04B) and funding of State Key Laboratory of Pathogen and Biosecurity (SKLPBS1509).", "www.ccmjournal.org" ] },{ "paper_id": "ae1f8642745871a574c0fe8193112b06a8b07212", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "human adenovirus | short fiber | polysialic acid | glycan receptor | glycan microarray", "ACKNOWLEDGMENTS. The neoglycolipid-based glycan microarrays contain several saccharides provided by collaborators whom we thank as well as members of the Glycosciences Laboratory for their collaboration in the establishment of the microarray system. We gratefully acknowledge support from the Swiss Light Source staff during X-ray data collection. " ] },{ "paper_id": "ae665e8da5fde86d27ddfb4b31851550c5db92be", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ae8ccebf81f9909e96af7c707cca66e5ed716b1f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Surveillance of Middle East respiratory syndrome coronavirus (MERS-CoV) was conducted to explore the possible introduction and circulation of this novel virus in Catalonia, northeastern Spain. Five hundred and sixty-three samples from mild and severe respiratory infections collected between January 2012 and April 2013 were screened using real-time RT-PCR. All samples were negative, suggesting that MERS-CoV is not circulating silently in Catalonia.", "The acute respiratory infections surveillance programme in Catalonia, PIDIRAC (daily information system for acute respiratory infections in Catalonia), performs surveillance during the influenza activity season from October to May (http://www.gencat.cat/temes/cat/salut.htm). This surveillance system is based on 38 sentinel primary-care centres in which physicians collect nasopharyngeal swabs from patients with acute respiratory infections as well as 11 sentinel hospitals that report cases of severe confirmed influenza virus infection admitted to their facility. Samples from the primary-care centres were screened at our laboratory for respiratory viruses using multiplex nested RT-PCR assays [8, 9] ", "The emergence of MERS-CoV represents a public health concern, although the virus does not seem to be as efficiently transmissible between people as the severe acute respiratory syndrome coronavirus. Many questions regarding the epidemiology of the virus remain unanswered, highlighting the importance of continued surveillance and research on MERS-CoV. To our knowledge, this is the first exploratory study of MERS-CoV in the general population using already established sentinel networks. Data obtained through active surveillance for MERS-CoV may be helpful for the global monitoring of the virus. Moreover, our results may serve as baseline reference data in case the virus starts to circulate in Catalonia, northeastern Spain." ] },{ "paper_id": "aeb155140e7a792d4af481ce9d14376046ba856d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The following plasmids were used: pLJ, a recombinant retrovirus expression vector (15), a gift of Dr. R. Mulligan, The Whitehead Institute, Boston, MA; pSP125E encoding the/~-iactamase signal peptide fused to chimpanzee c~-globin (40), a gift of Dr. V. R. Lingappa, University of California, San Francisco, CA; and pLaSl (13) , containing a 462-bp eDNA encoding anglerfish preproSRIF I to which 5' and Y Eco RI-Bam HI linkers were added (41) . Rabbit anti-human hemoglobin antiserum was purchased from Cappel Laboratories (Cochranville, PA).", "Peptide hormone-producing cells characteristically concentrate and store their secretory product in electron-dense secretory granules (32) . Upon stimulation by an extracellular signal, these granules fuse, through a calcium-dependent process, with the plasma membrane releasing their contents into the external milieu. This type of secretion is designated \"regulated\" or \"stimulated\" (see references 4, 14, and 33 for recent reviews). Hormone-secreting cells also undergo basal or \"constitutive\" secretion whereby nonhormone secretory proteins and plasma membrane proteins are neither concentrated nor stored and are transported in vesicles which continuously fuse with the plasma membrane in a calciumindependent manner (4, 14) . Since hormone-secreting cells undergo basal secretion, a mechanism must exist that discriminates between molecules destined for the regulated or constitutive pathways.", "Plasmid DNAs were amplified in Escherichia coli strain MC1000, grown in the presence of 40 #g/ml of kanamycin and plasmid DNA prepared. Infectious virus particles containing globin-related RNA transcripts were generated by transfecting Psi-2 cells (22) with plasmid DNA." ] },{ "paper_id": "aec2e91fcbfb520fd6c2996efe20c6f42afc9a69", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All data were analyzed using the SAS version 9 statistical software. As most of the statistical tests were performed one-sided, p values \u00a3 0.025 indicate statistical significance.", "Additional symptoms such as fever, fatigue or headache may occur.", "This is an open-access article distributed under the terms of the CC-BY-NC-ND 3.0 License which permits users to download and share the article for noncommercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is credited." ] },{ "paper_id": "aef9406b4054bc208dbb8735e5803fd25caa3eba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Mehmet Ceyhan, MD, Prof., received non-financial support from Pfizer, Turkey. Yasemin Ozsurekci, MD, received non-financial support from Pfizer, Turkey. Kubra Aykac, MD, received non-financial support from Pfizer, Turkey. Basak Hacibedel, MSc, is employee of Pfizer, Turkey. Egemen Ozbilgili, MD, is employee of Pfizer, Turkey.", "Data were analyzed using the Predictive Analytics Software (PASW) version 18.0 (SPSS Inc., Chicago, IL, USA). Descriptive statistics were expressed as number and percentage for categorical variables and as mean, standard deviation, median (interquartile range) for numerical variables. In comparing two independent groups, Mann-Whitney U test was used for nonnormally distributed numerical variables. A p value <0.05 was considered statistically significant. The human capital approach was used in the productivity loss calculation.", "This work was supported by Pfizer Pharmaceuticals." ] },{ "paper_id": "aefb4a29e4c933751675ed871bfa09305f1ffee2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "These authors contributed equally to this work.", "Functions of IDPs and IDPRs are widely varied, as they are influenced by their multiple dynamic conformations. Most known functions of IDPs and IDPRs involve recognition, however many other diverse functions have been identified.", "No potential conflicts of interest were disclosed." ] },{ "paper_id": "af0768141c00f1317b4fb9c74080d1510de93f32", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "From August 2014 to November 2014, the ASP/physician liaison collaborative team reviewed a total of 355 cases from 2 inpatient geriatric units. The mean age of patients was 73: 47%" ] },{ "paper_id": "af82e1f7e181393a18fb017ee98abdb17fb78d42", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CNS manifestations are of particular concern, as long-term deficits are possible. Both primary and reactivation HLH ", "A number of conditions are associated with secondary HLH. By prevalence, these include viral infections (29%), other infections (20%), malignancies (27%), rheumatologic disorders (7%), and immune deficiency syndromes (6%). 35 These inciting conditions are addressed below.", "The author has no disclosures to make in relation to this article.", "HLH is well known to occur in the setting of various autoimmune disorders. Lupus erythematosus is one of the more common conditions reported. 35, [169] [170] [171] [172] [173] [174] [175] [176] [177] [178] MAS is a serious and often fatal complication in children with systemic juvenile idiopathic arthritis (sJIA) 175, [179] [180] [181] [182] [183] [184] [185] [186] and in adults with Still's disease. 35 " ] },{ "paper_id": "af9e845d14fdb65bcb14b59b0f3ddc76a9517c5a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "afa3ae140a0daa1214d7e0f550ebf2e7843f9796", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "reading exonuclease (ExoN) that increases replication fidelity (9) (10) (11) (12) . Although nidoviruses are known to infect mammals, birds, fish, and crustaceans, no nonavian reptile nidovirus has been previously described.", "In nidoviruses, the ORFs 3= to the replicase genes encode structural and accessory proteins. The number and organization of these genes vary widely across nidovirus taxa, and in many cases there is little or no detectable similarity between sequences of more distantly related species (1, 9) .", "Transmission electron microscopy. Formalin-fixed lung samples from BP1 and BP6 were cut into 1-mm cubes and transferred to 4% paraformaldehyde-2.5% glutaraldehyde in 0.1 M sodium cacodylate buffer, pH 7.24. Fresh lung from BP6 was also cut into small cubes and fixed directly in 4% paraformaldehyde-2.5% glutaraldehyde in 0.1 M sodium cacodylate buffer, pH 7.24. Fixed tissues were processed with the aid of a Pelco BioWave laboratory microwave (Ted Pella, Redding, CA, USA). The samples were washed in 0.1 M sodium cacodylate buffer, pH 7.24, postfixed with buffered 2% OsO 4 , water washed, and dehydrated in a graded ethanol series, 25%, 50%, 75%, 95%, and 100%, followed by 100% acetone. Dehydrated samples were infiltrated in graded acetone-Spurrs epoxy resin (Electron Microscopy Sciences, Hatfield, PA) 30%, 50%, 70%, and 100% and cured at 60\u00b0C. Cured resin blocks were trimmed, thin sectioned (70 nm), and collected on Formvar-coated copper grids, poststained with 2% aqueous uranyl acetate and Reynolds lead citrate. Sections were examined with a Hitachi H-7000 TEM (Hitachi High Technologies America, Inc., Schaumburg, IL), and digital images were acquired using a Veleta 2k by 2k camera and iTEM software (Olympus Soft-Imaging Solutions Corp., Lakewood, CO).", "Ultrastructure of virus morphogenesis. Two cases with moderate to severe diffuse proliferative pneumonia were selected for ultrastructural examination by TEM (snakes 2 and 6) ( Table 1) (14) . Virus-like particles were observed within pneumocytes lining the faveoli of both snakes. These particles were observed within ciliated and mucous epithelial cells overlying smooth muscle bundles at the tips of faveolar septa and alveolar type II cells lining faveolar spaces of both snakes (Fig. 3A) . The particles corresponded to stages of a virus with both circular and bacillary (elongated rod-shaped) nucleocapsids and were seen within electron-lucent areas of the cytoplasm. At a higher magnification, bacillary nucleocapsids contained a lucent core that was surrounded by fine granular cytoplasmic material (Fig. 3B) . The uncoated intracellular capsids measured 10 to 12 nm. Nucleocapsids lined up along membranes of cytoplasmic vesicles of uncertain origin, and as they progressed into a vesicle, a membrane coat was acquired (Fig. 3C ). Cross sections of mature virions having a lipid envelope and surface spikes were also identified in cytoplasmic vesicles (Fig. 3D ). Bacillary virions were observed within vesicles subadjacent to epithelial cell membranes on the free cell surface (Fig. 3E ) and extracellularly between cilia and microvilli projecting into the air passageway (Fig. 3F) . The mature particles measured approximately 50 by 180 nm. In some sections, filamentous bacteria (200 nm by 200 m) were occasionally observed between cilia and closely associated with the cytoplasmic membrane (Fig. 3F) ." ] },{ "paper_id": "afa4ca223097866f6e31d75570448a22db0f72c5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "afaa73edec3f6944af5018e8426d3333d3a9986a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplementary materials are available at The Journal of 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.", "p3E5E-Luc plasmid, encoding the firefly Luc reporter gene, was kindly provided by Elke Muhlberger (Boston University, MA). Minigenome RNA was synthesized and minigenome activity measured as described previously [16] .", "Ebola virus (EBOV) is an emerging pathogen causing severe, often lethal hemorrhagic fever in humans and nonhuman primates. Despite significant progress, there are no licensed therapeutics to treat or prevent associated disease [1] . EBOV is a filamentous enveloped virus belonging to the family Filoviridae. The virion surface is studded with homotrimeric glycoprotein complexes, which are the sole viral determinant of binding to host cell receptors [2] . The majority of EBOV particles enter cells through macropinocytosis and subsequently traffic through endocytic compartments before release of the viral nucleocapsid into the cytoplasm, where genome replication takes place [3, 4] ." ] },{ "paper_id": "afb768d18ca2b01aacb890d056487c1a00681e72", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "None of these aforementioned findings have been replicated, thus prompting us to review the potential determinants of responsiveness.", "Among children discharged home, the time to complete recovery will vary widely between individuals.", "(iv) length of active treatment defined as duration between the first and last salbutamol inhalation.", "Oral corticosteroids are the cornerstone of acute asthma management in the emergency department." ] },{ "paper_id": "afc2f0a5be2fb3bd3355e04f45d827e9e73419bb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "RNA was tested for influenza A, B, and D, 4-6 coronavirus, 7 and enterovirus 8 using Superscript III One-step RT-PCR with Platinum Taq Polymerase. Extracted DNA was tested for adenovirus by realtime PCR using a QuantiNova Probe PCR kit (Qiagen) ( Table 1 ). 8 ", "Article texed for 15 s, and transferred to a cryovial tube and stored at -80\u02daC until further used. Styrene filters from SKC cassettes were swabbed with FLOQSwabs soaked in 0.5% BSA fraction V solution. Swabs were then placed in 50mL falcon tubes, vortexed for 15 s, and transferred to cryovials. QIAamp viral RNA kit and QIAamp DNA Blood kit (Qiagen) were then used to extract RNA and DNA, respectively, from the sample solutions following the manufacturer's protocol.", "In addition to bioaerosol sample collection and handling methods, environmental conditions can also influence the viability of airborne viruses and downstream virus recovery. For example, prolonged sampling periods can compromise stability of virus-laden aerosols and result in decreased viral recovery. 12 Additionally, it has been demonstrated that the survival of airborne influenza virus depends on ambient temperature, relative humidity (RH) and ultraviolet radiation levels. 13 Specifically, infectivity of influenza in a simulated examination room was reported to be the highest at 7-23% RH, moderate at 57% RH and lowest at 43% RH. 14 Although we did not record temperature and RH at our sampling site, a previous bioaerosol study recorded levels ranging from 54% to 68% RH in three different hospitals in Singapore. 11 High RH levels in Singapore could explain the low percentage of influenza A viruspositive aerosol samples in our study." ] },{ "paper_id": "b02e71f6059bdc0eb63e7e8999869e7c6e5c31fb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Details about published and standard methods (cell culture, plasmids, virus infections, replicon transfections, the TISS assay, rescue experiments, analysis of viral polyprotein processing, siRNA experiments, immunofluorescence microscopy and liposomal assays) are provided in the Supplemental Experimental Procedures.", "The family Picornaviridae contains many important human and animal pathogens. The genus Enterovirus includes poliovirus (PV), coxsackievirus (CV), echovirus, several numbered enteroviruses (e.g. enterovirus-71, EV71) and human rhinovirus (HRV). Except for PV, no vaccines are available to prevent infections with enteroviruses and no antiviral drugs are available for treatment. Other important human picornaviruses include hepatitis A virus and human parechovirus (HPeV). Well-known animal pathogens are foot-and-mouth disease virus (FMDV) and encephalomyocarditis virus (EMCV).", "Data are presented as means \u00b1 SEM. Replication data were analyzed by pair-wise comparisons of conditions using one-tailed Student's t-test. Statistics significance is indicated as * p<0.05, ** p<0.01, *** p<0.001." ] },{ "paper_id": "b03c7f6241f74f5934ebec0287004bf9ff784922", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b05030dae8169323463be3fd847e447f48d4f902", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b06f31e9139111afe43967edf19c19335b9e79a4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The expression of chimeric proteins in mouse Baib/c 3T3 cells was accomplished by direct microinjection of plasmid DNA into nuclei using a procedure described by Capecchi (5) . Subconfiuent cultures of Baibtc 3T3 cells wore grown on 12-ram diam. glass coverslips in DME medium (Gibco Laboratories, Grand Island, NY) supplemented with 10% FBS (Gibco Laboratories), 20 mM Hepes, pH 7.4, and 50 ~g/mi Gentamycin (Gibco Laboratories). Nuclei were injected with plasmid DNA purified using a plasmid purification kit (Qingen Inc., Chatsworth, CA) at 1 mg/ml in PBS containing 1 mM MgC12. The microinjection equipment consisted of an Eppendorf injector 5,242 and a Zeiss micromanipulator MR mounted on a Zeiss Axiovert 10 microscope (Zeiss, Oberkochen, Germany). After injection, the cells were returned to a 5% CO2 incubator at 37~ for 4-5 h.", "There are precedents for TMs serving as topogenic determinants. Most resident integral proteins of the Golgi membrane that have so far been analyzed are retained there by sorting determinants in their TMs (20, 23, 25, 28, 33, 35 , for review see 19) .", "5' ag cta ggt tac cca tac 8at gtt cca gat tac get age ttg ggt a 3' HA-1 3' t cca atg ggt atg cta caa ggt cta atg cga tcg aac cca ttc ga 5'", "The eDNA sequence of rat gp210 has been previously determined from a series of overlapping, partial eDNA clones (37) . To assemble a full-length eDNA molecule encoding rat gp210, we used the polymerase chain reaction (PCR) to synthesize three independent eDNAs each representing approximately one-third of the 5,658-nucleotide coding region: a 5' fragment (nucleotides -12-1,997), a middle fragment (nucleotides 1,988-3,854), and a 3' fragment (nucleotides 3,845-5,708). The templates used for amplification were the partial cDNA clones. Oligonucleotide primers were designed on the basis of the published eDNA sequence of gp210." ] },{ "paper_id": "b07181f9086788a6a4f7de90129118352320e993", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Human whole blood Micropillar array filter (21) White blood cells or whole blood from a patient's blood m-filter (65) Mice whole blood, and Nasal aspirate from a patient symptomatic of whooping cough m-SPE", "SUBSTRATES AND SURFACE TREATMENTS TO REDUCE BIOMOLECULE ADSORPTION" ] },{ "paper_id": "b08ae4f14b481f3eaa815fce88861d695fafeeb8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b09fe466052873919115ea1da6510a01704c6c3a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This prospective study was conducted between 2017 and 2018 with the approval of the institutional review board and human subject committee at LA Biomed/Harbor-UCLA Medical Center. Informed consent was obtained from all patients.", "We recruited 39 children from 1 to 14 years of age composed of 3 groups.", "Means or medians and standard deviations or interquartile ranges were computed for continuous variables. Frequencies and percentages were compared for categorical variables. Analysis of variance was used if the outcome followed a normal distribution. The Kruskal-Wallis test was used for nonnormal continuous outcomes. Chi-square or Fisher exact tests were used to compare differences in proportions among groups. SAS 9.4 Software (Cary, NC) was used for all data analyses.", "The editors gratefully acknowledge the assistance of Margaret Keller, MD, Lynn Smith, MD, and Joaquin Madrenas, MD, PhD, who reviewed the manuscript." ] },{ "paper_id": "b0a0f45be3069a32ba190502ab88b6df6d520199", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Double-stranded oligonucleotides for EMSA contained the following sequences: Nuclear extracts were prepared (42) and used for gel shift analysis after concentration (Microcon no. 10 columns, Amicon, MA). Quantification was performed on EMSAs under conditions that yield a standard curve for band intensity.", "Supplementary Data are available at NAR Online.", "Charles DeLisi is partially supported by NIH grants A08 POGM66401A and J50 01-130021. Daniel S. Roberts is supported by NIH training grant 2T32 GM00854. Shelley J Russek is supported by NIH/NINDS Grant NS050393. Funding to pay the Open Access publication charges for this article was provided by the Boston University Bioinformatics Program." ] },{ "paper_id": "b0d63875dbdde9df204257c33b47d6277c81b869", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b0d6f7e423d86c57973ae2ca6cbfff3a9acecc0a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b0f4f2cb1c392ec68afaa865ecdd5db824ccf457", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b153ef1a7cb22199b3f2e8901d25a93acf2c7570", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For hemorrhagic fevers, well-documented, relatively recent experience stems from a randomized controlled trial comparing CP (1 single unit of 500 mL) with normal plasma against Argentine hemorrhagic fever [7] . Mortality was 1.1% among the 91 patients who received CP compared to 16 .5% in the 97 patients treated with normal plasma. Of interest, a delayed neurological condition was observed in some patients after CP therapy, occurring several weeks after apparent cure. CP has also been explored against the hemorrhagic disease Lassa fever, with conflicting results [8] [9] [10] [11] .", "The logical next step is to produce hyperimmune globulins from the donated plasma, and several initiatives are focusing on this. As purified and concentrated products, hyperimmune globulins are generally considered to be safer and with higher, less variable antibody titers than CP (Table 2) . They can also be stored for prolonged periods. Animal production of hyperimmune globulins is also under exploration (http://www.faben techcom/technologie/technology/). Pending the building up of such expertise within Africa, production could be outsourced.", "Risk with ABO incompatibility", "Acceptability in EVD context and their family members, at least in the short term. However, a better understanding of plasma donor motivation is required to ascertain whether possible degrees of coercion have occurred. In all 3 high-transmission countries, EVD survivors have organized themselves into survivor associations. Although this has probably substantially eased donor mobilization, more indepth assessments of their potential role are merited." ] },{ "paper_id": "b16173612f53649fbd4db78654874bee5d4d607f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors declare no competing financial interests.", "CRI, cancer-related inflammation; TAM, tumor-associated macrophage; V-ATPase, vacuolar ATPase" ] },{ "paper_id": "b16cc9a6b9fa37d7b10f17e8b1d2c6dff8783911", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "RNA extraction and qRT-PCR were performed as our previously described [7] . Specific primers that were used are as follows: AIF sense, TGTGGAACGTCTTCAACCGA; AIF antisense, AGAGGAAGGCTGCGCAATAA. Actin sense GGACTTCGAGCAGGAGATGG; actin antisense: AGGAAGGAGGGCTGGAAGAG).", "The mitochondrial and nuclear proteins were isolated as the description of the Mitochondria Fractionation Kit and the CelLytic\u2122 NuCLEAR\u2122 Extraction Kit (Sigma-Aldrich, Burlington, MA, U.S.A.), respectively. Protein concentrations were measured using the BCA Protein Assay Reagent (Pierce, Rockford, IL, U.S.A.). The Western blot assay was conducted as we described previously [7] .", "The detection of apoptosis was performed as described by Ding et al [8] . Summarily, harvested cells were washed with PBS for three times and then resuspended in 500 \u00b5l binding buffer, followed by the addition of 5 \u00b5l of Annexin V-FITC and 5 \u00b5l of PI. After incubation for 30 min at room temperature, a total of 10,000 cells were examined. The positive cells was analyzed by flow cytometry using Beckman CytoFLEX FCM (Beckman Coulter, Brea, CA, U.S.A.)." ] },{ "paper_id": "b1870c85dae2f3bd004c29206c9a0281f4a9a249", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We thank Drs. M . Dailey and M . Stoltzfus for critical review of the manuscript, Candia Payne for help with the illustrations, and Paul Reinmann for photographic help.", "M ouse hepatitis virus (MHV),' a member of the coronavirus family, causes several diseases in small rodents, including hepatitis, gastroenteritis, and encephalomyelitis (1) . Strain JHM (MHVJHM) is a prototypic neurotropic strain and causes acute encephalitis as well as acute and chronic demyelinating disease in rats and mice (2-7) .", "Suckling mice inoculated with MHVJHM invariably develop a fatal encephalitis. This disease can be prevented if mice are protected with an infusion of mAb or if they are nursed by immunized dams. Similarly, mice inoculated with an attenuated strain of virus do not develop the acute encephalitis (8) (9) (10) (11) (12) (13) (14) ." ] },{ "paper_id": "b19635e3a0906506d07c05a4dc8ecd8f76f7e077", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b1ac4363950bdd885496d03b7b035ca8bb7e2b3b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Detailed materials and methods for construction of gene knockout cells, immunoblotting procedures, cell-death assays, caspase-3/7 assays, IR, immunofluorescence, and statistics are described in SI Appendix.", "RNase L (21). 2-5A binds to the inactive and latent monomeric form of RNase L, inducing dimerization and activation (also requiring ATP or ADP binding to the protein kinase-like domain of RNase L) (22) (23) (24) . Activated RNase L cleaves viral and cellular RNAs, suppressing viral replication, in part by eliminating virus-infected cells by apoptosis (25, 26) .", "To confirm that RNase L was responsible for AZA sensitivity, RNase L KO A549 cells were transiently transduced with lentiviral constructs encoding either WT or nuclease-dead mutant (R667A) RNase L (34) (Fig. 1G ). Knockin (K-In) of WT RNase L sensitized the cells to AZA, leading to decreased cell survival, whereas introduction of mutant RNase L (R667A) had a diminished effect on cell survival (Fig. 1H) . These results demonstrate that AZA-induced cell death requires RNase L with a functional catalytic domain." ] },{ "paper_id": "b1ce65cde86a570d32ed8ed5462bbff9c6a33fbb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "their Euclidean distance is calculated as follows:", "Evolutionary Bioinformatics", ", , , , , ," ] },{ "paper_id": "b1e4e816bbe16c3dd36ffdead29d576677983864", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b1eb120cfa12a756cba28ee8d08c63aa748f96a8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b1ef060481c45d71c380d4ac3ec6d8a4f0f26945", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b1f4160623b02307f923593f0830bd5ef47e14ed", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The five groups of recommendations set forth by the committee are specific and comprehensive, and are followed by a 'call to action' encouraging sustainable investment and coordination of vested groups.", "The report highlights the gap between current evidence supporting cost-effective health interventions, and low levels of implementation of these proven tools and technologies. There is also an emphasis on building and/or strengthening health systems toward more evidence-based and integrated health care delivery. The authors note the constraints of financing, infrastructure, and trained personnel, but also stress the fundamental role of favorable policy frameworks, capacity-building, and institutional development.", "The United States and global health (NICE) in the UK, provides an alternative model. All told, no single strategy would be infallible, but learning from a variety of contexts and applying a combination of strategies may help reduce expenditures and create a more sustainable US health system.", "Wider translation of available knowledge and technologies into health practice and policy globally must contend with a complex mix and different levels of challenges, and will probably require collective commitments from a number of wealthy nations. Even though the equity gap is large, and the process of addressing these issues looms lengthy and arduous, we cannot ignore our commitment to global health. In the words of Martin Luther King, 'Injustice anywhere is a threat to justice everywhere.' In much the same way, in today's world, poor health anywhere is a threat to good health everywhere. Note 1. Accessible from http://www.nap.edu/catalog/12642.html" ] },{ "paper_id": "b216cb3673df315302fa5747b0ad25ff7ba92162", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b22c9aa91ec989861466462585e303956e6ae949", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Total protein was extracted from cells using radioimmunoprecipitation assay (RIPA) lysis butter and quantified by bicinchoninic acid (BCA) method (Beyotime, Shanghai, China). Protein sample was loaded for electrophoresis and transferred on polyvinylidene fluoride (PVDF) membranes (Millipore, Billerica, MA, USA). After blocking non-specific antigens in 5% skim milk for 2 hrs, membranes were subjected to incubation with primary and secondary antibodies. Bands were exposed by chemiluminescence (ECL) reagents and analyzed by Image Software (NIH, Bethesda, MD, USA).", "The authors report no conflicts of interest in this work.", "Statistical Product and Service Solutions (SPSS) 20.0 (IBM, Armonk, NY, USA) was used for data analyses. Data were expressed as mean \u00b1 standard deviation. The differences among groups were statistically evaluated using Student's t-test when comparing only two groups or one-way analysis of variance (ANOVA) when comparing more than two groups. P<0.05 was considered as statistically significant." ] },{ "paper_id": "b233ca2dc15696ccb328ab3eed768e1ec006f55a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In other situations, such as the systemic treatment of live animals, multiple rounds of in situ phage replication may be required to achieve treatment over a more extended period. In these cases, measurements of phage sensitivity that include the phage's ability to propagate and infect new hosts would be appropriate.", "Across the different approaches, vaccination plays a critical and often cost-effective role in reducing antibiotic use by reducing the incidence and severity of high-impact diseases. However against certain respiratory diseases in cattle, yet it may be more economical to treat diseased animals with therapeutic doses of antibiotics when the need arises.", "To help ensure judicious antibiotic use, there is increasingly greater veterinary oversight. In 2014, the American Association of Avian Pathologists and the American Veterinary Medicine Association issued guidelines for judicious antibiotic use on poultry farms, guidelines including veterinary oversight, diagnostic testing prior to antibiotic administration, and treating \"as small a population as possible\" with \"as specific an antibiotic as possible\" for the indicated disease. 46 There are also greater efforts to educate independent producers that are not part of vertically integrated systems and who may have less veterinary oversight. The Pork Quality Assurance Plus program, revised in 2013, educates producers about strategies to reduce the level of antibiotic residue on farms and in food animal products. 47", "The most established approach to reducing antibiotic use in animal agriculture is through strategic management of poultry flocks and swine and cattle herds. This approach is multifaceted; there is no one single management practice that producers rely on, but instead a combination of practices, including stringent sanitation, waste management, biosecurity, vaccination programs, highquality nutrition, disease surveillance, and vector control at multiple stages of the production chain. The poultry industry is particularly conducive to this type of management because of the degree of vertical integration within the industry and the greater control at each production stage that this structure provides." ] },{ "paper_id": "b294375c51953d106bead1dd39809747c9f46466", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.00271-13/-/DCSupplemental.", "Text S1, DOCX file, 0.1 MB. Figure S1 , TIF file, 13.9 MB. Figure S2 , TIF file, 13.9 MB. Figure S3 , TIF file, 13.9 MB. Figure S4 , TIF file, 1.3 MB. Figure S5 , TIF file, 13.9 MB. Figure S6 , TIF file, 13.9 MB. Figure S7 , TIF file, 13.9 MB. Table S1 , DOCX file, 0.1 MB. Table S2 , DOCX file, 0.1 MB." ] },{ "paper_id": "b29af8a410b032d1159bf9cefe0654c43f3503d9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Initially submitted August 6, 2018; accepted for publication March 27, 2019." ] },{ "paper_id": "b2f0e12f8f1cb35be12a8b139547c7d570aedaf0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We report a case of primary bronchial carcinoma associated with bone marrow micrometastasis and monoclonal gammopathy in a cat. To the best of our knowledge, this is the first report of this metastatic pattern and paraneoplastic manifestation of feline bronchial carcinoma.", "An 8-year-old, female, neutered, domestic shorthair cat was admitted for appetite loss, dysphagia, weight loss, lethargy and coughing. Its body condition was 2/9 on the World Small Animal Veterinary Association score (Global Nutrition Committee). Clinical examination revealed dyspnoea and a non-productive cough. No other abnormalities were detected on physical examination.", "Based on these findings, a diagnosis was made of bronchial carcinoma associated with bone marrow metastases and paraneoplastic monoclonal gammopathy. Pneumonectomy and adjuvant chemotherapy was declined by the owner and palliative treatment with long-acting injectable glucocorticoid (Depo-Medrol; Zoetis, 1 mg/kg SC) was administered. The cat was euthanased 2 months later owing to anorexia and poor general condition." ] },{ "paper_id": "b2ff10bcb290b39b39f3f8a2206555baad677a5d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Bacteria were isolated from appropriate culture media and incubation conditions prior identification following microbiological standard procedures based on morphological, cultural, and biochemical or antigenic characters. Strains were identified if the bacterial load was at least 10 5 CFUs/mL. ", "Bacterial single infections were also very rare: S. pneumoniae (2%), M. catarrhalis (2%), and H. influenzae (1%).", "Data were analyzed using R statistical software version 3.3.1. 11" ] },{ "paper_id": "b322c2b004bb384ff72b6da2ee511e6b13792bc7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Finally, without loss of generality, we fix the removal time to 3 d (15, 47, 48) .", "Homogeneous Mixing Network. This model assumes a single fully connected network. Following the notation introduced above, we have a ij = w for each i and j, where w = 1/(N \u2212 1) and N is the total number of individuals in the population." ] },{ "paper_id": "b32f99009279a618af74a7990d891b38603c0b71", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Viruses exploit a number of strategies to evade host immune recognition and to facilitate viral replication. Some of these strategies involve viral-derived or endogenous cellular ncRNAs that interact with host immune responses [60] .", "The role of tRFs in cancer was first reported by Lee et al 3 .", "tRNAs are indispensable components of the translational machinery, hence one can surmise that tRNA cleavage affects protein synthesis. However, the mode of translational regulation by tRNA cleavage is not simply a result of change in the mature tRNA pool available for protein synthesis. Ivanov et al. showed that tRNA halves generated by ANG during stress play an active role in inhibiting protein synthesis and triggering the phospho-eIF2\u03b1-independent assembly of SGs [44] ." ] },{ "paper_id": "b36310af655a9ba95c32c0d8e88e5fb445edb7a1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For s > 0, F(s) represents the cumulative distribution function of the gamma distribution. We characterized the expected number of new incident cases E [c i,t ] in type i at symptom onset week t as follows,", "We estimated model parameters and made projections using a Monte Carlo Markov Chain (MCMC) method in a Bayesian framework. Point estimates and corresponding 95% credibility intervals were drawn from the posterior probability distribution. All statistical analyses were conducted in R version 3.5.2 (R Foundation for Statistical Computing, Vienna, Austria) and the 'rstan' package (No-U-Turn-Sampler (NUTS)) (see Table 1 ).", "None." ] },{ "paper_id": "b3707acee35230b2cb6c548837f7f6ca94a26f6b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Two months after completing the MWDT all research cats were transitioned over to a hairball control diet (Adult Hairball Control Light Dry; Hill's Science Diet) because some hairballs were noted in the enclosures of a few cats. The new diet contained a higher sodium level of 123 mg/100 kcal metabolizable energy (ME) vs the previous diet, which contained a sodium level of 90 mg/100 kcal ME. In an attempt to redirect the chronic polydipsic behavior additional enrichment was added to the cat's daily routine; for example, food pellets were placed in a treat dispenser apparatus (Egg-Cersizer Cat Toy; Petsafe) and grooming by animal caretakers was increased to twice weekly from once weekly. A cat wheel (The Cat Wheel) was also placed in the room for exercise during pen cleaning. Two weeks after instituting the ", "As both diagnostic trials of desmopressin failed it was decided to move forward with a gradual water restriction phase before the MWDT in order to minimize the reported negative effects that renal medullary washout can have on test results. 1, 2, 8 Water allotment was incrementally reduced over a 14 day period down to 100 ml/kg/day on the day prior to testing. This allowed close monitoring of the cat for changes in mentation, neurologic status, body weight, USG and serum osmolality levels ( Table 2) . A CBC and chemistry profile were repeated and determined to be within normal limits.", "Based on diagnostic results thus far, the three main differentials for PU/PD in this cat were complete or partial central diabetes insipidus (CDI), nephrogenic diabetes insipidus (NDI) and primary polydipsia (PP). Because of possible complications and reported difficulties in the interpretation of test results, 1-3 the modified water deprivation test (MWDT) was delayed and the cat was treated with desmopressin, a synthetic analog of the natural antidiuretic hormone arginine vasopressin. First, oral tablets (0.2 mg desmopressin acetate; Watson Pharma) were administered at 0.05 mg q12h. Owing to continual polydipsia and hyposthenuria, therapy was stopped after 10 days and a week later 0.1 mg/ml compounded desmopressin eye drops (0.01% desmopressin acetate; Diamondback Drugs) were administered at a dose of 1-2 drops into the conjunctival sac twice daily for 10 days. Both forms of desmopressin failed to decrease water consumption or increase the USG above untreated levels (Table 1) ; therefore, therapy was discontinued." ] },{ "paper_id": "b38c12ccd389c27706fcf2a50c2274352539fbc3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "It is of note that a destabilizing effect was previously observed in forming a DNA\u00b7dsDNA triplex upon DNA T to DNA U substitution in the Hoogsteen strand (44, 60) .", "RNAs often form complex secondary and tertiary structures, and in turn, interact with proteins and metabolites for diverse regulatory and catalytic functions (1) (2) (3) . Doublestranded RNAs (dsRNAs) are essential components of RNA secondary structures (4) (5) (6) (7) . RNA triplex structures, formed between dsRNA regions and single-stranded RNA (ssRNA) regions, are emerging as an important tertiary structure motif (8) (9) (10) (11) (12) (13) . It is thus of great potential to develop ligands that can selectively and sequence-specifically recognize viral and cellular dsRNA regions as chemical probes and therapeutics.", "Supplementary Data are available at NAR Online. " ] },{ "paper_id": "b39580b3bf3af68ed88977c56efdca4d41816b10", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "TRIzol (Invitrogen) was used for RNA extractions following the manufacturer's instructions. RNA integrity and concentration were evaluated by denaturing formaldehyde gel electrophoresis and Agilent 2100 Bioanalyzer. The RNA samples were sent to GeneTech Biotechnology Limited Company (Shanghai, China) for hybridization to the porcine Affymetrix GeneChip (Affymetrix, Santa Clara, CA). A total of 6 microarray analyses were conducted using the procedure described previously [15] .", "PAMs samples collected from three infected piglets at 5 dpi and three uninfected piglets were analyzed. A total of 12,775 transcripts (53% of all probesets) were expressed in infected and non-infected PAMs (Supplementary Table 1 ). After quantile normalization, 321 genes were identified as differentially expressed (DE) genes, with 219 being upregulated and 102 being downregulated, under the threshold of fold change (FC) of 1.5 or greater and a false discovery rate (FDR) of approximately 5% (Figure 2A and Supplementary Table 2 ).", "Post-mortem examinations were performed on all pigs. Macroscopic lung lesions were given a subjective score to estimate the percentage of the lung affected by pneumonia, following a scoring system described previously [12, 13] . For histopathology analysis, samples of the apical segment of the lower lung lobes were collected and fixed in 4% paraformalclehyde for 24 h. Fixed samples were dehydrated, embedded in paraffin, sectioned into 4 \u03bcm and stained with hematoxylin and eosin. Sections were examined by light microscopy.", "Based on the Database for Annotation, Visualization and Integrated Discovery (DAVID), 166 of the DE genes were classified into 47 categories, many of which shared the same genes, according to their functional correlation (Figure 2B and Supplementary Table 3 ). The majority of the genes related to the virus-host cell interaction could be assigned into the categories including cell death and apoptosis related, response to wounding, response to unfolded protein, response to oxidative stress, response to virus, innate immune response, response to cytokine stimulus, and endoplasmic reticulum (ER) overload response. Other DE genes that were not classified by DAVID were taken into account for further analysis below. " ] },{ "paper_id": "b399adcfb1d563f2c836e2c924fb0c090fca961a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We did not involve the participants in the formulation of study design, recruitment or conduction of the study. However, we assured them that the results would not reveal any participant identity." ] },{ "paper_id": "b3c6008294a172e0609ee1467e87ec64ad242985", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For a summary of the proposed categories for whole-genome sequencing of viruses, see Fig. 1 and Table 1 .", "Our primary goal here is to initiate a conversation. The rate at which viral genomes are being sequenced is only going to increase in the coming years, and without some standardization, it will be impossible for these valuable resources to be utilized to their full potential. We present these categories as a starting point, with the goal of adjusting and refining them over time as our capabilities and needs continue to change.", "High quality (HQ). Genomes should be considered high quality if no gaps remain (i.e., a single contig per genome/segment), even if one or more ORFs remain incomplete due to missing sequence at the ends of segments. An HQ genome can often be achieved with modest levels of HT sequencing coverage (~15 to 30\u03eb) or through Sanger-mediated gap resolution of an SD." ] },{ "paper_id": "b3c71d9d7dd9758f8328933f47d7d460bf24c98e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b3c7cd5491836d0e345797bad2673c79ceaffe67", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "[45]", "Upper respiratory tract infection Bifidobacterium animalis", "Intestinal antibody responses to polio-and rota-virus in infants Healthy 6 week full-term infants (prospective study)" ] },{ "paper_id": "b3ed8e8e1f4e6bb576910bc4506303b525c2a1e5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b3f6786ea67c035d20928aa4cb7eb6b9d853adb7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Respiratory tract infection is an important common cause of hospitalization across all age groups [1, 2] . Infectious respiratory diseases in humans may be caused by several pathogens, including viruses and bacteria that produce very similar clinical symptoms and make diagnosis difficult [3, 4] . For this reason, an effective diagnostic assay for these pathogens in individual samples is urgently needed [5] . Furthermore, the 2003 severe acute respiratory syndrome (SARS) outbreaks and, more re-cently, the human and avian H5N1/H1N1 influenza virus cases underscore the importance of a rapid and accurate laboratory diagnostic method to characterize respiratory infections [6] ." ] },{ "paper_id": "b411e12b20d883ef2ee5ca19d48eff9fccedf05f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "By the way, the convention of using abbreviations for prokaryotic names has been given up, as it becomes inconvenient when organism number gets enormous. The binomina with full strain specification are used instead.", "The CVTree result page shows the run-time information and displays the final results when calculation ends.", "Traditional molecular phylogeny makes use of small subunit ribosomal RNA (SSU rRNA) sequences or a few orthologous proteins. Some more recent phylogenomic studies are based on concatenation of a larger number of proteins. The ever burgeoning genome sequencing projects worldwide have prompted several whole-genome phylogenetic approaches. However, most-if not all-rely on sequence alignment at some stage and therefore depend on many parameters, such as the use of scoring matrices. As modern prokaryotic and fungal taxonomy depends more and more on the traditional phylogeny, there is an urgent need to develop alternative approaches.", "The key improvement to accelerate CVTree's speed consists in avoiding repeated calculations among all jobs submitted after a major update of the database. All intermediate results of raw and renormalized CVs are kept until a major change taking place in the database. The response to a new submission may be deceptively fast if one's genome list coincides largely with that of a previous job.", "All these improvements make the CVTree server a useful complement to various phylogenetic projects *To whom correspondence should be addressed. Tel/Fax: +86 21 6565 2305; Email: xuzh.fdu@gmail.com, xuzh@fudan.edu.cn \u00df 2009 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. such as AToL (Assembling the Tree of Life, http:// atol.sdsc.edu) or AFTOL (Assembling the Fungal Tree of Life, http://aftol.org) by providing independent verification and support to the SSU rRNA and few gene-based phylogenies (13) (14) (15) (16) (17) ." ] },{ "paper_id": "b41638f869301e2af9eef7913301d55516fcf4ce", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b416c44441bd1db0d8d535fa8046434a4ba0a357", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Vital signs on admission showed a blood pressure of 120/73 mmHg, heart rate of 163 beats/min, respiratory rate of 44 breaths/min, and body temperature of 38.4 o C. Physical examination revealed coarse breath sounds on both lung fields. Tenderness and rebound tenderness was present on the entire abdomen. No lesions were detectable on the entire body.", "On neurologic examination, her mental status was drowsy with Glasgow Coma Scale scores of 13. Both pupils were isocoric with prompt light reflexes. Due to her drowsy mental status, motor strengths and sensory were uncheckable. Deep tendon reflexes were normal and pathologic reflexes of Babinski sign and ankle clonus were absent.", "According to follow-up abdominal CT scans performed at the outpatient clinic approximately four months after discharge, the remaining pancreas was shown to constitute of the head, neck, and a small portion of the body (Fig. 4) . No abnormal peripancreatic fluid collection and pseudocyst was observed. The patient is currently well without occurrence of any other complications during the first following year after discharge." ] },{ "paper_id": "b41e1c74739ae2195dc07a54fd9decaff5639b45", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Immunohistochemistry. Tissue samples of spleen and LNs were frozen in OCT, and 10-m cryostat sections were prepared. Sections were fixed in acetone for 10 min, air dried, blocked with PBS/5% normal goat serum for 30 min, and incubated with the indicated primary antibodies for 1 h. Slides were then washed in PBS, incubated with either SA-AP and anti-rat HRP or anti-rat AP and SA-HRP for 30 min, and developed with 3,3'-diaminobenzidine (DAB) followed by Vector Red (Vector Labs) according to the manufacturer's instructions.", "Sequence Analysis. DNA fragments for sequencing were generated by PCR amplification of genomic DNA from \u03e9 / \u03e9 and plt mice with the following primer pairs (position of products relative to transcriptional start site is listed in parentheses): GTCAACCTGGTCTATGAATCCCAG and CACGACATC-ACACTGAACCGATC ( \u03ea 1025 to \u03ea 428); GCTCAGCACTTA-TGGAAGGGTG and GCCATGATTGTGGTTGAGTTGAG ( \u03ea 598 to 59); TCTCACCTACAGCTCTGGTCTCATC and GTGAACCACCCAGCTTGAAGTTC (12 to 779); CTGGA-AAGAAAGGAAAGGGCTC and ATGGAGAGCAGGTTCA-GGTCTTGG (571 to 1046); CTTCAACCATTACATCTG-CACGG and TTTACTCCTGCCTGGGGATAGG (873 to 1965). PCR was performed using a Perkin Elmer 9600 thermal cycler in a final volume of 50 l containing 5 U AmpliTaq enzyme with its 1 \u03eb buffer, 0.2 mM of each dNTP, and 1 M of each primer. Samples were heated to 94 \u040a C for 4 min, AmpliTaq was added, and samples were cycled for 35 cycles at 94 \u040a C for 30 s, 60 \u040a C for 1 min, and 72 \u040a C for 1 min. PCR products were cloned into PCRII TA (Invitrogen) according to the manufacturer's instructions and sequenced using dye terminator technology.", "S econdary lymphoid organs are the predominant site of lymphocyte sensitization to novel antigens. Their function requires the colocalization of two distinct populations of leukocytes: antigen-presenting dendritic cells (DCs) 1 and antigen-responsive naive lymphocytes (1) . Chemokines, a rapidly growing family of small chemotactic cytokines, are believed to provide the signals that guide leukocytes to their proper location within lymphoid organs (2, 3) . Several recently identified chemokines have been suggested to mediate the constitutive trafficking of leukocytes based on their in vitro characteristics and their expression in lymphoid tissues (4) . A role for chemokines in B cell localization was shown by a targeted disruption of the chemokine receptor Burkitt's lymphoma receptor 1 (5) (6) (7) (8) . However, the involvement of chemokines in the localization of either T cells or DCs within lymphoid organs has not been directly demonstrated." ] },{ "paper_id": "b432613a1d3f049f7c75942e8dca5e3af1de7b69", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.01062-13/-/DCSupplemental. Figure S1 , TIF file, 4.2 MB.", "Nucleotide sequence accession numbers. GenBank accession numbers for the new and previously published genomes are listed in Table 1 .", "The support of Kingdom of Saudi Arabia Ministry of Health staff at all the hospitals, the regional health directorates for all their efforts in collecting patient data, and the Jeddah, Riyadh, Madinah, and Dammam regional laboratory staff are gratefully acknowledged. We thank the Sanger Illumina C team for the sequencing support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. " ] },{ "paper_id": "b439deefbf5429abf9b27dc5bed6bee148c3dfa5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Acute respiratory infections (ARIs) are the main causes of morbidity and mortality worldwide, especially in children during the first years of life (Osterhaus 2008) .", "Exploratory analysis of the data was performed using the SPSS software package v.17.01 (SPSS Inc, USA).", "Ethics -The Research Ethical Committee of the Centre for Health Sciences of Federal University of Esp\u00edrito Santo approved this study, with the registration CEP-093/07." ] },{ "paper_id": "b43fc42df698fbc829757a0dac65d9bce3d8f054", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The present study was funded by Eiken Chemical Co., Ltd.", "The datasets used and/or analyzed during the present study are available from the corresponding author upon reasonable request.", "Primer design. A primer set for LAMP amplification of the partial sequence of the EGFR gene (NG_007726) was designed using Primer Explorer (primerexplorer.jp/e/). Fig. 1 presents the sequences of the primers used with forward and backward outer primers (F3 and B3), forward and backward inner primers (FIP and BIP) and forward and back-loop primers (LF and LB). The primers were synthesized and purified by Eurofin Genomics. Block oligo and fluorophore-labelled probes were synthesized and purified by Japan Bio Services Co., Ltd., or Gene Design, Inc. (Table II) ." ] },{ "paper_id": "b463342e6ef8e2537568f371e7e15b3020f37ab8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b4c159232c0fd198ffac37ccdf30ee4fc6f24518", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b5094dcef4e616a20092ca5e3a30d0e9369455fd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Since December 2019, 2019 novel CoV (SARS-CoV-2) has been making a large outbreak involving 49,053 laboratory-confirmed patients and 1,383 mortality in 25 countries including J Korean Med Sci. 2020 Feb 24;35(7):e84 https://doi.", "Among four genera of CoVs, beta-CoV includes five subgenus-embevovirus, sarbecovirus including severe acute respiratory syndrome (SARS)-CoV, merbecovirus including Middle East respiratory syndrome (MERS)-CoV, nobecovirus, and hibecovirus. Because CoVs can infect a variety of animals, SARS-CoV and MERS-CoV crossed the species barriers.", "Coronaviruses (CoVs), within the order Nidovirales, are enveloped, single-strand, positivesense RNA viruses with a large genome of approximately 30 kbp in length. CoV was cultured for the first time in human embryonic tracheal organ cultures by Tyrrell and Bynoe in 1965, 1 and it was named as 'corona' due to crown-like appearance of the surface projections on electron microscopy. All CoVs develop only in the cytoplasm of infected cells, bud into cytoplasmic vesicles, and then extrude in virus particles of 70-80 nm in diameter by exocytic secretory pathway." ] },{ "paper_id": "b51603b65f40d384c4aa0f11379f0dcc387e46b1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u25a0 Focusing on the production of low-maintenance, Web sitefriendly distribution mechanisms that are accompanied by explicit uploading instructions could be an effective way to enable providers to supply patients with the information they need from the source they trust most.", "Certain limitations of our study must be taken into account. We did not contact the practices to determine whether providers were using other mechanisms, such as brochures, to distribute Zika virus information. However, Web sites are advantageous compared with physical media, as they can reach patients who may not be scheduled to have a clinical encounter in the near future and cannot be misplaced once the patient leaves the office." ] },{ "paper_id": "b525a9de80ca7225b057a792dc3e27f1b7a43436", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b530a3db1f7e6d6f289cd4fa3df8a782dcb691ab", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Written informed consent was obtained from parents/legal guardians of all study participants. Assent was obtained from participants \u22657 years old.", "This prospective case-control study was conducted from May 2015 through October 2017 following a published study protocol. 21", "\u25ba Many pneumonia-causing pathogens are also detected in asymptomatic children, thereby confounding our understanding to their contribution to pneumonia in children." ] },{ "paper_id": "b533398000a2ca0d89d244e430d7eb5f3d82fc71", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Howell et al.", "Mouse Challenge Studies with EBOV-Female BALB/c mice at 6-8 weeks of age were purchased from Charles River Laboratories. Mice were challenged intraperitoneally (i.p.) with 100 PFUs of mouse-adapted EBOV (Mayinga strain) (maEBOV). At 2 dpi, mice were treated with the indicated mAbs or PBS by the i.p. route. Mice were observed a minimum of once per day, and pan weights and clinical signs of disease were recorded through day 14. Observations were increased to a minimum of twice daily upon onset of clinical signs of disease. Moribund and surviving mice were humanely euthanized on the basis of Institutional Animal Care and Use Committee (IACUC)-approved criteria. Mice were observed for a minimum of 21 days after exposure.", "This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). be an underappreciated phenomenon for viruses, with implications for the design and development of immunotherapeutics and vaccines." ] },{ "paper_id": "b55aa037b62821a2bcf4463f30caba8c8e662e2b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "There were 232 patients enrolled in our study, and 123 (53.0%) were male and 109 (47.0%) were female. ", "General ethics approval has been conducted by the Centers for Disease Control (CDC) in Beijing and the respiratory ", "The respiratory etiological surveillance monitoring system of the Centers for Disease Control (CDC) of Beijing is designed to monitor respiratory pathogens in Beijing." ] },{ "paper_id": "b55c993891c702e7ec32d579fd90f380c3814ab9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors declare that there is no conflict of interests regarding the publication of this article.", "Financial Disclosure Statement: This publication was possible due to the Polish Ministry of Science and Higher Education (grant no. KNOW2015/CB/PRO1/33 within the Scientific Consortium \"Healthy Animal -Safe Food\").", "Animal Rights Statement: None required." ] },{ "paper_id": "b616293107ee48ebc8884fc55ebc66965df4feb8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b625ef49ed4b9e6f2d32150303199ca3fca8bddb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dovepress submit your manuscript | www.dovepress.com Dovepress 2573 O r I g I N a l r e s e a r c h open access to scientific and medical research Open Access Full Text Article People's republic of china; 2 shandong Provincial Key laboratory of carbohydrate chemistry and glycobiology, shandong University, Jinan 250012, shandong, People's republic of china; 3 school of Pharmaceutical sciences, shandong University, Jinan 250012, shandong, People's republic of china *These authors contributed equally to this work", "submit your manuscript | www.dovepress.com" ] },{ "paper_id": "b64600216303a5d0ba53a87405af547758a9e90a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Omnibus repository under the following accessions: ", "Raw data and corresponding normalized matrices were deposited in the Gene Expression" ] },{ "paper_id": "b66704a03a688c4065abff41c4977c4c9939c230", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Safety was assessed at every visit via patient-reported adverse events, physical examination, and regular monitoring of multiple parameters, including vital signs and laboratory test results. Peripheral edema, which was defined as a > 10% increase in ankle circumference from baseline, was also monitored, along with pitting edema.", "We used a hexokinase method to measure FPG levels and an enzymatic colorimetric method to measure TG, TC, LDL-C, and HDL-C levels. Serum levels of liver enzymes and other profiles were measured by standard methods at each hospital. Ion-exchange high-performance liquid chromatography (Bio-Rad Laboratories, Hercules, CA, USA) was used to measure HbA1C levels. The serum GA level was measured by an enzymatic method, using Lucica GA-L reagents (Asahi Kasei Pharma Co., Tokyo, Japan) and a Hitachi 7699 P module autoanalyzer (Hitachi Instruments Service, Tokyo, Japan).", "This study complied with the Declaration of Helsinki, and is registered at clinicaltrials.gov. The registration identification number is NCT02285205. The clinical trial protocol was approved by the Institutional Review Board of each center. All patients in the present study provided their written informed consent." ] },{ "paper_id": "b66f94ce35f66aa3ce423a16a7e6c814966786d2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "doi: 10 .1292/jvms. jaundice, recurrent fever, iritis, or neurological signs and abdominal or pleural effusion [17, 23] .", "The Feline coronavirus (FCoV) is an important pathogen of domestic and wild felids, which can cause subclinical infection, mild enteritis or lead to feline infectious peritonitis (FIP), a fatal disease characterized by inflammatory lesions of serous membranes and systemic granulomatous lesions of parenchymatous organs [23] ." ] },{ "paper_id": "b6afd6aa34818636e4b69364980971be64bad8e2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "RNA modules capable of recognizing specific metabolites to regulate gene expression have been identified in the 5 UTR of a variety of prokaryotic genes (1) (2) (3) . Such riboswitches can control accessibility of Shine-Dalgarno (SD) sequences and intrinsic transcriptional termination hairpins to tune translation initiation and transcription termination efficiencies, respectively (1) (2) (3) . The ability to control RNA conformations by metabolites or artificial organic molecules to regulate specific gene expressions in higher eukaryotic systems could provide new opportunities in biomedical and synthetic biological applications (4, 5) .", "Transmitted light images were used for monitoring cell morphologies, and fluorescent images were obtained by epifluorescence microscope (Olympus BX51) with an Olympus DP71 camera system. The fluorescence-filter set (Olympus) used for Venus fluorescence detection was U-MYFPHQ/550 nm.", "Nucleic Acids Research, 2016, Vol. 44, No. 18 9007 " ] },{ "paper_id": "b6b49bfba83105940015b7b8280db74ce480c65c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.", "Several recent studies have also shown that respiratory allergy may partner with certain viral infections to synergistically produce airway inflammation and increase cold and asthma symp-toms. 4 Since there is currently no safe and effective antiviral for RV, the targeting of allergic inflammation may prove beneficial in reducing risk of severe virus-induced asthma symptoms. 5 There are several possible immunopathologic mechanism(s) that connect viral and bacterial infection, allergy, and acute asthma, as discussed in the following sections.", "can lead to improvements in IFN responses and reduced virusinduced exacerbations. 61 This suggests that IgE-mediated inflammation can inhibit antiviral responses and increase the risk for virus-induced exacerbations of asthma." ] },{ "paper_id": "b6b8a2c0c3b83decefa4174ba17271c7cad45c5b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b6ee8c246cde8fc8ab8df4d3e287ca0ca7679532", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A total of 282 feline specimens were simultaneously tested using the RDT kit. Presence of FeLV infections in the samples was confirmed by conventional PCR. As shown in Table 2 ", "The RDT was started by loading 10 \u03bcL of blood specimen into the hole of the cassette device, and then loading three drops (approximately 100 \u03bcL) of 0.1 M carbonate buffer (pH 9.0) containing 0.1% casein and 1% Tween-20 onto the sample pad. Approximately 20 min after application of the buffer, the results were interpreted. The control line was expected to appear in all tests. If a red band appeared at the test line, the specimen contained FeLV antigen.", "To confirm FeLV infection, viral DNA was isolated from the cat blood samples using Genomic DNA preparation kit (Qiagen) and PCR was performed with a commercially available FeLV Detection Kit (GeNet Bio, Korea). The kit is designed to amplify conserved fragment of the FeLV U3 long terminal repeat [16] . Total genomic DNA was directly extracted from the blood specimens using a Genomic DNA preparation kit (Qiagen). Target DNA was amplified by 35 cycles of PCR with three steps at 94 o C for 1 min for denaturation, 50 o C for 1 min for annealing, and 72 o C for 2 min for elongation. Finally, a further elongation step (72 o C for 5 min) was performed. The 166 bp fragment of amplified gene product was analyzed with 2% agarose gel electrophoresis." ] },{ "paper_id": "b70d27459fd8143edf76721da40cdbca399c9fb1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b71a289c291ad516b7990a8582c1fece5330e5f5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Albeit a widespread zoonosis, even in Westernized countries [2] , toxocariasis remains a neglected disease [19] , and this report demonstrates that numerous questions surrounding its pathophysiology and clinical manifestations remain.", "Human toxocariasis is generally a benign, self-curing disease, and neurologic involvement is quite exceptional. In this study, we report a case of toxocariasis caused by ingestion of an unusual transport host, namely live slugs. The clinical picture comprised eosinophilic lung involvement with severe neurologic disorders in relation to vasculitis as well as retinal detachment.", "Central nervous system involvement in toxocariasis is uncommon, with less than 60 cases reported in the English literature [7, 8] . In this series of publications, cerebral vasculitis was a rarity that was only observed in 5 patients (review by Lompo et al [17] ). Intense release of cationic proteins from activated eosinophil cells could be cited as a possible cause of this phenomenon, which is also reported in neuroschistosomiasis [18] . The protein content of eosinophil granules is toxic to endothelial cells and muscle cells, particularly in the heart. According to this hypothesis, this 3-week, high-dosage treatment with corticosteroids certainly avoided further major sequelae in our patient. Ocular involvement, which included retinal detachment and peripheral granuloma in this case, might occur during generalized forms of toxocariasis [6] but was never found to be associated with cerebral vasculitis." ] },{ "paper_id": "b73380f2ef930b1667b665389463cf944db47370", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Even though IRT has many advantages, there are several major limitations. Despite patient preparation, unforeseeable external and internal factors can affect ", "Reumatologia 2017; 55/1", "The author declares no conflict of interest." ] },{ "paper_id": "b73f2926cc2e4d4d9dc0c41e90c1df1fee07039c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This work was supported by the grant from National Key Technology R&D program (no. 2015BAI07B02), and Natural Science Foundation of Liaoning Province (grant no. 201202082).", "In conclusion, the study confirms the presence of D. immitis in domestic and feral cats and that the prevalence was significantly higher in feral cats, especially older feral cats. These results suggest that outdoor exposure time is one of the most important factors for D. immitis infection in cats. Therefore, the present study suggests that prophylaxis against the parasite is advisable to decrease the incidence of feline dirofilariosis in Liaoning Province, northeastern China.", "Dirofilaria immitis, the etiologic agent of canine heartworm disease, is commonly found in the pulmonary artery and right ventricle of dogs and other animals. It could infect dogs, cats, and various wild mammals, with increased incidence in temperate and tropical areas [1] . The heartworm parasite is transmitted by various mosquito species, including Aedes, Anopheles, and Culex [2, 3] . After mosquitoes feed on an infected microfilaremic reservoir host, the mosquitoes act as intermediate hosts, carrying infectious \"larvae 3\" (L3) stage larvae, which could be transmitted to a dog or a cat [4] ." ] },{ "paper_id": "b746698482bd440f4d6907df9d9119b49e618512", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b7573a8e8c03ee3851379dd2527a853ac7f92508", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supporting Experimental Procedures", "To quantify HBs protein by ELISA, microwell antigen capture plates (Maxisorp nunc-immuno plate, Nunc #439454) were prepared by overnight incubation at 4\u02daC with a sheep anti-HBs antibody at 1:5000 dilution, followed by coating with 0.2% BSA/0.02% NaN 3 /1 x PBS at 4\u02daC until use. For HBs detection, samples were incubated in individual wells of the capture plates for 2 h. After washing, horseradish peroxidase-labeled rabbit anti-HBs antibody was added for an additional 2 h incubation. The substrate solution (from the HCV core ELISA kit: Ortho) was reacted for 15-60 min before the OD 450 values were measured.", "Detection of cccDNA was achieved using 5'-CGTCTGTGCCTTCTCATCTGC-3' and 5'-GCACAGCTTGGAGGCTTGAA-3' as primers and 5'-CTGTAGGCATAAATTGGT (MGB)-3' as a probe. mRNAs for NTCP, CyPA, CyPB, and GAPDH were detected using a one step RNA PCR kit (Takara) following the manufacturer's protocol. " ] },{ "paper_id": "b76b1127689c03ddc50a70b8dc0057dac74fb805", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Currently, multiple antiviral targets have been identified; however, there are no licensed therapies for EV-A71. In 2012, a randomized", "This open-access article is distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC) (http:// creativecommons.org/licenses/by-nc/4.0/), which permits reuse, distribution and reproduction of the article, provided that the original work is properly cited and the reuse is restricted to noncommercial purposes. For commercial reuse, contact reprints@pulsus.com 1 (8) ." ] },{ "paper_id": "b793841edbf590d90716ed93f6c7614d142c01ea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "@ERSpublications Aetiology of community-acquired pneumonia in children following a pneumococcal conjugate vaccination programme", "Although not well explored, viral carriage is also a clinical possibility, leading to positive PCR results that do not necessarily correlate to the observed pneumonia [27] . Hence the results of PCR-based approaches can be limited in making a definite diagnosis of causative pathogens in pneumonia.", "We describe the aetiology of community-acquired pneumonia in children before and after the introduction of the pneumococcal conjugate vaccination (PCV) programme in 2006.", "Infection with nonvaccine pneumococcal serotypes continues to be a significant cause of pneumonia in children in the UK." ] },{ "paper_id": "b79db3d6eca01b53a667d32ce59b3f33b40a81ae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "B.subtilis cells only, opposite results from the two different electrodes are obtained. Another case is the inclusion of both cell types; not surprisingly, both electrodes have much higher signals than the background.", "Oligonucleotides and PCR reagents were obtained from Invitrogen (Carlsbad, CA, USA), unless otherwise stated. Other chemicals were purchased from Sigma-Aldrich (St. Louis, MO, USA). Electrochemical measurements were performed using a VMP multichannel potentiostat (Princeton Applied Research, Oak Ridge, TN, USA) controlled by EC-Lab software (version 6.70, Bio-Logic Science Instruments, Claix, France). The thermal control system for the PCR consisted of a data acquisition card (PCI-MIO-16E-1, National Instruments, Austin, TX, USA) along with a signal conditioning board (SC-2042-RTD, National Instruments) connected to the temperature sensors. A digital feedback proportional-integral-derivative (PID) control algorithm was implemented in LabVIEW software (National Instruments) to control voltage supply to the heater from a power source (HP6629A, Hewlett-Packard, Rockville, MD, USA).", "To date, several integrated NA-based analytical systems have been commercialized [http://www.cepheid.com/Sites/ cepheid/content.cfm?id\u00bc158 (GeneXpert from Cepheid), http://www.gen-probe.com/prod_serv/inst_dts.asp (Direct Tube Sampling Systems from Gen-Probe), http://www. idahotech.com/razor/index.html (RAZOR from Idaho Technology) and http://www.iquum.com/products/analyzer. shtml (Liat Analyzer from IQuum)]. Despite their wide use in clinical/central laboratories, their application for on-site pathogen monitoring on a routine basis is still limited due to the large footprint and high instrument cost (mainly the complex optics). A promising alternative would be the inherently simple and lost-cost electrochemical method. Over the past decade, despite a great deal of work having been carried out on electrochemical sequence-specific NA sensing (4) (5) (6) , little work has been undertaken on the integration of these with upstream functionalities. In 2004, Liu et al. (7) successfully demonstrated a fully integrated biochip for cell isolation and lysis, target amplification, as well as electrochemical amplicon detection. One relevant feature of their approach is the incorporation of on-chip mixers, valves, and pumps in a self-contained device. However, the design and fabrication of the chip involves many complicated steps, which limits its practical application." ] },{ "paper_id": "b7ab9571dc69783d3b84dc3c5a24656db182afb6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All patients over the age of 18 years, who received a single or double lung transplant between January 2009 and April 2012, at the Sahlgrenska University Hospital Transplant Centre, were Swedish residents and survived the initial postoperative intensive care period, were asked to participate. The study was approved by the regional ethical review board in Gothenburg (Dnr791-08), and all subjects provided written and verbal informed consent.", "There were 51 VRTI-positive patients, and no statistically significant differences regarding baseline characteristics between VRTI-positive and -negative patients (Table 1) .", "The long-term effects of early VRTI and the dominance of asymptomatic VRTI indicated by our findings suggest that improved VRTI prophylaxis might promote a more favorable outcome after LTx. However, at present, few effective drugs exist and new antiviral compounds that could be evaluated for treating LTx recipients are needed." ] },{ "paper_id": "b7aee99640edf75791f77fd9ab46534c27efdaae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "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." ] },{ "paper_id": "b7bf3bca72a759d1b1c4b003ce431ee58d0dbe27", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b7d7db5b12584c5fab0c2244a27d0653d8a59f7d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We did observe that peritoneal macrophages from chimeric mice, which express chimeric CEACAM1ba, were resistant to MHV, while chimeric CEACAM1 expressed in cultured cell lines, such as BHK, showed MHV susceptibility, slightly lower than that in cells expressing CEACAM1b. From these findings, it could be postulated that some cellular factor(s) other than CEACAM1 could modify animal susceptibility. This idea appears to be in accordance with findings by Stohlman and Frelinger (1978) , who postulated two factors to determine mouse strain differences in susceptibility to MHV infection. Studies to elucidate such factors are in progress.", "The molecule on MHV virion that binds to the receptor is the spike (S) protein with ca. 180-200 kDa class I fusion glycoprotein (Bosch et al., 2003) . One spike is composed of a trimer of the S protein. The S protein of most MHV is cleaved in the middle of the molecule, and the N terminal subunit is called the S1 and C terminal subunits S2, respectively (Sturman et al., 1985) . N terminal 330 amino acids in S1 are responsible for receptor binding (Kubo et al., 1994) , and S2 is critical for envelope-cell membrane fusion, namely, cell entry (Bosch et al., 2003) .", "In this review, we report that the receptor of mouse hepatitis virus (MHV), carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), is an important determinant of mouse susceptibility to MHV infection. This finding was revealed by using mouse strains with two different allelic forms of the MHV receptor, Ceacam1a and Ceacam1b. Although previous studies indicated that susceptibility is determined by a single gene, Ceacam1, our recent work in gene-replaced mice with chimeric Ceacam1 pointed toward the involvement of other host factors (genes) in the susceptibility. Studies on mouse susceptibility to MHV, as well as the factors involved in their susceptibility, are overviewed." ] },{ "paper_id": "b8664f2695036c9b4a78f07b4598f1f8d6f98386", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Standard Anterior-Posterior chest X-ray films confirmed the diagnosis of ARDS.", "Fowler \u2162", "ARDS, viral pneumonia, sepsis from unknown etiology." ] },{ "paper_id": "b891efc6e1419713b05ff7d89b26d260478c28df", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "China has the world's second largest tuberculosis (TB) burden after India [1] . Healthcare workers (HCWs) in China's National TB Control Programme have a significantly increased level of exposure to TB disease and patients. After the severe acute respiratory syndrome pandemic in 2003, the Chinese government made increased efforts to protect HCWs from nosocomial TB infections and other respiratory infectious diseases, especially for those HCWs working in chest hospitals and infectious disease hospitals. These efforts (although not universal throughout China) included the increased use of biosafety level 3 (BSL3) laboratories and respiratory isolation through negative pressure wards and rooms, and the practice of standardised biosafety protocols and procedures through continued training and education.", "Systematic TB screening in HCWs can improve their awareness of TB infection [2] . The tuberculin skin test (TST) has been widely used for the detection of TB infection for decades but due to cross-reactivity with the bacille Calmette-Gu\u00e9rin (BCG) vaccination and exposure to non-TB mycobacteria, the TST fails to provide sufficient specificity for the detection of TB infection [2] . In the past decade, interferon-\u03b3 (IFN-\u03b3) release assays have been developed and commercialised to measure the in vitro release of IFN-\u03b3 from effector T-cells stimulated with the Mycobacterium tuberculosis-specific antigens (the 6-kDa early secretory antigenic target and 10-kDa culture filtrate protein) as an aid to diagnosing TB infection. These new screening assays (QuantiFERON-TB Gold In-Tube (Qiagen, Venlo, the Netherlands) and T-SPOT.TB (Oxford Immunotec, Abingdon, UK)) have demonstrated higher specificity and at least comparable sensitivity for the diagnosis of TB infection compared with the TST [3].", "The importance of effective measures against nosocomial TB infection has been clearly emphasised by the World Health Organization Stop TB strategy and recent Policy on Infection Control [7] . Towards the goal of TB elimination, prevention and treatment of LTBI are essential elements of global TB control efforts " ] },{ "paper_id": "b89434ac6bfe4104f4c207a770a6858413e383cd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b8991fb0bcc563dc28c736e05639bc604f611e84", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The forced expiratory volume in 1 second (FEV 1 ) and the vital capacity were expressed as a percentage of predicted normal values, calculated by using published equations for children and adults [28] .", "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." ] },{ "paper_id": "b8b13fd5a49e6193135315c97de14fb7b9936286", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Perhaps the most significant barrier to widespread OV delivery is rapid neutralization and clearance of circulating virus particles. Antibodies and complement proteins can coat the virus blocking its ability to interact with its cellular receptor and accelerate Fc receptor-mediated clearance by splenic macrophages and hepatic Kupffer cells.", "\u2022" ] },{ "paper_id": "b8cd20475a12eda90f29fcf38b449c086e703144", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b8f3cb6fd720c0f2150816c37362174e61a1ca22", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This work was supported by National Institutes of Health grants AI051292 and AI57158 (Northeast Biodefense Center; to W. I. Lipkin), a National Institute of Allergy and Infectious Diseases grant (5R01AI079231-02), a U.S. Agency for International Development grant (PREDICT grant GHNA 0009 0001 000), and an award from the U.S. Department of Defense." ] },{ "paper_id": "b921ec0b4974533423b7af989620ff4ccc5e2f79", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This work was supported by a grant from the Ministry of Health and Welfare, Republic of Korea (HI15C2971).", "Analyses were performed using Prism 5 (GraphPad, San Diego, CA) or Excel program (Microsoft office). Differences between groups were analyzed by one-way analysis of variance (ANOVA) followed by Tukey's test. P values of < 0.05 were considered statistically significant.", "HEK 293 T/17 and 786-O cells (ATCC, Manassas, VA, USA) were grown at 37\u00b0C and 5 % CO 2 in Dulbecco's modified Eagle's medium (DMEM; Invitrogen, Waltham, MA, USA) supplemented with 10 % fetal bovine serum (FBS; Gibco, Waltham, MA, USA) and 1 % penicillin/ streptomycin (Invitrogen). Spodoptera frugiperda(Sf9) cells (Thermo Fisher, Waltham, MA, USA) were cultured in Sf-900\u2122 II SFM medium (Gibco) and 1 % penicillin/streptomycin (WELGENE, Daegu, South Korea) at 27\u00b0C, non-humidified, non-CO 2 incubator with 120 rpm suspension." ] },{ "paper_id": "b9462a00480f4a8e69d04678b4cff8a4bb7a7bcb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Respiratory; Syndromic; Public health", "To improve understanding of the relative burden of different causative respiratory pathogens on respiratory syndromic indicators monitored using syndromic surveillance systems in England.", "Influenza and RSV exhibited the greatest seasonal variation and were responsible for the strongest associated burden on general respiratory infections. However, associations were found with the other pathogens and the burden of streptococcus pneumoniae was important in adult age groups (25 years and over)." ] },{ "paper_id": "b9bca46e86a4f2ff88b88154c8db5ddbe9c329b9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b9c4627fca08e4d363dbd7c27da40834a048a262", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b9e6621f5b788746ecf6f648b00844b10634d43f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The analysisw as performed under the optimized conditions described above. Results are reported in Figures 3-5 (see below), in which ligands are grouped by chemical features (type of monosaccharide, degree of amide substitution) rather than by numbering. Ac omparative heatm ap for the four proteins is reportedi nt he Supporting Information, Figure SI -3.", "As discussed previously,M an-binding CLRs are expected to recognize l-Fucr esidues as well, due to the overlapping carbohydrate-specificity imparted by the EPN motif. Therefore, in analogyt ot he mannobiosidem imics, b-fucosylatedl igands 15 were synthesized by linking the cyclohexane acceptor (9)w ith an appropriatelyp rotected fucose-trichloroacetimidated onor (13)t oy ield the bis-p-nitrophenylester 14,w hich was reacted with as et of primary and secondary amines. This approacha fforded the 11 Fuc-based ligands 15.1-11 (Scheme 1, Figure 2 ).", "Stock solutions of the conjugates 1mm in water were diluted with sodium phosphate buffer (300 mm,p H8.5, 0.005 %T ween 20, 10 %D MSO) to af inal concentration of 50 mm.4 0mLo fe ach solution was placed into a3 84 well source plate (Scienion, Berlin, Germany), which was stored at \u00c020 8Ca nd reused if necessary.T hese solutions (750 pL, 3drops of 250 pL) were spotted onto NHS-functionalized glass slides (Nexterion Slide H-Schott AG, Mainz, Germany). Ligands were spotted in 4replicates (9 different ligands per row), establishing the complete microarray that was printed in 7copies onto each slide After printing, the slides were placed in a 75 %h umidity chamber (saturated NaCl solution) at room temperature overnight. The unreacted NHS groups were quenched by placing the slides in a5 0mm solution of ethanolamine in sodium borate buffer 50 mm,p H9.0, for 1h.", "A1 0mm solution of the ligands was prepared in water and when necessary for complete solubilization, 5% DMSO (Thermo Scientific Molecular Probes)w as added. The compounds were stirred overnight at room temperature with equimolar amounts of 16 (N-[(1R,8S,9S)-bicyclo[6.1.0]non-4-yn-9-ylmethyloxycarbonyl]-1,8-diamino-3,6-dioxaoctane, BCN-amine, Sigma Aldrich) in water and the conversion of the SPAAC-reactions was monitored by MALDI-TOF mass spectrometry by using 2,5-dihydroxybenzoic acid (DHB) as a matrix (5 mg mL \u00c01 in CH 3 CN/0.1 %a queous TFA, 3:7c ontaining 0.005 %N aCl). The MALDI data are reported in the Supporting Information." ] },{ "paper_id": "ba4c40b65eb342713e70c96a8d6336b22cca54fc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Mice. 4-6-wk-old B10.A mice were purchased from The Jackson Laboratories (Bar Harbor, ME). All studies were done with freshly isolated cells from 6-8 wk old B10.A mice.", "The purity of the sorted population, confirmed by flow cytometry, was \u202b\u0641\u202c 90%. In some cases, CD4 cells were separated on a Becton Dickinson FACSorter \u00ae after staining with tricolor conjugated rat anti-mouse CD4.", "Purification of CD4 T Cells. Fresh mouse lymphocytes from either spleen or lymph nodes were prepared after hypotonic lysis of RBCs and separation of dead cells by Ficoll Hypaque density centrifugation. Cells were stained with rat anti-mouse CD4 conjugated with magnetic beads from Miltenyi Biotec, Inc. (Auburn, CA). This antibody was used at a final dilution of 1:10 to stain 10 million live cells in a volume of 100 l on ice for 30 min. CD4 cells were then separated using a magnetic cell sorter (MACS)." ] },{ "paper_id": "ba4ec5cbbb67efa5caafb7f69b6591a83d59d3a7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ba581ccb585036d6220cfb461733c94584326d96", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "30." ] },{ "paper_id": "bab279da548d8bd363acd5033e9dc54e7dbb7107", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "bad4f135cd64a02e182260e7c1e4d9b6f3941695", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A single, easily derived equation is used to determine the likelihood of a community LAI:", "Recently reported escapes of LAIs from high-level biocontainment at CDC laboratories (4) and the long history of LAIs and other escapes from laboratories (5) also argue that Fouchier's value for P 1 is too low. Lipsitch and Inglesby (6) have supplied additional arguments as to why the Fouchier value for P 1 is likely much too low.", "Citation Klotz LC. 2015. Comments on Fouchier's calculation of risk and elapsed time for escape of a laboratory-acquired infection from his laboratory. mBio 6(2):e00268-15." ] },{ "paper_id": "bb59a75042a0be5861524532178e8becd8cda233", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Year Compared group Charging voltage (kv)" ] },{ "paper_id": "bb5dbff719709a95c6fbad1d9d4a7f3c3802d23b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We recommend that:" ] },{ "paper_id": "bb65c5259727bce9f1623452a0af39aa57f9b1bc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "bbaa88d5b0e10a260606dc92d0774816a3bb5861", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Antibiotics. Rats received medicated drinking water supplemented with bactrim, neomycin, and polymyxin B, as previously described (6) .", "StatisticalAnalysis. Results were analyzed by multivariate analysis or by the Xa test .", "mAh Murine antibodies directed against rat lymphocyte determinants were purchased from Serotec Bioproducts for Science, Inc. (Indianapolis, IN). The specific mAb from ascites fluid used in our studies consisted of OX19 (panspecific for rat T lymphocytes), W3/25 (specific for rat Th cells), OX8 (identifies the rat nonTh cell subset), OX7, (detects the Thy-1.1 antigen), andOX33 (specific for the K L chain) ." ] },{ "paper_id": "bbb6637a5feacde7301d594e1e1f96b339496c20", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "bbccfb72296dcfb544b20996414b7b70622214da", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "[t4C]GalNAcitol was prepared by acid hydrolysis of UDP-N-acetyl-D-[1-t4C]galactosamine (Cummings et al., 1983) , followed by reduction with NaBH4 (Li et al., 1978) . ", "The anti-E1 antibody (4-17-M1-F4-M1) was used for immunoperoxidase labeling after our standard protocol (Tooze et al., 1984) .", "nd, none detectable in undiluted supernatant.", "Glycopeptides were acetylated by treatment with acetic anhydride (Baenziger and Kornfeld, 1974) and desalted over an Amberlite mixed bed resin before mild alkaline hydrolysis. The eluate, after lyophilization, was resuspended in 0.2 M sodium carbonate, pH 11.6, then treated with an equal volume of 2 M NaBH4 in 100 mM NaOH, and incubated for 16 h at 45\u00b0C as described by Niemann and Klenk (1981) . After neutralization at 4\u00b0C with glacial acetic acid, the oligosaccharides were passed over a Dowex 50W-X8H + column and eluted with 1% (vol/vol) acetic acid. The peak fractions containing the oligosaccbarides were pooled and lyophilized. The borate was removed by repeated evaporation with methanol at 40\u00b0C. The oligosaccharides were finally resuspended in 200 ~t distilled H20. The final recovery of [3H]-Iabeled material was 80-90 %. One-half of the material was applied directly to a P4 (200-400 mesh) column (90 \u00d7 1.5 cm), equilibrated, and run in 0A M NaHCO3, pH 8.6. The remainder was first digested with neuraminidase from Vibrio cholerae at a final concentration of I U/ml in 50 mM sodium acetate buffer, pH 5.6, containing 154 mM NaCI and 9 mM CaC1,. After incubation under a toluene atmosphere for 24 h at 37\u00b0C (Niemann and Klenk, 1981) , the reaction was stopped by boiling, and the samples were lyophilized and then resuspended in 100 I.tl of distilled H.,O before application to the P4 column." ] },{ "paper_id": "bbf70aeba7b4a4b8d96db253e673881ac220e36c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Mice. Six-to eight-week-old female ICR mice were obtained from Shanghai Laboratory Animal Center, China, and housed in biosafety level 3 laboratory (Fudan University). Animal study was conducted in accordance with guidelines of Institutional Animal Care and Use Committee of Institute Pasteur of Shanghai.", "Statistical analyses. SPSS 16.0 (Chicago, IL) was used for statistical analyses. Viral yield, pathological score, and plaque count were compared by Student's t-test or one-way analysis of variance. Chi-square test was applied to assess difference between survival rates. P < 0.05 was considered statistically significant.", "Control of HPAI H5N1 human infection has been a severe challenge since the 21st century. This virus has evolved into phylogenetically distinct clades and subclades, among which, clades 0, 1, 2.1, 2.2, 2.3, and 7 have reported to cause human disease. 19 In China, clades 2.3.2, 2.3.4, and 7 co-circulated in poultry and threat public health. 20 Although vaccination is the most cost-effective IV intervention strategy, production of H5N1 vaccines faces more technical obstacles than season flu vaccines. Moreover, reappearance of drug-resistant H5N1 strains limits the use of currently available antiviral drugs and underscores the urgent demand for novel flu-specific agents. 21, 22 To this end, we developed the sequence-based H5N1 antiviral compound with the help of RNAi." ] },{ "paper_id": "bbfbefd19c9c471dbacabd1f57124d1ad36f24f5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Student's t-test analysis for unpaired samples was also performed to evaluate statistical differences between samples with and without poly I:C stimulation.", "Poly I:C stimulation PBMC, isolated from 15 mL blood of every pig, were diluted into 50 mL RPMI-1640 medium (Hyclone) supplemented with 10% fetal calf serum, streptomycin and penicillin, with the final cell concentration of ~2\uf0b410 6 /mL. The cell suspension was divided into two parts, one of 10ml, used as the uncultured and un-stimulated control, the other 40 mL, which was equally assigned into 16 wells (2.5 mL/well) for the stimulation test. Then, these 16 wells were divided into four time-point groups, which were cultured for 3 h, 6 h, 12 h, and 24 h at 37\uf0b0C with 5% CO 2 . Additionally, the four wells of every group were used for stimulation with different poly I:C concentration (0, 10, 20, 40 \uf06dg/mL, respectively) (Sigma-Aldrich).", "PBMC were isolated using Ficoll-Hypaque PLUS (GE healthcare) following the manufacturer's instructions. In brief, the whole blood was firstly diluted by an equal volume of balanced salt solution (PBS). Then, 15 mL of diluted blood was carefully added on the top of 10 mL of Ficoll-Hypaque solution in a 50 mL conical tube and centrifuged at 460\uf0b4g for 20 min at room temperature. After centrifugation, the middle whitish interface containing mononuclear cells was transferred to a new tube, and washed by adding 25 mL PBS followed by centrifugation at 150\uf0b4g for 10 min two times." ] },{ "paper_id": "bc0e1d6e96b004296ea87bde20bf39334df6d9b6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Competing interests None declared.", "Provenance and peer review Not commissioned; externally peer reviewed." ] },{ "paper_id": "bc47c74ccb7b9751aaa0fa71dd6b6a8265fdbc2c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Acute bronchiolitis is a clinical diagnosis that requires epidemiological and virological data. In infants, few days of runny nose, fever, and cough typically precede the signs of lower respiratory distress (nasal flaring, tachypnea, and subcostal recessions) ( Figure 2 ). 1,2 In such a case, respiratory crackles are suggestive of RVS etiology, whereas bilateral wheezing is suggestive of RV etiology. 16 A plethora of other respiratory sounds can also be heard.", "The initial response of the mucosa to RSV infection is a strong induction of antiviral type I and type III interferons and interferoninduced genes ( Figure 4A ). As RSV has developed potent mechanisms to evade this innate interferon response, the virus is able to infect most infants through RSV-NS1/2 proteins inhibiting IRF-3 and", "The authors thank Mrs Agnieszka Sierakowska for her assistance with preparing the illustrations and Miss Anna Eskola for editing the language for this article.", "The authors declare that they have no conflicts of interest.", "It is still not clear whether the type of virus detected in the nasopharynx could determine the degree of severity of the infection." ] },{ "paper_id": "bca792def155d06e618f4fe78f6f4178ed5e1b69", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Thoracic radiographs were unremarkable, with no evidence of pulmonary changes. Prior to biopsy results being obtained, a presumptive diagnosis of poxvirus was made and treatment with intravenous rFeIFN-\u03c9 (Virbagen Omega [Virbac] 1MU/kg SC q24h for 3 days) was commenced.", "Our previous case series detailed cats that had pulmonary CPxV-infection, complicated by concomitant infection with FeHV-1, Bordetella bronchiseptica and/or Mycoplasma species. 4 The cases described herein have novel findings which have not previously been described in relation to this infection, including central nervous system (CNS) involvement and presentation as a laryngeal mass.", "A further 2 days later, the area of ulceration affecting the ventral abdomen had progressed to a necrotic eschar (Figure 2) , with a concurrent increase in lethargy and discomfort. There were also multiple small raised nodules surrounding the central necrotic area, and crusting papules and nodules around the head and neck (Figure 3 ). Buprenorphine was administered (Vetergesic [Ceva] 20 \u03bcg/kg IV q8h) to provide analgesia." ] },{ "paper_id": "bcc562cf2076fa55f32a63255fa5f71d0bed4f14", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "SUPPLEMENTARY MATERIAL is linked to the online version of the paper at http://www.nature.com/mi", "Epithelial polymeric immunoglobulin receptor and platelet-activating factor receptor expression by flow cytometry. Stimulated (inflamed) and nonstimulated (noninflamed) cells were scraped from the wells after washing with cold PBS. Cell suspensions were incubated with platelet-activating factor receptor, human monoclonal antibody, and polymeric immunoglobulin receptor rabbit polyclonal antibody (both from Cambridge Bioscience, Cambridge, UK) at 4 1C for 15 min. Anti-human PE-conjugate and anti-rabbit FITC-conjugate antibodies were added for 15 min at 4 1C. Cells were washed and stored at 4 1C before acquisition using a BD LSR II flow cytometer. A total of 10,000 gated events were recorded. PE goat anti-mouse IgG2a and FITC donkey anti-rabbit IgG (both from Biolegend, London, UK) were used as isotype controls.", "Differences were considered significant if Pr0.05. Statistical analyses and graphical presentations were performed using Graphpad Prism5 (La Jolla, CA) and SAS9.3 (Cary, NC)." ] },{ "paper_id": "bd25781927e8eb5b121981ac6081cde159606c83", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Imatinib is a protein tyrosine kinase inhibitor that acts on the bcr-abl gene of the abnormal Philadelphia chromosome in chronic myeloid leukemia (CML). It is also used in www.e-trd.org", "In conclusion, as imatinib-induced pneumonitis can be fatal with irreversible results and can be confused with more common infectious diseases, it is important for clinicians to consider the possibility of imatinib-induced pneumonitis when patients develop respiratory symptoms or abnormal radiologic features during imatinib treatment. In addition, it should be kept in mind that susseccful rechallenge with imatinib coud be another option for a underlying disease after a recovery from interstitial pneumonitis related with imatinib mesylate.", "Imatinib mesylate is a targeted therapy that acts by inhibiting tyrosine kinase of the bcr-abl fusion oncoprotein, which is specific to chronic myeloid leukemia (CML), and the c-transmembrane receptor, which is specific to gastrointestinal stromal tumors. Interstitial pneumonitis is a rare adverse event of imatinib therapy. It is clinically difficult to distinguish from infectious pneumonia, which can frequently occur due to the underlying disease. The standard treatment for imatinib-induced pneumonitis is to discontinue the medication and optionally administer corticosteroids. However, there are a few cases of successful retrial with imatinib. We describe a case of successful rechallenge of imatinib in a patient with imatinib-induced interstitial pneumonitis and CML without a recurrence of the underlying disease after 3 months of follow-up." ] },{ "paper_id": "bd614a6233ff72830a79371d92a7680e1b8af33b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "bd667dbd5200c9f07fb07cef29435f7ca7c2639b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis: Significant differences were statistically analyzed using chi-square and Fisher's exact probability tests. P values of <0.05 were considered to be statistically significant.", "AcKNOWLEDGMENTS. This experiment was supported by grants from the Ministry of Health, Labour and Welfare of Japan (H24-Shinko-Ippan-006; H25-Shinko-Ippan-008) and by JSPS KAKENHI Grant Number 15H04599. ", "In addition, a cut-off value was arbitrarily set at OD=0.5." ] },{ "paper_id": "bd9abaeae84a3ecea684e6bc7ddc64d4c6bb7cc0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "bdb0493b6378d05d55db093b3b6ed45cd68d8a37", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Many thanks go to the 156 trainees that responded so quickly to this survey. Good luck with your experiments and best wishes for your exciting careers!", "[24%]), urogenital viruses (10%), eukaryotic/nonmammalian viruses (3.2%), bacteriophages (1.6%), and plant viruses (1.6%). Therefore, respondents study a diverse array of viral systems. Importantly, 68% of respondents said that they want to work on a respiratory virus in the future, making this an area of potential growth. Career goals among respondents were diverse: academic research faculty (54%), government research (31%), academic research scientist (23%), industry (large company [18%] and small company [16%]), policy or science writing (6.4%), foundation (3.9%), teaching (3.2%), clinical laboratory (1.3%), state public health laboratory (0.6%), consulting or entrepreneurship (0.6%), and technology transfer (0.6%).", "Citation Pfeiffer JK. 2015. Is the debate and \"pause\" on experiments that alter pathogens with pandemic potential influencing future plans of graduate students and postdoctoral fellows? mBio 6(1):e02525-14." ] },{ "paper_id": "bdb055fe1931f1117bc4cf30218e66a78e370044", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "VHC surveillance protocol were negative for Cases 2 and 3.", "doi: 10 .1292/jvms.17-0544 like activity. A gross necropsy performed on 1 calf by the referring veterinarian revealed pulmonary edema. At that time, serum total protein concentrations on 9 of the 11 surviving calves were 36 to 59 g/l (median 47 g/l; reference range for calves, 58 to 70 g/l).", "Physical examination on Case 1 revealed an increased rectal temperature (39.9\u00b0C; reference range, 38.6 to 39.4\u00b0C) and heart rate (150 bpm; reference range, 100 to 140 bpm), pale mucous membranes, bilaterally injected sclera with petechiae and hyphema OS, red urine, mucoid diarrhea with frank blood, lethargy, mild dehydration, weak suckle reflex, cardiac dysrhythmia, and increased bronchovesicular sounds. Physical examinations on Cases 2, 3 and 4 revealed mild bilateral epiphora (Case 2), watery diarrhea (Case 3), and mild dehydration (Cases 3 & 4) ." ] },{ "paper_id": "bddfc27eab5ed01ee09fcab0f11fd6c0a0bd458e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.01146-14/-/DCSupplemental. Figure S1 , PDF file, 0.5 MB. Table S1 , DOCX file, 0.1 MB.", "Citation Briese T, Mishra N, Jain K, Zalmout IS, Jabado OJ, Karesh WB, Daszak P, Mohammed OB, Alagaili AN, Lipkin WI. 2014. Middle East respiratory syndrome coronavirus quasispecies that include homologues of human isolates revealed through whole-genome analysis and virus cultured from dromedary camels in Saudi Arabia. mBio 5(3):" ] },{ "paper_id": "be0d6fb3b99b467756a0f5a26e3976a91d49ec2e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Emerging Microbes and Infections", "Attribution-NonCommercial-NoDerivative Works 3.0 Unported License. To view a copy of this license, visit http:// creativecommons.org/licenses/by-nc-nd/3.0", "The past few months have yielded disconcerting news about viruses carried in mammalian reservoirs. What is the relevance of virus discoveries mushrooming in the literature? Will bats yield the next pandemic virus? Animal ecologists and virologists need to join forces." ] },{ "paper_id": "be179ef4eaf04a9b155ac385eeabc06620a791b2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "be2d158bbbfa93b845e21ad069c6694de4ff7c7a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "be4f7c9109a242bfea7c73dbb551238cf598e690", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As MV is a human virus with no known animal reservoir, there is no risk for animals and plants.", "Humans are the only known natural host for MV. 23 Nonhuman primates can also be infected and are commonly used as model of infection. To date there is no known animal reservoir and no asymptomatic carrier state has been documented.", "No potential conflicts of interest were disclosed.", "Contaminated waste and personal protective equipment should be inactivated using an appropriate method (autoclave or incineration) before disposal and potentially contaminated non-disposable materials (e.g., the material used for the transport, preparation or administration of the GM vector, instruments, surfaces) need to be properly decontaminated." ] },{ "paper_id": "be9b45f1ce1542eb6c30e86b966a33f53eaac419", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Then, the probability of a susceptible individual to be infected reads", "where R 0~l N m is the basic reproduction number for the standard SIR model in well-mixed population of size N 40 . Integrating Eq. (5), we get", "The payoffs of different strategies and states are thus easily to be obtained, which are summarized in Table 2 .", "With the initial condition I(0) 5 I 0 /N 5 5/N, S(0) 5 1 2 5/N < 1 and R(0) 5 0 as well as the equation R(') 1 S(') 5 1 in the thermodynamic limit, we have" ] },{ "paper_id": "bf134be7dfc56c7d9a66f0cfe6afc7d3df112b9e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Epidemiological determinants of successful vaccine development were explored using measurable biological variables including antigenic stability and requirement of T-cell immunity. Employing a logistic regression model, we demonstrate that a high affinity with blood and immune cells and pathogen interactions (e.g. interference) would be the risk factors of failure for vaccine development.", "Understanding common biological features among the existing (recommended) childhood vaccines, in contrast to recent unsuccessful vaccines, would be useful for designing optimal avenues for future vaccine development. Here we report the results from a simple epidemiological analysis which aimed to identify virological, pathophysiological and eco-evolutionary factors that may lead to a successful vaccine.", "Despite our identification of the potential epidemiological determinants of successful vaccine, the abovementioned model was only aimed to learn from the existing armament of childhood vaccines. As long as truly novel approaches (e.g. adjuvants, new regimes of immunization and novel antigens) are effectively used for developing a new vaccine, future vaccine development may be granted an opportunity to refute the simple expectation." ] },{ "paper_id": "bf23011551b21af6538e43974e74e6078f538028", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "bf56dbf1f0c9734d135d18b33d9b7476b53d14a6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Quaternary prevention should be implemented to minimize harm to patients because the ultimate goal of medicine is to prevent disease and promote health. Primary care physicians have a major responsibility in quaternary prevention, and the establishment of clinical epidemiology as a distinct field of study would create a role charged with minimizing patient harm arising from over-medicalization.", "Medicine's ultimate aim is to prevent disease and to promote health. The framework of primary-secondary-tertiary prevention that was proposed by Leavell and Clark [1] in the 1940s has been widely used to assign roles to healthcare workers in charge of various strategies to attain this goal (Table 1). In the healthcare service system of the Republic of Korea (hereafter Korea), public health workers are in charge of primary prevention, that is, preventing the occurrence of diseases, while primary care physicians are in charge of secondary prevention through the early detection of diseases that have occurred, and medical specialists are responsible for tertiary prevention through appropriate treatment that is designed to prevent mortality and enable the patient to return pISSN 1975 -8375 eISSN 2233 to the community.", "The domain requiring quaternary prevention faces some risk for ethically unacceptable healthcare practices such as over-medicalization or over-diagnosis [4] . The over-diagnosis of screening in thyroid cancer is one example [5] . Therefore, the goal of quaternary prevention is to protect the safety of patients by preventing avoidable harm under a 'Do No Harm' ethical code [6] . As quaternary prevention means protecting consumers who require healthcare services from unexpected harm, safely protecting consumers from MERS who visited a medical facility for various healthcare service needs would fall under quaternary prevention. If the medical institutions in which the super-spreaders were hospitalized had understood quaternary prevention and had taken appropriate measures, no public health crisis would have emerged. In other words, a multi-faceted surveillance system should be implemented immediately to identify patients at risk of infection and to protect them from avoidable harm." ] },{ "paper_id": "bf573e1259148bb11f71b1dce3ad11c0a091ce36", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "bf5b3c8ca8f08950a6402469badcb792bed09e21", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "bf87996bb6c0dbed5de9512ac2bab800417a8956", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "DCssTPPDr for estimating TAP transport efficiency. The threshold for epitope identification was set at 0.5 to maintain sensitivity and specificity of 0.89 and 0.94, respectively. Finally, CTLPred 32 was implemented additionally for further confirmation about the prediction with default parameters.", "The findings from this study denote that integrated computational approaches are very much effective for designing vaccine candidates against some deadly viruses such as the CCHFV, with the formally delineated experimental procedure. Thus, co mputational studies save both time and cost for researchers and can lead the wet laboratory work with higher possibilities of getting the desired outcome.", "Highly conserved antigenic epitope for CCHF vaccine designing" ] },{ "paper_id": "bfa1dab8c91f41f59df39489115a8b2e19e537bf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.01102-13/-/DCSupplemental. Figure S1 , PDF file, 0.1 MB. Figure S2 , PDF file, 0.1 MB. Figure S3 , PDF file, 0.1 MB. Figure S4 , PDF file, 0.2 MB. Figure S5 , EPS file, 5.8 MB. Figure S6 , PDF file, 0.1 MB. Table S1 , DOCX file, 0.1 MB.", "Microarray data accession number. Raw microarray data have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO series accession number GSE49840. In addition, normalized matrixes and expression values utilized in this study can be found at https://viromics.washington.edu." ] },{ "paper_id": "bfaf24a34273d866bfa8ca32accf91d6a928c163", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Invertase activity was determined by the method of Goldstein and Lampen (29) with the modifications for measurement of periplasmic activity presented in Johnson et al. (44) .", "coli and purified on an amylose column according to the manufacturer's direction. The purified recombinant protein was used for immunization of a rabbit according to standard procedures (37) .", "The Escherichia coli strains used were XL1-Blue (supE44 thi-1 lac endA1 gyrA96 hsdR17 relA1 [ (this study). Yeast strains were grown on yeast extract, peptone, and dextrose or on synthetic dextrose (SD) medium supplemented as necessary (81) .", "To analyze the mechanism of integral membrane protein localization in the early Golgi apparatus of Saccharomyces cerevisiae, we have used Ochlp, a cis-" ] },{ "paper_id": "bfc521f036ead8d21f832497328d5be3e7852a66", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Drawing on disorder: How viruses use histone mimicry to their advantage Alexander Tarakhovsky 1 and Rab K. Prinjha 2 \ue840", "Nonpathogenic viruses affect transcription in a yet more stealthy fashion. Studies that have directly assessed the effects of chronic herpesvirus or polyomavirus infection on expression of host genes in different tissues have revealed substantial virusand organ-specific effects (White et al., 2012; Canny et al., 2014) .", "In their enormous diversity, human viruses can be pathogenic and disease-causing or opportunistic and relatively harmless. The pathogenic and highly destructive viruses such as influenza, dengue fever, yellow fever, HIV, and hepatitis C viruses (HCVs) affect the health of hundreds of millions people worldwide every year. By contrast, opportunistic viruses can benefit the host, and this virus mutualism is evolutionarily old. An impressive example of this mutualism is the rosy apple aphid, Dysaphis plantaginea-a major pest of apple trees-which is infected by a densovirus that induces wing development in the aphid. This morphotype is important in enabling aphids to move to new plants (Ryabov et al., 2009; Roossinck and Baz\u00e1n, 2017) ." ] },{ "paper_id": "bfe6cc567549b7922e6d17d202e5e35501d4d606", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 .", "(AIII).", ". in vitro (dose-dependent) [22, 25] . Ribavirin \ud575\uc2ec \uc9c8\ubb38 5. \uc784\uc2e0\ubd80\uc5d0\uc11c \ud56d\ubc14\uc774\ub7ec\uc2a4\uc81c \uce58\ub8cc\ub294?" ] },{ "paper_id": "bfffc49744be05481a8a3d0266b38c8c2a816f14", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "where Q t is amount of TEV RNA (in pg) per 100 ng of total plant RNA quantified at t \u00bc 2.67 dpi. Absolute fitness was then defined as W \u00bc e m (Crow and Kimura 1970) .", "Supplementary table S1 is available at Genome Biology and Evolution online (http://www.gbe.oxfordjournals.org/).", "Each mutation was introduced in the pMTEV infectious clone (Bedoya and Dar\u00f2 s 2010) by site-directed mutagenesis using the Quickchange II XL kit (Stratagene) and following the indications given by the manufacturer. To minimize unwanted errors during the mutagenesis process, the kit incorporates Pfu Ultra High-Fidelity Turbo DNA polymerase (Stratagene). The amplification conditions were 1 min at 95 C (initial denaturation), followed by 18 cycles consisting of 30 s at 95 C, 45 s at 65 C and 18 min at 68 C, and a final extension step of 28 min at 68 C." ] },{ "paper_id": "c042a8ca113beaec285ea086b0d1722eb838115f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In 1986, it was proposed that cytokines released by activated T-lymphocytes initiate and maintain the psoriatic process by stimulating keratinocyte proliferation [3] . Since that time it has become clear that, upon stimulation, keratinocytes are also able to secrete an array of different cytokines with a variety of functional effects on both themselves and other cell types, including T-lymphocytes [4] .", "Total RNA was extracted using QIA amp RNA extraction kit provided from QIAGEN worldwide companies. The concentration and purity of RNA were determined by measuring its absorbance at 260 nm (A 260 ) and 280 nm (A280) in a UV visible spectrophotometer. Total RNA (2 \u03bcg) was reversetranscribed to cDNA with High-Capacity cDNA Archive kit provided from Applied Biosystems. cDNAs were stored at -20\u00b0C until real-time quantitative PCR was performed.", "Psoriasis is a chronic inflammatory condition which is the result of persistent stimulation of T cells by antigens of epidermal origin [1] . This persistent stimulation of T cells is the result of an interaction between T cells, antigen-presenting cells, i.e. Langerhans cells, and antigens, and comprises the following steps: primary signals (signal 1) including T-cell receptor stimulation by peptide antigen, co-stimulation (so-called accessory signals) (signal 2), and T helper type 1 (Th 1) differentiation and proliferation [2] ." ] },{ "paper_id": "c055818c61327ee072c403cb911793c9c49ca7bf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Antigen . We tested whether the lack of T cell stimulation Table 1 ", "The potentiating activity has been described with polyclonal antibodies (5) , and subsequently with mAbs (6) (7) (8) . The mechanisms and the implications of receptor-mediated antigen uptake on presentation to T cells has been recently reviewed (23) .", "Proliferative response by human T clones was measured by culturing 2 x 104 T cells plus 105 autologous irradiated PBL in 200 /Al medium in flat-bottomed microtiter plates . After 30 h, the wells were pulsed with 0.5 p,Ci ['H]TdR (5 Ci/mmol; Amersham International, Amersham, UK) and harvested 12 h later. Complexes were prepared in the culture wells with antigen and antibody at 10-fold dilutions in 20 I1 volume. 2 h later, cells in 200,ul were added. Final antigen concentration and antibody concentration are shown in Results." ] },{ "paper_id": "c07b523c9bf9af72f5b6ee8b586b13ef619bb3ca", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Targeting proteasome subsets for inhibitionreducing overall toxicity and overcoming drug resistance", "DUBs have also been molecular targets for inhibitor development in recent years (Fig. 1) " ] },{ "paper_id": "c09931fd77525099b75d2b2a0a99bce246e9ec0a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c0f102738445b0a4c2af4323fe69d319d9e09eda", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CONCLUSION: Active SLE has the characteristics of seasonal distribution and is associated with temperature. The mechanism remains to be further studied.", "In summary, our study indicates that active SLE has seasonal distribution and its mechanism remains to be further explored.", "All study methods were approved by ethics committee of Affiliated Hospital of Guangdong Medical College. All the subjects enrolled in the study gave written formal consent to participate." ] },{ "paper_id": "c10a8172b1572b5f5d94ff56417549b51db7405c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c11d970819187c52f9f81d870637aec8779b05d3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c147fd685f974994cea6cb2329084754f655062c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Construction of vector miniTn-Puro-JCVI-1.7", "Mycoplasma strains transformed were M. genitalium strain MS5 (21) , M. mycoides subspecies capri strain GM12 (22, 23) and M. pneumoniae strain M129-B170 (ATCC 29343). All were cultured in SP-4 medium (24) at 37 C and 5% carbon dioxide (CO 2 ).", "Yeast transformations were performed as cited (26) , except that cultures were sometimes grown to less than the recommended optical density (OD; see Table 1 )." ] },{ "paper_id": "c15a612b305f3a174a6f69c0ec4de0dd85afb646", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c1909700d68a75f5d5390928295e7a4949c4cc41", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Diagnosis: A diagnosis of relapsing polychondritis (RP) was finally reached.", "Introduction: Fever of unknown origin (FUO) is a common initial presentation leading to a diagnostic challenge.", "Interventions: The patient received methylprednisolone 40 mg daily with a gradual tapering in a 4-month follow-up." ] },{ "paper_id": "c1a29945f51707d279560855da521ea878989333", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As previously described (27) , 293 T effector cells were transfected with plasmid pAAV-IRES-EGFP encoding the EGFP (293 T/EGFP cells) or plasmid pAAV-IRES-S-EGFP encoding the corresponding HCoV S protein (293 T/HCoV S/GFP cells) as the effector cells. Huh-7 cells, expressing various HCoV receptors on the membrane surface, were used as target cells, as described below. ", "Analyses of independent data were performed by Student's unpaired two-tailed t test. Statistical analyses were carried out using GraphPad Prism 6.0. P values less than 0.05 were considered significant; *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001. The IC 50 was calculated using the CalcuSyn software (65) .", "Six Balb/c female mice (8 weeks old) were randomly assigned to two groups and nasally administered with 20 \uf06dg of Cy5-EK1 in 50 \uf06dl of PBS (n = 3) or 50 \uf06dl of PBS without peptide (n = 3) as control for background fluorescence measurement. One hour later, mice were imaged for distribution of Cy5-EK1 by the IVIS Lumina K Series III in vivo imaging system (PerkinElmer, Waltham, MA, USA). Mice were euthanized by intraperitoneal injection of sodium pentobarbital to obtain the lungs, livers, kidneys, spleens, and hearts for imaging and measuring their fluorescence value. The relevant radiant efficiency (P s \u22121 cm \u22122 sr \u22121 ) (\uf06dW \u22121 cm 2 ) was then calculated by Living Image 4.4 software (56, 71, 72) .", "Circular dichroism spectra (195 to 260 nm) were collected on a J-815 spectropolarimeter (JASCO Inc., Japan) to evaluate the secondary structure of the peptides and their complexes (63, 64) , individual peptides or complexes dissolved in PBS with the final concentration at 10 \uf06dM. Thermal denaturation of peptide complexes was monitored from 20\u00b0 to 100\u00b0C at 222 nm with a thermal gradient of 5\u00b0C/min. The midpoint of the T m values was acquired by JASCO software utilities.", "Cytotoxicity of the peptides to the cells (293 T, 293 T/ACE2, Huh-7, A549, LLC-MK2, and Calu-3 cells) was tested by using the Cell Counting Kit-8 (CCK-8; Dojindo, Kumamoto, Japan). Briefly, each cell type was seeded into the wells of a 96-well microtiter plate (10 4 per well) and incubated at 37\u00b0C for 12 hours, replacing medium with DMED containing EK1 at graded concentrations. After incubation at 37\u00b0C for 2 days, CCK-8 solution (10 \uf06dl per well) was added, followed by an additional incubation for 4 hours. The absorbance was measured at 450 nm.", "Coronaviruses (CoVs) are enveloped viruses with a positive-sense, single-stranded RNA and are associated with various natural hosts. CoVs are divided into alpha, beta, gamma, and delta groups, and the beta group is further composed of A, B, C, and D subgroups (Fig. 1A) (1). Among them, six CoVs can infect humans (HCoVs), including HCoV-229E (229E) and HCoV-NL63 (NL63) in the alpha group, HCoV-OC43 (OC43) and HCoV-HKU1 (HKU1) in beta subgroup A, severe acute respiratory syndrome CoV (SARS-CoV) in beta subgroup B, and Middle East respiratory syndrome CoV (MERS-CoV) in beta subgroup C (2) ." ] },{ "paper_id": "c1ad13d83e926979dbf2bbe52e4944082f28dfea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "P2lucAZ1wt: TCGACGGTCTCCCTCCACTGCTGTAG-TAACCCGGGTCCGGGGCCTCGGTGGTGCTCCTGATG-CCCCTCACCCACCCCTGAAGATCCCAGGTGGGCGAG-GGAATAGTCAGAGGGATCACAACGGATC;", "P2lucAZ10sp: TCGACGGTCTCCCTCCACTGCTGTAG-TAACCCGGGTCCGGGGCCTCGGTGGTGCTCCTGAC-CCTCACCCACCCCTGAAGATCCCAGGTGGGCGAGG-GAATAGTCAGAGGGATCACAACGGATC;", "P2lucAZ1hp: TCGACGGTCTCCCTCCACTGCTGTAG-TAACCCGGGTCCGGGGCCTCGGTGGTGCTCCTGATG-" ] },{ "paper_id": "c2263b536f0cdd99a4e09e96859c007d44cef013", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c259227a2fb2036651025b4cf35fbd2d2942d26c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c25e786759a5c261fed053aeeb9298e36b8aed17", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The measurement was performed in late December 2017. We used three B&K 2270 (Bruel and Kjaer, Naerum, Denmark) and four LD 831c machines (Larson Davis, Depew, [29] . Measurement places and durations can be found in Table 1 .", "www.ejao.org 77", "Cho WH, et al." ] },{ "paper_id": "c28ae565308bfabbd784a23fa065a59a49d8cfc3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c2ad458ccf62686e340e51ea95c439e7c4e2bc29", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For RNA with a single melting transition, the average hyperchromicity can be fit by Equation (2) to measure \u00c1H and T m .", "In vitro frameshift assays were completed with each RNA reporter (experimental and positive control) using a Rabbit Reticulocyte Lysate (RRL) System (Promega, nuclease treated, L416A). Differences from our previously described protocol (56) include the following: translation reactions contained 1.25 mg RNA, 10 units of RNasin Plus RNase Inhibitor (Promega, N2615), and 8.75 ml of RRL in 12.5 ml. Following a 90-min incubation at 37 C, reactions were quenched with the addition of 0.5 ml 0.156 M EDTA pH 8.0 (6 mM final), as described previously (28) . For each reporter, a minimum of three independent frameshift assays were completed. Each independent assay included six replicate reactions.", "Microgram quantities of RNA for the frameshift assay were transcribed in vitro using linearized p2luc plasmid DNA, purified His6-tagged T7 RNA polymerase (10\u00c2), 11.25 mM NTPs and two units of RNasin Plus RNase Inhibitor (Promega), in 200 ml for 90 min at 37 C. Pyrophosphate was pelleted by centrifugation (10 min, 13 200 rpm, room temperature) and RNA was phenol/ chloroform extracted. Unincorporated NTPs and salt were separated from the RNA using size-exclusion chromatography [two Econo-Pac P6 cartridges (Bio-Rad) in series]. Monomeric RNA folding was achieved by denaturation at 95 C for 5 min followed by incubation on ice for 30 min. RNAs were lyophilized to dryness and resuspended in water to a concentration of 1 mg/ml and stored in aliquots ($25 ml) at \u00c080 C. RNA integrity and purity were checked with 1% agarose gel electrophoresis. Finally, RNAs used for UV spectroscopy were purchased from IDT." ] },{ "paper_id": "c2d4efc02a8e37fb93eafe7ddb9eff42e0c600b2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Administrative accountability includes monitoring and supervising health administrative management, as well as administrative procedures for people to bring complaints. Health officials are delegates of those government organs that carry out health strat-", "N U M B E R 1 Health and Human Rights Journal egies and policies. In this respect, there are two types of accountability mechanisms: general administrative mechanisms, which cover both hierarchical and horizontal levels, and supervisory organs for specific issues, such as food and medicine.", "The following case study illustrates how social accountability works in combination with professional accountability and judicial accountability. On finding that her colleagues were providing light quantum therapy by using unlicensed equipment on patients, which was harmful to their health, Dr. Chen wrote to the hospital's professional supervisory board. However, she did not get a satisfactory answer from the board; instead, she was dismissed from her position. She then wrote to the local professional supervisory office, but here too failed to get a satisfactory response. Next, she decided to turn to the judiciary. However, relevant regulations allow only patients and their families to sue a hospital for malpractice. 79 It thus became difficult for Dr. Chen to hold relevant duty-bearers to account. As a last resort, she decided to pretend to be a patient in order to expose the truth. Although she was a healthy person, the hospital still accepted her as a patient, immediately providing her with illegal treatment. Through her undercover action, Dr. Chen was finally able to collect evidence and file the case before a court. 80 Later, the media reported her story, which pressured the Shanghai Medicine Administration Office into initiating a special investigation on illegal treatments in all hospitals in Shanghai.", "Social accountability draws its authority from social moral values. In China, the main mechanism is public exposure through the media. Due to its lack of direct enforcement mechanisms, social accountability is seen internationally as relatively weak and as having less immediate effect. However, in Chinese political thought, society has a high moral expectation of the government and of other members of society. For example, to get promoted, one must have high moral standards.", "The right to health demands that health facilities, services, and medicines be available, accessible, acceptable, and of good quality. 56 This involves the allocation of resources, which is a two-stage process. At the first stage, resources from the whole state budget are allocated to health; at the second stage, these allocations are further distributed to satisfy different demands within the health system. In the context of health as a human right, the first stage requires the allocation of maximum available s. qiu and g. macnaughton / papers, 279-292" ] },{ "paper_id": "c2eb9541f460ced6480edf97d9b89f8e838dc01e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c39ece828769a97d7ab743e5bae232bc127ae6a3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c3a6451d69ba69ded9a9e9683d2668237482399f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "International Journal of COPD 2017:12 submit your manuscript | www.dovepress.com", "Abbreviations: IL, interleukin; TNF, tumor necrosis factor; NK, natural killer; DCs, dendritic cells. ", "The authors report no conflicts of interest in this work.", "Induces expression of G-CSF; it maintains the integrity of the epithelium by limiting cellular apoptosis and favoring regeneration processes." ] },{ "paper_id": "c3df72b290828f12274a34ec6f4ca15d17d885de", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c3e25d0cb02656c82dfac2860225f14588489066", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "I kl = 1, if k , l, I kl = 0, otherwise.", "Each variant allele frequency was tested by Z with a mean of E jb = n i=1 N ijb /n and a variance of", "when replicates were available for only n samples." ] },{ "paper_id": "c3e846076762b54e33385752eb27e086f6cb8b72", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. All analyses were performed using Prism 5 (GraphPad Software, La Jolla, CA). Statistical significance was determined using the two-way analysis of variance (ANOVA) test.", "Citation Mack EA, Kallal LE, Demers DA, Biron CA. 2011. Type 1 interferon induction of natural killer cell gamma interferon production for defense during lymphocytic choriomeningitis virus infection. mBio 2(4):e00169-11." ] },{ "paper_id": "c3e85c0632ee31d2327ceb70161066e29a02d499", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c40185936592afcdc0681000e25585dd58f5ef41", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We have used both CD8 and CIM as the reporter molecules.", "Oligonucleotides used in PCR reactions were generally synthesized with BamHI flanking sequences to facilitate easy cloning into plasmid vectors for sequencing. Oligonucleotides were used at I mM in PCR reactions. PCR products were ethanol precipitated, digested with BamHI, and cloned into the pBS plasmid (Stratagene Corp., La Jolla, CA) for sequencing. DNA sequencing was carried out using the dideoxy chain termination method and T7 polymerase (Tabor and Richardson, 1987) . Plasmid derivafives were digested with the appropriate enzymes to generate the correct 5' and 3' ends for cloning and construction of CD8 and CD4 eDNA chimeras.", "It is likely that other proteins on the exocytic pathway have both retention and retrieval signals. The sum of the two processes acting on these signals would determine the amount of protein found in a particular compartment. For resident proteins which should spend as much of their time as possible in a particular compartment one would expect retention rather than retrieval to be the dominant process. For recycling proteins, such as receptors, one would expect the opposite so that substantial amounts of protein would be moving between two compartments. It is not yet clear whether TGN38 is best considered as a resident or a recycling protein (Luzio and Banting, 1993; Stanley and Howell, 1993) . That will have to await discovery of its function." ] },{ "paper_id": "c436139975d97ef929b5d8452595de40bda0c11c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Refer to Web version on PubMed Central for supplementary material. ", "Nasal swab (log 10 copies/mL) Median (Q1, Q3), N = 81 3. Table 4 Serious Adverse Events that occurred in more than one participant by treatment actually received Adverse events that occurred between day 0 and 7 in more than one participant ", "This was a randomized, open-label, multicenter phase 2 trial conducted at 29 academic medical centers in the United States. All study participants provided written informed consent. The study protocol was approved by the institutional review board at each study site." ] },{ "paper_id": "c439e1028bc93d94f4eba1855c6b1eade676f732", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(1) Hemostatic principles (1) Hemostasis can be activated only by vascular injury.", "From these statements, we can conclude as follows:", "ORCID iD Jae C. Chang https://orcid.org/0000-0002-9401-7684" ] },{ "paper_id": "c445a1425736c454dd61d836d8f657dda8b1b104", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c4a46bccbf43ff75b7e20f5081f3c5b7a31b7b29", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "One to three of the primary antibodies were mixed together in a solution containing 0.1% gelatin, 1% BSA, and 0.05% sodium azide in TB (TGBA).", "We found orcinol staining on a band approximately at the same location as the X band, suggesting that the latter might be a glycolipid. It is not known to what extent this as yet unidentified component contributes to staining of our semithin frozen sections.", "For thin layer chromatography, lipid extracts and standards were loaded on Baker thin layer chromatography silica-gel plates and run in a chloroform/methanol/0.2% CaCI2 (60:40:9) solvent system. The plates were air dried and subjected to routine iodine or orcinol staining or to 04 immunostaining. For the immunostaining, plates were blocked for 1 h at room temperature with 10% FBS and 3 % BSA in MEM Hepes medium and incubated overnight at 4\u00b0C with 04 culture supernatant diluted 1:4 in MEM Hepes with 10% FBS. At~er washing in cold PBS, the plates were incubated 90 min with biotinylated goat anti-mouse IgG (H + L specific; dilution, 11200; Cappel Laboratories, Malvern, PAL washed, incubated with streptavidinperoxidase complex (Amersham Corp., dilution 1/200), and treated with di-aminobenzidin\u00a2 and hydrogen peroxide. Control plates followed the same procedure except that 04 antibody was omitted. The silica gel plates used remained intact throughout the prolonged immersion in aqueous solutions and no special treatment for stabilization was required." ] },{ "paper_id": "c4ad1eb3352c4b02e769ba152f1fa89209a0e70a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c4bffc76026b935fe454f98878510ab490e75bff", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The significance of the variability among the trials was analyzed by GraphPad Prism (version 5.0) software. The results were presented as means \u00b1 SEM and the statistical significance was represented by P values of < 0.05, 0.01, or 0.001.", "Six-week-old specific-pathogen-free White Leghorn chickens, half males and half females, were purchased from Guangdong DaHuaNong Animal Health Products Co., Ltd and housed in isolator cages. Whole blood samples were collected in EDTA anticoagulation tubes with negative pressure via jugular venipuncture. Collected blood volumes never exceeded 3% of the total blood volume (Dawes et al., 2014) .", "All animal research protocols were approved by South China Agriculture University's Institutional Animal Care and Use Committee. All animal procedures were performed according to the regulations and guidelines established by this committee and the international standards for animal welfare." ] },{ "paper_id": "c4c22747c9ab8d0c3b66d8c2d440cf505f492cba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c506acf42e11fa9de3408fd557799de21ec89080", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c55e262b24b28cbd200cae613d6de88c35807deb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cell lines stably expressing the (-1) or (0) dual-luciferase HIV reporter, or the in-frame construct, were generated following the manufacturer's instructions, using 293T Flp-in TM cells (Invitrogen). Individual clones that stably incorporated the plasmids were selected on the basis of their resistance to hygromycin B (Wisent) (250 mg/ml) and maintained in hygromycin B.", "293T transfectants, transfected with a siRNA mix, as described above, were harvested 48 h after the transfection, washed in PBS and lysed in 100 ml of Ripa-Doc (final concentration: 140 mM NaCl, 8 mM Na 2 HPO 4 , 2 mM NaH 2 PO 4 , 1% Nonidet P-40, 0.5% sodium deoxycholate and 0.05% sodium dodecyl sulphate), containing a cocktail of protease and phosphatase inhibitors. Equal amounts of proteins (15 mg) were separated on a 10% SDS-PAGE gel, transferred on a nitrocellulose membrane and immunoblotted with a mouse anti-PKR hybridoma supernatant (clone F9) (a generous gift from A. Koromilas, McGill University) and a horseradish peroxidase-conjugated goat anti-mouse secondary antibody (Amersham) diluted 1/1500. After detection of the antigen-antibody complexes, the membrane was washed with 25 ml of stripping buffer (final concentration: 0.08 M b-mercaptoethanol, 2% sodium dodecyl sulphate and 0.06 M Tris-HCl, pH 6.9) for 30 min at 508C, and immunoblotted with a mouse antia-tubulin monoclonal antibody (clone B-5-1-2 Sigma) diluted 1/5000 and a horseradish peroxidase-conjugated goat anti-mouse secondary antibody diluted 1/1500. Antigen-antibody complexes were detected with an enhanced chemiluminescence (ECL) system.", "The presence of a high amount of TAR decreases HIV-1 frameshift efficiency", "The Fluc versus the Rluc activities of the (-1) and (0) constructs were measured as relative light units with a Berthold Lumat LB 9507 luminometer, as previously described (8) . A Dual-Luciferase Reporter Assay System kit (Promega) was used for Jurkat cells and home-made reagents (25) were used for 293T cells. The Rluc activity is used to normalize the Fluc activity (Fluc/Rluc). The frameshift efficiency is equal to: \u00bdFluc\u00f0\u00c01\u00de=Rluc\u00f0\u00c01\u00de= \u00bdFluc\u00f00\u00de=Rluc\u00f00\u00de \u00fe Fluc\u00f0\u00c01\u00de=Rluc\u00f0\u00c01\u00de:" ] },{ "paper_id": "c57c03bb0a34cfdb6d05fce8c1502707de2e9175", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c58195e4e9894fdbf2e89872912cd0fb46c9f947", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The age-standardized prevalence ratios for ER visits per 100000 population in June 2015 was 0.72, which was lower compared to the rest of the year (0.85 to 1.01) ( Table 1) .", "Number of ER visits in 2015 \u00d7100.", "Data management and statistical analyses were conducted using SAS software version 9.4 (SAS Institute Inc., Cary, NC, USA)." ] },{ "paper_id": "c5c0550f37aa2212ccdc4608e7117c142965e119", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c5c3ad1af37fa848bbdb5fc237c0825aed3a100d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "BACKGROUND", "She had taken Azithromycin for 2 d, but there was no improvement.", "She denied any history of disease." ] },{ "paper_id": "c5e6b31b9d1b7d0b62564566e8deaf48a03a8f32", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c5f1c29433d6c5e4bed3a83ee1c94f003f597ea4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Antibodies Harvard", "Clone reagent", "Myriad Genetics, Inc." ] },{ "paper_id": "c62da850c36f3f10a1fa9289548460fa51b95f26", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The molecular modeling database (MMDB) is Entrez's 'Structure' database (1). Querying MMDB with text terms, e.g. one may identify structures of interest based on a protein name. Links between databases provide other search mechanisms. A query of Entrez PubMed database, e.g. will identify articles citing a particular protein name. Links from this set of articles to 'Structure' may identify structures not found by direct query, since PubMed abstracts contain additional descriptive terms. Currently, MMDB and its visualization services handle 25 000 user queries per day.", "The 'Related Structure' service", "CONTENT" ] },{ "paper_id": "c630ebcdf30652f0422c3ec12a00b50241dc9bd9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c63f31f1d46c5a3cd4d4f2baeab9ce8c3a1dd3bf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c6aea56ae2d57157e5a84857bc2c166d6a9a0105", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The need for ethical approval for this study was waived, based on the Korean Infectious Disease Control and Prevention Act. No. 4 and Enforcement Rule of Bioethics and Safety Act.No.33.", "In Study 1, attack rate of the swimming department was higher than that of others (RR: 1.90; 95% confidence interval (CI): 1.01-3.60) ( ", "As a result of the gene analysis on 14 specimen on which the sequence analysis was possible among 18 identified adenoviruses detected from the confirmed cases, the sequence was 100% identical in homology and the type was confirmed to be HAdV B-55. (3), surgery for nasal septum (1) . N, number. ", "Two to four students were sharing dormitory rooms based on their athletic department. No adenovirus was detected in the surfaces of the shower rooms, door knobs, and shelves where frequent contacts happen." ] },{ "paper_id": "c6b4bc9d758eb2542292da9540b16861b6e1b023", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 Persistently symptomatic patients worsen despite treatment with a disabling, potentially fatal clinical course.", "\u2022 We propose that sarcoidosis results from a chronic granulomatous infection from a treatable pathogen in certain susceptible individuals, much like granulomatous ileitis (Crohn's disease) which shows an encouraging response to multi-drug antimicrobial therapy.", "Demographic and clinical characteristics of the 30 sarcoidosis study patients are found in Table 1 . ", "Chest Figure 2 for typical example), and glucose avidity was seen in the abnormal abdominal nodes in the 4 patients with radiographic adenopathy below the diaphragm." ] },{ "paper_id": "c6be64927ed61a5ec6ad9e947934aea286e2f46e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Genomic DNA was isolated from blood using an AccuPrep The PCR-amplified samples were evaluated for the presence of PCR amplicons corresponding to FeLV, FIP, FIV, FPV, FHV, FCV, Heart worm, Feline Chlamydia, Toxoplasma, Babesia spp., Ehrlichia spp., Haemobartonella felis, Rickettsia spp. and Brucella spp. We were able to visualize bands that were 529 base pairs in length, corresponding to the FeLV amplicon ( Figure 5 ); other feline pathogens tested negative in the PCR assay ( Figure 5 ).", "In this study, the cat had uterine adenocarcinoma without pathognomic ovarian lesions or significant hormonal imbalances. The cat also suffered from FeLV infection and lymphopenia. We believe that the uterine adenocarcinoma in this case was probably related to immunogenic depression by FeLV infection, although we cannot rule out the contributions of other factors, such as old age, to the induction of this tumor. To the best of our knowledge, this is the first report of feline uterine adenocarcinoma with feline leukemia virus infection.", "The trimmed tissues were fixed in 10% neutral buffered formalin and embedded in paraffin. Four-micrometer sections were made and stained with hematoxylin and eosin (H&E) for histopathological examination. The histopathological analysis revealed adenocarcinoma in the uterus and omentum ( Figure 3 ), but no pathological changes were observed in the ovary. The adenocarcinoma had metastasized to the omentum, resulting in thickening and the formation of inflammatory lesions (Figure 4 ). Based on these histopathological findings, the case was diagnosed as uterine adenocarcinoma with abdominal metastasis. The cat made a complete recovery following an ovariohysterectomy and [21] ." ] },{ "paper_id": "c6e43ac8c7b2d8529078ad2645c39814b52d5015", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c6ea09cae9a6185a84ab731e86257d6507f5a102", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "RNA interference (RNAi) is a powerful approach to inhibit human immunodeficiency virus type 1 (HIV-1) replication. However, HIV-1 can escape from RNAimediated antiviral therapy by selection of mutations in the targeted sequence. To prevent viral escape, multiple small interfering RNAs (siRNAs) against conserved viral sequences should be combined. Ideally, these RNA inhibitors should be expressed simultaneously from a single transgene transcript.", "A" ] },{ "paper_id": "c709f22712bf719ea63619fad05d66ce640a7c38", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.", "In a highly mobile world today, more sporadic cases or clusters with MERS-CoV infection would emerge again in the coming future. We could not just pray for luck but keep heightening awareness of contagious disease. It is strongly suggested that different levels of health settings must strengthen their own optimal infection control requirements, such as negative-pressure wards and qualified laboratories for assaying the potential contaminated clinical specimens, especially in tertiary hospitals, also different levels of health care staffs nationwide must be trained well to MERS surveillance and alertness.", "It is so lucky for China to prevent efficiently from MERS because we share many similar habits and concepts in China as in South Korea with obvious regional characteristics. Social phenomena such as \"doctor shopping\" and \"family nursing\" are more common in Chinese health settings. Larger hospitals are believed to have better doctors. Patients would rather take a long time waiting in either clinic or the emergency rooms until a bed is available than going to community hospital. Those situations could generate a large herd of close contacts and hospital-acquired infection. In addition to that, the spread of the MERS-CoV would become a much more serious status than people could ever imagine since China has a larger and higher density of population, a more rapid mobility of population, and a more aging population than South Korea, such a great fortune for China." ] },{ "paper_id": "c70bdcb5ad0df2ac48e9e00f7c35625b7e90557d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Design and Methods. We conducted 140 face-to-face interviews in the Registry Office of the Municipality of Milan, Italy, from October to December 2012.", "The first research question therefore asks: How high is the readiness to get vaccinated against a novel pandemic influenza virus more than two years after the H1N1 pandemic?" ] },{ "paper_id": "c745ca78351211b549476ef12e4cccf3fc3f5b84", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Phylogenies were built for all protein products encoded in the MERS-CoV single-stranded RNA genome, except for NSP1, NSP2, NS3, NS4A, NS4B, ORF8b protein, and NSP11, all of which had insufficient sequence data (<10 sequence hits with BLAST).", "Multiple sequence alignments were constructed for the selected BLAST hits using MAFFT (Katoh et al. 2002) . Phylogenetic trees were constructed using MrBayes 3.2.2 with a four category gamma distribution and the mixed model for amino acid substitution (Huelsenbeck and Ronquist 2001; Ronquist and Huelsenbeck 2003) . Each tree ran for five million generations, with a sample frequency of 100. The final tree was constructed from the last 75% of samples, discarding the first 25% of samples as the default burnin, and using the half-compatible parameter, to avoid weakly supported nodes (i.e., with a posterior probability <0.5). All trees were midpoint rooted.", "Supplementary tables S1 and S2 and figures S1-S5 are available at Genome Biology and Evolution online (http://www. gbe. oxfordjournals.org/).", "NSP12 is often used as a measure for newly identified coronaviruses. According to the International Committee of Taxonomy of Viruses, a major criterion in determining if a coronavirus is considered novel is pairwise sequence identity below 90% for NSP12 in all comparisons to previously known coronaviruses (Bermingham et al. 2012) . Four main clades, alphacoronavirus, betacoronavirus, gammacoronavirus, and deltacoronavirus ( fig. 1) , are identified in agreement with the taxonomic classifications described by the ICTV (International Committee on Taxonomy of Viruses 2015). Coronaviruses not listed by the ICTV are assumed to be a part of the clade in which representatives with known classifications are situated in our NSP12 phylogeny." ] },{ "paper_id": "c761570812ca07ce01397ebabc220556f51e786e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "to elicit a strong response than other epitopes, such as GP276 or NP396. Analyzing these data in another way, we asked which epitope generated the strongest relative response in each mouse, and a nonrandom pattern evolved, with a hierarchy of NP205", "Raymond Welsh: Raymond.welsh@umassmed.edu Abbreviations used: CFSE, carboxyfluorescein diacetatesuccinimidyl ester; LCMV, lymphocytic choriomeningitis virus; PV, Pichinde virus; VV, vaccinia virus." ] },{ "paper_id": "c7a16d3975bbb4ad4f44786d1e5961d16d21f863", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Notable physical examination findings included a thin body condition score (9), hypothermia with a rectal temperature <37.0\u00b0C (2), pyrexia with a rectal temperature >39.2\u00b0C (2), cranial uveitis (2), abdominal distension (2), tachypnea (2), dehydration (1), and pale mucous membranes (1)." ] },{ "paper_id": "c7d39cd61dd94cb21128f5c07392786f2c9a5d2a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Antibody: Antisera against porcine epidemic diarrhea virus (PEDV), swine transmissible gastroenteritis virus (TGEV), porcine group A rotavirus (pGARV), classical swine fever virus (CSFV), porcine circovirus-2 (PCV-2), porcine pseudorabies virus (PRV), and porcine reproductive and respiratory syndrome virus (PRRSV) were kindly provided by the Division of Swine Infectious Diseases, National Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences. Monoclonal antibodies against histidine (His) and glutathione S-transferase (GST) tags were obtained from Tiangen Biotech Co., Ltd. (Beijing, China).", "In conclusion, the rPDCoV-N-ELISA has potential use for investigations of the epidemiology of PDCoV. Porcine deltacoronavirus has shown a low prevalence in limited serological investigations in Heilongjiang province, northeast China, and in the future, these results will need to be confirmed through more extensive serological investigation of PDCoV epidemiology. ", "Porcine deltacoronavirus (PDCoV) was first identified in a rectal swab collected in 2009 from a pig in Hong Kong, China, and it is related to avian and Asian leopard deltacoronaviruses that have been identified in apparently healthy wild animals [6, 22, 23] . Since first reported in swine in the U.S.A. in February 2014, PDCoV rapidly spread to other states in the U.S.A., as well as to Canada, and it caused significant economic losses in the swine industry [14, 16, [19] [20] [21] . Recently, PDCoV has been reported in the pig population from China and South Korea [5, 12] . Hu et al. reported the cell culture isolation, serial propagation, and biologic and genetic characterizations of cell-adapted PDCoV strains [9] . Jung et al. reported that two PDCoV strains, OH-FD22 and OH-FD100, are enteropathogenic in gnotobiotic pigs [10] . Chen et al. revealed the pathogenicity of a plaque-purified PDCoV cell culture isolate and characterized PDCoV pathogenesis in neonatal piglets [3] . The accumulating reports demonstrated that PDCoV is associated with diarrhea in pigs." ] },{ "paper_id": "c7ec0563ddbb18f183ddbd147056d8a2aca9fef2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c821803c55c6aad89b6d0c1d3ba252051e464017", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The images are published under agreement of the patient.", "Myongji Hospital Institutional Review Board (IRB) approved this study (No. IRB 2020-01-027) and written informed consent was given by the patient. ", "We thank to Myongji Hospital staffs for their efforts to cope with COVID-19 and CancerROP Co., Ltd., for providing a test diagnostic kit to measure SARS-CoV-2 virus titers. ", "At that time the initial confirmation of COVID-19 was made by pan-coronavirus conventional polymerase chain reaction assay and sequencing of the polymerase chain reaction (PCR) amplicons using a throat swab." ] },{ "paper_id": "c838ca724d9916867c83ad89c823ca61027bd046", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "carbohydrate. The positions of migration in this gel of VP2 (94k), VP7 (38k) (with high-mannose carbohydrate), and NCVP5 (29k) in infected cell lysates are shown.", "To examine the ultrastructural morphology of untreated COS 7-and of SA1 l-infected MA104 cells (5.5 h post-infection, infected according to published methods [12] ), coverslips were fixed in 2% glutataldehyde in 0.1 M cacodylate buffer, pH 7.4, for 45 min at 22\"C. Cells were postfixed in 1% osmium tetroxide in cacodylate buffer, stained in 1% uranyl acetate, dehydrated in ethanol, and embedded in resin before thin sectioning. Sections were stained with uranyl rinse and Reynolds lead stain for several minutes (33) and then specimens were examined and photographed in a JEOL 100 CX electron microscope at 80 kV.", "We wish to thank Ms. Alisa Kabcenell for her critical review of the manuscript and Mr. George Dominguez for his skillful preparation of the final photographs." ] },{ "paper_id": "c84aa58b12823cdd6f119b4da3b0c4ba488856b5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c8b0ef630df7327adda9757e8cca4aaac3fe69b3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This hybrid nanocarrier showed temperature-dependent assembly/disassembly properties, indicating that virus can modify synthetic materials to respond to environmental factors, such as temperature and pH.", "Although these strategies are promising to endow viruses with additional functions, intrinsic immunogenicity and safety issues of viruses remains.", "ADV, adenovirus; BNC, bio-nanocapsule; DDS, drug delivery system; EPR, enhanced permeability and retention; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV-1, human immunodeficiency virus 1; HSPG, heparan sulfate proteoglycan; IFV, influenza virus; LP, liposome; MHC, major histocompatibility complex; NP, nanoparticle; NTCP, sodium taurocholate cotransporting polypeptide; PEG, poly (ethylene glycol); RES, reticuloendothelial system; PAR, polymerized-albumin receptor; SFV, Semliki Forest virus; siRNA, short interfering RNA; VLP, virus-like particle; VSV, vesicular stomatitis virus." ] },{ "paper_id": "c8d6b93a43ec16e86c706d638d1de31ffd961588", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.", "Contributors ABP defined the study idea. AD, ABP, LP, CB and RWT conceived the paper. AD, CB and RWT wrote the study protocol. LP extracted the data and led the statistical analysis. All authors contributed to data interpretation. AD wrote the first draft with further contribution from RWT and ABP. All authors critically reviewed successive drafts and approved the final version of the manuscript.", "We identified 4107 patients with a first time ON-related hospitalisation (table 1). The proportion of patients with no hospital-diagnosed comorbidity recorded was much greater among controls than in ON cases (81.1% vs 59.0%). The proportions with mild, moderate and severe comorbidity levels among cases versus controls were 29.4% versus 15.6%, 7.2% versus 2.4% and 4.3% versus 0.8%, respectively.", "As presented in figure 1 , a fluctuating ON incidence was observed especially for the first half of the study period, between 1995 and 2004. An upward trend was noted from 2005 onwards, with a mean annual incidence reaching 5.5 per 100 000 inhabitants during the last 3 years, 2010-2012." ] },{ "paper_id": "c94cf364c4ceb68d6b7b7cbc252d32a53401779a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Singapore, by and large, has seen extraordinary growth in its average national income since its humble beginnings as a colonial outpost. In attaining its vision to become a \"distinctive global city\" [31] , its relatively affluent, well-educated, and upwardly mobile population have increased access to environments, goods, and services that are not previously experienced and their risks to individual health uncertain. Besides unusual outbreaks [32, 33] and stress-related disorders [34] , other curious aetiologies [35, 36] have occurred from time to time. In addition, changes in lifestyle by an ageing population-about 400 000 baby boomers will turn 65 years old between now and 2020-is a major force re-shaping our society.", "For outbreak management, investment needs to be wisely directed towards capability enhancement and Singapore has learnt that dealing with unknowns requires sufficient bandwidth in both infrastructure (i.e., hardware) and expertise (i.e., software). Recognising the importance of epidemic intelligence, a public health intelligence unit was set up in 2011 to monitor and analyse changes in local and overseas disease landscapes. Intelligence that is acquired from this process is used to track potential threats, trigger public health response, and facilitate risk communication to relevant stakeholders as necessary.", "Fear and uncertainty over an unknown disease could ignite widespread panic, with adverse repercussions on the economy and social fabric. Hence, in the aftermath of SARS, Singapore invested heavily into pandemic preparedness [14, 15] . Our national strategy is premised on a well established surveillance and response system that forewarns, detects, and contains the importation of a novel agent, and on mitigation measures when community spread is sustained (i.e., showing no epidemiological link to imported source cases). A national pandemic readiness and response plan was developed with the Disease Outbreak Response System Condition framework as its risk management centre-piece [16] . This framework helps calibrate outbreak response according to the nature and transmissibility of the agent.", "Similarly, the widespread dissemination of the novel influenza A (H1N1) in 2009 was thought to be related to the high number of flights out of early major centres of the epidemic. Investigations into a cluster of six cases confirmed transmission of the H1N1 on board a commercial aircraft [11] . These events illustrate the capability of diseases to transmit rapidly across borders, facilitated by convenient air travel [12, 13] ." ] },{ "paper_id": "c95aea18951cb2b0ba90fe898b92b09ac419c5b9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors confirm that the data supporting the findings of this study are available within the article and its Supplementary material.", "Keywords: prion infection; type I interferon (I-IFN); innate immune system. Abbreviations: I-IFN = type I interferon; IRF = interferon regulatory factor; MEF = mouse embryonic fibroblast; TLR = Toll-like receptor" ] },{ "paper_id": "c96149ec9735f620b4acd1c4da5c537ed2175619", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "a The circulating strain in bold type indicates its antigenic property is significantly different from that of the contemporary global vaccine strain of the same subtype. strains were also shared with the WHO Collaborating Centers in the United States (US Centers for Disease Control and Prevention) and Japan ( Japan National Institute of Infectious Diseases).", "On May 20, this unsubtyped influenza virus strain was sent to TCDC. After results of H1, H3, H5, H7, and H9 molecular diagnoses were all negative, the virus was further identified as the H6N1 subtype based on sequence analysis of its hemagglutinin and neuraminidase genes. Subsequently, TCDC developed the molecular diagnostic method and conducted enhanced active surveillance. From June 10 to August 13, a total of 125 individuals with influenzalike illness or pneumonia were reported; all of their respiratory specimens tested negative for H6N1. Six symptomatic contacts were identified, and serological analyses of the paired serum specimens collected from those contacts also showed undetectable antibody titers (&10) against the H6N1 virus, while titers of the first and second serum specimens of the index case were 40 and 80, respectively. 26 Therefore, no additional H6N1-infected cases were identified.", "To evaluate possible risks of the novel H7N9 viruses to public health, viral genetic markers that may be related to human adaptation and their antigenic properties were analyzed by TCDC. All 4 H7N9 viruses are antigenically similar to the A/Anhui/1/2013 vaccine candidate strain. However, they harbor markers related to enhanced polymerase activity (the 627K or 701N in the polymerase basic protein 2) and high-affinity binding of virus to human receptors (the 226L in the hemagglutinin protein), suggesting their better replication and infection capabilities in human population. 25 One virus also has markers that may confer oseltamivir resistance (the 292K in the neuraminidase protein). Furthermore, the phylogenetic relationship of viral full-genome sequences reveals that these 4 viruses were generated through various reassortment events in China, indicating their complex evolutionary history. 25 These findings are consistent with the initial viral characteristics reported by other research groups at the early stage of H7N9 outbreaks in China. 31 ", "Identification of the first global human infection with the influenza A(H6N1) virus in 2013 in Taiwan highlights the important role of the national influenza laboratory surveillance network. 26 Avian influenza A(H6N1) virus is a common virus isolated from migrating birds and domestic poultry in many countries. 32, 33 However, human infection with this subtype had not been reported prior to the confirmation of H6N1 infection in a 20-year-old patient with influenzalike illness by TCDC in May 2013. On May 8, 2013 , an influenza A virus isolated from the inpatient's throat swab specimen was identified by a regional authorized laboratory using an immunofluorescence assay. However, subsequent analyses by subtype-specific PCR assays showed negative results for human H1N1pdm09 and H3N2 viruses." ] },{ "paper_id": "c96cd1e79d3f1ea12887e2b4d9b3347b9ee07137", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The study was approved by the Ethics Committee of Central Hospital of Zibo (Zibo, China). The CVB3 virus was purchased from Cell Signaling Inc. at a titer of 100 TCID50 (50% tissue culture infective dose) /0.1 ml. Mg-132 was purchased from Calbiochem Inc. at a concentration of 0.75 mg/kg.", "As a viral infectious disease, VMC currently has no specific effective treatment in clinical practice, thus, VMC is one of the most challenging diseases in the diagnosis and treatment of cardiovascular field at present (13) . Besides, there are also great controversies regarding the pathogenesis of VMC, most of which support cytokine theory and immune theory (14) .", "Upstream primer Downstream primer" ] },{ "paper_id": "c97243d65788222d1cf09203e27ae04deaf0ef1c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c9796b987137402c163bb03519d8cd9de9ae99f9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Participants A random sample of 500 Singapore residents aged 21 and over, including 271 women and 229 men, was analysed.", "The authors declare no conflicts of interest. \"CaseNo\",\"Quarantine.A\",\"Isolation.A\",\"NoMassGatherings.A\",\"TempScreening.A\", \"Tax.A\",\"Infections.A\",\"Deaths.A\",\"Quarantine.B\",\"Isolation.B\",\"NoMassGatheri ngs.B\",\"TempScreening.B\",\"Tax.B\",\"Infections.B\",\"Deaths.B\",\"Choice\" 166,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 166,1,2,2,3,2,1,5 A\" 440,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario A\" 440,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 440,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 440,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario A\" 440,1,2,1,1,2,4,5,2,1,3,3,4 ,2,4,\"Scenario B\" 440,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario B\" 351,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 351,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario A\" 351,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 351,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 351,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario B\" 351,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 351,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario A\" 351,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario A\" 351,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 351,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 348,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 348,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 348,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario A\" 348,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario B\" 348,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 348,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario A\" 348,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 348,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario A\" 348,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 348,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 347,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario B\" 347,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario B\" 347,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 347,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario B\" 347,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario B\" 347,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario A\" 347,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 347,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario B\" 347,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario B\" 347,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario B\" 34,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 34,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario A\" 34,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario B\" 34,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario B\" 34,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario B\" 34,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 34,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario A\" 34,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario A\" 34,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 34,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario B\" 32,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 32,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario A\" 32,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 32,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario B\" 32,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario B\" 32,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 32,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario B\" 32,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario A\" 32,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 32,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 37,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 37,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 37,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario A\" 37,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 37,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 37,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario B\" 37,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario A\" 37,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario A\" 37,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 37,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 38,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 38,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario A\" 38,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario B\" 38,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario B\" 38,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario A\" 38,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario B\" 38,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 38,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 38,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario B\" 38,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario B\" 33,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 33,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario A\" 33,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario B\" 33,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario B\" 33,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario A\" 33,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 33,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario A\" 33,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario B\" 33,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 33,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario A\" 454,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 454,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario A\" 454,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 454,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario B\" 454,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario B\" 454,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 454,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario A\" 454,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 454,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 454,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario A\" 458,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 458,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 458,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario B\" 458,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 458,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 458,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario B\" 458,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 458,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 458,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 458,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario B\" 39,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 39,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario B\" 39,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 39,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 39,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario B\" 39,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario A\" 39,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario B\" 39,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 39,1,1,2,2,3,3,3,2,2,3,1 ,2,4,5,\"Scenario A\" 39,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 35,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 35,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario A\" 35,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario A\" 35,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario B\" 35,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario A\" 35,2,2,3, 1,1,1,1,1,1,1,3,3,3,4 ,\"Scenario B\" 35,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 35,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario A\" 35,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario A\" 35,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario A\" 36,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 36,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario A\" 36,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 36,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario B\" 36,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario A\" 36,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 36,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario B\" 36,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 36,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 36,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario A\" 327,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 327,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario A\" 327,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario A\" 327,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario B\" 327,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 327,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario A\" 327,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario A\" 327,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 327,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario B\" 327,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 328,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario B\" 328,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario B\" 328,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 328,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 328,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario A\" 328,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario B\" 328,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 328,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario B\" 328,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario A\" 328,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 370,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 370,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario A\" 370,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario B\" 370,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario B\" 370,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario B\" 370,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 370,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario A\" 370,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario B\" 370,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 370,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario A\" 368,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 368,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario A\" 368,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario A\" 368,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario B\" 368,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario B\" 368,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 368,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario A\" 368,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 368,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 368,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 456,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 456,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 456,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario B\" 456,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario B\" 456,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 456,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario B\" 456,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 456,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 456,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 456,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 438,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario B\" 438,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario B\" 438,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 438,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario B\" 438,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario B\" 438,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario B\" 438,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 438,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario B\" 438,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario B\" 438,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 408,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 408,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario B\" 408,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario B\" 408,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 408,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario A\" 408,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 408,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 408,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario A\" 408,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 408,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario A\" 357,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 357,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario A\" 357,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 357,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 357,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario B\" 357,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 357,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario A\" 357,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario A\" 357,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 357,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 356,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 356,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 356,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario A\" 356,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario B\" 356,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 356,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario A\" 356,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 356,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario A\" 356,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 356,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 441,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 441,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario B\" 441,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 441,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 441,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario B\" 441,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario B\" 441,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 441,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 441,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario B\" 441,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 358,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 358,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario B\" 358,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario A\" 358,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario B\" 358,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario A\" 358,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 358,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 358,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario A\" 358,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 358,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario B\" 341,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 341,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario A\" 341,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 341,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 341,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario B\" 341,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 341,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario A\" 341,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario A\" 341,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 341,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 355,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 355,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario A\" 355,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario B\" 355,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 355,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 355,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario A\" 355,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 355,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 355,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario B\" 355,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 233,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 233,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario B\" 233,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 233,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 233,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario B\" 233,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario B\" 233,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 233,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 233,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario A\" 233,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 354,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 354,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario A\" 354,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario B\" 354,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 354,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario B\" 354,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 354,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 354,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario B\" 354,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 354,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario A\" 457,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 457,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario B\" 457,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario A\" 457,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 457,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario A\" 457,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 457,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario A\" 457,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 457,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 457,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 404,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 404,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 404,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario A\" 404,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 404,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 404,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario B\" 404,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 404,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 404,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 404,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 403,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 403,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario A\" 403,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 403,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario B\" 403,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario B\" 403,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario B\" 403,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 403,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 403,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario A\" 403,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 369,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 369,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario A\" 369,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario B\" 369,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario B\" 369,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario A\" 369,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 369,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 369,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario B\" 369,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 369,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario A\" 455,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 455,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario B\" 455,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 455,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 455,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario A\" 455,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario B\" 455,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario B\" 455,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 455,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario A\" 455,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 60,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 60,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 60,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario B\" 60,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 60,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 60,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario B\" 60,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 60,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 60,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 60,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 7,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario B\" 7,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario A\" 7,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario B\" 7,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 7,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario A\" 7,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario B\" 7,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 7,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 7,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario B\" 7,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 62,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 62,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario B\" 62,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario B\" 62,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 62,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario A\" 62,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 62,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 62,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario B\" 62,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 62,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario A\" 4,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 4,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario B\" 4,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 4,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 4,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario A\" 4,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 4,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario A\" 4,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 4,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 4,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 63,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 63,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 63,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario A\" 63,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 63,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario A\" 63,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario B\" 63,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 63,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario A\" 63,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario B\" 63,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario B\" 422,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 422,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario B\" 422,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario B\" 422,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 422,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario A\" 422,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario B\" 422,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario B\" 422,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario B\" 422,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario A\" 422,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario B\" 68,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 68,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario B\" 68,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario B\" 68,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 68,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario A\" 68,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 68,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 68,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario B\" 68,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 68,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario A\" 423,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario B\" 423,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario A\" 423,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario A\" 423,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 423,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario A\" 423,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 423,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario B\" 423,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario A\" 423,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario A\" 423,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario A\" 306,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 306,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 306,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario B\" 306,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario B\" 306,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 306,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario B\" 306,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario A\" 306,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 306,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario B\" 306,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario B\" 376,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 376,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario A\" 376,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 376,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario B\" 376,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario B\" 376,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario B\" 376,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario B\" 376,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 376,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario A\" 376,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario B\" 305,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 305,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario A\" 305,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario A\" 305,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 305,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario B\" 305,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 305,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 305,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario A\" 305,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 305,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario B\" 409,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 409,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario B\" 409,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 409,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 409,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario B\" 409,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario B\" 409,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario B\" 409,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 409,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 409,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 410,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 410,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 410,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario A\" 410,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 410,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 410,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario B\" 410,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 410,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 410,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 410,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 461,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario B\" 461,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario B\" 461,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 461,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario B\" 461,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario B\" 461,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario A\" 461,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario B\" 461,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 461,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario B\" 461,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 437,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 437,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario B\" 437,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario B\" 437,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario B\" 437,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario A\" 437,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 437,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 437,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario A\" 437,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 437,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario B\" 451,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 451,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario B\" 451,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 451,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 451,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario A\" 451,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 451,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario A\" 451,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 451,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 451,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 446,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 446,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 446,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario B\" 446,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 446,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 446,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario B\" 446,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 446,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 446,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 446,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 320,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 320,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario A\" 320,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 320,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 320,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario A\" 320,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario A\" 320,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 320,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario B\" 320,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario A\" 320,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 449,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 449,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario B\" 449,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario B\" 449,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 449,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario A\" 449,2,2,3, 1,1,1,1,1,1,1,3,3,3,4 ,\"Scenario A\" 449,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario A\" 449,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario A\" 449,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 449,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario B\" 450,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 450,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario B\" 450,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 450,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario B\" 450,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario B\" 450,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 450,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario B\" 450,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 450,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario A\" 450,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 448,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 448,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 448,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario B\" 448,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 448,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 448,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario B\" 448,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 448,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 448,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 448,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario B\" 447,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 447,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario A\" 447,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 447,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 447,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario A\" 447,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario B\" 447,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 447,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario B\" 447,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario A\" 447,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario B\" 405,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 405,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario B\" 405,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario B\" 405,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 405,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario B\" 405,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 405,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario A\" 405,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario A\" 405,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 405,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario A\" 453,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 453,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario B\" 453,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 453,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 453,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario A\" 453,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 453,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario A\" 453,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 453,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 453,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 443,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 443,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 443,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario B\" 443,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 443,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 443,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario B\" 443,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario A\" 443,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 443,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 443,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 3,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 3,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario A\" 3,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario B\" 3,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 3,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario A\" 3,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario B\" 3,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 3,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 3,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario A\" 3,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 81,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario B\" 81,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario A\" 81,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario A\" 81,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario B\" 81,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario A\" 81,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 81,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario A\" 81,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario A\" 81,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 81,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario B\" 317,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 317,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario B\" 317,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 317,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 317,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario A\" 317,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 317,2,1,1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 F o r p e e r r e v i e w o n l y 367,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 339,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 339,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario A\" 339,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 339,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 339,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario B\" 339,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario A\" 339,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 339,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 339,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario B\" 339,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 61,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 61,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario B\" 61,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario B\" 61,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 61,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario A\" 61,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 61,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 61,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario B\" 61,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 61,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario A\" 67,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 67,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario B\" 67,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 67,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario B\" 67,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario B\" 67,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 67,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario B\" 67,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 67,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 67,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 64,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 64,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 64,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario A\" 64,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario B\" 64,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 64,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario B\" 64,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario A\" 64,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 64,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario B\" 64,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 6,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 6,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario B\" 6,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 6,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 6,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario B\" 6,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario B\" 6,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 6,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 6,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario A\" 6,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 10,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario B\" 10,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario A\" 10,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario A\" 10,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 10,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario B\" 10,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 10,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 10,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario B\" 10,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario A\" 10,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario B\" 8,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario B\" 8,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario A\" 8,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario A\" 8,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 8,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario B\" 8,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario B\" 8,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario A\" 8,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario A\" 8,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 8,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario A\" 9,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 9,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario A\" 9,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario A\" 9,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 9,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 9,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario A\" 9,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario A\" 9,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario A\" 9,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 9,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario B\" 5,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 5,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario B\" 5,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 5,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 5,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario B\" 5,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario B\" 5,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 5,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 5,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario A\" 5,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 65,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 65,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario B\" 65,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario B\" 65,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 65,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario A\" 65,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 65,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 65,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario B\" 65,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 65,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario A\" 66,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 66,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario B\" 66,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 66,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 66,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario A\" 66,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 66,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario A\" 66,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 66,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 66,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 395,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario B\" 395,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 395,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario A\" 395,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 395,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario A\" 395,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario A\" 395,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 395,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario A\" 395,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 395,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario B\" 181,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 181,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario A\" 181,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 181,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 181,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario A\" 181,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario B\" 181,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario B\" 181,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 181,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario B\" 181,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 177,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 177,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario B\" 177,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario B\" 177,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 177,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario B\" 177,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 177,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 177,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario B\" 177,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario A\" 177,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario A\" 397,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 397,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario A\" 397,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 397,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 397,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario A\" 397,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario B\" 397,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario A\" 397,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 397,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario A\" 397,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario A\" 179,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 179,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 179,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario B\" 179,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario B\" 179,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 179,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario A\" 179,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario A\" 179,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 179,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario B\" 179,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 82,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 82,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario B\" 82,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 82,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario B\" 82,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario B\" 82,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario B\" 82,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 82,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 82,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario A\" 82,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 239,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario B\" 239,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario A\" 239,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario A\" 239,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 239,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario B\" 239,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 239,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 239,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario B\" 239,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario A\" 239,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario B\" 83,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 83,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario A\" 83,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 83,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 83,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario A\" 83,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 83,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario A\" 83,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 83,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 83,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 267,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 267,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario A\" 267,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario A\" 267,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 267,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 267,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario A\" 267,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario A\" 267,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario A\" 267,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 267,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario B\" 240,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario B\" 240,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario A\" 240,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario B\" 240,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 240,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario A\" 240,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario A\" 240,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 240,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 240,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario B\" 240,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 84,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 84,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario B\" 84,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario A\" 84,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 84,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario B\" 84,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario B\" 84,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario A\" 84,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario A\" 84,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario A\" 84,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario A\" 269,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 269,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario A\" 269,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario A\" 269,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 269,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario B\" 269,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario B\" 269,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario B\" 269,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 269,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 269,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 85,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 85,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 85,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario A\" 85,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 85,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 85,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario A\" 85,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 85,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario A\" 85,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 85,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario B\" 86,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 86,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario A\" 86,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 86,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario B\" 86,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario A\" 86,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario A\" 86,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario B\" 86,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario B\" 86,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario B\" 86,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario B\" 295,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 295,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario A\" 295,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario A\" 295,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 295,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario B\" 295,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 295,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario A\" 295,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario A\" 295,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario A\" 295,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario B\" 87,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 87,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario B\" 87,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 87,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 87,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario A\" 87,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario B\" 87,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario B\" 87,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 87,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 87,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 238,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 238,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 238,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario B\" 238,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 238,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario A\" 238,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario A\" 238,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario A\" 238,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario A\" 238,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 238,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario B\" 88,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 88,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario B\" 88,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 88,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario B\" 88,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario B\" 88,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario A\" 88,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario B\" 88,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario B\" 88,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario B\" 88,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario B\" 89,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 89,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario B\" 89,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario A\" 89,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario B\" 89,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario A\" 89,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 89,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 89,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario A\" 89,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 89,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario B\" 268,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 268,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario B\" 268,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 268,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario B\" 268,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario B\" 268,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario B\" 268,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario B\" 268,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario A\" 268,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario A\" 268,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario A\" 106,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 106,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 106,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario B\" 106,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 106,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 106,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario B\" 106,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 106,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 106,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 106,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 107,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 107,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario B\" 107,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario B\" 107,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 107,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario B\" 107,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario B\" 107,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario B\" 107,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario B\" 107,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario A\" 107,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 108,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 108,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario B\" 108,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario B\" 108,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 108,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario B\" 108,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario B\" 108,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 108,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario B\" 108,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario A\" 108,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario A\" 109,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario B\" 109,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario B\" 109,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario A\" 109,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 109,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario A\" 109,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario B\" 109,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario A\" 109,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario A\" 109,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 109,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 110,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 110,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 110,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario A\" 110,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 110,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 110,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario B\" 110,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 110,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 110,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 110,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 111,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 111,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario B\" 111,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 111,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 111,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario B\" 111,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario B\" 111,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 111,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 111,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario A\" 111,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 112,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario B\" 112,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario A\" 112,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario A\" 112,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 112,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario B\" 112,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 112,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario A\" 112,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario A\" 112,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario A\" 112,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario A\" 113,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 113,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario A\" 113,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 113,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 113,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario B\" 113,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 113,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario B\" 113,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 113,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario A\" 113,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 114,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 114,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 114,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario B\" 114,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 114,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 114,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario B\" 114,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 114,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 114,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 114,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 115,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 115,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario B\" 115,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 115,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 115,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario A\" 115,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario B\" 115,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 115,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 115,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario A\" 115,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 31,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario B\" 31,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario A\" 31,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario A\" 31,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 31,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario B\" 31,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 31,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 31,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario A\" 31,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario A\" 31,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario B\" 30,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 30,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario A\" 30,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 30,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 30,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario B\" 30,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario B\" 30,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario B\" 30,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario A\" 30,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 30,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 462,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario B\" 462,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario A\" 462,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario A\" 462,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 462,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 462,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario A\" 462,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 462,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 462,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 462,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 424,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario B\" 424,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario A\" 424,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario B\" 424,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario B\" 424,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario A\" 424,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario A\" 424,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 424,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario B\" 424,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario A\" 424,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario B\" 28,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario B\" 28,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario A\" 28,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario B\" 28,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 28,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario B\" 28,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 28,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 28,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario A\" 28,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 28,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario B\" 401,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 401,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario A\" 401,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario A\" 401,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario B\" 401,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario A\" 401,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario B\" 401,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario A\" 401,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario A\" 401,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario A\" 401,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario A\" 427,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 427,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 427,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario B\" 427,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 427,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario A\" 427,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario A\" 427,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 427,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 427,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario B\" 427,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario B\" 433,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 433,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario B\" 433,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario B\" 433,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 433,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario A\" 433,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario A\" 433,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario B\" 433,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario B\" 433,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario B\" 433,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 428,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario B\" 428,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario B\" 428,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario A\" 428,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 428,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario B\" 428,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 428,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario A\" 428,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario A\" 428,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario A\" 428,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario A\" 29,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 29,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario A\" 29,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario A\" 29,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 29,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario B\" 29,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario B\" 29,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario A\" 29,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario A\" 29,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 29,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario A\" 387,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 387,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario A\" 387,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario B\" 387,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 387,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario A\" 387,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario B\" 387,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario A\" 387,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario A\" 387,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 387,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario B\" 426,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario A\" 426,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario A\" 426,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario A\" 426,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario B\" 426,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario B\" 426,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario A\" 426,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 426,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario B\" 426,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario A\" 426,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 434,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 434,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario A\" 434,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario A\" 434,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario A\" 434,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario B\" 434,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 434,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario A\" 434,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario B\" 434,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario A\" 434,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario A\" 425,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 425,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario A\" 425,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 425,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario B\" 425,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario A\" 425,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 425,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario A\" 425,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 425,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 425,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario A\" 180,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 180,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario A\" 180,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario A\" 180,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario A\" 180,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 180,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario A\" 180,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario A\" 180,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario B\" 180,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 180,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 90,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario B\" 90,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario A\" 90,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario B\" 90,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 90,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario A\" 90,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario A\" 90,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 90,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 90,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario B\" 90,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 91,2,1,2,2,3,2,1,1,2,3,2,1,5,4,\"Scenario A\" 91,1,2,2,3,2,1,5,2,1,1,1,4,3,3,\"Scenario B\" 91,2,2,1,1,2,4,5,1,2,2,2,3,1,1,\"Scenario B\" 91,1,1,3,3,1,4,1,2,2,1,2,4,3,2,\"Scenario B\" 91,2,1,2,1,4,2,3,1,1,3,3,1,5,3,\"Scenario A\" 91,2,2,3,1,1,1,1,1,1,1,3,3,3,4,\"Scenario A\" 91,1,2,1,2,3,2,4,2,1,2,2,2,5,3,\"Scenario B\" 91,2,2,3,3,4,3,5,2,1,2,1,3,5,2,\"Scenario A\" 91,1,2,1,1,2,4,5,2,1,3,3,4,2,4,\"Scenario B\" 91,1,1,2,2,2,1,1,2,2,3,1,1,1,2,\"Scenario B\" 92,1,2,2,2,4,3,2,1,1,1,3,3,4,3,\"Scenario A\" 92,2,1,3,1,2,5,4,1,2,1,3,4,2,1,\"Scenario B\" 92,1,1,1,3,1,4,5,2,2,2,2,2,3,5,\"Scenario B\" 92,2,1,2,2,1,4,1,1,2,2,1,3,1,2,\"Scenario A\" 92,1,1,3,2,2,2,3,2,2,3,3,1,2,4,\"Scenario B\" 92,2,1,1,1,4,1,2,1,2,3,2,2,5,3,\"Scenario A\" 92,2,1,1,2,1,4,4,1,2,3,1,3,3,5,\"Scenario A\" 92,2,2,2,3,3,5,4,1,2,2,3,4,4,1,\"Scenario B\" 92,1,1,2,1,4,3,5,2,1,1,2,3,5,1,\"Scenario B\" 92,1,1,3,1,1,1,2,2,2,3,3,2,4,1,\"Scenario B\" 93,2,1,2,3,1,3,1,1,2,1,1,1,2,2,\"Scenario A\" 93,1,1,2,1,2,2,3,2,2,3,2,4,1,2,\"Scenario B\" 93,2,1,3,2,3,5,5,1,2,1,3,4,4,4,\"Scenario A\" 93,1,2,3,3,1,4,3,2,1,1,1,2,1,4,\"Scenario B\" 93,1,1,2,1,4,5,5,2,2,1,2,3,4,1,\"Scenario B\" 93,2,1,2,3,1,1,3,1,2,2,1,2,3,1,\"Scenario A\" 93,1,2,1,2,1,3,4,2,1,3,3,3,5,1,\"Scenario B\" 93,2,2,3,2,1,1,5,1,1,2,3,4,2,2,\"Scenario A\" 93,2,2,3,1,2,4,2,1,1,1,2,2,2,5,\"Scenario A\" 93,2,2,1,1,3,3,4,1,1,2,3,1,3,5,\"Scenario A\" 94,1,1,3,3,3,1,2,1,2,2,3,2,2,5,\"Scenario B\" 94,1,2,3,2,1,1,4,2,1,2,3,4,5,3,\"Scenario A\" 94,2,2,1,2,3,4,2,1,1,3,1,1,4,5,\"Scenario B\" 94,1,2,1,1,3,2,1,2,1,1,2,4,3,1,\"Scenario A\" 94,1,2,2,2,2,3,2,2,2,3,1,4,5,1,\"Scenario A\" 94,2,1,2,1,2,1,4,1,1,1,3,2,5,2,\"Scenario A\" 94,2,1,1,3,1,2,1,1,2,3,2,4,3,4,\"Scenario A\" 94,1,1,3,3,1,5,2,2,2,2,1,3,1,3,\"Scenario A\" 94,1,1,2,2,3,3,3,2,2,3,1,2,4,5,\"Scenario B\" 94,1,2,2,3,1,5,4,2,1,3,2,4,2,5,\"Scenario A\" 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 " ] },{ "paper_id": "c98075a839f10763a8c30207b33c57e4455bc4ae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sputum culture, blood culture, nasopharyngeal swab for viral PCR, BinaxNOW pneumococcal urinary antigen test, and a urinary inhibition multiplex immunoassay (IMIA) to detect and serotype pneumococci were performed to identify the causative agents. 22, 23 Pneumococcal infection was defined as positive sputum or blood culture with S. pneumoniae, or a positive BinaxNOW or IMIA at inclusion.", "In cases where patients were discharged, blood sampling and biomarker assessment stopped. With clinical recovery we assumed biomarker normalization. To compensate for the missing values, the known half-lives of the biomarkers were applied (with normal value as minimum) to the last measured samples. For CRP, the half-life is 19 h (normal value 1 mg/L), for PCT it is 30 h (normal value 0.15 ng/mL) and for MR-proADM it is 4 h (normal value 0.36 nmol/L).", "Groeneveld et al." ] },{ "paper_id": "c98acd548c24c973cbad72af49a0080fce9cd2ee", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "well be hidden. As Lao Tsu suggested centuries ago, educational achievement is measured by what a learner learns more than by what the teacher teaches.", "Instructors should thus be mindful of addressing autonomy in different forms, as indicated in the following five subsections.", "Most science textbooks present decontextualized, or abstracted, knowledge. Cases, however, situate the knowledge in real-world contexts. Here, the cases provide the primary occasion for learning, rather than serve secondarily as illustrations or applications. Nor are cases merely \"teasers\" or \"hooks\" for opening a presentation of abstract content. Rather, the cases become integral to the structure of learning.", "At an impressive extreme, students-even nonscience majors or K-12 students-might participate in ongoing research. While tasks might not be any more demanding than gathering data, students may certainly understand the context of the work, see closely how it is structured, and take pride in contributing to developing original scientific knowledge (Crawford, 2012) ." ] },{ "paper_id": "c99640294d5862d4482de51f9a442deaf09b53be", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In vitro transcription reactions were performed from 600 ng of each PCR amplicon using the SP6/T7 transcription kit (Roche). To label the transcript with biotin, biotin-14-CTP (Invitrogen) was added to the transcription reaction at a final concentration of 0.16 mM in a 1:6.25 ratio to (Table 2) , labeled at the 3= end with biotin, were chemically synthesized (Sigma Aldrich).", "The TGEV PUR46-MAD strain (43) was used to infect ST cells, and the TGEV PUR46-C11 strain (44) was used to infect Huh-7 cells. In all cases, virus titration was performed on ST cell monolayers as previously described (45) .", "overlapping open reading frames (ORFs) named 1a and 1b. Both ORFs are directly translated from the viral genome, resulting in two large polyproteins (pp1a and pp1ab), which are autoproteolitically cleaved to release the replication-transcription complex components (8) . The 3= one-third of the genome includes the genes encoding the structural spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins, as well as the genusspecific proteins characteristic of each CoV, which are expressed from a nested set of 3=-coterminal subgenomic mRNAs (sgmRNAs) (2, 7, 8) ." ] },{ "paper_id": "c9bf6547ad546ca4338e790c4fbe75af4c5b6ee8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In conclusion, self-swabbing was acceptable and feasible in a low-income, urban minority population.", "We approached 31 households to take part in the pilot study and 30 (96.8%) agreed (28 unique households; two households took part twice). These represented 15 ill adults and 15 ill children (Table 1 ). All households reported in the follow-up call that they had obtained the sample, and we received 29 samples (96.7%) (most samples [n=28] by mail, and one specimen brought directly to the laboratory). Of those who mailed the specimen, most (78.6%) reported mailing it within 1 day; all reported mailing it within 2 days. The median time between the kit being dropped off and arrival to the laboratory was 8 days (range: 3-99 days).", "Community-based studies are an important component of surveillance for acute respiratory infections/influenza-like illness (ARI/ILI). Using nasal self-swabbing to obtain samples for laboratory analysis has advantages during outbreaks or pandemics, as this strategy would reduce the time required for health care professionals to obtain specimens, as well as lessen their risk of becoming infected. Furthermore, self-swabbing could be used to identify ARI/ILI etiologies in the community that might be missed from reliance on medically-attended disease surveillance." ] },{ "paper_id": "c9fc9152d225265c48f4b8023ffab0a26de38132", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The infiltrated tobacco leaves were ground into a fine powder in liquid nitrogen, using mortar and pestle. Subsequently, 0.5-mL extraction buffer (50 mM NaH 2 PO 4 , pH = 8, 300 mM NaCl, 0.1% Tween 20, 10 mM beta-mercaptoethanol, 1 mM PMSF, and 5 mM EDTA) was added to each gram of powdered leaf tissue. The total soluble protein (TSP) was removed from cell debris by centrifugation of the leaf extracts for 20 minutes at 4\u00b0C (14000 rpm).", "The E. coli-derived HCVcp (eHCVcp) and plant-derived HCVcp (pHCVcp) were purified through application of nickel-nitrilotriacetic acid (Ni-NTA) chromatography, as previously described (15, 34) . Protein concentrations were determined by Bradford assay (44) using bovine serum albumin (BSA) as standard." ] },{ "paper_id": "ca247deecd89fea456e741ed2a23a8e1213471c3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This project was reviewed by the University of Arkansas for Medical Sciences Institutional Review Board and determined to be QI.", "Between January 22-April 1, 2018, and February 8-April 17, 2019, due to significant influenza circulating in the community, only 2 parents/primary caregivers were allowed to visit.", "Starting in May 2017, we revised the employee illness policy such that absences due to potentially contagious illness were no longer considered unscheduled absences if approved by Employee Health. Before May 2017, there was no consistent documentation of employee absence due to contagious illness. The utilization of the new policy by NICU staff was minimal until October of 2017. Afterward, reduced presenteeism likely began to impact HARVIs positively.", "The average monthly HCW hand hygiene compliance in the NICU was consistently around 90%. Patients with respiratory symptoms or diagnosis of a specific viral respiratory infection were placed on both droplet and contact precautions. HCW compliance with posted isolation signs remained over 95%. Since the 2011-2012 influenza season, all HCWs were required to receive the annual influenza vaccination, resulting in HCW influenza vaccination coverage consistently around 99%." ] },{ "paper_id": "ca274e20fd535ce3666baf7a70daffcecd68d5ae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This case was presented as an oral presentation at the annual congress of the Japanese Society of Veterinary Neurology, Iwate, Japan, June 2018.", "Additional supporting information may be found online in the Supporting Information section at the end of this article. ", "Although 1 healthy cat serum (#1) antibodies bound to neurons (shown in the Supporting Information), other control sera did not bind at all (Figure 3) . A cell-based binding assay for LGI1 was performed, as" ] },{ "paper_id": "ca2fa034524ce26d06b3674b3c494635d7d5f13b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Meat Inspection Center is located in Abashiri-Gun, Hokkaido, Japan, and has 2 abattoirs, which receive 150,000 to 200,000 pigs annually for slaughtering, mainly from the eastern Hokkaido. At this facility, pig carcasses are inspected by gross pathological examination, and the carcasses harboring intestines with nodular caseous necrosis are diagnosed with swine mycobacteriosis.", "However, as Fig. 6 showed, the level of detection is low enough to detect outbreak even in the small-scale farms. Moreover, large-scale farms have multiple production units, and outbreaks can occur within a unit. Thus, the present model can detect such outbreaks at a sale to slaughterhouse, and we think this would not be a notable limitation.", "Mycobacterium avium-intracellulare Complex (MAIC) is a common pathogen that, like M. tuberculosis, causes tuberculosis in humans and opportunistic infections in those suffering from acquired immune deficiency syndrome (AIDS) [7, 15, 30] . Mycobacteriosis in swine caused by MAIC is a chronic infectious disease, which presents as caseous necrosis in submandibular lymph nodes and mesenteric lymph nodes. In swine, the most common lesion is the one found in mesenteric lymph node [32] . Mycobacteriosis is the only known disease that forms caseous necrosis in animals and humans. Japanese meat inspection service follows the statements of a manual [20] : 'a caseous necrosis suggests mycobacteriosis', and it regards such case as mycobacteriosis without further microbiological examinations. Intestines are condemned when the caseous necrosis is a single lesion, and whole carcasses are condemned when the systemic infection is found, causing a significant economic burden for the pig producer." ] },{ "paper_id": "ca3d3e317e5c694091583d23c1cbcd0b68c88d27", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cell Lines and Virus. CHO-K1 (American Type Culture Collection [ATCC] CCL-61) cells and pgsA-745 (ATCC CRL-2242) cells, a derivative deficient in xylosyltransferase (UDP-D-xylose/serine-1,3-D-xylosyltransferase), referred to as CHO745 in this study, were maintained at 37\u00b0C with 5% CO 2 in Gibco F-12 Nutrient K (Kaighn's Modification of Ham's F-12) Medium (Thermo Fisher Scientific) supplemented with 10% HyClone Cosmic Calf Serum (Thermo Fisher Scientific) and 1\u00d7 penicillin/streptomycin. The reverse genetics technique for the production of replication-competent, recombinant CedV was described previously (30) . The rCedV antigenome plasmid was designed based on the sequence available in the GenBank (accession no. NC_025351.1).", "Receptor Interaction Analysis by SPR. The interaction of CedV sG with different ephrins was monitored by SPR using a BIAcore T200 instrument and CM5 sensor chips (GE Healthcare) using adopted methods (69) . Detailed experimental procedures can be found in SI Appendix, Supplementary Experimental Procedures.", "Illustrations. All molecular representations were generated with PyMOL (Delano Scientific LLC). Figures were prepared using GraphPad Prism, Microsoft Excel, Adobe Illustrator, and Adobe Photoshop." ] },{ "paper_id": "ca46502bc5b38f9453f31a3f34ba1711e98d83a9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ca5a4a493d2bb7b970d36753a7eb36baf714a760", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ca70e687fe7d0471c95bc8e75b588860343fb0c6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cronbach's alpha for the index was 0.801 (n = 660). Data were collected on participants' sex, ethnicity, and age. Sex was defined as male or female. Ethnicity was defined as Caucasian, African American, Hispanic, Asian or South Pacific Islander, Middle Eastern, American Indian/Alaskan Native, or other. Participants were asked to provide their age, height, weight, and information about their family history of diabetes. Participants' BMI was calculated, and weight classifications were developed from height/ weight indexes.", "An analysis of variance (ANOVA) was conducted with the remaining 302 participants to test for sex-related differences. The results showed a statistically significant difference between the means of the sexes (F = 9.472, df = 1, P = 0.002).", "This cross-sectional study was conducted at a university located in Walker County, Tex. Faculty representing five colleges on the campus were contacted via e-mail before the start of the fall semester and asked to participate in the study. Fifty professors agreed to have researchers recruit students who were willing to participate voluntarily. A total of 660 students agreed to take part in the study. Researchers instructed the participating students to read and sign a consent form and to complete a 6-page, self-administered questionnaire that took 15 minutes to complete. The questionnaire included 27 questions and was distributed at the beginning of a class session. Completed questionnaires were placed in an envelope or box. The university's human subjects institution review board approved this project. Data analysis was conducted using IBM Statistics SPSS 20.0 software (IBM, Armonk, N.Y.)." ] },{ "paper_id": "ca8b14f351edca29473646f4bb9669c3ad03500c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "It is of particular interest that BAG3 deficiency can result in the loss of hematopoietic stem cells due to a defect in stem cell niche. 61 Therefore, BAG3 is required for the stem cellsupporting activity of microenvironmental cells. This finding suggests that BAG3 may also regulate the cancer stem cell-supporting activity of stromal cells in the hematopoietic and possibly in other compartments. Again, NF-kB factors could represent key targets of BAG3, not only for the expression of tumor cell genes that sustain cell survival, but also for the expression of stromal cells' soluble and cell surface molecules that mediate bidirectional interactions between tumor cells and their environment. 77, 78 ", "From the first evidence of BAG3-mediated survival in B-CLLs, 21 a number of reports confirmed the anti-apoptotic activity of the protein in tumors of the hematopoietic 2, 13, 21, 22, 25, 28, 30, 39, 40, 49 and other 2, 20, 24, 25, 29, 31, 34, 36, 37, 44 compartments. Two principal elements contribute to the role of BAG3 in vast range of tumors: bag3 induction by HSF1, 47 a transcription factor activated in many cancer types; 46 and BAG3 ability to sustain of NF-kB activity. 76 In addition, BAG3, because of its multifaceted ability to complex with many proteins, can regulate factors that are particularly relevant in the context of specific tumor types, such as BAX in glioblastoma cells. 36 Overall, studies on BAG3 expression and activity in normal and neoplastic cells, and of its regulation during the development, increasingly delineate a complex picture of BAG3 involvement in physiological and pathological processes. The pleiotropic functions attributed to BAG3 probably reflect the adapter nature of this multidomain (BAG, WW and PXXP) protein and its ability to assemble scaffolding complexes, which participate in more than one signal transduction pathway.", "It has been shown that bag3 silencing reduces adhesion and/or motility of epithelial (breast, prostate) tumor cells. 27, 32, 65, 66 In MDA435 human breast cancer cells, BAG3 overexpression resulted in a decrease in migration and adhesion to matrix molecules; the decrease was reversed on deletion of the BAG3 proline-rich (PXXP) domain, indicating that an interaction of BAG3 with a SH 3 domain-containing protein was involved. 65 Expression array studies showed that indeed BAG3 regulated, in a PXXP-dependent manner, the expression of CCN (Cyr61, connective tissue growth, NOV) 1, a matricellular signaling protein that promotes cell adhesion through integrins and heparan sulfate-containing proteoglycans. 32 In addition, BAG3 seems to regulate cell adhesion through binding to guanine nucleotide exchange factor 2 (PDZGEF2). This protein induces the activation of Rap1, a regulator of cell-cell junction formation and remodeling, and increases integrin-mediated cell adhesion. The PPDY motif at the C-terminus of PDZGEF2 was shown to bind to the WW domain of BAG3, and PDZGEF2 knockdown reduced BAG3 ability to induce cell adhesion in Cos7 cells. 67 Similarly to what we described above for apoptosis, the ability of BAG3 to regulate cell adhesion appears to rely on multiple interactions of this protein through different structural domains. It is important to note that modulation of cell adhesion has profound effects on cell vitality, as cell detachment from matrix induces the apoptotic process known as anoikis. 68 Therefore, BAG3 alterations could underlie effects on both cell detachment/motility and resistance to associated anoikis, thereby favouring metastatization. Finally, we recently reported that BAG3, through its interaction with the cytosolic chaperonin CCT (chaperonin containing TCP-1), regulates actin folding. 66 This property of BAG3 highlights its involvement in cytoskeleton organization, possibly influencing not only cell survival and migration, but also membrane trafficking and organellar dynamics." ] },{ "paper_id": "caaa1e0e60a860b078465c328e73a2c201b53554", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cac688a10fc20a83e2a43abc2297738c26b8afb4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To collect the clinical and epidemiological data, patient's history, including farm, breed, sex, age, season, recovery period, and prognosis, was recorded. Physical examination of each patient was conducted. The fecal samples were classified as pasty, watery, mucous, and hemorrhagic.", "DNA and RNA were extracted from fecal samples using Patho Gene-spin DNA/RNA Extraction kit (iNtRON Biotechnology, Inc., Korea) according to the manufacturer's instructions. Real-time polymerase chain reaction (RT-PCR) was performed on BVDV, coronavirus, and rotavirus using an i-BD Multi Detection Kit (iNtRON Biotechnology, Inc.). In addition, RT-PCR for adenovirus, norovirus, kobuvirus, parvovirus, and torovirus was performed as previously described [9, [23] [24] [25] .", "As it is difficult to predict the diarrheal causative agent based on the clinical symptoms of KNC, it is necessary to accurately diagnose calf diarrhea using tests that may be performed in the laboratory or at farm site." ] },{ "paper_id": "cae1f2fd5785845caa42d6497361eba46a68f11d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Atherosclerosis is a common type of degenerative disease of the vessel wall characterized by the accumulation of apolipoprotein B-lipoproteins in the inner lining of large and medium sized arteries [41] . It underlies the leading cause of death in developed countries and is likely soon to attain this status worldwide [42] .", "Given the crucial roles of varied phenotypes of macrophages in promotion and progression of atherosclerosis, intervention with macrophage polarization may provide a novel therapeutic opportunity to atherosclerosis and cardiovascular diseases.", "Obesity and its attendant metabolic disorder challenge the public health of modern society worldwide. Nearly 75% adults in America are overweight, and more than one-third of them are obese [53] . Furthermore, the persistent increase in obesity, especially in children, will halt or even decrease the life expectancy of America within the first half of this century [54] . As a disease with metabolic disturbance, obesity could lead to insulin resistance, glucose intolerance, dyslipidemia as well as hypertension. In addition, recent studies had uncovered that obesity was involved in cancers, hepatic and renal failure, thrombotic disease, and many infectious diseases [55] . Those findings suggest that obesity should pay more attentions than ever before." ] },{ "paper_id": "cb5a49679732abf852dec6e61e435602706289c3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Histopathology and immunohistochemistry. Histopathology and immunohistochemistry were performed on macaque tissues. After fixation for 7 days in 10% neutral buffered formalin and embedding in paraffin, tissue sections were stained with hematoxylin and eosin (H&E). To detect influenza A virus antigen, immunohistochemistry was performed using an anti-NP monoclonal HB-65 antibody (EVL, the Netherlands) as a primary antibody.", "de Wit et al.", "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." ] },{ "paper_id": "cb62f467ee641118d0b7d0b6244c6f7aa800416f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Several investigations have observed that NMI is involved in signaling mechanisms that contribute to tumor initiation (Fig. 2) .", "Multiple studies have been focused on elucidating the roles of transcription factors, but less attention has been given to proteins that indirectly influence specific transcriptional events. These proteins are of critical importance because of their organ-specific, spatio-temporal regulatory ability. Understanding these indirect influences may hold the key to revealing intricate, biologically relevant details of signaling pathway regulation.", "The distinction between cancer initiation and progression has grown more pronounced with the discovery of signaling pathways specific to each process. Progression of cancer from early to late stage is a critical step after which therapeutic intervention becomes increasingly difficult. At a cellular level, progression often involves gaining resistance to therapeutic agents and assumption of a less differentiated state. These characteristics can result in metastatic disease. Recent studies propose that the loss of NMI enhances the cellular acquisition of these characteristics that ultimately lead to cancer progression (Fig. 3) ." ] },{ "paper_id": "cb690769762bb2fc4b4d9b898b03623b589fe8c1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cb6ac0e6f129a47a228c217485d17d091c8c2421", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cbc7ee25347acd1ad2fef88420dca328d27d8f5d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The protocol of the present study was reviewed and approved by the Institutional Review Board (IRB) of Seoul National University Hospital (IRB No. 1809-072-973). The patient provided written informed consent.", "Here we describe the first imported case of MERS-CoV infection after a large outbreak in Korea in 2015. Although 21 close contacts were identified by an epidemiological investigation, no additional cases of MERS-CoV infection were found. 5", "As the patient presented with diarrhea and he had few respiratory symptoms, he did not meet the case definition of MERS when he arrived at the airport, 16 and the quarantine officer did not isolate him. This raised a question whether the case definition should be revised to include diarrhea symptom. The answer depends on whether MERS-CoV is excreted into stool and transmissible to others, however, no fecal transmission has been reported so far. Moreover, as diarrhea is a common and non-specific symptom, many patients with traveler's diarrhea without MERS-CoV infection would undergo unnecessary screening tests. Therefore, inclusion of diarrhea symptom in the case definition for MERS-CoV surveillance requires more data and ensuring evidence." ] },{ "paper_id": "cc11d6ace6db8abceb7213e6b37d93ce5417f696", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Conflict of interest statement. The authors declare competing financial interests. All are employees of Fluidigm Corporation. (19) .", "Supplementary Data are available at NAR Online.", "Funding for Open Access charge: Fluidigm Corporation." ] },{ "paper_id": "cc6cb3af2ef6432cf20dd2c84b56fdb8be780078", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "One commander and 1 deputy commander are assigned by the Ministry of Health and Welfare in each network region.", "They review relevant plans of communicable disease control, and they supervise and provide consultation to local health bureaus. During an outbreak, the command center leads case investigation; infection control and patient transport in medical facilities; coordination; expropriation; requisition; and allocation of hospitals, hospital beds, and manpower.", "In a post-Ebola time, training programs of comprehensive core clinical and infection control skills, such as hands-on practices while wearing PPE and mental health and behavior changes, should be further developed with reference to the WHO and other countries' guidance in response to future emerging disease epidemics. In addition, strategies are needed to incentivize participation of frontline medical workers to ensure a robust response team. Further, fair risk compensation payments for caring for highly infectious diseases by healthcare workers is still a topic of debate despite existing regulations governing the operation procedures and compensation for requisitioned health personnel. However, these have not been reviewed since the SARS outbreak." ] },{ "paper_id": "cc977f7fb011becc54322dc88f6b6d417c7ecc00", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cc9cf437db5ffe6c085e9b72a6d20d067a3c7c03", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Translation experiments were carried out in buffer A at 37 \u2022 C by rapidly mixing initiation complexes of 70S ribosomes from Escherichia coli, mRNA and initiator fMet-tRNA fMet (0. ", "The density of FS band The density of FS band + The density of NFS band \u00d7 100", "The mRNAs containing Renilla luciferase (Rluc) and either a truncated firefly luciferase (trFluc) or triple-tags were prepared as follows. We adopted the trFluc mainly because of easier detection of the -1PRF product. The respective constructs (see S2 in Supplementary Information) were linearized by digestion with BamHI and used as templates for in vitro transcription. The mRNAs were transcribed in vitro from the linearized DNA with T7 RNA polymerase (T7-Scribe\u2122 Standard RNA IVT Kit, CELLSCRIPT). A typical 20 l reaction contained the linearized DNA template (500 ng), NTPs (ATP, CTP, GTP, and UTP, 7.5 mM each), DTT (10 mM), and 2 l of T7-scribe\u2122 Enzyme Solution. The reaction mixture was incubated at 37 \u2022 C for 12 h, followed by digestion of the template with DNase I. RNA transcripts were purified on a NAP-5 column (GE Healthcare), and precipitated with ammonium acetate and isopropanol. The RNA concentration was determined by UV absorbance. The Flexi \u00ae rabbit reticulocyte lysate system (Promega) was used for in vitro translation. The mRNA (100 ng) was translated in a rabbit reticulocyte lysate (RRL) containing amino acid mixture (20 M) and KCl (70 mM). The reaction mixture was incubated at 30 \u2022 C for 1 h in the absence or presence of NCTn. The reaction was quenched by adding 2 \u00d7 SDS buffer before western blot analysis." ] },{ "paper_id": "ccb533d872f914aee01fd533f330c6d768da14c5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In this section we focus on the commonly used methods to create MI in small animals.", "This section of the review focuses on viral infection, genetic abnormalities, and autoimmune animal model and the application of stem cells to treat DCM.", "No competing financial interests exist." ] },{ "paper_id": "cccc79beb9b80834fd6302ddec0eb65633ce3f95", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "According to the Nationwide Children's Hospital Institutional Review Board (Columbus, OH, USA), approval is not required for presentation of single case report. The child's parents provided written informed consent for the publication of this case report.", "Given the lack of a clear etiologic event in our patient, the option of proceeding with spinal anesthesia was discussed and offered to the parents when our patient returned. As the decision was made to proceed with spinal anesthesia, the surgical procedure was converted to an open procedure given Local and Regional Anesthesia 2017:10 submit your manuscript | www.dovepress.com", "Spinal anesthesia in high-risk pediatric patients has been described in prior studies, but the focus of these studies has been avoidance of apnea in ex-preterm infants or, more recently, as a means of avoiding the potential negative neurocognitive effects of general anesthetic agents. Spinal anesthesia is appropriate in many cases where avoidance of general anesthesia is desired, regardless of the reason. In our patient, spinal anesthesia provided several advantages, including intraoperative hemodynamic stability, effective surgical anesthesia, elimination of the need for opioids or inhalation anesthetic agents, patient immobility, and adequate operating conditions without the use of neuromuscular blocking agents. [32] [33] [34] 36, 37 " ] },{ "paper_id": "ccdfa546c3c6de3c6a91ad713d56d320eac3e6e4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Case of a hospital 40-60 km from the Fukushima Daiichi NPP", "There have been cases of discrimination against people from Fukushima [33] . Similar discrimination has been reported in connection with other nuclear disasters and radiation accidents. Victims of a radiation accident in Goiania, Brazil, had to be issued certificates declaring them to be free of contamination because passengers refused to fly with contaminated persons aboard airplanes [34] . Such discrimination would strengthen the sense of isolation and desperation.", "An additional concern regarding damage to reputation, called 'Fuhyohigai,' was reported after the Fukushima disaster [35] . 'Fuhyohigai' refers to social and economic damage caused by an unfounded negative rumour spread by the media, causing decreased sales of local products, trade, and tourism. However, 'Fuhyohigai'is not only an economic issue, but also applies to psychosocial problems and self-stigmatization [37] . For example, concerns about discrimination because of supposed dangerous levels of radiation exposure can lead a change in risk perception, stigmatization by ii110 \u2022 H. Nukui et al." ] },{ "paper_id": "ccfba5ba6e11eff35a72dead3fac7f7daebda11d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Both media and cell lysates were precleared by a brief incubation with Zysorbin followed by spinning in a microfuge (Beckman Instruments, Stanford, CA) before further analysis. Immunoprecipitation was performed using rabbit anti-rat recombinant ProB (refer to Materials and Antibodies ). For immunoblotting of cathepsin B, samples analyzed by SDS 12%-PAGE were electrotransferred to nitrocellulose and then blotted with an equal mixture of both rabbit antisera to recombinant cathepsin B (refer to Materials and Antibodies ) at a dilution of 1:1,000, and then detected with a peroxidase-conjugated secondary antibody by enhanced chemiluminescence.", "Pancreatic and parotid glands were dissected from 200-g Sprague-Dawley rats that had been subjected to an overnight fast with water available ad libitum. Parotid or pancreatic tissue was dissected and cleaned of connective tissue as described (Arvan and Castle, 1987) , and then lobules were prepared as described by a modification of Scheele and Palade (1975) . For electron microscopy, male Wistar rats were anaesthetized and then sub-jected to perfusion fixation as described in Slot et al. (1991) . The fixative solution consisted of 2% paraformaldehyde and 0.2% glutaraldehyde in 0.1 M sodium phosphate buffer, pH 7.4.", "A second vesicle pathway originating from the TGN, the constitutive secretory pathway, involves protein incorporation into small transport vesicles that rapidly convey their contents to the plasma membrane. Cells differentiated for a third TGN-derived exit route, the regulated secretory pathway, also contain secretory granules, which undergo fusion with the cell surface only at low levels under resting conditions, and at amplified levels when a stimulus for exocytosis is received." ] },{ "paper_id": "cd226106aef486ea318b5426295de4059cc88c10", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cd92f91038067e7a10aa27d676ce696e1e4d67ce", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Immunohistochemistry was performed using antibodies specific for CD31 (1:200; ab24590; Abcam) and HIF-1\u03b1 (1:100; ab8366; Abcam). In brief, these sections were rehydrated and incubated with primary antibodies at 4\u02daC overnight, then incubated with biotinylated secondary IgGs (1:500; BA1001; Wuhan Boster Biological Technology, Ltd., Wuhan, China). Sections were treated with ABC complex and developed with 3,3'-diaminobenzidine (both Wuhan Boster Biological Technology, Ltd.), then stained with hematoxylin. All sections were consistently maintained in liquid, and sections incubated without primary antibodies were used as a control.", "Animals. Healthy New Zealand rabbits weighing 2.5-3 kg and aged 2-3 months were provided by the Experimental Animal Centre of Shanghai Jiao Tong University affiliated Sixth People's Hospital (Shanghai, China). Animals were maintained in single cages at a controlled temperature (15-25\u02daC)under a 12-h light/dark cycle and fed with a standard diet. Animals received humane care in compliance with the Guide of the US Department of Health for the care and use of laboratory animals (23) . The experiment protocol was approved by the Animal Ethics Committee of Shanghai Jiao Tong University.", "Statistical analysis. Data are expressed as the mean \u00b1 standard deviation. One-way analysis of variance with an Student-Newman-Keuls post hoc analysis was applied to determine statistical significance. P<0.05 was considered to indicate a statistically significant difference. Statistical analysis was performed using SPSS software, version 12.0 (SPSS, Inc., Chicago, IL, USA)." ] },{ "paper_id": "cdfa3f7c065622bfb2c811f71fc0dbae5b1a4d3d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Health, Swedish University of Agricultural Sciences, Sweden.", "The data that support the findings will be available at NCBI Sequence Read Archive (SRA) with accession number: SRP109282.", "http://orcid.org/0000-0003-4899-9637" ] },{ "paper_id": "cdffb72af0749246fd5f957fda4e793e29911a83", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The field of RNA biology has exploded in recent years with the discovery of non-coding RNAs (ncRNAs) that regulate essential processes in all living organisms (1) . These processes include transcription, translation, and evasion in bacteria and archaea (1, 2) as well as replication, persistence, and cellular transformation in viruses (3) . Within the human genome, protein-coding genes are vastly outnumbered by regulatory ncRNAs that can influence a wide range of cellular functions (2, 4) . Many of these ncRNAs are dysregulated in and implicated as drivers of various human diseases, including metastatic cancers and neurologi-cal and neuromuscular disorders (2, 5, 6) . This 'RNA revolution' is radically changing our understanding of the role RNA plays in fundamental biology and is rapidly driving scientific innovation.", "S-amino acid conjugates", "Supplementary Data are available at NAR Online." ] },{ "paper_id": "ce0ea5e3b418366d8dab2a4c5a98266c8880a156", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ce5f0965088e41390e671d3d16d65ccd777efa21", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ce6717ad3bb0da86077a5cbb8111576ea8230b2c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cec09e3b5beea8a13cd359b3aa53e5ee0d40b969", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "At the initial stage of the response, monitoring of close contacts focused on healthcare personnel and the patients who shared the same hospital room with the index patient, along with the family members who visited the room. If the response had been successful in containing the spread, the outbreak could have been ended as hoped. On May 28, however, another patient who had not been included in the initial group under monitoring was diagnosed with MERS-CoV infection. By this time, several other patients among the firstgeneration cases who were also not included in the monitoring, had already been transferred to other hospitals, where new outbreaks emerged [1, 3] .", "It is worth asking what can be done better in the future. To answer this question, systematic assessment needs to be performed on the actions taken and the outcomes of such actions, with detailed analysis of the data. In order to guide such analyses, this paper will explore a conceptual framework, and suggest a new measure to monitor the adequacy of a public health response.", "When an initial case of MERS-CoV is confirmed, immediate public health responses should include thorough epidemiologic investigation of the case, contact monitoring, an active search for additional cases, and enhanced surveillance [4] . Contact monitoring, often called contact tracing, is particularly important for two reasons: to find any cases that might have already occurred among the close contacts, and to quarantine those who are at high risk of infection to contain further spread." ] },{ "paper_id": "cf410c7fd76487d1244517521fbe521465e75310", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The current outbreak of EHF highlighted the importance of prevention strategies. Health care workers have represented a considerable proportion of all infected cases. So educating and training the medical staff on universal precautions, risk assessment, and use of personal protective equipment is crucial. Patients initially identified as having a possible viral hemorrhagic fever should be isolated until the results of their specific diagnosis are obtained from reference laboratories. It is important not to delay diagnosis and treatment of more common diseases, such as malaria or typhoid, during this period. Follow-up of contact cases is essential for infection containment in case the patient tests are positive. Specially equipped ambulances and trained staff should be prepared to do the transferring when needed (1, 10, 24) . Early diagnosis and rapid laboratory confirmation along with isolation of patients and following their contacts, as well as access to protective equipment and environmental decontamination are the mainstay of prevention.", "Ebola hemorrhagic fever (EHF) was first reported in 1976 with two concurrent outbreaks of acute viral hemorrhagic fever centered in Yambuku (near the Ebola river), Democratic Republic of Congo, and in Nzara, Sudan. The current outbreak of the Ebola virus was started by reporting the first case in March 2014 in the forest regions of southeastern Guinea. Due to infection rates raising over 13,000% within a 6-month period, Ebola is now considered as a global public health emergency and on August 8 th , 2014 the World Health Organization (WHO) declared the epidemic to be a Public Health Emergency of International Concern. With more than 5000 involved cases and nearly 3000 deaths, this event has turned into the largest and most dangerous Ebola virus outbreak in the world. Based on the above-mentioned, the present article aimed to review the virologic characteristics, transmission, clinical manifestation, diagnosis, treatment, and prevention of Ebola virus disease.", "There is no specific antiviral agent or vaccine against Ebola viruses. Therefore, supportive care is the most important aspect of its management. Aggressive prevention of intravascular volume depletion is critical to avoid life-threatening complications by using proper fluid therapy, oxygen therapy, correcting profound electrolyte abnormalities, and preventing the complications of shock such as acid-base derangements. Treatment of other infections, if they occur, and close monitoring of vital signs and regular biochemical and blood gas checks should be done. These proceedings are considered as the foundation of critical care medicine and should be applied to both resource-rich and resource-constrained settings. With improving supportive cares, EHF outcomes may also improve. Symptom control with taking narcotics and benzodiazepines were often reported as the end-of-life therapy in some patients (2, 5, 14) . A variety of chemotherapeutic agents have been tested for different stages of development. Recombinant human activated protein C and recombinant nematode anticoagulant protein C2 are also among them. One drug identified as ZMAPP, has been used on several patients, however it remains unclear if it is effective or not. Therefore, no Food and Drug Administration (FDA) approved agent exists against Ebola (4, 6, (18) (19) (20) (21) (22) (23) . Figure 1 shows the latest CDC algorithm regarding emergency department evaluation and management for possible Ebola infected patients." ] },{ "paper_id": "cf6a16717c4b118d2e8bca72fe7dd28c2f2c2cdb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "OKTll (anti-CD2), OKT3 (anti-CD3), OKT4A (anti-CD4), OKT8 (anti-CDS), OKT1 (anti-CD5), OKT26a (anti-CD25), OKT10 (anti-CD38), and OKT9 (anti-CD71) mAbs were purchased from Ortho Pharmaceutical (Raritan, NJ). Anti-Leu-M5 (anti-CD18/LFA-1 fl chain) and anti-Leu-19 (anti-CD56) mAbs were purchased from Becton Dickinson & Co. (Mountain View, CA); anti-CD54 (anti-ICAM-1) mAb was from Immunotech (Marseille, France); anti-CD58 (anti-LFA-3; TS 2/9 clone) was obtained from T. A. Springer (19, 20) . The W6/32 mAb to monomorphic determinants of class I Ag was purchased from Cappel Laboratories (Malvern, PA). The Q5/13 mAb to framework determinants of HLA-DR was kindly provided by P. Giacomini (Regina Elena Cancer Institute, Rome, Italy). Anti-HLA-DQ and anti-HLA-DP were purchased from Becton Dickinson & Co. The purchased anti-MHC molecule mAbs were used after dialysis.", "inhibited presentation of the 1-21 peptide and the unrelated TT antigen.", "Target cells were washed, and cultured (5 x 103) for 4 h with antigen-specific T clones, at a 10:1 E/T ratio into 96-weU roundbottomed plates in triplicate. Plates were then centrifuged, cell-free supernatants were collected from each well, and SlCr release was evaluated in a gamma counter. Percent specific lysis is expressed as the mean of triplicate determinations and is calculated as follows: 100x (experimental release -spontaneous release)/(maximal release -spontaneous release).", "The selective blocking of specific lysis, observed by pulsing the presenting T or EBV-B cells with HBenvAg after treatment with soluble Tf, further suggests that TfK/HBenvAg interaction is a crucial, initial step required for antigen processing and presentation. Endocytosis and recycling of the TfK with either its ligand or anti-TfK mAbs have been extensively analyzed in both lymphoid and nonlymphoid cells (30) (31) (32) (33) . In agreement with these findings, we found that OKT9 does not inhibit Tfbinding to its receptors, but downregulates surface Till on T cells when incubated at 37~ This is followed by a decrease of iodinated Tf and HBenvAg bindings, confirming that this mAb blocked HBenvAg presentation by interfering with its internalization (data not shown)." ] },{ "paper_id": "cf899b3942af5e7e734cca1ce4f6ff1a1c82a9d9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The precise function of the PB1-F2 protein remains unclear. Research on this protein has indicated that the PB1-F2 protein has strain-specific functions that could vary in different hosts [120, 121] .", "Aquatic birds are the reservoirs of all influenza A virus subtypes. Most influenza viruses infect wild and/or domestic birds with limited or no signs of the disease and are thus # The two authors contributed equally to this work. * To whom correspondence should be addressed.", "Since 1999, when the first human infection of LPAI H9N2 was detected in Hong Kong, this virus has been infrequently isolated from humans [30] . The symptoms associated with H9N2 infection are generally mild, and there is no evidence of human-to-human transmission [30] [31] [32] ." ] },{ "paper_id": "cfa3dd16b97bf8c51a0106577a0a639bcc706142", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Submit your manuscript here: https://www.dovepress.com/risk-management-and-healthcare-policy-journal", "The SS can function as an early warning system. \u2022 Identifying the clusters of signs and symptoms in order to initiate remedial measures to reduce complications and mortality related to MERS-CoV infection.", "This commentary presents a novel outlook for public health authorities in the affected countries to detect and respond quickly to the emerging public health threats such as Middle East respiratory syndrome coronavirus (MERS-CoV). Implementing an innovative electronic surveillance system called syndromic surveillance system is essential for global health security." ] },{ "paper_id": "cfb3735e8a8570efe9bc510fb05fe73441b00314", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study was conducted under the approval of the Institutional Review Board of Dongtan Sacred Heart Hospital (2015-069), Hwaseong, Korea." ] },{ "paper_id": "cfb3f090f09ba13429edc88b5f1d8a595df81fc1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "database generated a list of close matches to hypothetical proteins from related insect species, in addition to more distantly related viral hits, so we did not fully eliminate this as a false positive hit.", "This encompassed a wide range of genetic diversity, while using the longest sequence from each group ensured high phylogenetic resolution (Table 3 and Fig. 6 ).", "Supplementary tables accompanying this text are available at https://arusso1.github.io/NIRVS/." ] },{ "paper_id": "cfe337afa069a02e96adf6894819e7928f8c4534", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study was presented as an abstract at the 32nd ESVN-ECVN Symposium in Wroclaw, Poland." ] },{ "paper_id": "cff7fb355c096e08503caf3108f7b01525318634", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A severe respiratory ongoing outbreak of pneumonia associated with 2019 novel coronavirus was recently emerged in China. Here, we reported the epidemiological, clinical, laboratory and radiological characteristics of 19 suspect cases. We compared J o u r n a l P r e -p r o o f", "We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company. J o u r n a l P r e -p r o o f", "As Table1 shown, the median age was 33 years, and 57.89%were women. According to the results of the oropharyngeal swab NAAT, nine patients were confirmed to be infected with 2019-nCoV, and the other ten cases were negative for 2019-nCoV based on the nucleic acid test results. We found that all nine confirmed patients and five out of the ten negative cases showed bilateral distribution of patchy shadows and patchy ground-glass opacities in CT scans (Figure 1 ). To avoid false negative results, we recollected oropharyngeal swab specimens for these negative cases and reconducted " ] },{ "paper_id": "d00f4dabc58eca254f3b2ca4efafda00d671c3da", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d02f9e2414da034e0aded233a37de3077f40c93b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Real-time reverse transcription PCR (RT-PCR) was performed as described earlier (32) . The primers used were OAS1 forward, 5 0 -AGG TGG TAA AGG GTG GCT CC-3 0 and OAS1 reverse 5 0 -ACA ACC AGG TCA GCG TCA GAT-3 0 ; RIG-I forward 5 0 -GAG GCA GAG GAA GAG CAA GAG G-3 0 and RIG-I reverse 5 0 -CGC CTT CAG ACA TGG GAC GAA G-3 0 ; GAPDH forward 5 0 -TCA CTG CCA CCC AGA AGA CTG-3 0 and GAPDH reverse 5 0 -GGA TGA CCT TGC CCA CAG C-3 0 . The primers for HCV detection were 5 0 -CGC TCA ATG CCT GGA GAT TTG-3 0 and 5 0 -GCA CTC GCA AGC ACC CTA TC-3 0 .", "A short-hairpin RNA directed at CyPB induces IFN production in human embryonic kidney cells", "The primary sequence of the RNAs is not important in RISC formation, and RNAi can suppress virtually any target as long as rules of sequence complementarities between the small RNA and the target RNA are satisfied." ] },{ "paper_id": "d040e6d03a6e02e8f21012e1fbd04b6d21da5284", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Prior to late 2013, the prevalence of PEDV infection was relatively low with only sporadic infections. However, starting in December 2013, a remarkable increase in PEDV outbreaks occurred in Taiwan.", "The phylogenetic relationship and sequence analyses of the Taiwanese PEDV strains indicate that the recent Taiwan PEDV isolates differed from previous Taiwanese PEDV isolates. Our data suggest that all recent Taiwanese PEDV isolates are genetically similar to US isolates identified in 2013. Additional PEDV cases should be investigated using continuous surveillance and sequence analysis.", "The spike (S) protein of coronavirus plays key roles in receptor binding for viral entry and neutralizing antibody induction for protective immunity [2] . CO-26K equivalent (COE) from the S protein of PEDV contains epitopes that are capable of inducing PEDV-neutralizing antibodies [1] . COE was found to be 1,495-1,914 bp of the coding sequence of spike protein gene of the PEDV strain Brl/87 [1] ." ] },{ "paper_id": "d0445a006b72980b50bccc09a785a688457bbede", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d0464b088c3c7a939a2f1862f7e910ffd9340eeb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis was performed using IBM SPSS Statistics ver. 20.0 (IBM Co., Armonk, NY, USA). Data were expressed as mean\u00b1 standard deviation or as percentages, as appropriate. A multipleway analysis of variance was run to test differences between viral groups. Then, each viral group was compared with the other viral groups using chi-square tests for categorical data and unpaired Student t tests for continuous data. A P-value <0.05 was considered statistically significant.", "This retrospective cohort study was approved by the Institutional Review Board of Korea University Guro Hospital (KUGH). Hospitalized patients under 15 years of age with a discharge diagnosis of ARI from January 2013 to December 2015 were enrolled. ARI was diagnosed based on one of symptoms or signs; fever of more than 37.8\u00b0C, cough, rhinorrhea, sore throat, tonsillar injection, wheezing, crackle, chest wall retraction.", "Respiratory samples from children were collected by nasopharyngeal aspiration. The presence of each virus was determined using the Seeplex RV15 RT-PCR assay (Seegene, Inc., Seoul, Korea). Two sets of primers were designed based on conserved regions of genetic sequences for the 15 respiratory viruses mentioned above. Amplified PCR products were analyzed by electrophoresis on 2% agarose gel and were compared with the reference band size provided by the manufacturer. 7)" ] },{ "paper_id": "d0571fb440ff2f4ce7014760267fb9f273311415", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d062f22e831a424fc1bd0ebdbcad0175926d6038", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Seyed M Moghadas PhD 1 , Margaret Haworth-Brockman MSc 2 , Harpa Isfeld-Kiely MA 2 , Joel Kettner MD 2", "Effective partnerships require willingness and commitment, alignment of values, mechanisms to engage early and continuously, and plans to regularly review goals, objectives, roles, and responsibilities and outcomes." ] },{ "paper_id": "d08bd8440ea92be5251562480f44eb57ae84f498", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d095e5dd57f0cce04d19b803d2eff03b87febf8f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Thirty minutes after hospital admission, the neurological deficit disappeared and neurological examination was negative. The BT was 38.5\u00b0. Chest x-ray showed an accentuation of bronchovascular marking, indicating an interstitial pulmonary edema and ischemic chronic vascular disease, without acute event at computed tomography. The electrocardiogram showed a right bundle branch block and widespread abnormalities of ventricular repolarization. The echocardiogram showed a dilated left cardiomyopathy with a reduced ejection fraction (35%), with mild aortic and mild to moderate mitralic regurgition and normal right heart function and pericardium.", "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.", "The blood tests showed a white blood cell count of 6.290 \u00d7 10 3 uL (neutrophils 90%, lymphocytes 2.1%); red blood cell count of 3.666 \u00d7 10 6 uL; hemoglobin of 11.2 gr; and a platelet count of 179.000 \u00d7 10 3 uL. Moreover, he had normal liver function and coagulation tests, no electrolyte alterations, creatinine of 1.10 mg/dL, and C-reactive protein of 1.37 mg/dL (normal range, 0-0.5). Blood cultures were negative. Markers of myocardial injury were above the normal range, in particular, high-sensitive Troponin (hs-cTn) of 0.352 pg/mL (normal range, 0-0.34 pg/mL) and Creatine kinase-MB (CK-MB) of 8.40 ng/mL (normal < 7.2 ng/mL). The patient was transferred to a subintensive care unit in stable condition with a fever (39.8\u00b0C) and was started on a therapy with furosemide, clodiprogel, acetylsalicylic acid, bisoprolol, paracetamol, ceftriaxone, and azytromicin. After 9-hour admission in subintensive unit care, the patient died of acute cardiac arrest." ] },{ "paper_id": "d0c1b37380fd7838db1f135fd702c8fd0cd67361", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Background Severe Acute Respiratory Syndrome (SARS) was first reported in November 2002 in China, and spreads to about 30 countries over the next few months. While the characteristics of epidemic transmission are individually assessed, there are also important implicit associations between them.", "For each network, the BW join-count statistics was calculated for each day, and statistics changes were plotted over time.", "Note: 'C $ T' denotes that C and T are associated (connected).", "By way of a summary, the following datasets were systematically used in the present SARS study:" ] },{ "paper_id": "d0c4236f95ba2b3d5cdc71fde524b26262f05dd3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In theoretical physics, there exist two basic mathematical approaches, algebraic and geometrical methods, which, in most cases, are complementary. In the area of genome studies, however, algebraic approaches, such as Markov chain models and hidden Markov chain models, have been widely used, while geometrical approaches have been less explored for a long time. The Z-curve theory is a geometric approach to genome analysis.", "A , R 2 C , R 2 G and R 2 T , i.e., the 240\u00b0 rotation along AO, CO, GO and TO axes, respectively." ] },{ "paper_id": "d0e4a23b392c97a4cce74b1da7bffffa6eee36ed", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Claudia Der-Martirosian VEMEC REVIEW RETURNED 17-Jul-2019", "Reply 2.", "Reply 4." ] },{ "paper_id": "d11a76dee8f03c0def1b8b254af658b685252588", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "where X i,t represents the conditional variables including gross domestic product per capita, and population of province i at time t.", "Sigma is calculated as follows: ", ", ," ] },{ "paper_id": "d1268a2b5aa5778f15fbd10152728dc936a6809e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Uniformly 13 C/ 15 N-labeled queC36 and C14U/C17U constructs were prepared by in vitro transcription as described previously (33) . Unlabeled wild-type (WT, 5 0 -AUAAAAAACUAA-3 0 ) and A29C (5 0 -AUAACAAA CUAA-3 0 ) RNAs were purchased from Integrated DNA Technologies (IDT) and purified using a C18 column (Waters) followed by lyophilization and reconstitution in NMR buffer (15 mM sodium phosphate, pH 6.4; 25 mM sodium chloride, 0.1 mM EDTA) containing 10% D 2 O by volume. 100% D 2 O samples were prepared by repeatedly lyophilizing the sample and replacing with 99.99% pure D 2 O (Sigma) three times. RNA concentrations ranged from 1.5 to 2.8 mM. AMP, UMP and CMP (Sigma) were directly dissolved into NMR buffer with no additional purification to 5 mM. For RDC measurements, samples were dialyzed into Millipore-purified ddH 2 O using 1 kDa dialysis tubing (Spectrum Labs), lyophilized, and reconstituted into 52.4 mg/ml Pf1 phage solution (34) (35) (36) in NMR buffer with 100% D 2 O (Asla Biotech). RNA concentrations in Pf1 phage ranged from 1.5 to 2 mM.", "UV/Vis melting RNA samples (0.25-0.5 mM) were prepared in NMR buffer and the melting profiles measured between 275 K and 368 K using a Varian Bio 300 UV/Vis instrument equipped with a Cary Temperature Controller. The absorbance at 260 nm was recorded every 0.5 with a ramp rate of 0.5 /min. The two-state helix to coil melting transition was analyzed using", "Supplementary Data are available at NAR Online: Supplementary Figures S1-S9. " ] },{ "paper_id": "d12bc5a4eb0ce72c95fd2fba8d5768fcb6036833", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The ODE model can be rewritten in the following form. :", "We applied the cubic spline method to interpolate the microarray data to obtain data containing 49 desired samples. For convenience, we substituted the derivative values with the central difference. ", "Network construction. The framework of the network construction was shown in Fig. 1 ( Step #1) and Supplementary Fig. S1 , which mainly included three steps.", "\u00f02\u00de", "Filtering the highly noise-induced interactions. Two interacting proteins always have a positive or negative temporal relationship between their expression profiles. To filter the highly noise-induced interactions, we calculated their Pearson's correlation coefficients (PCCs) based on their gene expression data and then deleted any PPI pairs with a PCC rank in the bottom 10% rank. Because the correlation value was only the first discrimination parameter in the overall procedure of gradual refinement, it is necessary to avoid missing any possible PPI pairs at this early stage. The primary aim in this step is to delete only the highly unlikely PPIs. After selecting possible PPIs, we obtained the refined network." ] },{ "paper_id": "d132c2b351eee236fe4f5c1c06bf90bd75ade661", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d1a63ffc7f247f2e825680e974760a8f73676d3c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "H&E staining. Lung samples were fixed in 10% formalin solution at 4\u02daC for 24 h, and dehydrated. The samples were wax embedded and cut into 4-6 \u00b5m sections on a microtome. The sections were flattened, mounted and heated on blank glass slides. Histological evaluations were performed by H&E staining and pathological examination using a CTR 6500 microscope (Leica Microsystems GmbH, Wetzlar, Germany).", "Statistical analysis. All statistical analyses were performed using SPSS software, version 19.0 (IBM SPSS, Armonk, NY, USA). Data are expressed as the mean \u00b1 standard deviation. Statistical comparisons were performed using one-way analysis of variance, followed by Scheffe's test. Statistical differences between two groups were determined using the unpaired Student's t-test. P<0.05 was considered to indicate a statistically significant difference.", "Immunohistochemical staining of NGAL. Following deparaffinization and dehydration, the sections were immersed in 10 mM sodium citrate buffer (pH 6.0) with 0.05% Tween-20, for 5 min at 58\u02daC, and subsequently treated with 0.25% Triton X-100 for 5 min. Following blocking with 5% bovine serum albumin (Beijing Solarbio Science & Technology Co., Ltd., Beijing, China) at room temperature for 20 min, the slides were incubated at 4\u02daC with a rat monoclonal anti-NGAL antibody (MAB1857; 1:100; R&D Systems, Inc.) overnight. Finally, slides were incubated with a rabbit anti-rat biotin-conjugated IgG H&L secondary antibody (ab6733; 1:1,000; Abcam, Cambridge, MA, USA) at room temperature for 1 h, and detected using an avidin-biotin complex system (Vectastain ABC-kit; Vector Laboratories, Inc., Burlingame, CA, USA)." ] },{ "paper_id": "d1b24d21f2004ee1ed983d5fd7526ff2809443e6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This brief review will illustrate the potential applications of molecular farming to One Health, with examples drawn from the recent literature and from our lab's work.", "Our group accordingly used Agrobacterium-mediated transient expression in N benthamiana plants of a codon-optimised CCHFV N genewhich encodes the genome-associated nucleoprotein (NP) -to make a N-terminal 6xHis-tagged NP, that yielded \u00bb2mg protein / kg fresh plant material, was soluble, and was easily purified by a combination of ammonium sulfate precipitation and immobilised metal ion chromatography. The protein was used in an anti-IgG ELISA with a standard panel of 13 serum samples collected 5-15 y post infection from patients confirmed to have anti-CCHFV IgG using commercial immunofluorescent antibody tests. Serum samples from 13 volunteers with no CCHFV infection history were used as a negative control panel. The plant-produced NP detected anti-CCHFV IgG in all positive serum samples, while all negative serum samples gave results below the cut-off value. The results suggest that recombinant NP expressed in plants has significant potential for use in both diagnosis and surveillance, while probably being a better, more easily produced and purified reagent than what is available presently.", "While the One Health concept is far wider than simply considering vaccines and diagnosticssomething that is shown very effectively here (http://www.onehealthinitiative. com/about.php) -provision of vaccines to combat the spread of disease agents, and of reagents to enable quick and inexpensive diagnosis of these, are an important component. A useful breakdown of the kinds of vaccines that would be useful is given here, 2 and is summarised below." ] },{ "paper_id": "d1d5731887f0cd5d6aa82905be71655febb4d8b5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "-A ratio of PaO 2 to FIO 2 < 100." ] },{ "paper_id": "d1f8d3907931e02487816f3a62224659d65f872e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "However, the very same authors also state:", "What should be the Target?", "(c) Intervention: Certain preventive actions, P, towards I based on T, are likely to decrease the risk brought by F. 4 (d) Ethics: The (possible) costs and drawbacks of applying D and P are justified by the value of the obtained preventive effect.", "Stigma effects are about how the perception of I as possessing a negative feature will affect the close social surroundings of I (family, friends, school, neighbourhood and workplace). Negative stigma effects are typically of three kinds: overprotection (impeding I from developing), distancing (impoverishing I's social support) and preventive defence (treating I as an acute danger). Such effects may become embedded in the wider culture and societal institutions, creating widespread discriminatory effects, which barr I from social goods (Horstk\u00f6tter and de Wert, 2013) . We hypothesize that such a development is particularly likely in the Lombrosian case, as crime and criminal offenders are already strongly viewed as undesirable phenomena warranting social exclusion." ] },{ "paper_id": "d1f933dc26c6379a87598a2954792f4943c6c426", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "primer binding sites for selected CV strains. The reverse primer for CV is degenerate owing to sequence differences among strains in this region [23] . These primers amplify a 746 bp fragment from several B and A strains (data not shown).", "RNeasy Micro Kit (Qiagen, Valencia, CA); a mixture of oligo(dT 15 ) and random hexamers (pdN6) as primers; and AMV reverse transcriptase (Promega, Madison, WI) as previously described [4, 20] . In vitro transcribed and infected cell RNA templates represent in vitro and in vivo replication, respectively. PCR amplification with HAV or CV specific primers was carried out in 50 l reactions using 5 l of each RT reaction as template or 5ng of pHAV/7 plasmid DNA as previously described [20] . PCR products (5 l) were analyzed by agarose gel electrophoresis to confirm authenticity of product formation (data not shown).", "Viruses and Plasmids. Hepatitis A virus strains HM175/clone 1 and 18f, and coxsackievirus (CV) serotypes B1, A3 and A5 strains used in this study were obtained from ATCC (Manassas, VA) and further grown in FRhK4 cells [18] . The plasmid pHAV/7 contains a full length cDNA copy of wild type HAV strain HM175 cloned into the vector pGEM-1 [19] that was grown and purified as previously described [20] . HM175 clone1 and 18f are culture-adapted strains derived from continuous culture passage of the wildtype strain HAV HM175 [21] ." ] },{ "paper_id": "d212d002cb2b3bd66d6633aea1cc8c816be9c114", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "An upper respiratory tract infection (URTI) is a nonspecific term used to describe acute infections", "Objetivo: Exploramos los patrones de prescripci\u00f3n de los m\u00e9dicos en Trinidad Norte para el tratamiento de infecciones del tracto superior respiratorio (URTI) en pacientes pedi\u00e1tricos y la adecuaci\u00f3n de los medicamentos prescritos. M\u00e9todos: Se realiz\u00f3 un estudio observacional retrospectivo, con un tama\u00f1o de muestra de 523 pacientes pedi\u00e1tricos diagnosticados con una URTI entre junio 2003 y 22 junio de 2005. Este estudio fue realizado en 5 centros de atenci\u00f3n primaria en Trinidad Norte. Resultados: Las 3 URTI m\u00e1s frecuentemente diagnosticadas fueron, por orden, URTI no espec\u00edficas, resfriado com\u00fan, y amigdalitis aguda. Se identificaron 4 patrones de prescripci\u00f3n, (1) sin tratamiento farmacol\u00f3gico [ [29,1%] ; y gotas de suero salino normal [14,2%] . En 112 casos con an\u00e1lisis de torundas, de los que el 98,2% revel\u00f3 crecimiento de comensales, mientras que en el 1,8% crecieron microorganismos pat\u00f3genos. De los casos que mostraron crecimiento de comensales s\u00f3lo, se trataron con antibi\u00f3tico el 84,6%, con agentes sintom\u00e1ticos solos el 14,5% y el 0,9% no recibi\u00f3 tratamiento alguno. Conclusiones: A una gran proporci\u00f3n de pacientes pedi\u00e1tricos diagnosticados con una URTI en Trinidad Norte se le prescribi\u00f3 antibi\u00f3ticos aunque no estaban indicados. El uso inadecuado de antibi\u00f3ticos puede potenciar la tendencia mundial hacia las resistencias antimicrobianas." ] },{ "paper_id": "d2192e89ad3965f129fd046a675854c177e5070a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Pyruvic acid, nicotinamide adenine dinucleotide (NAD + ), reduced form of NAD (NADH), Coomassie brilliant blue G-250, bovine serum albumin (BSA), acrylamide, N,N'-methylene-bis-acrylamide, N,N,N',N'tetramethylethylenediamine (TEMED), bromophenol blue (BPB), DL-lactic acid, nitro blue tetrazolium (NBT), phenazine methosulfate (PMS), and anti-rabbit IgG (peroxidase conjugate) were purchased from Sigma-Aldrich Co. (St. Louis, MO). The anti-LDH A 4 isozyme [22] and anti-B 4 isozyme [23] were obtained from the Animal Physiology Laboratory (Cheongju University, Korea).", "LDH activity assays were performed in 0.1 M potassium phosphate buffer (pH 6.85) containing 1.50 mM pyruvate and 0.14 mM NADH. Changes in absorbency at 340 nm were measured using a spectrophotometer (UV-160A, Shimadzu Co. Ltd., Kyoto, Japan). One unit was defined as the amount of enzyme activity catalyzing the conversion of 1 \u00b5mole of substrate per min. Protein content of the extracts was determined according to the method described by Bradford [25] using BSA as the standard.", "Findings with P-values < 0.05 were considered statistically significant by following the Student's t-test." ] },{ "paper_id": "d230ca9dcc54e1d5c0ed4503752774eb44711dff", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Given that helicases significantly contribute to normal cellular metabolism, are they similarly essential to viruses?", "In conclusion, by studying helicase proteins one can gain insights into normal cellular metabolic processes, abnormal inherited human diseases (e.g. Bloom syndrome, Werner syndrome, Cockayne's syndrome and xeroderma pigmentosum; all diseases with mutations in cellular helicases), and remarkably also the biology of viruses.", "Although less ubiquitous, helicases are also found in other types of viruses (see some examples listed in Table 1 ). Direct mutagenesis studies have confirmed that a helicase function is biologically required for the replication of many viruses including vaccinia virus (19) , poliovirus (20) , alphaviruses (21) , brome mosaic virus (22) , nidoviruses (23, 24) and flaviviruses (25) (26) (27) ." ] },{ "paper_id": "d233d152df533dd90a4441a904c1652244ee5aaf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nasopharyngeal aspirate specimens were collected at the time of hospitalization by carefully irrigating the young child's nostrils with sterile saline solution. Nasopharyngeal aspirate specimens were analyzed within 24 hours of aspiration for respiratory syn cytial viruses (RSV) (A and B), human metapneumovirus, human rhinovirus, influenza A and B viruses, parainfluenza virus (A, B, and C), coronavirus (A and B), and adenovirus. Total viral RNA was obtained from nasopharyngeal aspirate specimens (300 \u03bcL) by utilizing Viral Genespin Viral DNA/RNA Extraction Kits (iNtRON, Seongnam, Korea) and stocked at -80\u00b0C. incorporated with 5\u00d7 buffer, 0.2mM of each dNTP, 0.5\u03bcM of each primer 1316) , 1 \u03bcL of the enzyme mix, and diethylpyrocarbonate incorporated ultrapure water to a total volume of 25 \u03bcL. After being incubated at 50\u00b0C for 30 minutes and at 94\u00b0C for 15 min utes, the reactions underwent 40 cycles of denaturation for 30 seconds at 94\u00b0C, annealing for 90 seconds at 60\u00b0C, and extension for 90 seconds at 72\u00b0C, followed by a final extension at 72\u00b0C for 10 minutes. The amplified specimens were analyzed on 2% agarose gels comprised of 0.5g/mL ethidium bromide.", "All radiographs were read at admission by physicians and at a later date by a highly experienced radiologist, who is regarded as an expert in pediatric lung diseases (HKC). A second senior staff radiologist (THK) also read the initial 279 radiographs to confirm the \"expert\" reading. Both study radiologists acknowledged that the children were hospitalized due to respiratory tract illnesses, but were blinded to the details of presentation and the findings of the other participating radiologist.", "The diagnostic performance of hsCRP levels (>0.3 mg/dL) was a sensitivity of 80.8% (95% CI, 60.7-93.5), specificity of 48.5% (95% CI, 42.5-54.6), positive predictive value of 13.0% (95% CI, 8.3-19.2), and negative predictive value of 96.4% (95% CI, 91.7-98.8) for predicting pathologic chest radiographic findings.", "Acute respiratory tract infection is one of the most common diseases encountered in the outpatient and/or Emergency Department settings in childhood 1) . Of these infections, bronchiolitis is the most frequent cause of hospitalization among young children 2, 3) . Ac cording to an epidemiologic study, approximately 100,000 bronchiolitis hospitalizations occur annually in the United States 4) . Another study looking at 1,503,239 children under 18 years of age who visited the Emergency Department in Korea in 2012 found that 18,313 children (1.2%) were diagnosed with bronchiolitis and 6,321 children of them (34.5%) were admitted 5) ." ] },{ "paper_id": "d24afd9ee025b53015824be203db539009964fbd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d25529180f950874e0b4f62a976959d683a2ceaf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Mutations were introduced into the corresponding fragments by using QuickChange site-directed mutagenesis kit (Stratagene), and confirmed by sequencing of the whole fragments.", "PCR products covering the IBV sequence from 25 957-26 352 nt were amplified by using the forward primer 5 0 -CG-GGCATATGTCTTCTGGAAATGCATCTTGG-3 0 and the reverse primer 5 0 -CGGGATCCTTACAGGGGAATGAAGT-CCCAAC-3 0 . The PCR fragments were digested with NdeI and BamHI, and ligated into NdeI-and BamHI-digested pET-16b (Novagen). Each mutation was introduced by tworound PCR and the mutation introduced was confirmed by automated nucleotide sequencing.", "His-tagged wild type and mutant N-terminal domains of IBV N protein were expressed in E.coli BL-21 by induction with 1 mM isopropyl-b-D-thiogalactopyranoside (IPTG). Cells were lysed by sonication and purified by metal affinity chromatography with Protino-Ni 150 kit (Macherey Nagel).", "PCR fragments covering the IBV genome from 27 100 to 27 608 nt were cloned into a plasmid in either forward or reverse orientation under the control of a T7 promoter. The Dig-labeled sense (+) and anti-sense (\u00c0) RNA probes were made in vitro using the DIG RNA labeling kit according to the instructions of the manufacturer (Roche).", "Five micrograms of purified proteins were resolved on an SDS-15% polyacrylamide gel and transferred onto nitrocellulose membranes (Hybond C-Extra, Amersham Biosciences) using a semi-dry transfer apparatus. Membranes were washed for 10 min with the probe buffer [1\u00b7 Denhardt's Reagent, 1 mM EDTA, 10 mM Tris-HCl (pH 7.5) and 50 mM NaCl], blocked for 1 h with 25 mg/ml yeast tRNA (Ambion) and subsequently incubated with 10 mg of DIG-labeled RNA probe in the same probe buffer for 1 h. Membranes were washed three times for 15 min each with the probe buffer, before proceeding to detection with CDP-Star (Roche) according to the manufacturer's instructions." ] },{ "paper_id": "d255417190eeff9a19aad24ac65faff0030ce157", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d256d493f1987779fa7f2b417941d497bed6b878", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Peptidyl-tRNA was precipitated with the cationic detergent cetyltrimethylammonium bromide (CTABr), as described previously (12, 16) . The method for the preparation of samples for SDS gel electrophoresis and subsequent fluorography has been described (12) . The radioactivity in specific polypeptides was quantitated by scintillation counting of hydrated excised gel slices in 10 ml of Soluscint A, containing 300 ~1 of Solusol (National Diagnostics).", "Before transcription of mRNA with SP6 RNA polymerase, the plasmids were linearized within the protein-coding sequence with the following restriction enzymes: Ava II (pDM9G) and Hinf I (pSPHNI). The linearized DNA templates were transcribed at a concentration of 0.1 mg/ml in 40 mM Tris-Cl, pH 7.5, 6 mM MgCI2, 2 mM spermidine, 12.5 mM NaCI, 10 mM dithiothreitol (DTT), 0.5 mM each of ATP, GTP, UTP, and CTP, 0.5 U/pl placental RNase inhibitor, and 400 U/ml of SP6 RNA polymerase (Promega Biotec, Madison, WI). The mRNA transcripts were purified after transcription by previously described methods (9, 20) . Wheat germ translations were conducted at 25\u00b0C in a volume of 100 pl, containing 30 pl of staphylococcal nuclease-treated wheat germ S 23 (10) , 100 uCi of 135S]methionine (New England Nuclear, Boston, MA), human placental RNase inhibitor (RNasin; Promega Biotec), and a mixture of protease inhibitors compatible with in vitro translation (42) . Translations of the mRNA transcripts were adjusted to either 140 mM KOAc, 2.5 mM Mg(OAc)., (VSV G mRNA transcript), or 90 mM KOAc, 2.5 mM Mg(OAc)2 (HN mRNA transcript).", "The plasmid pDM9G containing a cDNA insert for the G protein of VSV was constructed by insertion of an Eco RI fragment from the plasmid pSVGL (30) into the Eco RI restriction site of pSP65. The plasmid pSPHNI containing a cDNA insert for the entire coding sequence of the HN glycoprotein of NDV was prepared by ligation of portions of three partial cDNA clones of HN (pTL119, pTL709, and pTL2253), which were described previously (23) . The resulting 1,872-base fragment containing the entire coding sequence of HN was inserted between the Pst I and Sac I sites of pSP64." ] },{ "paper_id": "d25e73fba5d8ef3d694dcc923c5f7776efa46954", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d2685fbd92927824244e9d90a145f59f44317db0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "It is intriguing that the CC genotype 4 is rare in Northern Europeans and common in Asian populations. As many other viral infections are restricted by IFITM3 in vitro, including severe acute respiratory syndrome (SARS) coronavirus, Dengue virus and West Nile virus 1,7 the high population allele frequencies may have been influenced by complex virus exposures.", "MCP-1 quantification. EDTA-separated serum was stored at \u00c0 80 1C until analysis. MCP-1 was analysed using a Human Cytokine multiplex assay (Bio-Rad, USA) and Luminex multi-analytic profiling technology (Bio-Rad, USA) according to the manufacturer's instructions as described previously 8 . In brief, serum samples were diluted 1 in 4 with sample diluent, while standards were reconstituted in standard diluent. Standards and samples were incubated with the magnetic beads in a 96-well plate for 30 min at room temperature. After this, detection antibody was added to each well, and incubated at room temperature for a further 30 min. Streptavidin-PE was used as the fluorochrome for antibody detection. Using Bio-Plex Manager software version 6.0, standard Luminex maintenance procedures were performed, and Bio-Plex CAL1 and CAL2 beads were used to calibrate the system.", "Haemagglutination inhibition assay. Antibody titres in the serum samples were determined by haemagglutination inhibition assay as described previously 9 . In brief, the serum samples were treated with receptor destroying enzyme from Vibrio cholerae by diluting one part serum with three parts enzyme and were incubated overnight in a 37 1C water bath and then were heat-inactivated at 56 Ex vivo interferon-c ELISpot assay. 12-16 h interferon-g ELISpot assays were performed using cryopreserved peripheral blood mononuclear cells (PBMCs) as described previously 10 . Two lakh fifty thousand PBMCs were used in each ELISpot well in the final volume of 100 ml. The end concentration of peptide in each well was 2-3.5 mM when testing peptide pools and 2 mM when testing individual peptides. For negative and positive controls, PBMCs were incubated with media alone and with phytohemagglutinin (Wellcome), respectively. Spot forming units (SFU) were counted using an automated ELISpot reader (AID). Responses were considered positive when the number of SFU per well was greater than three times the average negative control value for the given assay, and four times the mean negative control value obtained from the peptide pool screening of all participants. Adjusted SFU after subtracting average negative values were expressed as SFUs per 1,000,000 PBMCs." ] },{ "paper_id": "d279bf13512bd679f95fc43b64aa11b3eac47ded", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d2c536058f4f78ea00836ff72187c4c1b43e47da", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Citation Rozo M, Gronvall GK. 2015. The reemergent 1977 H1N1 strain and the gain-offunction debate. mBio 6(4):e01013-15.", "I n 1977, an H1N1 influenza virus appeared and circled the globe." ] },{ "paper_id": "d311964341e7e167635e150212eee7d7a70130e8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In our study, the expedited lung biopsy helped us to establish a treatment plan for the patient who showed localized infiltration, although the etiology of the disease was not clear.", "DAD typically shows a bilateral diffuse infiltration pattern in the lung. Thus, a localized lesion in the lung is considered as a rare event, and Yazdy et al. 3 reported that the localized incidence of DAD is 1.2% 4 . We report asymptomatic, localized, and idiopathic DAD, which does not comply with the diagnostic criteria of AIP and AEIIP.", "Diffuse alveolar damage (DAD) is a typical pathological finding in cases of acute interstitial pneumonia (AIP). However, DAD is caused by various such as infection, transplantation surgery, medication, acute respiratory distress syndrome (ARDS) that develops after radiation treatment, acute exacerbation of idiopathic interstitial pneumonia (AEIIP), acute exacerbation of allergic alveolitis, and viral lung infections (e.g., severe acute respiratory syndrome, H1N1 influenza A) 1, 2 . From a clinical aspect, AIP and AEIIP are most commonly diagnosed, but the etiology of these disease remains unclear." ] },{ "paper_id": "d32ec6ce72c16f7fbedc8ac60fbdc9f8c74c6de4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. All data were analyzed using SPSS version 19.0 statistical software (IBM Corp., Armonk, NY, USA). The results of immunohistochemistry were analyzed by Image Pro Plus software version 1.48 (Media Cybernetics, Inc., Rockville, MD, USA). P<0.05 was considered to indicate a statistically significant difference. One-way analysis of variance was conducted followed by Bonferroni method as a post hoc test for multiple comparisons. Kaplan-Meier survival plots were generated and comparisons were constructed with log-rank statistics. P<0.05 was considered to indicate a statistically significant difference.", "ST and YG conceived and designed the experiments; ST, FS, YL and YG performed the experiments; ST, KW and YG analyzed the data; ST, KW, FS and YG contributed reagents/materials/analysis tools and ST and YG wrote the manuscript." ] },{ "paper_id": "d33bb76df69173f5bfcd44b6ae9cfeea362f0875", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d383ffc5115974fdaa97c744e2a579960a6c7cb2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Log-rank tests were performed on Kaplan-Meier survival curves. Significant differences in weight loss between groups were assessed by two-way analysis of variance (ANOVA) and Bonferroni post-tests were performed. A Student's t-test was carried out on viral yield data to assess significant differences (p \u2264 0.05) between experimental groups.", "Nitric oxide (NO) is an important cellular signalling molecule synthesized from L-arginine by NO synthase (NOS). There are three types of NOS: constituent and calcium-dependant isoforms that are principally present in endothelial and neuronal cells (eNOS and nNOS, respectively), and the inducible or Ivyspring International Publisher calcium-independent isoform, iNOS (16) . In the airways, NOS is present in a variety of cells, including macrophages, vascular endothelial cells, airway epithelial cells and neurons where NOS activity is known to mediate neurotransmission, smooth muscle contraction and mucin secretions. NO is also a well known biological mediator in the host response to infection (16, 17) . Various inflammatory stimuli such as LPS and cytokines including IFNg and TNF can cause high and sustained NO production by iNOS; depending on the species, strain, infection dose and pathogen entry route, iNOS activity can result in proor anti-inflammatory responses, cytotoxicity, or cytoprotection [reviewed in (16) ].", "Systematic reviews and meta-analysis of randomized controlled trials have shown that iNO, when used therapeutically in the management of ARDS, results in a transient improvement in arterial oxygenation but does not reduce mortality (34) (35) (36) . Moreover, iNO therapy for ARDS may increase the risk of iNO treated patients developing renal dysfunction (35, 36) . Despite this, 39% of critical care specialists surveyed reported using iNO for the management of patients with ARDS in Ontario, Canada (37) ." ] },{ "paper_id": "d429ec26fa0c9d7bcb427bd485a6ae042add26cc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Steric-blocking antisense oligonucleotides (AOs) are considered potential therapeutics for genetic diseases such as Duchenne muscular dystrophy (DMD) and b-thalassemia. For their potential to be realized, however, the AOs must be effectively delivered to cell nuclei.", "The HeLa pLuc705 (pLuc705) (14) cell line was obtained from Gene Tools, LLC (Philomath, OR). Human liver cell line HepG2 was from American Type Culture Collection (ATCC, Manassas, VA). Cells were cultured in RPMI 1640 medium supplemented with 2 mM L-Glutamine, 100 U/ml penicillin and 10% fetal bovine serum (FBS) (HyClone, Ogden, UT) at 378C in a humidified atmosphere containing 5% CO 2 . All treatments were carried out in OptiMEM medium (Gibco, Inc., Carlsbad, CA.) with or without FBS.", "Nuclear antisense activity.", "The hemolytic activities of the conjugates were determined in fresh rat blood according to a method described elsewhere (18) ." ] },{ "paper_id": "d43c9028fc460b667d7b8e54c16f0a85de6f3c4d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u25ba Large size study within the setting of a healthcare registry system that grants complete and uniform data collecting.", "\u25ba Information on important confounders were lacking (lifestyle factors or medication).", "All analyses were performed using SAS statistical software (version 9.2; SAS Institute, Cary, NC, USA)." ] },{ "paper_id": "d443900c4eef6494eeaf138236a955c0a040f3bd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The laboratory findings of all patients included in the study are shown in Table 2 .", "This study was approved by the Institutional Review Board of the Keimyung University Dongsan Medical Center (approval number: 201501003).", "KD and incomplete KD were observed in 40 and 9 patients, respectively. All patients with KD were initially treated with 2 g/ kg IVIG and 60-100 mg/kg oral aspirin, and 38 patients were classified as responders and 11 patients as nonresponders." ] },{ "paper_id": "d4510e8bc12acbeaa9fc8dd88429b14c02ed6ab1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "There are no conflicts of interests Financial Disclosure: There was no financial support for this study.", "Funding/Support: There was no grant support or funding source for this study.", "Authors' Contribution: Study concept and design, acquisition of data, and critical revision of the manuscript for important intellectual content, Safak Goktas; analysis and interpretation of data, statistical analysis, drafting of the manuscript, Mumtaz Cem Sirin." ] },{ "paper_id": "d458129464b755df1acadea361d6ea8e18d321b9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d45f0042fd65b1a24873bab4fb027c22d122d3d3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In an effort to identify potential functional domains, the seven ORFs were compared by psiBLAST to a database restricted to nidoviruses ( Table 2) .", "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.00077-11/-/DCSupplemental. Figure S1 , PDF file, 0.420 MB. Figure S2 , JPG file, 0.315 MB. Table S1 , PDF file, 0.204 MB.", "diversity (1) (2) (3) . Microbes are dependent on their hosts, and hot spots of host biodiversity may also be rich in pathogen diversity. Intensive land use changes in West African rainforests began in the 1960s by industrial deforestation, leaving only remnants of the equatorial forest belt (4) (5) (6) . Patches of forest are typically surrounded by agricultural land and human settlements. Logging is linked to a profound decline in biodiversity (4, (7) (8) (9) (10) (11) (12) . Declines in biodiversity are associated with an increased risk of infectious disease emergence in humans and domestic animals (reviewed in reference 13) . Nevertheless, links between anthropogenic habitat modification and virus emergence remain to be confirmed (13, 14) ." ] },{ "paper_id": "d48ae48fa33c489b576489afc16c00f5b1532178", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Citation Briese T, Kapoor A, Mishra N, Jain K, Kumar A, Jabado OJ, Lipkin WI. 2015. Virome capture sequencing enables sensitive viral diagnosis and comprehensive virome analysis. mBio 6(5):e01491-15.", "Clinical samples included a human nasal swab sample known to be positive for EV-D68 (30), liver specimens from deer mice infected with deer mouse hepacivirus (31), a sample of bat feces pellets in which rotaviral sequences had been identified (unpublished), and serum samples from hemophilia patients coinfected with hepatitis C virus (HCV), GB virus C (GBV-C), human immunodeficiency virus (HIV), and torque teno virus (TTV)." ] },{ "paper_id": "d4ae876b5fb0b3c64650915ca3970c0a58d6433c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Viral respiratory infections are frequently eliminated from human bodies without any sequelae. Nevertheless, in some occasions viruses can evade the immune reaction of the airways, leading to austere respiratory diseases. 1 Potent mechanical and immunosuppressive methods protect the lungs against external infections, but a solitary respiratory tract infection can change immunity and pathology. 2 Secondary serious bacterial infection (SBI) in children with acute bronchiolitis has been an apprehension expressed by health care providers. 3 Several published studies have shown an association between acute bronchiolitis and secondary bacterial infection, including urinary tract infections (UTI). [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] However, the proposed mechanism by which a virus can induce UTIs is not yet known.", "Viral respiratory infections are frequently eliminated from human bodies without any sequelae. Secondary serious bacterial infection (SBI) in children with acute bronchiolitis has been an apprehension expressed by health care providers. Several published studies have shown an association between acute bronchiolitis and secondary bacterial infection, including urinary tract infections (UTI). However, the proposed mechanism by which a virus can induce UTIs is not yet known. The aim of this commentary is to update the current evidence of risk of UTI in children with bronchiolitis. We present several clinical studies related to the topic as well as a brief review of the potential pathophysiology of secondary infections that could present with viral respiratory illness.", "In a review of the literature, the percentage of patients with fever with positive urine cultures ranged from 4.2% to 20.0% in infants <3 months of age and 0% to 7.4% in older children (3 to 36 months of age). 14 Ralston et al 3 conducted a systematic review delineating the risk of occult SBI in young febrile infants presenting with either \"clinical bronchiolitis\" or \"proven RSV infection\". The review included 11 studies. [4] [5] [6] [7] [9] [10] [11] [12] [13] 15, 16 The rate of urinary tract infections in the 11 studies analyzed was 3.3% (95% confidence interval, 1.9-5.7%). The authors concluded the rate of urine cultures positive for bacteria was noteworthy, though asymptomatic bacteriuria may have muddled the results. Recently, McDaniel et al 17 conducted a systematic review and meta-analysis exploring the prevalence of UTI in infants and young children with bronchiolitis when positive urinalysis (UA) results being incorporated into the UTI definition. The investigators included 18 studies, [4] [5] [6] [7] 9, [11] [12] [13] 15, 16, [18] [19] [20] [21] [22] [23] [24] [25] seven of which had UA information. 4, 11, 16, 18, [20] [21] [22] The definition of positive UA varied among the studies. Some considered positive UA as having more than 5 white blood cells per high-powered field, while others considered the UA positive by having bacteriuria, positive leukocyte esterase, or positive nitrite. The prevalence of UTI in bronchiolitis in the 18 studies was 3.1% (95% CI, 1.8-4.6%). The authors further analyzed the data of the 7 studies where the presence of pyuria or nitrites was a diagnostic criterion to define UTI and the prevalence of UTI was 0.8% (95% CI, 0.3-1.4%)." ] },{ "paper_id": "d4b843968ab01451c9553576eff63a52ad8ba9a4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ ".", ". . , (1) where i represents the identity of each pair, ( (http://github.com/aakhmetz/nCoVSerialInteval2020)." ] },{ "paper_id": "d4c836458692801c907aaca8ec7fc1c52b41df43", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d4f0247db5e916c20eae3f6d772e8572eb828236", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d50ec2ab542eef07b9df564017f4c537e1c5d13a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Abbreviations: ARI = acute respiratory illness, CI = confidence interval.", "Our study suggests that outdoor hand washing during field training may be an effective precaution for reducing ARI incidence among recruits participating in military training.", "Hand washing plays a key role in preventing respiratory infection in many clinical settings. However, its effectiveness in preventing acute respiratory illness (ARI) during field training in military training facilities has been not studied." ] },{ "paper_id": "d51dd0a976e0d01e1be8d21d301c7ed8843fc89e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d58b1736b91a0fd016aa5a22ca12da23235d637a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d5957419c56ec4aaf3fc7702330f84b0d5951cc1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Growth assays were performed using both stab inoculation as in McCann et al. (2013) an initial inoculum of 10 8 cfu/ml and four replicate plants at day 0 and day 6 at all subsequent sampling time points. Bacterial density in inoculated tissue was assessed by serial dilution plating of homogenized tissue. Statistical significance between each treatment at each time point was assessed using two-tailed t-tests with uneven variance.", "Freebayes variant calling includes indels and multiple nucleotide insertions as well as single nucleotide insertions; however only SNPs were retained for downstream phylogenetic analyses. An implementation of ClonalFrame suitable for use with whole genomes was employed to identify recombinant regions using default settings and a maximum likelihood starting tree generated by RaxML (Stamatakis 2014; Didelot and Wilson 2015) . All substitutions occurring within regions identified by ClonalFrameML as being introduced due to recombination were removed from the alignments. The reference alignments were manually curated to exclude substitutions in positions mapping to mobile elements such as plasmids, integrative and conjugative elements, and transposons.", "Supplementary data are available at Genome Biology and Evolution online." ] },{ "paper_id": "d5aa58e876fa5f90ddab30ed7c410546713d8f01", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The 3\ufffd " ] },{ "paper_id": "d5b981ab9223ede1243af2a7030ced8570c82edc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The potential role of climate change in triggering Ebola viral disease outbreaks and other emerging diseases", "In a bid to overcoming some diagnostic bottlenecks, Formenty and colleagues, demonstrated that oral fluids can be used to detect Ebola virus during outbreaks. 64 The findings were based on 24 patients and 10 controls during an outbreak in DRC in 2003 and clearly, this non-invasive procedure could be useful during outbreaks for several reasons. The procedure may be more acceptable culturally in settings where communities view blood as sacred. It will eliminate the risk of needle injuries and will not require cold chain and rapid transportation and above all, it may be cheaper and safer to conduct compared to blood tests. But despite these advantages, the technique has not received sufficient research attention.", "Bio-security threat of EVD is arguably the most challenging global health problem at the moment. This threat is amplified by the magnitude, longevity and non-availability of drugs or vaccines against the disease. Sadly, containment measures are expensive and unsustainable in resource-poor settings with lean health budgets. The rising GDP in West Africa enhanced by transport technology (including aviation) in increasingly inter-connected world further amplifies the threat of global spread.", "The authors reviewed mainly 5 online data-bases and a hand search of the reference list of key articles. We reviewed 51 articles that were relevant up until the end date of the search on August 18, 2016 We limited article searches to those published in either English or French, as those were the ones we had resources to translate. We included not only articles but also editorials and letters. We excluded articles on Ebola cases outside Africa. In Table 2 there is a summary of the inclusion and exclusion criteria.", "Aside experimental serum, the R&D pipeline for vaccines against EVD has undergone a considerable expansion in recent years. Indeed, according to the 2012 Jordan Report-a document that provides a thorough report on R&D status of new biologics, there were a total of 12 candidates against EVD in the R&D pipeline, 6 of which were in pre-clinical trials (Table 4) . 102 One candidate, which is being developed jointly by the National Institute of Allergy and Infectious Diseases and GlaxoSmithKline biological (NIAID/GSK), has been shown to be safe in healthy American and British volunteers, 103 and is currently being evaluated in Malian adults. 104 Besides NIAID/GSK, NewLinks Genetics has also received regulatory approval from US Food and Drug Administration to evaluate its rVSV candidate in Phase I studies, which will be conducted in North America, Europe and Africa. 105 Additionally, a Dutch company (Crucell), in collaboration with NIAID, is developing a multivalent Ebola/Marburg vaccine and Phase I trials are anticipated to begin in the later quarter of 2015. 106 " ] },{ "paper_id": "d5bd631a3627f3ef1fef60860af608871fa52271", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "By comparison, CLP studies carried out in internal medicine settings have been of a higher caliber. Zuo and colleagues [43] [44] [45] have carried out several in-depth CLP studies about psychosocial factors and cognitive functioning among patients with type 2 diabetes mellitus and Zhou and colleagues [46] conducted impressive CLP research on hemodialysis in the early 1990s.", "The main focus of CLP in China continues to be psychiatric consultations for disturbed patients in medical departments, but there has also been a gradual increase in the adoption of psychiatric theories and practices by other departments.", "At present, China's CLP research is still largely limited to psychiatric consultation in general hospitals. Using the keyword 'consultation-liaison psychiatry', the authors searched for relevant literature in the comprehensive China Wanfang database over the last 10 years. The results for the 20 articles identified [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] are shown in Table 1 .", "CLP is not yet part of the curriculum for most medical schools and even where it is part of the curriculum the training primarily consists of theoretical classes taught by social scientists that are completely unrelated to the necessary skills in doctor-patient communication." ] },{ "paper_id": "d5f6841f61ab1b11599f16043c48b9268be6e134", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org/ lookup/suppl/doi:10.1128/mBio.01280-15/-/DCSupplemental. Figure S1 , PDF file, 0.5 MB. Figure S2 , PDF file, 0.4 MB.", "Genetic recombinant analysis. Similarity plots and bootscanning analysis were generated by SimPlot (22); a sliding window of 200 nucleotides was used, moving in 20-nucleotide steps. Singlenucleotide-difference analysis was used to confirm the recombination event.", "index patient in South Korea on 16 May 2015 (Fig. 1) , as well as a suspected second-generation patient. The timeline of the travel history, potential virus exposure, onset of disease, and diagnosis of the first imported MERS-CoV case in China are presented in Fig. 1 ." ] },{ "paper_id": "d5fc202cbd1c346056d079c45f0577b767206fc0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The budget function (B) is calculated using Eq. 3:", "A graphical output is generated to illustrate the results.", "Ethics approval and consent to participate Ethical approval was not required for this study as it is entirely based on publicly available data and did not include personal data." ] },{ "paper_id": "d639dcd741bb9859008178d4f6b2c49e6398b861", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d657cc5e24009f5081425da4d8c3b6467b85df1d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Enzymes used in molecular cloning were obtained from Boehringer Mannheim (Indianapolis, IN), New England Biolabs (Beverly, MA), or Promega (Madison, WI). DME (4.5 g/1 glucose) and RPMI-1640 medium were from GIBCO BRL (Grand Island, NY); FCS from Hazleton Biologics (Lenexa, KS); Nusera from Collaborative Biomedical Products (Bedford, MA); DEAE-dextran, chloroqulne, CNBr-activated Sepharose 4B, and protease inhibitors were from Sigma Chemical Co. (St. Louis, MO); ECL western blotting reagents from Amersham Corp. (Arlington Heights, IL); nitrocellulose from Schleicher and Schuell (Keene, NH); protein A-Sepharose beads from Repligen Corporation (Cambridge, MA); FITC goat antimouse IgG from Cappel OVestchester, PA); cell culture dishes from Falcon (Becton Dickinson Co., Lincoln Park, NJ); multichamber slides from Nunc Inc. (Naperville, IL); and human plasma fibronectin from the New York Blood Center.", "Oligonucleotides were synthesized with a solid phase synthesizer (380A; Applied Biosystems, Foster City, CA) by the Protein Chemistry Facility of Washington University.", "All mutants were verified by sequencing at the level of the final plasmid.", "Quantification of autoradiograms was carried out by means of a Molecular Dynamics Personal Densitometer (Sunnyvale, CA).", "T HE Secretory pathway of eukaryotic cells is composed of a series of different compartments through which newly synthesized proteins are transported en route to their final destination in the cell (Paiade, 1975) . Each of the subcellular organelles along this pathway contains a characteristic set of proteins that maintain their structural and functionai integrity. A challenging question in contemporary cell biology is to understand how resident components, unlike itinerant proteins, achieve specific localization in a given intracellular compartment." ] },{ "paper_id": "d666c86af7eeaee9a830f99d863045f52571ea5f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d690af2217392d3b4686d86b6cb0434918f71f9b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The World Health Organization (WHO) has published a list of priority pathogens 1 as those diseases with high morbidity and mortality or with strong epidemic potential. One of the clear gaps affecting both public health efforts and vaccine development programs for any of these pathogens is a lack of standardized reagents and methods to test for evidence of current or prior infection.", "ARTICLE HISTORY" ] },{ "paper_id": "d690e4df20380e92f907315e831f39116b1c460d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Studies comparing immune responses in EVD survivors are currently ongoing (C\u00e9sar Mu\u00f1oz-Fontela, Florian Klein personal communication).", "ARTICLE HISTORY" ] },{ "paper_id": "d6951136eb1f783092f894b3d7c98e896cf3e921", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data S1. Dog Park Study Questionnaire." ] },{ "paper_id": "d6bbcc059331dda0ac8c4a897f4d7171d0d1cb99", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The study and consent exemptions were authorized by the Institutional Review Board (IRB) of the NCMH (IRB No. 116271-2016-03).", "Among 26 victims (10 men, 38.5%; mean age, 46.2 years; standard deviation [SD], 11.2), 11 (42.3%) had reported the exposure period to HD substances, which was a minimum of 3 months to a maximum of 120 months (median 6 months). Forty-seven family members of victims (21 men, 44.7%; mean age, 42.7 years; SD, 7.6) included 32 (68.1%) parents and 13 (27.7%) spouses. Forty-five bereaved family members (25 men, 55.6%; mean age, 42.8 years; SD, 7.0) included 28 (70.0%) parents and 11 (27.5%) spouses of the deceased.", "However, the bereaved showed a relatively higher rate of alcohol/smoking abuse and insomnia than other psychological responses." ] },{ "paper_id": "d6ce322684cccda1ff72e7dacf22da2259cf65c6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "HeLa pLuc705 cells were cultured as exponentially growing subconfluent monolayers in DMEM medium (Gibco) supplemented with 10% fetal bovine serum (FBS), 1 mM Na pyruvate and nonessential amino acids.", "Large unilamellar vesicles (LUV) were prepared as described previously (16) . In short, lipids dissolved in benzene/methanol (95:5) were freeze-dried overnight and the resulting dry lipid powder was hydrated in a buffer containing the ANTS fluorescent dye 8-aminonaphthalene-1,3,6-trisulfonic acid, disodium salt (Invitrogen, Carlsbad, CA, USA) together with a DPX quencher p-xylene-bispyridinium bromide (Invitrogen, Carlsbad, CA, USA) at a final lipid concentration of 10 mM. The suspension was vigorously agitated with a Vortex, freeze-thawed 10 times and then extruded 10 times through two stacked 100 nm polycarbonate filters (Nucleopore, Whatman). Free dye and quencher were then removed by gel filtration on a PD-10 desalting column (Amersham Biosciences, Piscataway, NJ, USA). To mimic the lipid composition of late endosomes we used the following lipid mixture: dioleoylphosphatidylcholine (DOPC)/dioleoyl-phosphatidylethanolamine (DOPE)/phosphatidylinositol from soybean (PI)/bis(monooleoylglycero) phosphate (LBPA) (5:2:1:2) (23). All lipids were purchased from Avanti Polar Lipids Inc., Alabaster, AL.", "(R-X-R) 4 " ] },{ "paper_id": "d6da8802866acb6cd35ee1c4a0ec6c64d06b8345", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. Data are expressed as the mean \u00b1 standard deviation of at least three independent replicates. All data were analyzed by SPSS software, version 19.0 (IBM Corp., Armonk, NY, USA) and Graphpad Prism version 5.0 (GraphPad Software, Inc., La Jolla, CA, USA) using one-way analysis of variance, followed by Tukey's multiple comparison post hoc tests. P<0.05 and P<0.01 values were considered to indicate differences that were statistically significant.", "Not applicable.", "Not funding was received." ] },{ "paper_id": "d6e8f2abf8928e3b52ba19ff95a4919e3e2d5768", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d6f4597aa9fb819ab0adf5c68601e967ef9970e5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "negligible. Further study is required to determine if IMHA contributes to anemia in some FIVinfected cats.", "The evidence for Mycoplasma gatae causing IMHA cats is low, and currently limited to a single case report. Based on the observation that Mycoplasma spp.", "infection cause cold agglutinins in other species, M. gatae may be considered as a possible etiology of feline IMHA, but further studies are needed to confirm this possibility and the clinical significance of cold agglutinins in cats.", "One case report identified a cat with visceral leishmaniosis and concurrent pancytopenia thought to be of immune-mediated origin, 1 yielding an IME value of 2.62. The cat had persistent autoagglutination, and Leishmania amastigotes were identified in the bone marrow, peripheral blood, and other body tissues.", "Few cases of cats with focal bacterial infections suspected to cause IMHA have been reported in the literature. [3] [4] [5] Owing to the presence of multiple co-morbidities in individual cats, an IME value (1.70) could only be assigned for abscessation." ] },{ "paper_id": "d733c0afa475ed9c4f57c2540c0353d36cbc58e3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cells are covered by a dense thicket of glycans. Though attached to proteins and lipids, these oligo-and polysaccharides are more than decoration. With a structural complexity vastly exceeding that of proteins and nucleic acids, they act as molecular tags in cell recognition and signaling events. Mammalian glycans form linear and branched chains of variable size and composition yet commonly with sialic acids (Sias) as terminal, surface-exposed residues. In consequence of this topology, Sias are key elements of the glycotopes of many regulatory cellular lectins (Crocker et al., 2007; Schauer, 2009 ). For the same reason, they have become attachment factors of choice for a range of pathogens including protozoa, fungi, bacteria, and viruses.", "Glycan microarrays were prepared with epoxide-derivatized slides and processed, essentially as described (Padler-Karavani et al., 2012) . For detailed procedures, see the Supplemental Experimental Procedures.", "Graphical Abstract" ] },{ "paper_id": "d74ca96879ef6d9982cb7ddaf5396940697dc8dc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors appreciate help from Ms Erica Litschi, Department of Microbiology and Immunology, Drexel University College of Medicine, for manuscript preparation and the United States National Institutes of Health (R01 AI104636) and the Hepatitis B Foundation and Commonwealth Wealth of Pennsylvania for support. Broadly active anti-filovirus agents J Chang et al 5", "As for many other enveloped viruses, 29-36 the morphogenesis of filoviruses appears to depend upon ER a-glucosidases mediated processing of envelope glycoproteins. Therefore, the amplification and propagation of filoviruses are sensitive to imino sugar derivatives that inhibit the ER a-glucosidases I and II. 37 Due to their unusual antiviral mechanism, imino sugars should be complementary to the other antiviral approaches and have the advantage of being broadly active.", "Emerging Microbes and Infections" ] },{ "paper_id": "d77e2f4df800eddf41d5b9f10859005ce352f820", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Medical and pediatric services In China, most people receive medical technology and specialized neurological care provided by public hospitals. In general, patients who are suspected of having ADEM are taken to the hospital as emergencies, and soon after, a neurologist will be invited to take care of them. Patients younger than 16 years old who are affected by neurological diseases are usually taken to pediatric hospitals.", "Cases from all hospitals that may have admitted ADEM patients were searched and reviewed through the hospital information systems (HIS). Cases were identified by the 10th revision of the International Classification of Diseases (ICD-10) diagnostic ", "There is a sharper age-specific incidence curve in males than in females ( Figure 2 )." ] },{ "paper_id": "d7b736173972c7e1e61d44115b79fdb2e1b24a5d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Forf urther confirmation that synthetic IFITM3 was incorporated into the membrane,w ep repared aH 2 N-S1-KA segment with an N-terminal 5(6)-carboxyfluorescein by Fmoc-SPPS.R esin cleavage,o xidation of the cyanosulfurylide,a nd ligation with Opr-S2S3-ArgTAG (4)a fforded the protein with the fluorescent dye.T he fluorophore-modified IFITM3 (9)w as incorporated into medium-sized vesicles, passed through the size-exclusion resin, and observed by fluorescence microscopy.A ss hown in Figure 3 , IFITM3 is clearly localized in the membrane of the vesicles,asexpected from the previous experiment." ] },{ "paper_id": "d7df17379b5a79dd5917ea5f26051eef8bfe5011", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Assuming that R t is normally distributed, the approximate (1\u2212\u03b1)\u00d7100% confidence interval is E[R t ] \u00b1 z 1\u2212\u03b1/2 s(R t ).", "Appendix Figure 1 illustrates this dose-response relationship for different values of VE (5) with VE(1) = 1." ] },{ "paper_id": "d7f54f3f478888e9b3f3571a391ce869f0eac789", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d800e113c0f37fea4586a18115d07a7bbb3e5464", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Bands obtained after development with ECL reagent (GE Healthcare, Piscataway, NJ, USA) were detected using a Chemidoc XRS imaging system (Bio-Rad).", "Data analysis. One-way analysis of variance was performed using INSTAT 3 for Windows. For multiple comparisons, Dunnet's correction was applied. Data are presented as means \u00b1 S.D. Differences were considered statistically significant at a P-value ofo0.05.", "In conclusion, apoptosis induction, caspase activation and later modulation of the UPR might be advantageous for ASFV as these processes block the effects that are detrimental to the infection, while maintaining those that are beneficial." ] },{ "paper_id": "d82be8a4aaa62cde9678615d95b22163fa35c8dc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "No specific treatment currently exists for HBoV infection. Our administration of corticosteroid with antibiotics failed. The significance of corticosteroid use in the treatment of pneumonia remains controversial (13) , and our patient's condition progressively deteriorated until her death despite its use. Further studies are needed to establish an effective treatment for this infection.", "Several cases of severe, life-threatening, and even fatal respiratory HBoV infection have been reported, most of which were in children. Adult cases include one patient with hematologic malignancy who had severe pneumonia due to HBoV (10) and another with no underlying disease (11) . To our knowledge, there have been no reported cases of fatal HBoV infections in immunocompetent adults.", "One limitation of the present study is that we were unable to measure the quantitative HBoV viral loads in the respiratory BAL fluid of our patient. Although a previous pediatric study showed that this measurement can quantitate disease severity (14) , viral loads for HBoV infection are not routinely assessed in our hospital." ] },{ "paper_id": "d843363f9656abc2037bd77bd018dcbbd541d849", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d84514633b2de3a00d06955978cb5a2eebe0ea7d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d8452b6817c6ae38d642d42f6177244fa06d3bd6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All mqPCR assays detected only the target pathogen and did not produce any non-specific amplification products or products of other pathogens in repeated experiments. In addition, there were no false positives due to cross-talk between dye signals within each reaction. Standard curves for all multiplex assays generated from 10-fold serial dilutions of each template showed correlation coefficients (R 2 ) ranging from 0.970 to 0.995 and slopes of 3.41-3.59 (Fig. 1) , indicating good linearity of PCR amplification.", "Meningoencephalitis (ME) results from concurrent inflammation of the meninges (meningitis) and brain (encephalitis) [22] . ME can be classified as granulomatous meningoencephalomyelitis, necrotizing meningoencephalitis, or necrotizing leukoencephalitis based on histopathologic features [28] . However, in veterinary practice, this classification is challenging because it requires biopsy and histopathologic examination. Thus, a simple and rapid strategy for identifying the causative agent of ME would be useful for selecting an appropriate therapeutic regimen.", "Lyme disease is a zoonotic tick-borne disease caused by B. burgdorferi that affects various organs in dogs, including the skin, lymph nodes, aorta, and kidney [4, 9] . Although the bacterium also infects the meninges and choroid plexus, CNS involvement is not pathognomonic of Lyme disease [18] . In the present study, two cases positive for B. burgdorferi had a history of ixodid tick infestation. In both cases, the locations of CNS lesions included the choroid plexus, which can be associated with neurologic signs in dogs afflicted by neuroborreliosis. However, it was not possible to confirm whether the lesions were caused by B. burgdorferi because the owners declined additional tests and therapeutic trials.", "Multiple infectious agents can cause ME in dogs. [4, 15, 17, 19, 23, 25, 31] . The pathogenesis of ME can also involve immune-mediated or idiopathic etiologies that provoke aseptic inflammatory responses in the central nervous system (CNS)." ] },{ "paper_id": "d84ced2c3a06936bb56ee529a5bdca5f6adaf857", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. Data were processed using SPSS 13.0 statistical software (SPSS Inc., Chicago, IL, USA), and expressed as mean \u00b1 standard deviation (x \u00b1 s). Analysis of variance was performed, as was Pearson's correlation analysis and linear regression. P<0.05 was considered to indicate a statistically significant difference.", "Empty " ] },{ "paper_id": "d89b71dc9725043b0a554e5b55791ef59e51d05a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d8b4bb30789355b295394864873228a15c4868b3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d8b7b5e4c3daa4fc5444223319456deecad9acfb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.", "This article is a part of a series of reviews covering Fc Receptors appearing in Volume 268 of Immunological Reviews.", "During the initial stages of the antibody response, IgM is the main antibody isotype produced. IgM forms pentamers through association with the common joining chain (J-chain). IgA is the main isotype at mucosal barriers and the second most prevalent isotype in serum at 2-3 mg/ml compared to 12 mg/ml for IgG. Two subclasses of IgA exist, IgA1 and IgA2, and each is expressed as monomeric (mIgA), dimeric (dIgA), and secretory (S-IgA) forms (88) ." ] },{ "paper_id": "d8ece7a7ece002e0a2fcdb9be3f1a85194079c1e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Infection Assay. Gonococci (1.5 \u03eb 10 7 ) were added to 24-well plates containing the transfected cell cultures on coverslips, in 1 ml DMEM (without serum) for 45 min at 37 \u040a C and 5% CO 2 . Nonadherent bacteria were removed by three washes with HBSS. Infected cultures were fixed with 2% formaldehyde in PBS for at least 30 min.", "Transfection Procedure. Chinese hamster ovary (CHO) cells (Pro5) were obtained from the American Type Culture Collection and were grown in RPMI 1640/5% FCS in 25-cm 2 flasks to 50% confluency. Plasmid preparations of pTracer-CMV2-CD66b mutants were made by the Wizard miniprep procedure (Promega Corp.). Pro5 cells were incubated in 2 ml DMEM/10% Nuserum (Collaborative Biomedical Products) containing 4 g plasmid DNA and 0.2 mg/ml DEAE-dextran ( M r 5 \u03eb 10 5 ; Amersham Pharmacia Biotech) for 4 h at 37 \u040a C. Cells were then shocked with 2.5 ml 10% DMSO in PBS for 1 min at room temperature, washed once with HBSS, and subsequently cultured overnight in RPMI 1640/5% FCS (23) . The next day, the transfectants were trypsinized and seeded onto 12-mm-diameter circular glass coverslips in 24-well plates (10 5 cells per coverslip). Cells were cultured for 2-3 d before infection assays were carried out.", "Bacterial Strains. N . gonorrhoeae MS11 variants were propagated on gonococcal clear typing agar (20) . Wild-type variants MS11mk expressing chromosomally encoded Opa proteins were provided by J. Swanson and are designated according to Swanson et al. (21) by capitals, e.g., OpaA-OpaK. Recombinant MS11 Opa variants (5) were a gift of T.F. Meyer (Max-Planck Institut f\u00fcr Biologie, T\u00fcbingen, Germany). Opa protein expression was verified by SDS-PAGE and immunoblotting of bacterial lysates followed by detection with anti-Opa antibody 4B12 (21) . Only nonpiliated bacteria were used. For experiments, bacteria were grown for 3 h in 10 ml Hepes medium (10 mM Hepes, 145 mM NaCl, 5 mM KCl, 0.5 mM MgCl 2 , 1 mM CaCl 2 , 5 mM glucose, and 1.5% proteose peptone no. 3 [Difco]), pH 7.4, in a gyratory shaker at 37 \u040a C. Bacterial suspensions were pelleted and resuspended in 1 ml Hepes buffer (Hepes medium without proteose peptone).", "Mutants on the Surface of Epithelial Cells. To confirm that these results obtained with soluble recombinant His-tagged N-domains reflect interactions taking place at the cell surface, we introduced the identified key residues into full-length CD66b cDNA, transfected CHO cells with these constructs, and performed infection assays to determine Opa receptor activity. All transfectants stained positive with mAb Kat4C, which recognizes an epitope in internal CD66 domains (26; data not shown), as well as with a polyclonal anti-CD66 serum (Fig. 3) , indicating that the receptors were expressed at the surface of the cells." ] },{ "paper_id": "d8fafccc9ce11f09e43780f5ce9311095fa897c0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d92992c5c544e78fdc31b8d52a1aa14c84ef0807", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d92d741f65164c7fe568413caebac49e13c4916e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d93f7790f05612e0984dba1bf0e720d2771ac304", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In another comparative study, the bactericidal activity of PVP-I and BEC gargles against Bordetella ", "PVP-I can also be used as part of routine hygiene practices, for which gargling followed by rinsing of the mouth for 30 s using 10-15 ml of diluted or undiluted mouthwash is suggested. While PVP-I gargle or mouthwash can be diluted in defined clinical settings, if done by a patient, careful instructions on proper dilution should be strongly advised.", "\u00aa" ] },{ "paper_id": "d949e3b7ef8b7cc48399d5ab806e0257218c6307", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "where the contributions h k of the hidden layer are weighted by k .", "protein APP transcript is highly structured (>65% doublestranded). Similarly, the mRNA of serpin peptidase inhibitor SERPINE3 is predicted to be highly structured (>55%), as reported in PARS screenings (4) . We predict that 45% of Xist is structured in domains, as revealed by DMS profiling (16) ." ] },{ "paper_id": "d99acb4e99be7852aa61a688c9fbd38d44b5a252", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Viruses and cells. RSV A2 strain was obtained from ATCC (Manassas, MA). EZ vaccine strain was from Serum Institute of India (Pune, India). Vero and HEp-2 cells were maintained in Dulbecco's modified Eagles's medium (Invitrogen, Carlsbad, CA) supplemented with 2% fetal bovine serum (FBS), 2mM L-glutamine, and 1% penicillin/streptomycin at 37\u00b0C with 5% CO 2 .", "Statistics. GraphPad Prism software was used to analyze the data (GraphPad Software Inc., San Diego, CA). All data were expressed as the mean and standard error. The data were also analyzed by Mann-Whitney rank sum test to compare data distribution between any two experimental groups. Titer comparison between viruses in replication kinetic experiment was performed using the Kruskal-Wallis test, assuming non-parametric distribution.", "Proteins from culture supernatant or cell lysates were separated by electrophoresis and transferred onto a PVDF membrane. Viral proteins were detected with anti-measles nucleoprotein (clone 2D7, Santa Cruz Biotechnology), polyclonal rabbit EBV gp350 [33] or monoclonal antibody against RSV F proteins (palivizumab, MedImmune, Gaithersburg, MD) antibodies. Intensities of the bands were quantified by ImageQuant software (GE Healthcare, Piscataway, NJ). Relative intensity was determined by comparing pixel intensity of the band relative to the rEZ control." ] },{ "paper_id": "d9e24a56fd02e643de973aab5753dbf7accc1e90", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "showed discrepant results demonstrating that AD assay had the highest rate of concordance with original results.", "agreement, nucleic acid amplification test, respiratory virus", "The nucleic acid extraction system was used for each RV assay. For " ] },{ "paper_id": "da5f78374b6b0b58d01188a2029fe9d74336e473", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "da700649fef6382fec2ae238b91ffdbbc0e2c301", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Citation Kindler E, J\u00f3nsd\u00f3ttir HR, Muth D, Hamming OJ, Hartmann R, Rodriguez R, Geffers R, Fouchier RAM, Drosten C, M\u00fcller MA, Dijkman R, Thiel V. 2013. Efficient replication of the novel human betacoronavirus EMC on primary human epithelium highlights its zoonotic potential. mBio 4(1):e00611-12.", "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.00611-12/-/DCSupplemental. Table S1 , DOCX file, 0.1 MB. Table S2 , DOCX file, 0.1 MB." ] },{ "paper_id": "da70e84ba93bb87634a681d7f61a44be543e8549", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "causative and commensal pathogens in specimen obtained by nasopharyngeal aspiration. Data on viral pneumonia are increasing; however, severe rhinovirus pneumonia resulting respiratory failure in an immunocompetent host is still regarded as extremely unusual.", "No potential conflict of interest relevant to this article was reported." ] },{ "paper_id": "dab074e75c2dae02b60e8094aa5a06e553122831", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The ELISA, HI antibody titres and gross lesions between groups were analysed statistically using analysis of variance followed by Tukey's test for comparison of means. Differences were considered to be significant when P\u22640.05. All analyses were conducted using the GraphPad Prism software, V.6.0.1.", "Day-old commercial broiler chicks with IBV maternally derived antibodies (MDAs) were obtained from a commercial hatchery. The parent flock of these chicks had been vaccinated with live IBV H120+ D274 vaccines and with an inactivated IBV M41. Chicks were kept in an isolation unit at the University of Liverpool. The chicks were reared on deep litter with water and feed provided ad libitum.", "There were no clinical signs found in the unvaccinated control chicks. In both vaccinated groups, mild clinical respiratory signs began to appear at six days post vaccination (dpv). The signs included head shaking, tracheal r\u00e2les and sneezes. These signs subsided by 12 dpv." ] },{ "paper_id": "dab21bebc7d9ee2f77332c23b420280ee74772fd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Relationships were deemed to be statistically significant if the P value was less than 0.05. All associations were calculated using Fisher's Exact Test. The analyses were performed using JMP 8 (SAS Institute, Cary, North Carolina, USA).", "The aim of the present study was to ", "The number of herds tested and their distribution by county is presented in Table 3 .", "The results of the serological and bulk milk screen were compared for herds that underwent both tests." ] },{ "paper_id": "dac4e5ddd4e1b0a3ec755a573674371f724462a8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Differences of means of 3 independent repetitions were tested for significance applying repeated measures 1-way analysis of variance followed by Dunnett's multiple comparison testing using GraphPad Prism for Windows, version 7.04 (GraphPad Software, La Jolla, CA; www.graphpad.com).", "Author contributions. S. F., C. G., and E. S. designed the study. S. F. performed all of the experiments. M. F. and V. P contributed to experiments. S. F., D. T, C. G., and E. S. analyzed the data. S. F., C. G., and E. S. wrote the article. S. F., D. T., and E. S. prepared the figures. M. F., G. S., and E. S. provided essential tools.", "Financial support. This work was funded by Deutsche Forschungsgemeinschaft (German-African" ] },{ "paper_id": "daee7f7d31f4bf1c0ef883bcd6c124b6e94cbee7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "McCrate -S2", "(1). Partial atomic charges were calculated for ms 2 t 6 A, mcm 5 s 2 U and \u03c8 ( Figure S1 ), derived by fitting Hartree-Fock (2) restricted electrostatic potentials (RESP) (3) using the 6-31G* basis set (4-6) and normalizing the charges to have the same net charge as the corresponding unmodified base adenine or uridine. All electronic structure calculations were carried out using Gaussian 03M, Revision A.6 (7).", "All-atom root mean square deviations (RMSD) from starting structures were found to fluctuate around constant values ( Figure S3 ). Convergence of helical parameters was monitored over the 4.0 ns production run for all simulations. The moving averages of the average value over the duplex region for three helical parameters base-pair twist, base-pair inclination and xdisplacement form the global axis are shown in Figures S4-S6 ." ] },{ "paper_id": "daf06fe518af2567566bd71fca278c8bc5fecddf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "HuMig is induced in macrophages (18) by the lymphocyte product IFN-% and HuMig in turn targets activated T cells. Experiments in vivo have demonstrated lymphocyte recruitment into skin at sites of IFN-y injection (68) , and our results make Mig a reasonable candidate for mediating these effects. Similarly, our demonstration that rHuMig can function as a chemotactic factor for TIL makes HuMig a candidate for mediating the lymphocyte chemotaxis induced by supernatants from explanted tumors (69) and for mediating lymphocyte infiltration of tumors in vivo.", "IgG was purified from rabbit serum using protein A-activated Acti-Disk cartridges (FMC Bioproducts, Rockland, ME) according to the manufacturer's protocol.", "man basophils (13) ; the CXC chemokine IL-8 is an angiogenic factor (14) ; and other CXC chemokines, platelet factor 4 (15) and , can inhibit angiogenesis.", "Both chemokines and nonchemokine cytokines have been demonstrated to cause T cells to chemotax (reviewed in 38). Studies of the actions of chemokines on lymphocytes have concentrated primarily on the CC or 13 chemokines, and these studies, while not always in agreement, have reported differential chemotactic effects for macrophage inflammatory protein (MIP)-lo~ versus MIP-I[3 (7) (8) (9) and for regulated upon activation in normal T cells expressed and secreted (RANTES) (6) on subpopulations of lymphocytes. It has been demonstrated recently that monocyte chemotactic protein (MCP)-I is able to induce transendothelial lymphocyte migration (39) .", "Given that other CXC and CC chemokines that act on lymphocytes have been found to target also either monocytes or neutrophils, HuMig's T cell specificity is unusual. In this regard, HuMig resembles lymphotactin (3), a recently described cytokine that is similar to the CC chemokines but that lacks two of the four invariant cysteines found in the CC and CXC subfamilies." ] },{ "paper_id": "db4a4b2bde1bf1bb981bf87f9c6c25462834a25e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study did not generate code or dataset.", "Refer to Web version on PubMed Central for supplementary material.", "This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)." ] },{ "paper_id": "db633ad6a8771828545a8f3d7419722897c4fa9f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "db6ef4648f49c12082d38056e00a106f8c2c510b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "No potential conflicts of interest were disclosed.", "% of cell lysis = 100 \u00d7 [A490 (sample) -A490 (AICC)]/[A490 (High Control) -A490 (Low Control)].", "The Data were plotted and analyzed using GraphPad Prism 5 (GraphPad Software, Inc.)." ] },{ "paper_id": "db71883643ea4dbc79a8f3e5248811d9c3385c3e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Publish your work in this journal Nanotechnology, Science and Applications is an international, peerreviewed, open access journal that focuses on the science of nanotechnology in a wide range of industrial and academic applications. It is characterized by the rapid reporting across all sectors, including engineering, optics, bio-medicine, cosmetics, textiles, resource sustainability and science. Applied research into nano-materials, particles, nano-structures and fabrication, diagnostics and analytics, drug delivery and toxicology constitute the primary direction of the journal. 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. ", "As relatively complicated DNs, DNA dendrimer with a branched configuration can be developed by the facile modular assembly. DNA dendrimers are layer-by-layer selfassembled functional branched DNA units (eg, Y-shaped building blocks) made through predesigned base-pairing hybridization. These somewhat bulkier DNs form promising scaffolds for versatile biomedical applications ( Figure 6 ). For example, they can accommodate more docking sites for loading drugs or other functional materials.", "Together, the facile assembly of DNA structures to welldefined architectures capable of crossing physiological barriers, being stable in biological fluids inside the body plus potential for biosensing and performing tasks on target cells with nanometer precision, if achieved, can deliver an unprecedented opportunity for timely cancer detection and therapy at the level of one single cell." ] },{ "paper_id": "db94e7aa6b683896a9ff5a239003a0c351f60041", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "db9a1efb58ae0ed12ff657b5cc78fcc2615f0c73", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "PCR detected significantly more H. influenzae, S. pneumoniae, M. catarrhalis, S. aureus, E. coli, and K. pneumoniae than standard culture-based methods (Supplementary Table 2 ).", "See the Editorial Commentaries by Musher on pages 824-5 and Jain and Pavia on pages 826-8.)", "Supplementary materials are available at http://cid.oxfordjournals.org. 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": "dc7ae96ed471da2388e3d63cc70fe1ee30a297ae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The images are published under agreement of the patient.", "The initial symptoms of the patient were fever, myalgia, and sore throat, which are common to any acute respiratory virus infection. The only clue to 2019-nCoV infection was her travel history. This case highlights that taking travel history is of paramount importance for early detection and isolation of 2019-nCoV patients.", "In December 2019, a viral pneumonia outbreak caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV), began in Wuhan, China. We report the epidemiological and clinical features of the first patient with 2019-nCoV pneumonia imported into Korea from Wuhan. This report suggests that in the early phase of 2019-nCoV pneumonia, chest radiography would miss patients with pneumonia and highlights taking travel history is of paramount importance for early detection and isolation of 2019-nCoV cases." ] },{ "paper_id": "dca3423350c6278fe7b9479eb894a578ffeeeb68", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "dcce6e45fd562d7a15633fc5a55aed8d3ce37f49", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Text S1, DOCX file, 0.03 MB. Figure S1 , TIF file, 1.6 MB. Figure S2 , TIF file, 2.1 MB. Figure S3 , TIF file, 0.1 MB. Figure S4 , TIF file, 0.7 MB. Table S1 , DOCX file, 0.03 MB.", "We acknowledge the Systems Virology Center (NIAID contract no. HHSN272200800060C) for transcriptomics data used from a previous study. This work was supported by NIH grant no. U19 AI100625 to R.S.B. and M.T.H. and NIH grant no. U19 AI106772 to R.S.B." ] },{ "paper_id": "dcd5c4f4081c90fa1c4672cbe00246e62dcc440a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "pollution is a main cause of COPD; indeed, approximately 15% of smokers suffer from this disease (49) . COPD differs from asthma in that the main characteristic is irreversible airflow obstruction (49, 50) . The physiological abnormalities that characterize COPD are emphysema and obliteration of small airways (50) . Although emphysema can occur independently of small airway narrowing, and vice versa, these 2 pathologies usually coexist in COPD (50) . Narrowing of the small airways is caused by inflammation, increased airway muscle mass and fibrosis in the airway wall, and accumulation of inflammatory mucus exudates in the lumen (50) .", "Autophagy is an essential process that maintains cellular homeostasis and cell function by delivering cytosolic constituents, including organelles, denatured proteins, or invading pathogens, to lysosomes for degradation and amino acid recycling (1) (2) (3) . Through autophagy, cells eliminate damaged or harmful components, thereby ensuring survival after exposure to stressors such as hypoxia, ROS, DNA damage, aggregated proteins, damaged organelles, or intracellular pathogens (4) . Aberrant regulation of autophagy can result in cancer (5) , neurodegenerative disease (6) , and myopathies (7) . Generally, autophagy is categorized into 3 different types: macroautophagy, chaperone-mediated autophagy, and microautophagy (8) . Usually, macroautophagy is regarded as \"autophagy\"; we also referred it as autophagy in this review.", "Although the major inflammatory cells involved in COPD are CD8 + T cells, neutrophils and macrophages, some patients have eosinophil involvement (similar to that in asthma) (47) . As mentioned before, eosinophils migrate in response to cytokines (IL-5 in particular) and specific chemokines (such as eotaxin I and RANTES). Exacerbation of COPD is triggered by persistent inflammation, which is itself caused by eosinophil-derived proinflammatory mediators such as basic proteins, cytokines, and growth factors (51) ." ] },{ "paper_id": "dcf0fae6dc17737b792734169c7d16468ab7a9dc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "dd0863296aa29156993cde032a4f7f42f5133fff", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Mice. Pathogen-free C57BL/6 mice were purchased from the National Cancer Institute (Frederick, MD). Mice deficient in IFN-\u2423/\u2424 receptor expression (IFNAR \u03ea/\u03ea ) or in MyD88 expression (MyD88 \u03ea/\u03ea ) were kindly provided by John Harty (University of Iowa, Iowa City, IA) or by Shizuo Akira (Osaka University, Osaka, Japan) and Madhu Singh (University of Iowa, Iowa City, IA), respectively.", "Statistics. A Student's t test was used to analyze differences in mean values between groups. All results are expressed as means \u03ee standard errors of the means (SEM). P values of \u03fd0.05 were considered statistically significant. HPRT GCGTCGTGATTAGCGATGATG CTCGAGCAAGTCTTTCAGTCC IFN-\u2424 CCCTATGGAGATGACGGAGA TCCCACGTCAATCTTTCCTC IFN-\u24234 TCCATCAGCAGCTCAATGAC AGGAAGAGAGGGCTCTCCAG MDA5 CGATCCGAATGATTGATGCA AGTTGGTCATTGCAACTGCT RIG-I CAGACAGATCCGAGACACTA TGCAAGACCTTTGGCCAGTT IL-12 p40 GAAGTTCAACATCAAGAGCAGTAG AGGGAGAAGTAGGAATGGGG CCL2 AGCACCAGCCAACTCTCACT TCATTGGGATCATCTTGCTG CXCL10 AAGTGCTGCCGTCATTTTCT TTCATCGTGGCAATGATCTC ISG15 GGCCACAGCAACATCTATGA CGCAAATGCTTGATCACTGT TNF GAACTGGCAGAAGAGGCACT AGGGTCTGGGCCATAGAACT IL-6 ACAACGATGATGCACTTGCAGA GATGAATTGGATGGTCTTGGTC IL-10 TGGCCCAGAAATCAAGGAGC CAGCAGACTCAATACACACT" ] },{ "paper_id": "dd0d61765564577b04e2b012930936fcb7b3f7fc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "dd154082007ef8be3cb53089778c04ea285e6b8d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In these holoendemic regions, children with repeated P. falciparum infection acquire semi-immunity early in life, leading to asymptomatic parasitemia episodes [8] .", "Descriptive statistics were applied to summarize patient data. Categorical variables were displayed with percentages, and continuous data with the median and interquartile range (IQR). Patient diagnoses were presented stratified by age or malaria parasitemia manifestation. Data analysis was performed with Stata version 14 software (StataCorp, College Station, Texas). Details of the statistical data analysis can be found in the Supplementary Statistical Analysis Plan." ] },{ "paper_id": "dd215aa15c6f212275cacf2f9db5c2e8d4145217", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Functions (1) ", "), and full subsidy ( \u03b1 \u00b5 = = 5 5 ," ] },{ "paper_id": "dd286ebc387ae032200bd0b1c1d4f659e278d7b0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Indeed, such a strategy has allowed the prediction of novel biochemical activities and has laid the foundations for further systematic investigations of the toxin-antitoxin and peptide-modification systems of prokaryotes (9, (13) (14) (15) .", "Identification of the SUKH superfamily and associated nucleic acid modifying toxin systems has considerable implications for understanding bacterial genetic conflicts, evolutionary forces acting on strongly linked multi-gene loci, and potential biotechnological applications. We briefly discuss some of these implications that emerge directly from our observations.", "The third major linkage we observed was between SUKH superfamily genes and those encoding gigantic bacterial surface proteins with repetitive motifs such as the hemagglutinin-repeats, RHS repeats (YD) and another previously uncharacterized a-helical repeat motif. All these proteins showed a characteristic feature of possessing a highly variable but globular domain at the extreme C-terminus of the protein, downstream of the repetitive region. These proteins also usually contain 'h' in red, a-helix). The numbers in bracket are indicative of the excluded residues from sequences. 'hash' indicates the residues involved in metal ion-binding, 'percent' symbol indicates the conserved histidine which is required for activation of the water molecule for hydrolysis and 'asterisk' indicates the conserved asparagines. On the right, structures of HNH and EndoG families are shown as cartoon representations with the central structural core colored by structural element type (a-helices in purple, b-sheets in yellow), and key catalytic residues highlighted. For those newly identified families, inferred topology diagrams of their core nuclease domains are shown with conserved catalytic residues." ] },{ "paper_id": "dd4ce30ff12f64b4cc7327406db2d77e5a9a66b9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "dd5267fbf9f6d0890db801e94fa7f0612d11bb18", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This was a retrospective analysis of 174 cases of hospitalized children with CAP. The following indicators were recorded: vital sign, inflammatory indexes, PA, and respiratory pathogens immunoglobulin M antibody test results. A total of 33 healthy children were selected as the control group. The results of laboratory tests between CAP and control groups were compared. CAP group was further divided into mild CAP and severe CAP groups, and vital signs and laboratory examination results of 2 groups were compared.", "Combined with traditional inflammatory markers, PA may improve the diagnostic efficacy of CAP in children. PA can be used as a reference marker to complement the chest X-rays for severity assessment of children CAP.", "Abbreviations: CAP = community-acquired pneumonia, CRP = C-reactive protein, ESR = erythrocyte sedimentation rate, LRI = lower respiratory infections, MP = Mycoplasma pneumoniae, PA = prealbumin, PCT = procalcitonin, RR = respiratory rate, WBC = white blood cell count." ] },{ "paper_id": "dd969a7721176db21314930b62e62a37e902dae5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "and open novel perspectives for the development of heparan sulfate-targeting therapeutic approaches for these emerging infections.", "All animals were handled in strict accordance with good animal practices as defined by the French National Charter on the ethics of animals experiments, and all efforts were made to minimize suffering. Animal work was approved by the regional ethical committee CECCAPP (P4_2010_008), and experiments were performed in the INSERM Jean M\u00e9rieux BSL4 laboratory in Lyon, France (French Animal regulation commitee number A69 387 05 02)." ] },{ "paper_id": "ddb9dfdd7b98f39f282347a314eefb4a04e722f3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ddf5a29103d06a6ab0fef7f8c15c169050e493c2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "de02275827ee3b513a51e620b7f040a6ee959d0b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "de4399a1034294c5aecf4f318fd99ca559a762ea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "dec136aeb4b48f3a2f506fa208d892cbe3ccd4af", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "dedc4700c705e92f673764ae9959fac57f1e2e7b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "dedfabd7d2b04bcc8274b1f49667c821281d3c63", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. The quantitative measurement results are expressed as the means \u00b1 standard deviation. One-way ANOVA t-test was used to determine statistical differences between the means: a value of P<0.05 was considered to indicate a statistically significant difference. These t-tests were performed using Prism 5.0 software (GraphPad Software Inc., La Jolla, CA, USA).", "The JE causal agent, JEV, is a member of the genus Flavivirus, of the family Flaviviridae. The virion is spherical, small in size (40-60 nm) and contains an electron dense core ~30 nm in diameter that is surrounded by a lipid bilayer envelope. The viral genome is composed of a positive-sense, 10,976-nucleotide, single-stranded RNA, which features a methylated cap at the 5' end and does not contain a 3' poly (A) tail (11) . Flanked by hundreds of nucleotides in non-coding regions (NCRs) on both termini, the viral RNA encodes a single long open reading frame (ORF) and translates into a large polyprotein precursor that is subsequently processed into structural (C, M and E) and non-structural (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) proteins by cellular and viral proteinases (12) .", "JEV propagation, purification and titration. The JEV strain SA14 (isolated in Xi'an, China in the 1950's, and stored in a refrigerator in our laboratory ever since) was propagated in C6/36 cells (ATCC \u00ae CRL-1660\u2122; Institute for Microbial Epidemiology, Academy of Military Medical Sciences, Beijing, China) cultured at 28\u02daC in a closed incubator in RPMI-1640 medium (Invitrogen Life Technologies, Carlsbad, CA, USA) containing 10% foetal calf serum (FCS; HyClone Laboratories Inc., Logan, UT, USA), 1% lactoalbumin hydrolysate (LH) and antibiotics (penicillin and streptomycin). When CPE was apparent, the culture supernatants were harvested following centrifugation at 500 x g at 4\u02daC for 10 min. The supernatants were then received a serial centrifugation in 10,000 x g for 20 min, 45,000 x g for 10 min and 70,000 x g for 4 h at 4\u02daC (Optima L-100XP Ultracentrifuge, Beckman Coulter, Brea, CA, USA). Viral particles were condensed in aliquots and preserved at -80\u02daC for use in subsequent experiments.", "In MS experiments, the peptide sequences from the gels were quested in the monkey database but generated no matches, as the African green monkey (Cercopithecus aethiops) database is not available. Therefore, the human database (Homo sapiens) had to be used instead, and the 95-kDa-molecule was probed as HSP90\u03b2, with a moderate score of 60.3 (Table I) , and then selected as an entire functioning protein for further investigation." ] },{ "paper_id": "dee0aa9ba97f07a5635f79ce50cf17abaa2b699a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All analyses were performed using SPSS software (version 17.0) and Joinpoint (version 4.3.1)." ] },{ "paper_id": "deea74c59b21622d228c43adea5340e8a2447081", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Contrary to the transcriptome, the proteome encompasses the effectors that exert and control the immune response.", "R.R., E.R., H.M., B.M. and G.K. wrote the review.", "The authors declare no competing interest." ] },{ "paper_id": "def69723f3ff30495aab9e155921db015a6aac41", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "this study (Fig. 5 ).", "Quantitative real-time polymerase chain reaction (qPCR) was performed with SYBR Green dye by using a Step One Plus Real-Time PCR system (Life Technologies). For relative quantitation of gene expression, we used the comparative cycle threshold (Ct) method (2", "Yearly, even seasonally, new or variant viruses and bacteria are reported globally, and such microorganisms can threaten the health of people, regardless of nationality, race, gender, or age. Occasionally, pandemic microorganisms, such as avian influenza or Middle East respiratory syndrome, can rapidly become pervasive globally, and they can impair their host's immune, cardiovascular, respiratory, and other systems and, even worse, can result in death. To prevent and manage these varied epidemics, whether relatively simple or severe, numerous vaccines are produced. In urgent situations, vaccines need to be mass-produced in a short time; however, verification of their safety may be inadequate, particularly confirmation of their brain safety.", "Band intensity generated from western blotting was determined by using NIH Image 1.59 software to transform the mean gray level through application of the following formula: optical density = log (256/mean gray level). Data are presented as mean \u00b1 SE values for each experimental group. Differences between means were analyzed by using Student's t-test for single comparisons. P values of less than 0.05 were considered statistically significant." ] },{ "paper_id": "defb3d3bd1f210f27426c5f20d48c398f6600587", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "defb6d472091880138cc95da0589cb3bccbd51b2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We were not able to detect oligomer formation comparable to that seen with other viral proteins (15, 50) in sucrose gradient velocity experiments; however, it is possible that any higher order structures (e.g., trimers) formed may dissociate during centrifugation (16) .", "Rubella virus (RV) has been reported to", "Proteins were separated on 10% polyacrylamide gels (26) . Gels were fixed in isopropanol:water:acetic acid (25:65:10) and soaked in Amplify (Amersham Corp.) before drying and exposure to Kodak XAR film at -80\u00b0C.", "For routine morphology studies, cells were fixed (1 h) with 2 % glutaraidehyde, 3% paraformaldehyde in 100 mM cacodylate-HCl buffer, pH 7.2, scraped from the culture dish, and pelleted in a microfuge. The cell pellets were then postfixed (1 h) in 2% OsO4 in the same buffer, stained in block (2 h) with 2 % uranyl acetate (pH 6.0), dehydrated in graded ethanols and embedded in Epon." ] },{ "paper_id": "df1b6713549bcbe22ec020aaf62275280f096b9a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Subjects attended two study days separated by a mean (SD) 7.5 (4.7) days (range 2-21). A sputum sample was collected from each patient with CF on the day of testing. Cough manoeuvres were supervised by a healthcare professional and emergency equipment was available.", "practices recommended currently for the CF community may need to be re-evaluated.", "Forced expiratory volume in one-second (FEV 1 ) and forced vital capacity (FVC) were measured on all subjects according to ATS/ERS guidelines. 22 Respiratory muscle strength was measured by maximum inspiratory (MIP) and maximum expiratory (MEP) mouth pressures using a Micro Medical Respiratory Pressure Meter at TPCH. Weight, height, age, sex and clinical status (exacerbation or clinically stable) were recorded." ] },{ "paper_id": "df5763298a47b06f4efcd3ae836e0d0a487d1d97", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "df62b9ff3b2b95896d4b90ccefc9f3d756be1abf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nine cases were successfully treated, 1 case succumbed to respiratory failure, and the success rate was 90%.", "Short-term intubation ventilator was utilized when there was: i) Respiratory arrest or respiratory and cardiac arrest; ii) sputum congestion, dyspnea, serious cyanosis; and iii) blood PaCO 2 >60 mmHg, in order to accelerate the discharge of PaCO 2 and reduce respiratory acidosis.", "Treatment. After admission, comprehensive emergency treatment measures were taken, such as improving the ventilation function, oxygen uptake, maintaining airway patency, administration of cardiac and diuretic drugs, reduction of intracranial pressure, and conducting anti-infection and symptomatic support measures." ] },{ "paper_id": "df638f8a7a456418b116ca93f6b20b9cd8c7f791", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "dfa3dbdc7b28b9075361efcb919d3a1b19636edd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Assembly and budding", "Several genome-wide siRNA screens were recently performed to identify ISGs or IFN-mediated effector genes (IEGs) that mediate IFN antiviral functions. These studies have identified many new ISGs or IEGs and have revealed interesting features of the actions of ISGs.", "Liver Cell" ] },{ "paper_id": "dfaf551127ff5cc102d0ced7f3d9d15a5d3de8a7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ethical Considerations: This paper was based on the review of existing and publicly-available information. Conflict of Interest: The authors" ] },{ "paper_id": "dfe23d64895beefb7e0fec49126c49d982ffe8da", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "T cell epitopes do not protect against infection; however, they may protect against disease", "ADG and WDM are senior officers and majority shareholders at EpiVax, Inc., a privately owned immunoinformatics and vaccine design company located in Providence, RI, USA. LM is an employee and holds stock options in EpiVax. LE and RWM have been paid consultants of EpiVax on vaccine development programs. JB and MC are employees and stockholders at Aldevron, Inc. The authors of vaccines against infectious disease, successful implementation of the T celldriven approach in a range of contexts suggests that it is worth pursuing.", "pathogens. The design process-from genome to gene sequence, ready to insert in a DNA plasmid-can now be accomplished in less than 24 h. While these vaccines are by no means \"standard,\" the need for innovation in the vaccine design and production process is great. Should such vaccines be developed, their 60-d start-to-finish timeline would represent a 2-fold faster response than the current standard." ] },{ "paper_id": "e008bb9bd16411df2029bfbfd2df3fef72a7e575", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Inclusion criteria were as follows :", "Literature type : published articles ; official publications.", "Exclusion criteria were as follows :" ] },{ "paper_id": "e012c42cc9de8f02ca1e254e76a85a67286070ea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "After the amplification process, the amplified products were hybridized with their respective probes that were immobilized at different sites on the array. Then, they were incubated with streptavidin peroxidase to generate an insoluble product that precipitates at the hybridization sites in the array. Hybridization occurred in a low-density microarray containing triplicate DNA probes that are specific to the respiratory virus studied. All these products were visualized by using CAR automatic reader (Clinical Array Reader) (Genomica S.A.U.).", "Abbreviations: CI = confidence interval, OR = odds ratio, PCR = polymerase chain reaction, PIV = parainfluenza virus, RSV = respiratory syncytial virus, RT-PCR = reverse transcription-polymerase chain reaction." ] },{ "paper_id": "e0187a691be1237e922515d56bcfbc7ec988fa3e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Multiple sequence alignment and phylogenetic analysis. The amino-acid sequence alignment and the phylogram of G6PD homologues were generated by online software Clustal W2 provided by EMBL-EBI (www.ebi.ac.uk). The abbreviation and accession number of each G6PD homologues are as followed: Hs, human (AAA92653); Mm, mouse (NP_032088); Dr, zebrafish (XP_699168); Dm, fruit fly (AAA99107); Ce, nematode (CAA97412); Sc, yeast (CAA93357); Ec, bacteria (AP_002472).", "Western blot. The C. elegans protein lysate extracted from staged adults were resolved by SDS-PAGE and immunoblotting against a rabbit antiserum to human G6PD, C. elegans CEP-1 (Santa Cruz Biotechnology, Dallas, TX, USA), human actin (Santa Cruz Biotechnology), or C. elegans tubulin (Santa Cruz Biotechnology) according to the instructions provided by manufacturers.", "Materials and Methods C. elegans strains. N2 (wild type), pmk-1(km25), sek-1(km4), mek-1(ks54), cep-1(gk138), and bcIs39 (P lim-7 ced-1::gfp) were obtained from Caenorhabditis Genetics Center, University of Minnesota. All C. elegans strains were maintained on NGM agar plate seeded with bacterial lawn at 20 1C according to standard protocols." ] },{ "paper_id": "e0875b937adb61d120554efed78760b89fda64b8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Chi-squared and Fisher's exact probability tests were used for statistical analysis. P values of <0.05 were considered to be statistically significant.", "RNA was extracted from CCoV-infected cells and filtrated fecal swabs using RNeasy Mini kit (Qiagen, Hilden, Germany) and Viral RNA Mini Kit (Qiagen), respectively.", "Felis catus whole fetus-4 cells (fcwf-4 cells; ATCC Number: CRL-2787) [11] were maintained in Dulbecco's minimum essential medium (DMEM; Life Technologies, St. Louis, MO, U.S.A.) containing 10% heat-inactivated fetal calf serum (FCS; Sigma-Aldrich), 100 units/ml penicillin and 100 \u00b5g/ml streptomycin (Life Technologies). Fcwf-4 cells in 6-well plates were inoculated with extracts from CCoV-positive feces and were then incubated at 37\u00b0C in a 5% CO 2 incubator. Cells were observed daily for cytopathic effects (CPE). If there were no CPE, cells were blind-passaged five times." ] },{ "paper_id": "e0c0c5277a24320d44e9b356e13c5801dad521af", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e0d4c25b7e80c41abb0a816770a803b29746b2ee", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "FITC-conjugated goat F(ab')2 fragment anti-mouse or anti-rat Ig, rabbit F(ab')2 fragment anti-goat Ig, and affinity-purified rabbit antiserum against rat, mouse, or goat Ig, were purchased from Cappel Laboratories (Cooper Biomedical Inc., Malvern, PA). LM, both from a murine Engelbreth-Holm-Swazm (EHS) sarcoma (Gibco Laboratories, Grand Island, NY) and from human placenta (Calbiochem Corp ., San Diego, CA) was used in adhesion assays.", "On the basis of the molecular alterations, several mechanisms including cytoskeleton association, interaction with other intracellular moieties, receptor clustering, and exposure of activation epitopes may underlie the increased integrin avidity.", "We thank Anna Maria Bressan, Alessandro Procaccini, and Antonio Sabatucci for expert technical assistance, and Sergio Ferraro for photographic assistance . We thank Drs . M . Hemler, G. Tarone, A. Sonnenberg, A . Sacchi, P. G. Natali, C. E. Klein, and G. Trinchieri for kindly providing some of the antibodies used in this study.", "were gifts from Dr. C. E. Klein (Department of Dermatology, University of Ulm Oberer Eselsberg, Germany) and Dr. P. G. Natali (Cancer Institute, Regina Elena, Rome, Italy), respectively; antiVLA-1 was purchased from T Cell Sciences Inc. (Cambridge, MA); anti-cat was from Telios Pharmaceuticals Inc. (San Diego, CA); and anti-CD16 (B73 .1 and 3G8) and anti-MHC I (W6/32), were kindly provided by Dr. G. Trinchieri (Wistar Institute, Philadelphia, PA). The following rat mAb were used : GoH3 (9), specific for the a6, was a gift from Dr. A. Sonnenberg (Laboratory of the Netherlands Red Cross, AD, Amsterdam) ; and 439-9B (15) (anti-04) was kindly provided by Dr. A. Sacchi (Cancer Institute, Regina Elena) . A goat antiserum against the 01 subunit was provided by Dr. G. Tarone (University of Turin, Italy) (16) ." ] },{ "paper_id": "e100d3d45507da10018bc2b410c93072756fef47", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Text S1, PDF file, 0.1 MB. Figure S1 , PDF file, 0.1 MB. Figure S2 , PDF file, 0.1 MB. Figure S3 , PDF file, 0.3 MB. Figure S4 , PDF file, 0.3 MB. Figure S5 , PDF file, 0.1 MB. Figure S6 , PDF file, 0.1 MB. Table S1 , PDF file, 0.1 MB.", "Supplemental material for this article may be found at http://mbio.asm.org /lookup/suppl/doi:10.1128/mBio.02145-14/-/DCSupplemental.", "Electron microscopy. CsCl gradient-purified Patience particles were applied to glow-discharged Formvar-and carbon-coated copper grids (400 mesh) (Ted Pella). They were stained with 1% uranyl acetate and imaged with a Morgagni 268 transmission electron microscope fitted with a Hamamatsu Orca HR side-model digital camera and AMT540 software. SDS-PAGE. Patience particles were concentrated and purified via CsCl gradient and ultracentrifugation. The visible phage band was dialyzed against two changes of phage buffer; 500 l of the dialyzed CsCl band was pelleted by a 30-min spin at 14,000 rpm in a microcentrifuge. The pellet was resuspended in 75 l of 20 mM dithiothreitol (DTT), and then 2 l of 0.5 M EDTA and 1 l of 1 M MgSO 4 were added. The phage was disrupted by being heated to 75\u00b0C for 2 min and then sonicated on ice six times for 30 s to disrupt the DNA. The sample was then mixed with 25 l of 4\u03eb SDS sample buffer and heated in a boiling bath for 3 min at 95\u00b0C. The sample was electrophoresed through a 12% polyacrylamide gel containing SDS and stained with Coomassie brilliant blue in methanol." ] },{ "paper_id": "e1253d2bfe05e4fa4a42f9a542ca45c32a1e2264", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org/ lookup/suppl/doi:10.1128/mBio.00593-15/-/DCSupplemental. Figure S1 , TIF file, 0.6 MB. Figure S2 , TIF file, 0.7 MB. Figure S3 , TIF file, 0.4 MB. ", "Pathogenicity study in neonatal pigs. All animal studies were performed as approved by the Institutional Animal Care and Use Committee of Virginia Tech (IACUC no. 14-105-CVM, 5 June 2014). Thirty-five 2-day-old piglets, purchased from the Virginia Tech Swine Center, were housed as 7 animals/group in HEPA-filtered level 2 biosecurity facility." ] },{ "paper_id": "e14c267f2323c8a137e2698dcf29a87713898166", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Bars, 100 nm.", "In some experiments using SLO-permeabilized cells, we found a high background labeling using control (irrelevant) antibodies. This was reduced by both diluting antibodies two-to threefold more than normal and by incubating both control (as well as the p23) antibodies in the presence of 0.1% Tween 20 in 2x PBS plus 1% fish skin gelatin (Sigma Immunochemicals, St. Louis, MO).", "In some experiments, HeLa cells were additionally labeled with BSA gold before fixation to mark the late endocytic structures (16 nm gold) or early endosomes (5 nm gold). As is evident in Fig. 2 , A and B, these organelles were invariably devoid of any label for the KDEL-R." ] },{ "paper_id": "e14d8123b56a1b4825bf8aa262ff4f4d0f9549b4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e1708119ebab348a08e39cff86b1baeda126ce09", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. Statistical analyses were performed using Excel 2007. Significance was assessed using T-Tests after determination of the variance equality using an F-Test.", "In summary, these various lines of evidence culminate in the hypothesis that MALAT1 must be an important and most likely essential gene given its high and ubiquitous abundance, its specific regulation and localization patterns, its evolutionary conservation, its many interaction partners, molecular mechanisms and the strong impact of its deregulation on many cellular phenotypes including fundamental processes such as proliferation, migration or invasion.", "No potential conflicts of interest were disclosed." ] },{ "paper_id": "e18ac727e1edc13aeab67e5d458ee00a190ace7b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e1b312167d5ea6a1ed3c071b05b7bd0a48a975df", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "On a related note, allocation of responsibility and authority, and regulation of roles should clearly be designated to the rapid response teams that are formed in the event of a disaster. A critical review of preparations should be conducted based on the lessons learned from the controversy during the MERS-CoV crisis surrounding the organization and role of the rapid response team, which consisted of mainly clinical personnel and were sent to major hospitals. Furthermore, a professional response team should be formed and trained for each type of disaster with clear and distinct roles for team members.", "Furthermore, confusion revealed in the initial stages of the MERS-CoV responses between the central and local governments and potential role conflicts that may exist among government agencies should be resolved. Efforts to establish cooperative governance should also be constantly strengthened, even in ordinary times. The efforts to establish a chain of command on site and improve the decision making abilities of the authority should also be enhanced on an ongoing basis.", "From the first MERS-CoV occurrence to the super-spreading events, the MERS-CoV outbreak in Korea is known to have many direct and indirect causes. Rather than simply listing these factors, determining how the factors are structurally related to one another will be more beneficial for understanding what led to this unprecedented national crisis and developing strategies to curtail such a crisis in the future (Figure 1 )." ] },{ "paper_id": "e1b336d8be1a4c0ccc5a1bf41e48b3b004d3ece1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The model describing a homogeneous population onboard can be described by:", "The model describing a stratified population onboard can be described by:", "where denotes susceptible, exposed, infected and recovered or removed, , and the subscript and are indicating guest and crew respectively. Overall, we assume mortality is negligible.", "We set out to study the empirical data of COVID-19 confirmed infections on the Cruise ship Diamond" ] },{ "paper_id": "e1ca13fb1fabab727830bd615d92049fc6502383", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e1d7c0ed2db49bcc8e49814b1bb24bd01f9ba8c4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. all graphs were generated and statistical analysis of data was performed using one-way analysis of variance via Friedman test by GraphPad Prism software (version 7.04 for Windows; GraphPad Software, inc., la Jolla, ca, uSa). Subsequent to the initial measurement/analysis, the experiments were repeated twice for cell density measurement (n=3 in total) and three times for cell inhibitory effect analysis (n=4 in total) to confirm the consistency, repeatability and reproducibility of the results. all values are expressed as the mean \u00b1 standard deviation. P<0.05 was considered to indicate a statistically significant difference.", "cancer chemotherapy uses drugs to prevent the growth of cancerous cells or kill cancerous cells in the human body (1) . in general, chemotherapy can be applied for three primary purposes: as an adjuvant therapy, in order to prevent the cancer cells from re-emerging following initial surgery or radiation; as a neo-adjuvant therapy, shrinking the tumour size for its easier removal with surgery; and as a treatment for metastatic disease, to reduce the number of cancer cells and kill cells that have spread to other parts of the body from the primary cancer location, such as to the lymph nodes under the arm in patients with breast cancer.", "The yeast-based strategy described in the present study was developed when constructing Pichia with multiple copy numbers of ToPoi for the expression and purification of the target enzyme (13, 20) . GS115 and SMd1168 yeasts were found to be better than Pichia strains in accommodating the exogenous recombinant ToPoi expression, and an enzyme activity of ~3.02x10 5 u/l of crude culture was obtained in the recombinant yeast; however, only SMd1168 was able to stably express the enzyme in the culture supernatant at room temperature (13) . This prototype development is based on our present original research, and provides innovation and novelty to screening processes within the medical biotechnology sector." ] },{ "paper_id": "e1e8903986998f998a4ee66cbbf1c0b05ebf2eb1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "IgG1, \u03ba chain 10 -5 3", "IgG1, \u03ba chain 10 -5 2", "IgG2b, \u03ba chain 10 -3 1.5", "Most importantly, BV is a biosafety level 4 (BSL-was similar with glycoprotein D of HSV-1 and4) pathogen; currently BV-infected cell lysates are used as a diagnostic antigen in serological tests and only maximum containment laboratories (BSL-4) have the qualification to produce it, this requirement limits the amount of facilities, which provide the antigen. When compromising outcome measures based on assays using these antigens, the antigens may also suffer from lot-to-lot variation. The glycoprotein D (gD) of BV is a 35-kDa glycoprotein identified in the BV envelope and is among the main surface antigens shown to elicit antibodies in sera of infected animals." ] },{ "paper_id": "e2173589087169565c3aab50650c965bd545124d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data sharing statement: Technical appendix, statistical code, and dataset available upon request with proper ethical approval.", "Design: Prospective cohort study." ] },{ "paper_id": "e222c3bbd05eb665b185124594a7d85712735418", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Obtained data were statistically analyzed using Statistical software (Prism system). Data were presented as mean \u00b1 standard error of mean. The significance of variations between control and disease was determined using T-test.", "Standard biochemical tests for detection of E. coli were performed on EMB positive isolates according to Kreig and Holt (1984) including indole production test, methyl -red test, Voges-Proskauer test, Simmon's citrate test, triple sugar iron (TSI) and urease test.", "Fecal samples were collected directly from the rectum of apparently healthy and diarrheic calves using sterile swab tube, labelled, placed into a small Coleman cooler and transferred immediately to the laboratory for microbiological examination against E. coli." ] },{ "paper_id": "e24e6736123c670928dd233196d473f81e998b24", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "No absorption was demonstrated, but the loss of virus in control tubes without cells was sufficient to obscure a differential absorption.", "In order to test the permanency of the alteration produced by PRI extracts,", "PLATES 45 ~o 50", "The destructive effect of undiluted virus on C3H cultures might be explained by a toxin. To test for this, the virus particles were inactivated with UV light 1 I General Electric sterile lamp, 15 watts, 1760 ergs/minute mm 2." ] },{ "paper_id": "e27e8c74a021090c4f54ccfca13646232741638a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e2b26fb1febcce2de00f4e178958e710cf468416", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "doi: 10 .1292/jvms.19-0009 [5, 14] . Fluorescent (fLAMP) reagents are commercially available, and this real-time amplification approach allows extremely rapid and accurate diagnosis through the use of an improved chain replacement enzyme and annealing analysis compared with tLAMP [4, 6, 17] ." ] },{ "paper_id": "e2d29009210b2e9a2e3273cb541c7298b1bbb3cb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplementary materials are available at The Journal of Infectious Diseases online (http://jid.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.", "To assess virion stability, pseudotypes bearing EBOV-GP or the GP of VSV (VSV-G) were normalized for comparable infectivity. Subsequently, the pseudotypes were incubated at defined temperatures for increasing periods, frozen at \u221280\u00b0C at a given time point, and used for transduction of 293T target cells. Seventy-two hours after transduction, transduction efficiency was quantified by a luciferase assay.", "The adherent human and simian cell lines cells were cultivated in Dulbecco's modified Eagle's medium (PAA Laboratories) and the suspension cells in Roswell Park Memorial Institute 1640 medium (PAA Laboratories), supplemented with 10% fetal bovine serum (Biochrom) and antibiotics. The following cell lines were used: 293T (human embryonic kidney), Huh7 (human hepatoma), U373 (human glioblastoma), HOS (human osteosarcoma), HeLa (human cervix carcinoma), RPE (human retinal pigment epithelial), EA-hy (human endothelial hybrid), Raji (human B cell), Jurkat (human T cell), CEMx174 (human T-cell/B-cell hybrid), sMAGI (rhesus macaque mamma carcinoma), LLC-MK2 (rhesus macaque kidney), Vero (African green monkey kidney), and COS (African green monkey kidney). Differentiation of human THP-1 monocytes into THP-1 macrophages was achieved by incubation with phorbol-12-myristate-13-acetate (PMA; 10 ng/mL) for 48 hours. Bat cell lines were propagated as described elsewhere [20] . All cells were grown in a humidified atmosphere at 37\u00b0C and 5% CO 2 .", "Ebolaviruses, from the family Filoviridae, cause a severe and frequently fatal disease in humans [1] . The first documented outbreak of Ebola virus (EBOV, formerly Zaire ebolavirus) disease (EVD) occurred in Zaire and was associated with a case-fatality rate of 88% [2] . Subsequently, 22 EVD outbreaks were recorded in sub-Saharan Africa [2] . These outbreaks generally occurred in relatively remote areas, were contained by quarantine measures, and caused a maximum of 425 cases per outbreak (during the 2000-2001 EVD outbreak in Uganda). The ongoing EVD epidemic, which originated in Guinea [3] , differs markedly from previous outbreaks: it affects Western Africa and is associated with a higher death toll than all previously recorded outbreaks jointly [4] . The massive scale of the epidemic is likely due to the delayed public health response. However, the currently circulating viruses harbor >30 unique amino acid substitutions [5] , and it is currently unclear whether these mutations allow for more-efficient spread in and between humans, compared with viruses responsible for past outbreaks." ] },{ "paper_id": "e2e23d6985639b6aa9671a1006fe80a41abded5c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The cell pellets were resuspended in 5 ml of 50 raM Tris-HCl buffer, pH 7.5, containing 1 mM CaCI2 and 1 mg/ml of pronase. A few drops of toluene were added to prevent bacterial growth, and the tubes were incubated for 18 h at 37\u00b0C. An additional 5 ml of pronase solution was added, and incubations were continued for 18 h. The digestion was terminated by addition of trichloroacetic acid to a final concentration of 5 % and, after cooling, the precipitate was removed by centrifugation. The supernatant liquid was extracted five or six times with diethyl ether to remove the trichloroacetic acid, and the aqueous layer was concentrated to a small volume and analyzed by chromatography on columns of Biogel P-4.", "In seven experiments, we consistently observed an enhanced tendency of neurites to fasciculate in the presence of the drug (Fig. 2, B and D) . This effect varied in magnitude in different parts of the outgrowth surrounding the ganglion, as did the extent of fasciculation in control cultures (Fig. 2 C) .", "Sudan Black Staining. Number and length of myelin segments as well as morphology of ceils were assessed in Sudan black-stained cultures fixed and processed as described above under \"Neurite OutgrowthY Myelin was quantitated by counting numbers of internodes in 60 fields in Sudan black-stained cultures . The lengths of individual myelin segments were measured using an eyepiece micrometer at 250\u00d7 on a Zeiss Universal microscope calibrated by means of a stage micrometer; 50 segments were measured in control and castanospermine-treated cultures.", "It is difficult to quantitate precisely the oligosaccharides that retain normal structure in the presence of castanospermine. Rough estimates based on the material that chromatographs with control oligosaccharides as shown in Fig. 1 , A and B suggests that maximally 10-15 % of the oligosaccharides have normal structure, representing that fraction of the mannose-labeled oligosaccharides that has an apparent size identical to that of control material." ] },{ "paper_id": "e3169377d59bbef414c6f7e4b2b36ef7f65e2b1a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "There was no evidence of OH activities in the Maldives, which has a small livestock population and veterinary services provided by Sri Lanka.", "The One Health Association of South Asia is a second regional OH network facilitated by the EcoHealth Alliance with the mission of facilitating communication and cooperation among scientific and government agencies in member countries through meetings, workshops, research, and information exchange (63) .", "The Department of Livestock Services and the Department of Health Services have collaborated to control HPAI (H5N1), Japanese encephalitis, and rabies, producing " ] },{ "paper_id": "e32449e2444438d63a3b088859156405a461ba2e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ ",\" where the body refers to CAMMS and two wings Tsinghua and Peking Universities.", "Although it is very difficult to predict the scenario in 2025, we would not be surprised if the relative contribution by these two methodologies reciprocates relative to that in 2005. Thankfully, those of us who used to rely exclusively on X-ray crystallography are increasingly inclined to turn to EM for tackling research problems. We are optimistic that the biological EM community will greatly benefit from the joining of the X-ray crystallography experts.", "Haixiao Gao included a Titan Krios microscope as a must-have item on her list of requirements. The price tag of approximately 4 to 5 million US dollars, or approximately 35 million Chinese Yuan, was an astronomical number to Tsinghua University. With strong support from Zhixin Wang and Sen-Fang Sui, Shi turned to the Tsinghua University administration for help in early May 2008. The possibility of installing Asia's first operational Titan Krios on Tsinghua campus and the huge research potential convinced the leadership, which decided to make an investment of 30 million Yuan after listening to a brief presentation by Shi. These funds were supposed to cover both the purchase, room preparation, and the operation of the Titan microscope. 11 joined Tsinghua in 2014. Jiawei Wang ( ), a classically trained Xray crystallographer, shifted his research focus to EM data analysis. A critical mass on EM methodology and application began to take shape at Tsinghua. Such a build-up would have been flawless if it were not for the unexpected and sudden departure of Haixiao Gao at the beginning of 2010.", "In plant photosynthesis, a series of supramolecular machineries embedded in the thylakoid membrane of the chloroplast mediate the initial biochemical reactions driven by light energy. Among them, photosystem II (PSII) is the most upstream machinery capable of converting light energy and splitting water molecules under ambient temperature. PSII is powered by a series of peripheral light-harvesting complexes termed LHCII. As a graduate student, Zhenfeng Liu ( ) in the laboratory of Wenrui Chang ( ) at the IBP solved the first X-ray structure of plant major LHCII. 49 However, little was known about how the LHCII complexes assemble with the PSII core complexes at specific locations, so as to deliver excitation energy efficiently. Through close collaborations with Xinzheng Zhang and Mei Li at the IBP, Liu determined the structure of spinach PSII-LHCII supercomplex at 3.2 \u00c5 resolution using single-particle cryo-EM (Table II) . 50 This unveiled intricate innerworkings of a 1.1 MDa homodimeric supramolecular system containing 50 protein subunits, 210 chlorophylls, 56 carotenoids, and many other cofactors. The energy transfer pathways between three different LHCII complexes and the PSII core are suggested." ] },{ "paper_id": "e3298846caa5271bd93b410c46b8ab6cee3eff8e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e3529239dbaaf991ccae7b5501f26e531e9be74c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e35295b96d9cee71829be853fe2a43accd1dff37", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e3b596fd33a870737d10b8f5c7fbcf9d3d0aa514", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Drugs like Viagra and Cialis work by deactivating the enzyme PDE5-a chemical that takes away an erection after sex by limiting blood supply.", "However, scientists now think that malignant melanoma is fueled by a faulty gene (a family of serine-threonine protein kinases, BRAF) which suppresses the enzyme PDE5, suggesting that PDE5 plays an important role in preventing the spread of cancer cells, including prostate cancer cells. It is feared that Viagra, and drugs like it, could be mimicking the effect of the mutated BRAF gene.", "This year, the Editorial Board has given much attention to convergence. By systematically combining diverse fields of study, efforts have been made to overcome the limitations of existing interpretations. The convergent status of rehabilitation exercises and the need to overcome medical and societal problems through convergence, which was emphasized during the MERS (Middle East respiratory syndrome) outbreak, were introduced. Now, in the last issue of the year, we reconsider the concept of penile rehabilitation, which has until now been recognized as safe. We suggest an urgent need to conduct high-quality prospective studies with regard to the biochemical recurrence of cancer, specifically with regard to the mechanism by which phosphodiesterase type 5 inhibitors (PDE5I) may affect the course of prostate cancer when taken after radical prostatectomy." ] },{ "paper_id": "e3bc735859aa567bbb943a3c48e8e0da30b3c99e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The WHO's International Health Regulations (IHR) were first defined in 1969. The IHR encouraged member states to follow guidelines for establishing preventive measures and preparedness for outbreaks of diseases that pose a threat at the international level. 23 However, the 1969 IHR had limitations, including a scope limited to quarantinable diseases.", "IRCA establishes the responsibilities of the National Biosurveillance Integration Center (NBIC), which coordinates and integrates biosurveillance data from member agencies. Figure 4 shows the process of biosurveillance according to IRCA.", "The 2011 amendment of the Food and Drug Administration's FSMA does not outline the concept of biosurveillance. However, Section 205(1)(I) of the Act states that foodborne illness data are to be integrated into biosurveillance systems." ] },{ "paper_id": "e3db3c2e1b832030eda8db862a8eb2ab647c0528", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Coronavirus is a single positive-strand RNA virus with a genome size of approximately 30kbp and has been classified into the Family Coronaviridae, Subfamily Coronavirinae. Subfamily Coronavirinae is further classified into 4 genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus [4] . Canine coronavirus (CCoV) of the Genus Alphacoronavirus and canine respiratory coronavirus of the Genus Betacoronavirus have been identified in dogs [4] .", "CCoV-II-infected dogs develop enteritis and gastroenteritis, and the condition is aggravated by mixed infection with CCoV-II and other pathogens [8, 16] . CCoV-I viral genes have been detected mainly in pups with diarrhea symptoms [11] , but CCoV-I has not yet been successfully isolated, and many points remain unclear. CCoV infection has been observed worldwide, but no seroprevalence study of CCoV-I has been performed.", "The CCoV-I infection rate may be influenced by the maintenance environment of dogs. All samples were derived from household dogs, but it was unclear whether or not they were maintained alone or in a group. Considering the presence of cats infected with CCoV-like virus, it is also necessary to investigate maintenance with a cat. It is necessary to perform an epidemiological survey of CCoV-I taking these into consideration." ] },{ "paper_id": "e3dd1ad4bb9542f0f8fc13f5faab78ee531ae89b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The transcription reaction was carried out in 50 ml containing 20 pmol of PCR product, 500 mM rNTPs, 3.3 mM guanosine, 40 U of ribonuclease inhibitor RNase Out (Invitrogen) and 400 U of T7 RNA polymerase (Ambion). The reaction was carried out at 378C for 2 h and the transcript was purified from a denaturing 10% polyacrylamide gel, and 5 0 -end-labeled with T4 polynucleotide kinase and [g 32 P]ATP (4500 Ci/mmol; ICN). The labeled RNA was again purified by electrophoresis on a denaturing 10% polyacrylamide gel.", "Mutagenic primer #1 (forward):", "Mutagenic primer #2 (reverse): 5 0 -GAAGAGGCAATCACCTAAAACACCCAAGGG TTACATAGCAAAGG-3 0" ] },{ "paper_id": "e3f5b91907bbd807d31fa063a9d629e574b4dbde", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "less some remaining luminal sequence also plays some role in retention.", "Analysis of [35S]methionine-labeled proteins was as described (Cooper and Bussey, 1989) . Briefly, cells were grown to an OD600 of 0.4-0.45 in selective medium (YNB) and then labeled with Trans35S (100 ~Ci; ICN Biochemicals Inc., Montr6al, Canada) for 10 min at 30\u00b0C. Yeast cells treated with tunicamycin (10 ~g m1-1) were preincubated before radiolabeling for 30 min at 30\u00b0C. Tunicamycin is a hydrophobic analogue of UDP-N-acetylglucosamine that blocks the addition of N-acetylglucosamine to dolichol phosphate, the first step in N-linked oligosaccharide formation. Chase conditions were achieved by addition of L-methionine and L-cysteine to a final concentration of i mM.", "To establish possible Golgi modifications that Kre2p might acquire, and to attempt to assess to which Golgi subcompartments it had been exposed, the size of the Kre2plinked oligosaccharide chains was examined in specific N-linked glycosylation mutants. The mnn strains carry mutations at various loci resulting in glycosylation defects ( Fig. 2 ; Ballou, 1990; Ballou et al., 1990) . The N-linked carbohydrates from an mnn9 strain lack the outer chain. The mnnl strain produces glycoproteins with N-linked chains lacking terminal c~l,3-mannosyl residues (Fig. 2) ." ] },{ "paper_id": "e46e1768a48965ba42073cc744b7278055859174", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e47a7616bf5b35202811dcb713b4025735dd2500", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A very recent study demonstrated that synthetic (GlyArg) 20 and (ProArg) 20 dipeptides encoded by sense and antisense C9ORF72 repeats, respectively, are toxic to cells. These dipeptides have ability to enter cells, migrate to nucleus, bind to nucleoli and induce cell death. The ProArg dipeptide toxicity manifests in aberrant pre-mRNA splicing similar to that observed in ALS patients, and in alteration of ribosomal RNA biogenesis (39) .", "of ITAFs, affecting both their subcellular localization and IRES-binding affinity, thus modulating their activity (67) .", "Supplementary data are available at NAR Online. " ] },{ "paper_id": "e484923f000ae4706e2213031654865cef348def", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Although there is only one pathogen, respiratory syncytial virus, for which a mAb is licensed for use, there are a number of other infectious disease indications-such as Ebola virus disease treatment and human immunodeficiency virus primary and secondary prevention-for which mAbs are being tested in advanced phase clinical trials (www.clinicaltrials.gov). Despite all of these advantages, the timelines and costs of mAb research and development (R&D) are respectively longer and higher than that for polyclonal antibody preparations.", "As the life cycle and genetic sequence of this new coronavirus has become better elucidated, the rational design and development of novel and approved agents with potent antiviral activity have become possible. The advent of high-throughput screens of licensed compounds and small molecules has also allowed researchers to efficiently evaluate large libraries of drugs for their in vitro antiviral activity against novel targets [61] [62] [63] [64] [65] [66] . To date, several dozen licensed drugs have been reported to inhibit MERS-CoV replication. Using slightly different screening technologies, different groups have converged on some common classes of compounds, including nucleoside analogues, antibacterial protein synthesis inhibitors, kinase signalling modifiers, antimetabolites and antiprotozoal agents.", "Despite intensive efforts to develop a MERS-CoV vaccine, the prevalence and transmissibility of this emerging pathogen are both relatively low [3, 26] , making it difficult to define a target population for vaccination. mAbs, on the other hand, can be administered in the setting of an outbreak without the need to discriminate who might be at greatest risk for infection. They can be used to treat cases early in their natural history and for post-exposure prophylaxis of case contacts. mAbs also carry the benefits of higher potency, greater specificity, more extensive pre-licensing evaluation and consequently a more vetted safety profile. Additionally, mAbs can help define immunogenic epitopes through crystallographic analysis, thereby providing atomic-level detail for the design of better immunogens. They also have been proven as effective therapies in the areas of cancer treatment and autoimmune disease management." ] },{ "paper_id": "e494ed8c504a8312c9df7936a8fc832e86d444e6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The sequence analysis of selected PCR fragments using the R1 and R2 primer pair (R1/R2 fragment) obtained from H. longicornis showed similarity to each other, with 0 to 3 nucleotide sequence differences in 475 bases (99.3-100% homology). The similarity of the R1/R2 fragment of A. testudinarium to that of H. longicornis was 96.2% (457/475). The R1/R2 fragments were subjected to phylogenetic analysis to confirm the association with previously reported rickettsial sequences (Fig. 2) . The R1/R2 fragment from H. longicornis (R17K-Ti187F) clustered into the spotted fever group of rickettsia, including R. japonica, R. conorii and R. slovaca, whereas those from A. testudinarium were divided into clusters other than SFG rickettsia.", "Arthropods transmit zoonotic pathogens to animals including humans [12, 22] . In Japan, tick-borne encephalitis [29] , Lyme disease [17] , Japanese spotted fever [21] and other tick-borne diseases have been classically reported. Additionally, some cases of severe fever with thrombocytopenia syndrome (SFTS), whose etiological agents were potentially transmitted by ticks, were reported in early 2013 in the western region of Japan [28] . Ticks might also harbor unknown pathogens that could cause emerging infections in animals and humans. Therefore, it is important to study tick ecology and to survey the vector-borne pathogens in ticks.", "Genus Rickettsia consists of obligate intracellular, gram negative bacteria. The tick has been identified as the vector of these pathogens. The spotted fever group of rickettsiae is the causative agents of rickettsiosis manifested by rash, fever, headache and eschars. In Japan, over 100 patients with Japanese spotted fever caused by Rickettsia japonica are reported every year [23, 24] . The increasing distribution of the disease has raised concerns for public health. Therefore, the prevalence of ticks on the plants and wild boars and their harboring rickettsia were investigated in Kyoto city, Japan." ] },{ "paper_id": "e4b23ec957446463f8d7be44f3ddbbf6155ae10c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e4bd7b82d8631ca8edb9f41160a6a6094793964e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Standing on the road of history, this is an important moment for the WHO and the Republic of Korea to convey the past history of connection and collaboration, identify where we stand at the present moment, and prepare for our future contribution in global health and development.", "The book was finalized with support of WPRO and the Ministry of Health and Welfare, and a Korean version of this book will be available in the near future. This historical work would contribute to record current and future stories of public health in Korea.", "As the primary collection processes began, the Advisory Board Committee, comprised of public health society members from the 1960s to until now, was established to bring thoughts and insights together on defining the value to be presented by the book. Extensive on-line and off-line communications were made, shaping the vision, structure, contents, and the purpose of presenting the book." ] },{ "paper_id": "e4f3286ca688e25cd8917943c36686416005afbe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e4ff00b9e8eec242803472b134846a7dbec01989", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplementary data are available at Genome Biology and Evolution online.", "Sialic acids are a family of more than 50 nine-carbon sugars that are typically found at the terminal ends of N-glycans, Oglycans, and glycosphingolipids that are secreted or attached to the cell membrane. They are involved in recognition processes, frequently serving as ligands for receptor-mediated interactions that enable intercellular or host-pathogen recognition. Sialic acids may also function as a class of \"self-associated molecular patterns\" (SAMPs), whose presence/absence in a species serves as a signal to modulate innate immune responses (Varki 2011) . Sialic acids are found predominantly in deuterostomes (the group including chordates, hemichordates, and echinoderms), being uncommon in other organisms (Warren 1963; Corfield and Schauer 1982; Staudacher et al. 1999; Angata and Varki 2002; Schauer 2004) .", "The most common sialic acids are N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc)." ] },{ "paper_id": "e52ecf4b22e9dcb340ccf67f0251b5a3f9373f02", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The knowledge obtained from this study can contribute to the development of a prevention program and early system warning against MERS-CoV infection.", "All statistical analyses were conducted using SPSS, version 21 (IBM Inc., Armonk, NY, USA). Quantitative and qualitative variables were presented as absolute frequencies, proportions for categorical variables, and interquartile ranges for continuous variables. Independent t-test was used for surveying the mean difference of some quantitative variables by gender. Logistic regression was used to assess the relationship between probable risk factors and outcome (death/survival) of laboratory-confirmed MERS-CoV cases. A P-value of less than 0.05 was considered to indicate statistical significance." ] },{ "paper_id": "e53183332e36bd1da462d867651d2e259d341567", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Les bureaux de sant\u00e9 autonomes remplissent-ils leur mandat mieux que les bureaux qui sont int\u00e9gr\u00e9s aux structures municipales? C' est ce que pensent plusieurs observateurs du syst\u00e8me de sant\u00e9 ontarien, mais cette hypoth\u00e8se se fonde sur bien peu de donn\u00e9es probantes. Cet article vise \u00e0 combler cette lacune en comparant, \u00e0 la lumi\u00e8re de la litt\u00e9rature sur la gouvernance multiniveaux, les d\u00e9cisions de d\u00e9penses de deux bureaux de sant\u00e9 qui fonctionnent selon des structures de gouvernance diff\u00e9rentes. L'\u00e9tude a permis d' observer qu' apr\u00e8s un accroissement", "[72] HEALTHCARE du financement provincial, le comportement du bureau autonome de Middlesex-London \u00e9tait plus conforme aux attentes provinciales que celui des Services de sant\u00e9 publique de Hamilton, un bureau de sant\u00e9 int\u00e9gr\u00e9 \u00e0 la Ville de Hamilton. L' article poursuit en fournissant des explications th\u00e9oriques et empiriques sur la variation au sein des bureaux de sant\u00e9.", "T" ] },{ "paper_id": "e546b975c39f4fd2c5c35fb0320cacc3ded2adac", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e552060ddffa5574e514e54986f35acb95bcc4dc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e58abcf656686d9df482b7b9288a61243ba2eb13", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Virus supernatant (5\u00b5l/well) was added to a 96-well plate along with 1 \u00d7 10 4 HEK293T target cells and 200 \u00b5l total medium per well and incubated as above for 48 hrs. Next, 50 \u00b5l Bright-Glo luciferase reagent (Promega) was added, incubated for 5 min at room temperature and luminescence measured using a GloMax 96 luminometer and Relative Luminescence Units (RLU) per ml (auto-luminescence normalised using cell only control) determined.", "Viral RNA was extracted from allantoic fluid using the QIAmp viral RNA extraction kit (Qiagen). The full haemagglutinin gene was amplified by Titan One Tube RT-PCR (Roche) using custom primers (Invitrogen) binding to the gene termini:", "On the following day the medium was replaced and 1U of exogenous soluble Clostridium perfringens NA (Sigma) was added to facilitate sialic acid cleavage and pseudotype virus egress. Cell culture supernatant was harvested after further 24 hrs, passed through a 0.45 \u00b5m pore sterile syringe filter, aliquoted and stored at -80\u00b0C." ] },{ "paper_id": "e5eaa60c56eee1eab42525423bbd85b4e99453db", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e60a7630d751366b6ea36f9c0b60eed8e20a00f6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "DG is an employee of MSD Wellcome Trust Hilleman Labs Pvt. Ltd, who funded the research.", "ARTICLE HISTORY" ] },{ "paper_id": "e656205a61b48b8617e2ceb45b63b9caf753d2e3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Klenow) and T4 DNA Ligase were from Boehringer Mannheim Biochemicals (Indianapolis, IN). [35Slmethionine, [35S]cysteine, and [35S]sulfate were from Amersham Corp. (Arlington Heights, IL). Trans-[35S]label was from ICN Radiochemicals (Irvine, CA). t25I-ACTH, used as a tracer in the ACTH RIA was obtained from the Metabolic Research Lab at The Univer-", "Materials and Methods", "Synthetic DNA linkers, restriction endonucleases, and polynucleotide kinase were from New England Biolabs (Beverly, MA). DNA polymerase I" ] },{ "paper_id": "e67d4c945d10fe5783c1289f45611cec25143564", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e68ff81b1cbbfd6bb525f60a9efdfacf899dabd5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplementary data are available at http://humrep.oxfordjournals.org/." ] },{ "paper_id": "e695e6821ad966d7e370bc12a7ec162b264eff0e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e6cb0165f7a39a1721da4e100aee26666a5e5c50", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e6d882be4961d1bdd7507b4a29d86b650de0895d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The epidemic curve is shown in Fig. 2 .", "A single, missed case may trigger a huge, nationwide outbreak", "Huge socioeconomic impact with an estimated 8.5 billion US dollars" ] },{ "paper_id": "e6f57228e6eddee590adad7a9b9021146e21c201", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "After necropsy, Gram staining performed on lymph node homogenates was negative. Standard cultures and mycobacterial cultures remained sterile after 15 days and 2 months of incubation of the culture media, respectively.", "Both lungs were diffusely enlarged and red-gray, red-black, and white in color. Numerous small white-brown nodules (approximately 0.5 cm in diameter) were observed along the cut surface (Fig. 3) . No gross abnormalities were detected in the remaining organs.", "Panniculitides are a group of heterogeneous inflammatory diseases involving the subcutaneous fat that are characterized by the development of inflammatory nodules or swelling within subcutaneous tissues. The lower extremities are most frequently affected, and lesions are typically accompanied by systemic symptoms. Despite a wide range of causes, most forms of panniculitis involve the same clinical features." ] },{ "paper_id": "e6fcd7b5c6235d17f46c1721bd8695775f1df236", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e735e236eed867ac5bb27abb3089f7cf9bde28f1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "week-regardless of the kind of alcohol-was defined as the high-risk drinking (Table 1) .", "in the United Kingdom, and 80% in the USA. 16) These rates are much higher than the 15.6% rate in South Korea observed in this study.", "The rates of having a regular doctor in countries with well-established primary care systems, were 88% in Australia, 84% in Canada, 92% in Germany, 100% in the Netherlands, 89% in New Zealand, 89%" ] },{ "paper_id": "e75a5247e38dcdbb6e6a03fca1a920923e62cfe4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e7b8761e03a3ce7edd5c0df23946c4ac8618c708", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To address this issue, we developed a novel detection system that can simultaneously identify 19 of the known diarrhea-causing pathogens in cattle, including viruses, bacteria and protozoa, in a single reaction. Using this system, clinical samples from cattle with diarrhea were evaluated to identify the specific agents causing an individual animal's diarrhea.", "Diarrhea in cattle is a disorder that causes economic loss by decreasing fertility and productivity, including milk production and weight gain [11, 20] . In particular, young calves are strongly affected by diarrhea and may die from malnutrition and dehydration depending on the situations [25] . The United States Department of Agriculture (USDA) reported that 57% of deaths of weaning calves in the US were because of diarrhea (http:// nahms.aphis.usda.gov/dairy/index.htm). Although the cattle industry has taken measures to prevent diarrhea, such as improvements in hygiene and feeding management, it still occurs throughout the world [5] .", "In this study, we describe the development and validation of a novel tool for differential diagnosis of infectious diarrhea in cattle. Dembo-PCR has the advantage of being able to detect known and unknown diarrheal pathogens. This system will be a powerful tool for rapidly diagnosing the causes of this nuisance disease." ] },{ "paper_id": "e7fbca71f16c3fbb78d754c95f24f58afc944c68", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Raw data can be retrieved from the Github repository https://github.com/ CSSEGISandData/COVID-19", "The ARIMA model includes autoregressive (AR) model, moving average (MA) model, and seasonal autoregressive integrated moving average (SARIMA) model [2] . The Augmented Dickey-Fuller (ADF) [3] unit-root test helps in estimating whether the time series is stationary. Log transformation and differences are the preferred approaches to stabilize the time series [4] . Seasonal and nonseasonal differences were used to stabilize the term trend and periodicity.", "\u00a9 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/)." ] },{ "paper_id": "e8c88bae765a67eb93e119820caa702994e13c1d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Diagnoses: Pulmonary computed tomography indicated diffuse interstitial fibrosis in both lungs. All tests for possible infectious pathologies provided negative results.", "ILD is a lung disorder that can be caused by several substances, radiotherapy, or other diseases. [2] It is a progressive disease that can prove fatal, and early recognition is essential. In the case reported here, other possible pathogeneses such as tuberculosis, CMV infection, EBV infection, M pneumoniae infection, rubella, toxoplasmosis, and HSV were ruled out before prednisone treatment initiation. Tests for rheumatism also showed negative results, and peripheral eosinophils accounted for 1.3% of all WBCs; these findings excluded an immune allergic mechanism." ] },{ "paper_id": "e8d81153777e9f92cbc2bc9ea03ed1f0d0b78543", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Viruses in the genus Betacoronavirus include pathogens that cause emerging pandemic diseases, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), in humans. It has been suggested that bats are major reservoirs for these zoonotic pathogens [9] . This justifies surveillance for coronaviruses (CoVs) in bats throughout the world. In Japan, CoVs belonging to the genus Alphacoronavirus have been detected in intestinal and fecal specimens of Eastern bent-winged bats (Miniopterus fuliginosus) in Wakayama Prefecture [8] . Here, we report the first demonstration of group B betacoronaviruses in little Japanese horseshoe bats (Rhinolophus cornutus) in Iwate Prefecture, Japan.", "We report group B Betacoronavirus infection in little Japanese horseshoe bats in Iwate prefecture. We then used reversetranscription PCR to look for the coronavirus RNA-dependent RNA polymerase gene in fecal samples collected from 27 little Japanese horseshoe bats and found eight were provisionally positive. We had a success in the nucleotide sequencing of six of the eight positive samples and compared them with those of authentic coronaviruses. We found that these six samples were positive in coronavirus infection, and they belonged to the group B Betacornavirus by phylogenetic analysis. Virus isolation using the Vero cell culture was unsuccessful. Pathogenic trait of these bat coronaviruses remained unexplored.", "Our results indicate that betacoronaviruses closely related to SARS CoV were prevalent among little Japanese horseshoe bats in Iwate Prefecture, Japan. Currently, pathogenic trait of these betacoronaviruses is unknown. Although there is no evidence of human infection by these bat CoVs, the existence of group B betacoronaviruses in bats may be predictive of the emergence of a disease, such as SARS, since the Isari cave is also used as a den for civets, which is another potential intermediate species. During this study, we marked the bats with aluminum bands to identify them for further investigation of their habitat. This may provide further information, so we can achieve a better understanding of the relationship between rhinolophid bat behavior and betacoronavirus ecology in the future." ] },{ "paper_id": "e8f1edfb8249017f774ccc05dea2ab17be144313", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis was performed with Prism 6.0 software (GraphPad). An unpaired two-tailed t-test with a 95% confidence interval was used for calculation of P values. Group sizes, reproducibility, and P values for each experiment are given in the figure legends.", "For packaging of pseudolentiviruses, HEK 293FT cells were transfected with lentiCRISPR v2, psPAX2 (packaging vector), and pMD2.G (envelope-expressing vector). After 48 h, the supernatants were harvested and stored at \u221280 o C. The 48 h supernatants were used for further knock-out experiments." ] },{ "paper_id": "e9457327ddb51cf3ceb3698660ff08f526a09d44", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "severe-type changed to common-type; critical-type changed to severe-or common-type. , creatinine and albumin), infection indices (procalcitonin and C-reactive protein), D-dimer, and partial pressure of oxygen.", "SPSS software version 25.0 (SPSS Inc., Chicago, Illinois, USA) was used for statistical analysis. A two-sided P < 0.05 was considered statistically significant.", "None. Extracorporeal membrane oxygenation; qd: every day; iv: intravenously. ", "Therefore, respiratory indices should be one of the top priorities in the efficacy evaluation." ] },{ "paper_id": "e95276ff8455b1bb0a87994f9db6ca3a9c884399", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Pneumonia is the third most frequent cause of death in Japan.", "CRs.", "A retrospective assessment of CRs was conducted to compare chest computed tomography (CT) images of patients admitted to Kesennuma City Motoyoshi Municipal Hospital who were diagnosed with pneumonia from Results: Eighty-three patients were included, and their average age was 83.8 years. Sixtyeight patients (81.9%) were officially certified as requiring long-term care or support." ] },{ "paper_id": "e9624e13395487f67a1beb7c42f952e1f0b475bb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This case highlights the need for thorough metabolic evaluation in patients presenting with neurological signs.", "ORCID iD Patricia L Newton https://orcid.org/0000-0002-0378-4416" ] },{ "paper_id": "e984059fedde6d22ac47555e59c76449a5d8a589", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The lamin B receptor (LBR) is a polytopic 1. Abbreviations used/n th/spaper: LBR, lamin B receptor; NLS, nuclear localization signal.", "All recombinant plasmids were analyzed by restriction analysis. Plasmids in which PCR was used to generate coding sequences were also analyzed by DNA sequencing performed on a Model 373A Automated Sequencer (Applied Biosystems, Inc., Foster City, CA) at The Mount Sinai School of Medicine DNA Core Facility (New York,.", "Unless otherwise indicated, routine chemical re.agents were obtained from either Sigma Chemical Co. (St. Louis, MO) or Fisher Scientific (Pittsburgh, PA). Restriction enzymes, restriction enzyme buffers and DNA ligase were obtained from New England Biolabs (Beverly, MA). FBS was obtained from JRH Bioscienccs (Lencxa, KS). Other media and reagents for cell culture were obtained from either GIBCO BRL (Gaithcrsburg, MD) or Mediatech (Washington, DC)." ] },{ "paper_id": "e9ec6a0a861b00f2ead5addb565a7187163a3c07", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ea08d7bb1c95436e9ed7af4ed5419cc8fc56e7b7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ea5d20e07d05c8b241f90e6429f3daaacc844ecd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Electron microscopy. All the EM data (2-D and 3-D) were acquired in a FEI Tecnai12 BioTWIN electron microscope operating at 120 kV and equipped with an Eagle 4k cooled slow-scan charge-couple device (CCD) camera (FEI Company), using binning mode 2." ] },{ "paper_id": "ea6c3d35646adfcd7e1c55d7d1f0998ba1107d89", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Spot Picking, Protein Processing, and MS-Selected protein spots were cut from the gel using the Investigator ProPic automated 2D spot picking robot and digested with trypsin using the ProGest automated digestion unit (both from PerkinElmer Life Sciences).", "Data were analyzed using the MASCOT 1.9 search engine (Matrix Science) to search against the human (148,148 sequences) MSDB protein database (Release 20063108). Search parameters allowed for one missed tryptic cleavage site, the carbamidomethylation of cysteine, and the possible oxidation of methionine; precursor ion mass tolerance was 150 ppm, and fragment ion mass tolerance was 0.25 Da. All identified proteins have a MASCOT score greater than 64 (the default MASCOT threshold for such searches), corresponding to a statistically significant (p \u03fd 0.05) confident identification.", "been suggested that this protein may inhibit cap-dependent translation while promoting internal ribosome entry site-mediated translation (43) . This too may be significant because at later times in infection adenovirus makes use of a ribosome shunting method to promote the translation of its structural proteins at the expense of cellular mRNA translation (61) . In a similar vein, ribosome assembly is regulated by eIF6, and it too may be used by adenoviruses to maximize the suitability of the infected cell for viral protein expression (41, 62) ." ] },{ "paper_id": "eac8ac161c5889bb47d90400f3bc2fb1ab32f3ff", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "On physical examination, a body weight of 4.4 kg, body temperature of 39.0\u00b0C, heart rate of 180/min, and rhonchi lung sounds (respiratory rate: 30/min) were observed. A complete blood cell count revealed neutropenia (Table 1) . The general chemical profile", "ACKNOWLEDGMENTS. The authors would like to thank Japan Clinical Laboratories, Inc. for culture of clinical specimens and providing advice on diagnosis NTM infection. And the authors would like to thank Drs Tomotada Iwamoto (Kobe Institute of Health) and Kaoru Umeda (Osaka Institute of Public Health) for helpful advice." ] },{ "paper_id": "eaeab732c9c3e204526d8e1ea34cf40e7f37731f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The study protocol was reviewed and approved by the University of Pennsylvania Institutional Animal Care and Use Committee and informed owner consent was obtained.", "Sex (F/M) 10/8 9/6 .62", "Age (years) 8 (6.8-10) 12 (11) (12) (13) (14) .0001", "A biotin-free polymeric IHC detection system consisting of horseradish peroxidase conjugated anti-rabbit IgG then was applied for 25 minutes at RT. Finally, slides were counterstained in hematoxylin, scanned (Leica Aperio Versa slide scanner, Leica Biosystems, Buffalo Grove, Illinois), and images acquired (ImageScope, Leica Biosystems, Buffalo Grove, Illinois). Additional details regarding IHC methods can be found in the Supporting Information." ] },{ "paper_id": "eb136cf532bef626a3f5d4d32fef88e7b43ef3fb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Selected XZAP II clones were subcloned into M13 and sequenced by the dideoxy\" chain termination method (43) using deoxyinosine triphosphate in place of dGTP and Sequenase (United States Biochemical) as described by the manufacturer. Sequence data were obtained from successive deletions in M13 using T4 polymerase (Cyclone Biosystem, International Biotechnologies Inc., New Haven, CT) or using synthetic oligonucleotide primers. Oligonucleotides were synthesized on an Applied Biosystems (model 380B) DNA synthesizer.", "R", "ce'Pr:~:C\"sWeeftec~:\"c.Wr\"r~~ar \"\"sr; Computer Methods DNA sequence data was assembled into a contiguous sequence database by the method of Staden (49) . Sequence comparisons against the GenBank or GenPept sequence databases were performed using the FASTA program (39) . Statistical analysis of sequence similarity between two protein sequences was determined using the Bestfit program of the University of Wisconsin Genetics Computer Group (version 6.2) or the sequence similarity investigation program (DIAGON) of Staden (49) ." ] },{ "paper_id": "eb5476698f1fd39bed192f7ec8211953f78537b3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "hours. Following centrifugation gradients were displaced with 60% sucrose solution through a flow cell recording absorbance at 254 nM." ] },{ "paper_id": "eb627ab77c71445ccc0b05f2193fe9289ac142ee", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Computational/mathematical approaches, such as structural bioinformatics [1] , structural class prediction [2, 3] , molecular docking [4] [5] [6] [7] [8] [9] , molecular packing [10, 11] , pharmacophore modelling [12] , Mote Carlo simulated annealing approach [13] , diffusion-controlled reaction simulation [14] , graph/diagram approach [15] [16] [17] [18] [19] [20] [21] , bio-macromolecular internal collective motion simulation [22] , QSAR [23] [24] [25] , protein subcellular location prediction [26] [27] [28] [29] [30] , protein structural class prediction [31, 32] , identification of membrane proteins and their types [33] , identification of enzymes and their functional classes [34] , identification of proteases and their types [35] , protein cleavage site prediction [36] [37] [38] , and signal peptide prediction [39, 40] can timely provide very useful information and insights for both basic research and drug design and hence are widely welcome by science community.", "FM = n _ ss n _ ss + n _ sd n _ ss n _ ss + n _ ds (4) where M = n _ ss + n _ sd + n _ ds + n _ dd .", "NNput" ] },{ "paper_id": "eb7432cee2519eefd1a6672e1f0bc483c9527a8d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Journal homepage: http://www.kcdcphrp.org", "A web scraping method has recently been developed and data mining is actively used to collect and analyze large-scale web documents automatically [8] . This is enabled by many open-source libraries available for data mining where it is possible to analyze big data with only a small amount of coding necessary.", "The data were preprocessed in 4 steps. In Step 1, a basic dictionary for extracting Korean words was selected. In this study, the Hangul morpheme dictionary (NIADic) provided by the National Information Society Agency (https://www.nia." ] },{ "paper_id": "eb828bb9f9c3a58b135f382517a9ebbe65fa6fc6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "eb93befc89c6e31c873386d95150e87dfd849e73", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "eb9c9eb7292778494ca76eccd9f5646139d026de", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ebc7bbdf4d1954bd8575aa830977118cc1990759", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Autoclaves were the most common method used for sterilization (77.8%), followed by ultraviolet sterilizers (54.5%), automatic cleaners (21.2%), ultrasonic cleaners (4.5%), and other methods (17.9%). A separate space for the disposal of infectious waste was infrequently available (10.1%).", "The results of the multiple regression analysis are presented in Supplemental Table 1 . The regression model for resources showed good fit, with R-squared and adjusted R-squared val- ues of 0.115 and 0.106, respectively. The Durbin-Watson statistic was 1.515 in a model summary, and the regression model showed a value of p<0.001 in a one-way ANOVA table. The regression model for activities likewise showed good fit, with R-", "During the Middle East Respiratory Syndrome (MERS) outbreak in the Republic of Korea (hereafter Korea) from May to July 2015, two emergency medical personnel were infected with MERS, among a total of 39 healthcare workers who developed MERS occupationally [1] .", "A cross-sectional survey was conducted in five representative large metropolitan cities in the Korea. This study used a self-reported anonymous questionnaire. Completion of the survey took approximately 15 minutes." ] },{ "paper_id": "ebfc471829e1303889bd23779d1c2ffb9467ab7e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Continuous data are expressed as medians and ranges since they were non-normally distributed (the data was checked for normality of distribution by Kolmogorov-Smirnov test), and categorical data are presented as counts and percentages.", "None.", "Chinese Medical Journal 2020;Vol(No) www.cmj.org" ] },{ "paper_id": "ebfe84418eef9017bbf2bdb93d8bebdb3eef8eac", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ec0a48de352326aecc319e76ea1f47b989ffcd8f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Virus . Wild type murine coronavirus JHM stock virus was isolated and cloned as previously described (3)." ] },{ "paper_id": "ec53f9de631ca4386bc32b0947afc297418480f8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ec66e69291414e8f29b5db27eecbc8e9cdcf2c20", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Citation Al-Mulla HMN, Turrell L, Smith NM, Payne L, Baliji S, Z\u00fcst R, Thiel V, Baker SC, Siddell SG, Neuman BW. 2014. Competitive fitness in coronaviruses is not correlated with size or number of double-membrane vesicles under reduced-temperature growth conditions. mBio 5(2):e01107-13.", "The results of a stop/resume assay for Brts105 are shown in Fig. 2E and were typical of the mild phenotype. Stop/resume assays were performed at least twice, with three replicates per time point. Results for other viruses are summarized in Fig. 2F . Brts105, Brts31, and Albts16 displayed mild ts phenotypes. This was consistent with the previously described mild ts phenotype of Albts16 (23) . The ts phenotype of Albts22 was found to be severe, as pre- viously reported (23) , and was equivalent in severity to treatment with cycloheximide, which blocks translation and has been shown to result in inactivation of replicase components in about 1 h (23, 35, 36) ." ] },{ "paper_id": "ecbdaacec058ed09ad1fc9b930fdb70e77b62f19", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Conducting animal studies in a BSL-4 facility 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, limits the power of statistical analyses. Consequently, data are presented as the mean calculated from replicate samples, not replicate assays, and error bars represent the standard deviation across replicates.", "Supplementary materials are available at http://jid.oxfordjournals.org. 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.", "Animal studies were completed under biosafety level 4 (BSL-4) biocontainment at the Galveston National Laboratory and were approved by the UTMB Institutional Laboratory Animal Care and Use Committee, in accordance with state and federal statutes and regulations relating to experiments involving animals, and by the UTMB Institutional Biosafety Committee.", "Complete blood counts, coagulation dynamics, and serum blood chemical analyses were performed on blood, serum, or plasma specimens obtained from each experimental animal. Analysis of tumor necrosis factor \u03b1 (TNF-\u03b1), nitrite (a marker for nitric oxide production), and coagulation parameters measured in serum or plasma specimens was also performed as detailed in the Supplementary Methods." ] },{ "paper_id": "ecd341e70316d124587fb8370d949fbf5524bd2f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Viral titer was detected as described . Briefly, mouse lung tissues were homogenized in DMEM plus antibiotics to achieve 10% (w/v) suspensions, which were then titrated on monolayers of Vero cells in quadruplicate. The CPE was observed daily under phase-contrast microscopy for 3 days. The viral titer was calculated by the Reed-Muench method and expressed as log 10 TCID 50 /g of tissue.", "Statistical analyses were performed using GraphPad Prism version 5.01. The significance between survival curves was analyzed by Kaplan-Meier survival analysis with a log-rank test. Other data were analyzed using the 2-tailed unpaired t-test with Welch's correction. p < 0.05 was considered significant. ", "Refer to Web version on PubMed Central for supplementary material.", "Animal studies were performed in strict accordance with the recommendations of the Guide for the Care and Use of Laboratory Animals. The animal protocol was approved by the IACUC of the Laboratory Animal Center, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology (Permit number, BIME 2015-0023). All procedures involving MERS-CoV were carried out in an approved biosafety level 3 facility." ] },{ "paper_id": "ecf580f9baf30b1e7c860068c834f34d175dbda0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ed21f99a11ebb65e8c3a6fb8d00b7141011916b0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "occurring in infancy and childhood (4, 5) . These developments and changes highlight the demand for undergraduate and postgraduate medical education in Paediatric Virology, which combines Paediatrics with Virology, Epidemiology, Molecular Medicine, Evidence-based Medicine, clinical Governance, Quality Improvement, and Pharmacology and Immunology (5) .", "Non-vaccinated children will continue to be affected by paediatric HPV-associated diseases and vaccinated children by HPV types not covered by vaccination. Increasing vaccine coverage may reduce HPV prevalence not only for anogenital infections, but also oral infections. However, vaccination programmes continue to face challenges, in part due to parental fears regarding vaccine safety (58) . Large population-based studies have confirmed vaccine safety (59) . Educational efforts regarding the importance of HPV vaccination and the vaccine's efficacy and safety profile are necessary to achieve higher vaccination coverage.", "HPV, human papilloma virus." ] },{ "paper_id": "ed3dae51cc8af4b99b820ce4eaf28f9c9995b060", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ed52c50fb3ff01140790f21c6e9716a8cd3c9fa8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analyses were performed using Prism 6 software and the P-values were calculated using two-tailed t-tests.", "Circular Dichroic (CD) spectra were recorded on a JASCO J-1500 spectrometer (Jasco Inc. Easton, MD, USA), as previously described (42) . Briefly, oligonucleotides (Table 1) were diluted to a final concentration of 5 M in Sodium cacodylate buffer (10 mM, pH 7.4) without or with KCl (100 mM). Circularly polarized UV light was used to record CD spectra on a progressive scan from 320 to 200 nm in a quartz cell of 10 mm optical path length. An average of six progressive scans for each sample were recorded for each oligonucleotide.", "Supplementary Data are available at NAR Online." ] },{ "paper_id": "ed610e3cb3696b2a25490d26ad19a1ef8229663d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All experiments with prokaryotic translation components, including kinetic measurements summarized in Supplementary Table S1 , were carried out in HiFi buffer (50 mM Tris-HCl, pH 7.5, 70 mM NH 4 Cl, 30 mM KCl, 3.5 mM MgCl 2 , 8 mM putrescine, 0.5 mM spermidine, 1 mM 1,4dithiothreitol (DTT)) at 37 \u2022 C if not stated otherwise.", "fined at the translocation step, because the partitioning between 0-and -1-frames takes place before decoding by Glyand Arg-tRNAs ( Figure 1E ). The ratio of the rate constants of Gly and Arg incorporation (0.53 and 0.04 s \u22121 , respectively; Supplementary Table S1) gives the -1FS efficiency after Leu incorporation.", "To understand the kinetic switch between the two different -1FS regimes, we monitored translation and -1FS efficiency using the codon-walk approach (56) in the absence and presence of Leu-tRNA NAA Leu . Rate constants were calculated by global fitting of the time courses using numerical integration according to the models shown in Figure 3 . As additional information, we estimated the rate constants of Arg and Gly incorporation in independent experiments using model mRNAs without frameshifting elements (Supplementary Figure S3B and C) ." ] },{ "paper_id": "ed6b1dc674893e435945a5efbd1eef13a7c56bc1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Keywords adenovirus, feed-safety, porcine epidemic diarrhoea virus, porcine sapelo virus 1, spray-dried porcine plasma, thermal and physical inactivation.", "Correspondence Marcel M. Hulst,", "1931" ] },{ "paper_id": "ed836dbe62d537006fc207428b489d208836a949", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Retrovirus Moloney murine leukemia virus (M-MuLV) matures by budding at the cell surface.", "Taken together these BFA-, monensin-and 20\u00b0C block results strongly suggested that Pr65 gag that is released from cells does not initially associate with internal membranes, but instead is directly inserted into the plasma membrane." ] },{ "paper_id": "ed94f0bd0fe17c099f8cdff4bf9edbbd29ebf41f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The generated MEV models were further refined by ModRefiner and GalaxyRefin. 60, 70 GalaxyRefine performs repeated structure perturbation along with subsequent structural relaxation by dynamics simulation to refine a protein structure.", "For vaccine development, proteins critically involved in virus-host cell interaction, viral proliferation, and host cell disruption were chosen. Thirteen proteins of MERS-CoV proteome chosen for epitope screening included the following: S glycoprotein; E protein; N protein; M protein; ORFs (ORF3, ORF4a, ORF4b, and ORF5); ORF1a (4P16), a papain-like protease (PL(pro)); ORF1a (4RSP), a protease ", "To avoid breaks in model structures, GalaxyRefine uses the triaxial loop closure method.", "\"Natural Peptides Module for Beginners\" module of the PEPstrMOD tool (http://osddlinux.osdd.net/raghava/ pepstrmod/nat_ss.php) was used to generate tertiary structures of the selected epitopes. 44 Prediction was carried out with a simulation time window of 100 ps, and the peptide environment was set to vacuum." ] },{ "paper_id": "ed9bd29d43d2781618f8c3133dd85492af8960ce", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Reporting key issues by quarter 1st quarter ", "Background A/H1N1, more commonly referred to as swine flu, emerged in Mexico in spring 2009. It rapidly spread across the world and was classed as a global pandemic on 11 June 2009. Objective To analyse UK newsprint coverage of the swine flu pandemic. Methods Content analysis of 2374 newsprint articles published in eight UK national newspapers between 1", "Despite predictions, the second peak in cases in the UK as the 'normal' flu season came around failed to exceed the first peak, and as many cases also proved to be mild, swine flu was no longer front page news. Its perceived threat may have reduced as many people experienced swine flu for themselves with few adverse consequences, and the drop-off in reporting may itself have acted to reassure people. However, during this period newspaper reports continued to mention UK deaths, and articles gave greater attention to identifying those at most risk. This coincided with the introduction of the swine flu vaccination programme targeting those at highest risk. However, throughout the period there was little attention paid to vaccine development or vaccine safety, suggesting again that the concerns about vaccine safety which were so prominent in the MMR controversy 12 have not been projected forward onto reporting of newer vaccines.", "To develop a coding frame, a random selection of 100 articles were read through to identify the key discourses around A/ H1N1. These discourses became thematic categories in an initial coding frame. Using the principles of grounded theory, further batches of 20 articles were read and coded until no new categories emerged from the newspaper articles. At this point we assessed that we had reached 'saturation' and had identified all the relevant thematic categories. 20 The coding of the articles was carried out over a five-week period by five coders who worked together in close collaboration with the first author, checking and validating each others' coding. The coding framework recorded the publication, date, page, word count, newspaper section, and whether there was any reference to 44 thematic categories. The tone of the headline was also rated, because headlines are used to anchor and encapsulate what the journalist/editor defines as the most newsworthy aspect of the story and its main trajectory. 21 Headlines, and the overall tone of the article, were separately rated as 'alarmist', 'reassuring' or 'neither': 'alarmist' headlines were those that were judged as potentially able to cause the reader anxiety; 'reassuring' headlines were judged to be potentially able to allay the reader's fears. The remaining headlines tended to be factual and use bland language. To test the inter-rater reliability of all aspects of coding, just over 10% (n\u00bc250) of the 2374 articles were double coded by SH independently of the coders. Using Cohen's k coefficient we found an inter-rater agreement of k\u00bc0.62. This corresponds to a substantial level of agreement." ] },{ "paper_id": "ee106840a4b1667303e4b84d25795de3617bd7ef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ee254e8dd94c816c9b5cd80c56b4b7e07eb5aa03", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CoVs (range \u00bc 1,200-6,000 CoVs), most of which have yet to be described.", "Supplementary data are available at Virus Evolution online.", "Conflict of interest: None declared." ] },{ "paper_id": "ee4e69f64556d94a481199be5f3b517f1de5d947", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "eea1eb720701f6b9dbb08915e800964d963a933e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "eec44b63232c7b965ed908e716003135f358ab57", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Helminth coinfections may strongly affect human condition. For example, concomitant schistosome, hookworm and whipworm infections increase the severity of anaemia in children (27) .", "To summarise, laboratory, clinical or theoretical models regularly stressed negative impacts of multi-infection on hosts.", "(3) The integration of immunity in disease ecology. New methodologies and concepts in immuno-ecology have revolutionised the way host\u00c1parasite interactions are investigated. The difficulty to disentangle immune responses facing multiparasitism in an ecological context will be only resolved by field manipulation.", "(1) The monitoring of complete parasite communities in host individuals or populations, which can be realised thanks to new fast-improving technologies such as high-throughput sequencing approaches (103) . (2) The re-foundation of community ecology of parasitism in the light of polyparasitism-related impacts in order to re-analyse patterns observed in so many studies, to infer new testable hypotheses based on likely processes and potentially to establish some laws." ] },{ "paper_id": "eed4463e9a2c736a3e76c379689d2aca6247981e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ef1efc8936a33b9ffb3a691071a4372f9ee173f6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ef6dbb94ddc618e006e993f32893043b9fa87463", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Generally, dual infections were predominant in CIRDC suffering dogs (42.2%), followed by single (28.4%) and triple (22.6%) infections. With regards to the sampling site, the frequency of positive results was not statistically different between the OS and NS sampling sites (P>0.05).", "After taking the NS and OS using sterile rayon tipped applicators (Puritan \u00ae , Guifolrd, ME, U.S.A.), the swabs were immersed in 1% phosphate buffer saline (PBS) and kept at \u221280\u00b0C until assayed. The study protocol was approved by Chulalongkorn University Animal Care and Use Committee (No. 1431005).", "The 51 dogs with respiratory clinical illness included in this study were 29 males and 22 females. Most of the dogs were puppies (37.3%) or senile (23.5%). Most presented with a nasal discharge (80.4%), coughing (47.1%), loss of appetite (56.9%) and bronchopneumonia (41.2%). Only 29.4% (15/51) of dogs were vaccinated." ] },{ "paper_id": "ef941da966e9e5a3f54360843a1d3aeefd37e598", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To validate the quantification of reads attributed to each variant, the balanced read 1 and 2 BLAST hits were aligned competitively to three reference genomes using the 'Map to Reference Tool' within Geneious.", "A Bioinformatics pipeline was developed to accommodate the large amount of variation found within the DWV species complex. First, the quality of the raw reads was verified using FastQC (Babraham Bioinformatics, Cambridge, UK). Samples were then converted from fastq to fasta using the fastq_to_fasta script that is part of the FASTX-toolkit (Hannon Lab) (http://hannonlab.cshl.edu/fastx_ toolkit/).", "Bioinformatics pipelines designed for eukaryotes and prokaryotes are not necessarily suited to studying viral systems. For example, pipelines incorporating reference assemblers could hinder the discovery of novel virus variants. The genome sequences presented here are representative of the different variants found within a sample; however, the Vicuna pipeline is not suited to analysing the further level of diversity around these variants, for which diversity models are better suited, such as those developed by Wood et al. (2014) .", "Vicuna contigs 4200 bp in length were imported into Geneious (Version 7.04, created by Biomatters, Auckland, New Zealand) and the 'Map to Reference tool' was used to align the contigs with the DWV and VDV-1 reference genomes. For several of the samples the Vicuna assembly yielded full-length contigs that covered the whole genome, whereas for others consensus scaffolds were created from two or more contigs. The ends of the contigs were then trimmed of any assembly or sequencing artefacts." ] },{ "paper_id": "efa709d35a459e7655763486cc6d5ee29aca19a6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Tissue culture RT assays RT assays were performed using the dual luciferase reporter constructs, as previously described (62, 63) . To control for possible differences in stability of specific mRNA sequences, each RT construct was compared with a control construct that was identical except that the TGA stop codon was replaced with a TGG codon. RT efficiencies were calculated as (firefly activity/renilla activity) for the RT sequence normalized by (firefly activity/renilla activity) for the corresponding TGG control sequence. Standard deviations were calculated based on six independent transfections.", "Virus sequences were obtained from GenBank in May 2009, updated in October 2010, and processed using BLAST, EMBOSS and ClustalW (52) (53) (54) . The accession numbers of all sequences used are given in the Supplementary Data. Coding sequences were extracted, translated, aligned with ClustalW and back-translated to nucleotide sequence alignments, and manually adjusted in a few cases. For the synonymous site conservation plots, alignment columns in which the reference sequence ( Figure 4 ) contained gap characters were removed so that the plots are in reference sequence coordinates. RNA structures were predicted using a combination of Vienna RNA RNAfold and alidot, pknotsRG and manual inspection (55, 56) .", "The sequences encompassing the RT site and the predicted 3 0 stem-loop structure for VEEV and SINV were synthesized by GenScript and cloned into the XhoI and BglII sites of pDluc, a derivative of the p2luc vector (61, 62) . The firefly luciferase gene is in the same reading frame relative to the upstream renilla luciferase gene such that RT of the stop codon results in a renilla-firefly luciferase fusion product. Derivative constructs were generated by PCR using appropriate primers and recloning into pDluc. All plasmids were verified by DNA sequencing." ] },{ "paper_id": "efcd4f058d2b435a17c63793904cbf85c899b982", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We carried out enhanced surveillance of norovirus outbreaks from all in-patient wards in five tertiary care hospitals serving two cities in England, with a combined catchment of approximately two million people.", "Harris JP, Lopman BA, Cooper BS, et al. BMJ Open 2013;3:e003060." ] },{ "paper_id": "efd6ea1e3d5223f220c6c09084ac5fb043618b03", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Viral titer assay: Viral titer was measured using 50% tissue culture infective dose (TCID 50 ) assays. Serial 10-fold dilutions of supernatants from the treated and viral samples were added onto a monolayer of bHK-21 cells in 96-well culture plates and incubated for two days. Virus concentrations were measured by direct fluorescent antibody staining (DFA), as described above, and the viral titer for each sample was calculated by the Reed-Muench method [15] .", "The animal research in our study was approved by the Jilin Province Animal Disease Control Center. Statistical analysis: Statistical significance of differences between experimental groups was determined through the use of the paired, nonparametric Student's t-test. P<0.05 was consider a significant difference.", "So, these results provided evidence that rAAV-N796 treatment could inhibit RAbV replication and conferred partial protection against lethal rabies challenge." ] },{ "paper_id": "effcf4c34945a660c3328cead86eeb69e387213d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "METHODS", "upstream of the participant and at the sampling inlet by HC2-CO4 probes and a HygroLog NT data logger (Rotronic AG, Bassersdorf).", "[10]", "Where:" ] },{ "paper_id": "f0599dcb6c670aea2ede76599a9aed614faa92d3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f0813fe3f70fb9a52ec5944b43bdd953a08cc49a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "should abolish the signal's Golgi-retention capabilities. The final two constructs have a section of TGN38, a TGNlocalized protein, encoding the transmembrane domain and C-terminal tail (amino acids 284-340) fused to v-sis. A mutant form was made by truncating the cytoplasmic tail region, and thus uses only amino acids 284-311 of TGN38. This construct should not be retained intracellularly.", "The parental vector contains an XhoI restriction site just upstream of the v-sis coding sequence. For use in transfection and infection of NIH3T3 cells, DNA fragments encoding the above described v-sis-fusion proteins were subcloned as XhoI-ClaI restriction fragments into the murine leukemia virus (MLV) expression vector pMS177, which was derived from the previously described retroviral vector pDD102 (Bold and Donoghue, 1985) ." ] },{ "paper_id": "f084dcc7e442ab282deb97670e1843e347cf1fd5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f0a7684b84d874e9d61eee9c4cff37bb45bb2547", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The images are published under agreement of the patient.", "Myongji Hospital Institutional Review Board (IRB) approved this study (No. IRB 2020-01-027) and written informed consent was given by the patient. ", "We thank to Myongji Hospital staffs for their efforts to cope with COVID-19 and CancerROP Co., Ltd., for providing a test diagnostic kit to measure SARS-CoV-2 virus titers. ", "At that time the initial confirmation of COVID-19 was made by pan-coronavirus conventional polymerase chain reaction assay and sequencing of the polymerase chain reaction (PCR) amplicons using a throat swab." ] },{ "paper_id": "f0c369c6a223586d56037b92314080d4654c7d94", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f0dd1cca2c2cc4ff4f1a37a74ca694382ba9eed4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f0e75f3b4aeda66ce88ca4a58a785c8fdf32b9ab", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f0ec075fb3dafe5c5815a641fc8ae543b30f36fd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "RNA membrane was ultraviolet-crosslinked and blocked in 1\u00b7 PerfectHyb Plus hybridization buffer (Sigma) for 1 h at 70\u00b0C. HIV RNA was detected using PCR-amplified nef fragment originating from nucleotide positions 8475 to 8900 40 of pNL4-3. Amplification was accomplished with the following primer sets: forward primer (anneals upstream of nef and introduces the unique restriction site BamHI CCTAGG) 5\u00a2-GAGACAGAGACAGATCCATTCGATTA GTGAACGGATC-3\u00a2 and reverse primer (anneals downstream of nef and introduces the unique restriction site ClaI TAGCTA) 5\u00a2-GCCATCGATATTGTTAGCTGCTGTATT GCTACTTGTG-3\u00a2.", "Before overnight hybridization, nef probes were radiolabeled with [a-32 P] dCTP using the Rediprime II DNA labeling system (GE Healthcare). Blots were rinsed afterward in wash buffer containing 2\u00b7 saline sodium citrate (SSC) and 0.1% sodium dodecyl sulfate (SDS) for 10 min, thrice, and finally in wash buffer containing 1\u00b7 SSC and 0.1% SDS for 10 min. Radiolabeled RNA membrane was exposed to Bio-Max MS film (Kodak) overnight and developed for detectable RNA fragments. Relative density of each spliced fragment was analyzed using ImageJ software (http://rsbweb .nih.gov/ij).", "ARIZALA ET AL." ] },{ "paper_id": "f12dac6dd672f51fbf89bec56df7f7a8af5331df", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To perform a detailed histopathological analysis of the open lung biopsy specimens from five patients with ARDS with confirmed H1N1.", "Lung specimens underwent microbiologic analysis, and examination by optical and electron microscopy. Immunophenotyping was used to characterize macrophages, natural killer, T and B cells, and expression of cytokines and iNOS.", "BACKGROUND: Cases of H1N1 and other pulmonary infections evolve to acute respiratory failure and death when co-infections or lung injury predominate over the immune response, thus requiring early diagnosis to improve treatment." ] },{ "paper_id": "f17b881cc20dbd7330c1b396037fc872a4ff47ee", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(1) fecal consistency, content and color; (2) defecation frequency (>4 times per day); and (3) intensity (abundant aqueous, mucous, bloody) and duration of diarrhea. 28 Calves with congenital malformations or surgical problems were excluded from the study.", "Animals: Seventy neonatal calves (60 with acute diarrhea and 10 healthy)." ] },{ "paper_id": "f1880ad327af15c85665a90198a7088d32390e34", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The current study has certain limitations. First, evaluation of treatment efficiency mainly depends on a routine body check, MRI examination and patient's interview, lacking precise pathology evidence. Second, we only compared treatment efficiency among 3 different approaches, but did not further analyze any difference between single and combined therapy.", "This is a retrospective study. A total of 44 post-SARS ONFH patients (including 74 femoral joints) were recruited between November 2013 and November 2015. Inclusive criteria: 1) matching diagnostic guideline of ONFH; 10 2) with history of SARS infection; 3) received combined treatment including alendronate, extracorporeal shock wave, and hyperbaric oxygen; and 4) obtained patient's written consents. Exclusive criteria: 1) traumatic ONFH; 2) atypical imaging manifestation or not matching diagnostic guideline; and 3) surgery treatment. This study has been approved by the ethical committee of Tianjin Hospital.", "In our study, the average age of post-SARS ONFH patients was 29.9 years. Due to more daily activity in young people leading to heavy load on hip joints, hip joint surgery in early stages may encounter the risk of resurgery. Stringent challenge may result in patient's psychological, physiological and economic burden once undergoing surgical failure or complications. Some surgeons thus suggested conserving the femoral heads maximally instead of artificial hip joint replacement. Before making a diagnosis based on imaging evidence showing femoral head collapse, conservation treatment mainly aims to recover the function of the hip joint, to alleviate pain, and to block or retard collapse progression for curing necrosis lesion, thus improving prognosis and reducing surgical risks." ] },{ "paper_id": "f1b5cde5a242e912703bae5311866136ef780c9d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Equal numbers of counts (corresponding to approximately one-twentieth of the total lysate) were then prepared for SDS-PAGE on a 10-15 % polyacrylamide gel.", "Cells grown on plastic petri dishes were fixed for 1 h with modified Karnowsky's fixative containing 2% glutaraldehyde. Fixed cultures were postfixed in 2 % osmium tetroxide in 0.1 M cacndylate buffer pH 7.9 for I h and then dehydrated, removed from the dishes with propylene oxide, and embedded in Epon. Thin sections were viewed in PhUips electron microscopes after contrasting with uranyl acetate and lead citrate.", "Coronavirus MHV-A59, propagated on sac-cells as previously described (Tooze et aL, 1984) , was used to infect ART20 cells at a multiplicity of infection of 102-103 pfu/cell. The virus was applied in 1 rrd of culture medium per 35-ram dish for 1-2 h at 37~ in a 5% CO2 incubator." ] },{ "paper_id": "f1ed23f642ae10aad709176ea8025687b34d5c27", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f2286bb839d74a844ed5bd6510eab4137d3920b8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. Categorical and continuous factors were compared using a chi-square and Mann-Whitney tests, respectively, for comparisons between the patient groups. Multivariate analyses to identify the independent factors for RVI and LRI were performed for significant factors in univariate analysis using a binary logistic regression analysis. IBM SPSS Statistics for Windows, version 21.0 (IBM Corp., Armonk, NY, USA) was used for statistical analyses, and statistical significance was defined as a p-value <0.05.", "The rate of RV positivity was highest in autumn; however, no significant differences were found among the four seasons (range, 31.6-61.5%, p=0.258). Seven RSV infections occurred within a one-month interval in the same ward, six (85.7%) of which were hospitalacquired infection." ] },{ "paper_id": "f24242580be243d5fc3f432915d86af6854bb8b7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The timing and location of the outbreak facilitated the rapid transmission of the virus within a highly mobile population. The initial reporting of observed cases occurred during the traditional Chinese New Year, when the largest population movement takes place every year (Ai et al., 2020) . Further, Wuhan is a highly populated city with more than 11 million residents and is connected to many cities in China through public transportation, such as buses, trains, and flights (Lai et al., 2020; Read, Bridgen, Cummings, Ho, & Jewell, 2020) . In the absence of pharmaceutical interventions, rapid action was required by the Chinese government to mitigate transmission within and outside of Wuhan.", "Not applicable.", "Data will be made available in an online repository upon acceptance of manuscript. " ] },{ "paper_id": "f245596ffe228f1eb183e60f02428bf156bea645", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Reverse transcription (RT). Viral RNA was subjected to reverse transcription using a First Strand cDNA synthesis kit (Thermo Fisher Scientific, Germany) according to the manufacturer's instructions.", "The authors declare that there is no conflict of interests regarding the publication of this article. ", "Isolations of genotype C were in China, South Korea, and Japan. In addition, all three genotypes have been reported in Argentina (23) ." ] },{ "paper_id": "f2659697647ee6bef684444c4bc46b433b51ef76", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f266600e61a8c0fbceb48929b7250a9f16771c9f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f2948dc01fd28774bb06b6c6995bec2a2f466f2a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Word count: Main Text word count: 3393;", "Data were collected from April to September 2015. A research team comprising ten trained researchers and postgraduate students from Harbin Medical University visited the selected households. Verbal informed consent was obtained prior to the survey. One adult member from each household was interviewed. The questionnaire was administered anonymously, which took about 20 minutes to complete. Of the 3,650 invited households, 3,580 (98.1%) completed the questionnaire survey. The final data analyses included 3,541 (98.9%) questionnaires that contained no missing values.", "No additional data are available." ] },{ "paper_id": "f2b1074882bd3bdb8794c79fb4ab6fb72fbbf2ee", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f2e2f923e6fad608a3d34daf4f0ccaa0e4507c44", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Spontaneous pneumomediastinum is caused by elevated intra-alveolar pressures that trigger alveolar rupture which often leads to subcutaneous emphysema [1] . A case of spontaneous pneumomediastinum and subcutaneous emphysema in a 79-year-old gentleman with pneumonia but no pre-existing lung disease is presented. This case highlights spontaneous pneumomediastinum as a rare complication of pneumonia.", "LEARNING POINTS \u2022 Pneumomediastinum and subcutaneous emphysema are rare complications of pneumonia. \u2022 Computerised tomography is a valuable diagnostic tool for identifying pneumomediastinum in patients with subcutaneous emphysema. \u2022 While pneumomediastinum is typically a benign condition, aggressive management may occasionally be required. Evidence regarding use of non-invasive/invasive ventilation remains limited but it may theoretically aggravate any air leakage." ] },{ "paper_id": "f318f417880d9beb2ce5c8444f3597a8808eae30", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data are mean \u00b1 SD of at least three replicates. The expression of the \u03b1-1,2-mannosidase levels were compared between groups using the Student t test. Statistical analysis was performed using SPSS software. Differences were considered statistically significant at a value of P < 0.05." ] },{ "paper_id": "f342d276133084c4e742dfa29ee97481fc03e7f7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Thus, by two independent assays, 5 mM DTT does not appear to significantly affect the assembly of the IMV.", "These data show that disulfide bonding occurs posttranslationally, adding further support to the evidence that they do not arise from artifactual post-lysis oxidation.", "Negative staining EM after immunolabeling of the particles isolated from nontreated or DTT-treated cells was performed as described (13)." ] },{ "paper_id": "f3469557b37bfea7f3aebded4172020ad1d6e484", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Fatty acid methyl esters were analyzed by gas chromatography using a fully automated HP5890 system (Agilent) equipped with a flame-ionization detector. GC conditions: column SP-2560 (Supelco) 100 m\uf0b40.25 mm \uf0b40.20 \uf06dm. Oven 140\uf0b0C for 5 min, 10\uf0b0C/min to 220\uf0b0C, hold 50 min. Injector/Detector 260\uf0b0C carrier gas helium at about 5 psi. Identification of components was done by comparison of retention times with those of authentic standards (Sigma-Aldrich, MO, USA).", "The cell cycle change before and after transfection was analyzed using Flow CytoMeter, Propidium Iodide approach (PI) according to the manufacturer's protocol (Lecoeur, 2002) .", "All paired comparisons were subjected to two tailed Student t test with p<0.05 considered statistically significant." ] },{ "paper_id": "f3725ca2fdaeaaf188c63878e4c6263408e52aa2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All patients received a combination of 80 mg of sulfametoxazol and 400 mg of trimetoprim thrice weekly to prevent Pneumocystis jirovecii infection. Patients seropositive for CMV at the pretransplant evaluation were given valganciclovir at a dose of 900 mg daily for 3 months. Patients seronegative for CMV pretransplant while the organ donor tested positive (ie, CMV mismatches) were given the same treatment for 6 months.", "The study was approved by the Regional Ethical Review Board in Gothenburg (DNR: 791-08), and all subjects provided written and oral consent to participate.", "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.", "TTV load was quantified on the QX200 Droplet Digital PCR system using the ddPCR supermix for probes (No dUTP; Bio-Rad, Hercules, CA). Primer and probe concentrations in the 20-\u00b5L final reaction were 300 and 200 nM, respectively. The PCR conditions were 50\u00b0C for 2 minutes followed by 95\u00b0C for 10 minutes, then 30 seconds at 95\u00b0C and 1 minute at 58\u00b0C for a total of 40 cycles, and finally a step at 98\u00b0C for 10 minutes. After overnight incubation at 4\u00b0C, the droplet fluorescence signal was determined. Data analysis was done using Bio-Rad Quanta Soft analysis software." ] },{ "paper_id": "f37e28d5d912f4361695c361f5400b0045b88005", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As T-bet imposes repression of CD103, the downregulation of T-bet reciprocally leads to the expression of integrin aEb7.", "This review will focus primarily on influenza and parainfluenza virus infections and discuss recent insights into the course of CD8 + T RM cell establishment in the lung interstitium/ parenchyma and airways, from initial priming, to tissue migration, local differentiation, and maintenance.", "It is well established that effector CD8 + T cells recruited to the lung subsequently encounter respiratory DC subsets that present cognate antigen. This ''second hit'' with cognate antigen at the site of infection improves the cell capacity to secrete IFN-c (88) and induces additional rounds of proliferation (87) . In addition to stimulating the CD8 + T cells, respiratory DCs trans-present IL-15 to prevent rapid apoptosis of the cells (89) . While these antigen stimulation processes regulate terminal effector differentiation, several studies have indicated that local antigen recognition also serves as a primary tissue-derived instructive factor requisite for effective T RM differentiation (9, 59, 90, 97, 123, 133) .", "It is well known that sphingosine 1-phosphate (S1P) plays a key role in the egress of lymphocytes from the lymph nodes and thymus (4, 86) , and recent studies indicate that this is also the case for the nonlymphoid tissues (71, 78, 115, 123) . S1P is present at high levels in the blood and lymph, which results in the continuous downregulation of its receptor S1P receptor-1 (S1P 1 ) on circulating T cells (102, 110) . Upon tissue entry, CD8 + T cells instantly recover surface expression of S1P 1 due to the relatively low concentration of S1P in the parenchymal tissues (15) and are thereby subjected to opposite chemotaxis toward the lymphatics (78, 115) . Hence, a balance between the S1P-mediated exit signal and the chemokine-mediated migratory signals controls the direction of T cell migration, which potentially reflects the differential dynamics between T EM and T RM cells within the peripheral tissues." ] },{ "paper_id": "f39b51bbd9ece044b1af4f83b6ff05053810e7d9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "FCS was from Atlanta Biologicals (Norcross, GA); fumonisin B1 was from Calbiochem (La Jolla, CA); chromatography plates were from E. Merck (Darmstadt, Germany); endoglycosidase H (endo H) from New England Biolabs (Beverly, MA); N -hexanoylsphingosine (C 6 Cer), lipid standards, and PDMP were from Matreya (Pleasant Gap, PA); [ 3 H]palmitate (50 Ci/mmol) was from DuPont-NEN (Wilmington, DE); Pro-Mix ( \u03fe 1,000 mCi/mmol [ 35 S]methionine) was from Amersham Intl. (Arlington Heights, IL); DME, tissue culture-grade trypsin, and penicillin-streptomycin were from GIBCO BRL (Gaithersburg, MD); all other reagents were from Sigma Chemical Co. (St. Louis, MO).", "Cell Culture. Tissue culture cells were grown in DME supplemented with 5% (BHK-21) or 10% (Vero) FCS. Cells were grown at 37 \u040a C in an atmosphere of 5% CO 2 .", "Antibodies were obtained as follows: monoclonal anti-Bip, Stressgen (Victoria, BC, Canada); monoclonal anti-giantin and monoclonal anti-ERGIC-53, Hans-Peter Hauri (Basel, Switzerland); polyclonal anti-\u2424 -COP, Jennifer Lippincott-Schwartz (National Institutes of Health, Bethesda, MD); polyclonal \u2423 -mannosidase II, Marilyn Farquhar (University of California at San Diego, La Jolla, CA) and Kelley Moreman (University of Georgia, Athens, GA); polyclonal antibodies to IBV M and vesicular stomatitis virus (VSV) were prepared as described (Machamer and Rose, 1987; Weisz et al., 1993, respectively) ; Texas red-and FITC-conjugated secondary antibodies, Jackson ImmunoResearch (West Grove, PA)." ] },{ "paper_id": "f3a90e6992ef81870180a64caea939eccefee16c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The underline represented restriction enzyme cutting site. RT-qPCR (real-time quantitative polymerase chain reaction).", "BmNPV T3 strain was kept in our laboratory. On the first day of the fifth instar, all larvae were starved for 24 h; 30 silkworm larvae in each of the three independent experiments were administrated 5-\u00b5l BmNPV inclusion bodies suspended in water (5 \u00d7 10 5 /ml) per os, and the control was treated with 5 \u00b5l of sterile water. After 24 h, 30 larval midgut were dissected and mixed together to eliminate individual genetic differences; then, the sample was frozen in liquid nitrogen and stored at \u221280\u00b0C for further use.", "Sequences of primers (5\u02b9-3\u02b9) Purpose" ] },{ "paper_id": "f3cb4102ee8c1aeb8e68595843292801a08effe3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f3fa89e819a64d2d6c74f6d590661ca435878c26", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f41bb45e2257663c953fd7d3ff1c78f9b37ba268", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We queried PubMed and ISI Web of Science, without time and language restriction up to 31 EndNote X7 was used to eliminate duplicates and manage the search results. 9", "The " ] },{ "paper_id": "f46ad7149ec602bd131fd370682f1b73235cfacc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [10] . The study protocol was registered with the National Institute for Health Research international prospective register of systematic reviews [11] ." ] },{ "paper_id": "f477cb32c61ef1a690f4b9afe74d38f8e147f39f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "'336 (-2%8) ", ",%68)6)( &= 8,) ?140)1)28-2+ )'311)2(%8-327 3* 8,) 311-77-32 '8 3* @ 9&0-' %;", "%'-0-8%8-2+ '300%&36%8-32 %003;)( 7,%6)( 7-89%8-32%0 %;%6)2)77 %2( )2,%2')( ()'-7-32 1%/-2+ &= 7)2-36 0)%()67,-4 3* *)()6%0 %+)2'-)7" ] },{ "paper_id": "f4998df4f550be136b50f7d4d6234e2cf916b583", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f4c7da2c6eb641d6c76db9f8220b3f0c01850874", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The incubation period, that is, the duration from the midpoint of the exposure to the symptom onset, was 6.5 days (median; range, 2 to 16 days). The median time from symptom onset to confirmation was 5 days (0 to 17 days), that from symptom onset to death was 13 days (1 to 41 days), and that from symptom onset to discharge from the hospital was 20 days (8 to 41 days).", "Based on this fact, the most important intervention for preventing the spread of the disease is to identify patients who show initial symptoms early on and to provide treatment in isolation before they progress to a severe status.", "The number of confirmed cases associated with each hospital that has been affected by the outbreak are as follows: Among the confirmed cases, 77 patients (41%) had underlying diseases, and the most common initial symptoms included fever (93.5%), followed by cough (41.4%), myalgia (25.9%), sputum (18.8%), diarrhea (11.8%), shortness of breath (7.5%), and nausea and vomiting (7.5%)." ] },{ "paper_id": "f510e7651315b8a000b2271107451ba284f10292", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The photochemical mechanism of action of riboflavin is mediated by both Type I and Type II redox reactions. Upon activation with UV light, riboflavin oxidizes guanine residues in DNA and RNA via direct electron transfer reactions, which occur in the absence of oxygen. The primary photoproduct of riboflavin under these conditions is lumichrome, though other intermediate metabolic and/or photochemical degradation products have been identified, including formylmethylflavin, 2 0 keto-flavin, and 4 0 keto-flavin. These by-products occur at very low concentrations (44) (Fig. 1) . Riboflavin is able to penetrate the mitochondrial membrane and may facilitate mitochondrial function in its role as a flavin molecule (45) .", "Interestingly, Mirasol may also prevent alloimmunization. Studies have shown impaired binding of Mirasol treated leukocytes to responder cells and no antigen presentation after Mirasol treatment or proliferation of responder cells in a mixed leukocyte culture. A possible explanation may be that the Mirasol-treated cells have significantly reduced expression of several surface receptors that are involved in T-cell activation and adhesion, specifically HLA-DR, ICAM 1-3, CD80 and CD86, in addition to inhibition of cell to cell interactions (58) . There was no allo-antibody formation in a rat transfusion model (59), a findingwhich could have significant implications for patient care and general transfusion practices for transplant patients and multiply-transfused individuals.", "For comparison, numerous photo-independent methods of pathogen inactivation have been developed and a brief description of these techniques is provided below." ] },{ "paper_id": "f59470fcae185cd02092b4e6e986a558ab811e92", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The purified RNAs were analyzed on a 20% nondenatured polyacrylamide gel (29:1 acryl:bisacryl ratio) in the 1\u00c2 TBE (Tris-Borate-EDTA) buffer. The gel was run at a constant voltage of 150 V for 8 h at room temperature. The results were visualized by the staining of ethidium bromide.", "The roles of loop-closure constraint within a Z1 PRF pseudoknot stimulator", "non-coding RNA may use a similar mechanism to regulate gene expression although the \u00c01 PRF efficiency observed here is not dramatic compared with the reported examples (20, 21) . However, further enhancement of frameshift efficiency for application purpose is possible, such as that demonstrated by the use of modified oligonucleotides (20) ." ] },{ "paper_id": "f5a7b8b5e36fb9c710990a5adbe057fdc1682ec5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Patients were excluded if 1) the cause of admission was something other than AECOPD, such as heart failure, arrhythmia, acute pulmonary edema, acute pulmonary embolism, or pneumothorax; 2) they had a comorbidity that can affect immunity, such as cancer or autoimmune disease; 3) no laboratory or culture test was conducted within 24 hr of hospitalization; or 4) they exhibited mild to moderate exacerbation of COPD.", "All cultures, antigen detection assays, and polymerase chain reaction (PCR) assays of blood, sputum, urine, or naso-or oropharyngeal swab samples were obtained by a physician within 24 hr of admission.", "COPD was diagnosed based on the guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). AE-COPD was defined as \"an acute event characterized by a worsening of the patient's respiratory symptoms that is beyond normal day-to-day variation and leads to a change in medication. \" 13, 14 All patients had a previous pulmonary function test, and a ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) of <70%. All patients were >40 years old." ] },{ "paper_id": "f5b032ddcc2c69fa564eec3ac027060064d7b255", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We made systematical searches through the PubMed data base for articles published before March 5, 2011 and indexed with the following search terms: elderly; and influenza H5N1 virus; influenza H1N1 virus; metapneumovirus; coronavirus SARS, NL63, or HKU1; bocavirus; rhinovirus C or D; polyomavirus KI or WU; or torque teno virus. We reviewed only articles published in English.", "Vaccines are being developed against these new viruses. The most promising preclinical results have been reported for vaccine candidates for MPV and SARS-CoV, but their efficacy have not been studied in humans [181, 182] .", "Data on the occurrence of these viruses in the elderly are lacking but are urgently needed, since PyVs are potentially oncogenic and can persist in human tissues [103, 111] . KIand WUPyV become reactivated at similar frequencies as the BK and JC viruses during immunosuppression [111, 112] . Diagnostics is based on PCR and serology [107, 109] .", "With the exception of the influenza viruses, there are no specific treatments or vaccines available to combat the new viruses. In this sense, there is no clinical need for a viral diagnosis. Viral detection may still have practical importance with regard to isolating practices of infected patients in hospitals or in long-term care settings to prevent transmission of disease [128] and for proper supportive treatment, including avoidance of unnecessary antibiotic treatments [146] ." ] },{ "paper_id": "f5de8066a6e6df907e2389816f2372a427235a9f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Serum samples for cytokine analysis were obtained at admission and stored at -70\u00b0C until assayed. Ten cytokines were assayed Several laboratory values were obtained on the admission day including: white blood cell count (WBC), neutrophil subset, lymphocyte subset, erythrocyte sedimentation rate (ESR), C-reactive protein levels, and liver function test results.", "A correlation between cytokine levels and laboratory or clinical results was not found.", "Study approval was obtained from the Institutional Review Board (IRB) at the Keimyung University School of Medicine (2016-02-048). Written informed consent was waived by IRB." ] },{ "paper_id": "f5faed882955e964aa9ea7ac455746bcfec521ba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f601587d47e1c6f922247d571299bb21624ac0da", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "VSFs are underestimated in our census Viral genomes often integrate into cellular genomes and contribute proteins to their makeup. These proteins become part of XV Venn groups.", "Phylogenomic networks were generated using the Neighbor-Net algorithm (126) implemented in the SplitsTree package (version 4.13.1) (127) . An NJ tree was calculated from the pairwise phylogenetic distance matrix using the \"Phangorn\" and \"ape\" packages in R version 2.15.2.", "Finally, we stress that our conclusions are the \"most likely\" and \"most parsimonious\" scenarios inferred from both comparative genomic (for example, Venn diagrams and f values) and phylogenomic approaches (ToD, ToP, and evoPCO). Studying viral and cellular evolution is a difficult problem complicated by many logical and technical considerations. In light of these, we hope that our study will initiate further discussions of this topic and that a consensus regarding viral evolution will be reached in the near future to benefit both viral biology and taxonomy." ] },{ "paper_id": "f633ec24c26ab3db499227405678f21cc6ab2af5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f64a7539cff0d59ff66885154be0f6d105e4a3ad", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "One reason is that all protein-protein interactions defined by functional associations and/or genetic interactions between proteins were discarded from BIND and HIV-GENERIF.", "From 2294 PMIDs for which at least one protein-protein interaction was defined, database curation led to the validation of 2261 redundant interactions found in 789 papers, corresponding to 1374 confirmed non-redundant proteinprotein interactions (Supplementary Table 2 ). Strikingly, our experts confirmed 20% of BIND and GENERIF (HIV) against 90-95% for MINT and INTACT data.", "A bioinformatics pipeline was developed to fully integrate virus-virus, virus-host and host-host protein-protein interactions gathered from a wide range of public databases, with those mined from scientific literature and curated by VirHostNet experts (Figure 1 ). In addition to the management of this large protein interaction resource, VirHostNet integrates contextual information concerning interacting proteins, like structural and functional annotations of proteins: Gene Ontology term (28) , KEGG pathway (29) , INTERPRO domain (30) . All these data were integrated into a knowledge-based system implemented by using PostgreSQL DataBase Management System (release 8.2.6).", "continuously from data published in scientific journals. The update of public databases will occur at least once or twice a year in order to keep the data as current as possible. In the next future, integration of other host species, such as mammals or insects, is envisaged. This will facilitate comparison of interaction profiles among different hosts and thus may help to elucidate the molecular basis underlying the ability of some viruses to overcome the inter-species barrier. Efforts will be made to facilitate data exchange with other generalist databases (MINT, INTACT) and to add Web2.0 capabilities to the Web interface (save, comparison and analysis of user customized networks). Altogether, VirHostNet provides an entry gate for proteome wide analysis of the virus-host system and will greatly help scientists willing to take advantage of functional genomic and systems biology to decipher viral infection, evolution and pathogenesis mechanisms and/or to rationalize anti-viral drug design." ] },{ "paper_id": "f6b6ab22699e8c898e0de1614c8ce506ce99dd8a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A further area of active research at Rfam is how best to distribute genome annotations. We plan to make annotations available in a variety of formats including the distributed annotation service (DAS) (27) , General Feature Format (GFF) (http://song.sourceforge.net/gff3.shtml) and EMBL format, together with links to relevant genome browsers, e.g. ENSEMBL, UCSC and Genome Reviews.", "The rate of discovery of new RNA families is accelerating rapidly, facilitated by advancements in new sequencing technologies (12, 13) and targeted computational screens (14) (15) (16) (17) . Keeping abreast of these updates whilst still ensuring the quality of alignments and secondary structures is an ongoing challenge for Rfam. We continue to evaluate new technologies and techniques as they emerge and will adopt new procedures for building and checking Rfam families as necessary.", "We have been actively updating Rfam families and database crosslinks using more specialized RNA databases such as miRBase (18) , IRESite (19) , Pseudobase (20), snoRNABase (21) , the plant snoRNA database (22) , TransTerm (23) and the Yeast snoRNA database (24) . As a result of these efforts, the next release of Rfam (version 9.1) will contain more than 700 entirely new families, bringing the total number of Rfam families to over 1300." ] },{ "paper_id": "f6b7e95bba8fc989701322484c6318774eb1ed6b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Diarrhoea, defined as three or more loose stools on a given day, will trigger impact diary completion.", "Non-random recruitment and enrolment requires awareness and assessment of potential bias and confounding prior to broad-based generalisation." ] },{ "paper_id": "f6cb05b1b2874e3aabdc66876575cda7d7477d31", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Feline infectious peritonitis virus (FIP virus: FIPV), a feline coronavirus (FCoV) of the family Coronaviridae, causes a fatal disease called FIP in wild and domestic cat species. Several organs, including the liver, lungs, spleen and central nervous system, are affected in cats that develop FIP, and the formation of lesions in these organs is accompanied by necrosis and pyogenic granulomatous inflammation [13] . Pleural effusion and ascitic fluid were reported to accumulate in some cats. Macrophages/monocytes play an important role in the pathogenesis of FIP. For example, differences in the proliferation of macrophages/monocytes were shown to be related to differences in pathogenicity between feline enteric coronavirus (FECV) and FIPV [2, 16] . FECV and FIPV cannot be serologically or genetically distinguished from each other; however, FECV infection is normally asymptomatic in cats.", "Cell cultures: FO mouse myeloma cells (ATCC CRL-1646) and WEHI-164 murine sarcoma cells (ATCC CRL1751) were obtained from the American Type Culture Collection. The hybridoma mAb 2-4 cell was developed in our laboratory [4] . FO cells and hybridoma mAb 2-4 cell producing the antibody to feline TNF-alpha were maintained in Dulbecco's modified Eagle's minimum essential medium supplemented with 10% FCS and antibiotics. WEHI-164 cells were maintained in RPMI 1640 growth medium supplemented with 10% FCS, antibiotics, 50 \u00b5M 2-mercaptoethanol and 2 \u00b5g/ml of polybrene.", "Western immunoblotting assay: Purified mouse mAb 2-4 and chimeric mAb 2-4 were incubated without 2-mercaptoethanol at RT for 5 min (non-reducing condition). mAbs were incubated with 2-mercaptoethanol at 100\u00b0C for 10 min (reducing condition). mAbs were run using 15% sodium " ] },{ "paper_id": "f6e907e13f516564479fe71e2904d14cad572f15", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplementary data are available at LabArchives under doi: 10.6070/H4NP22XX.", "Fitness (W) data were fitted to a generalized linear model with a Normal distribution and an identity link function. The model incorporates two random factors, the TEV genotype (G) and the replicate plants (P), with the second nested within the first:", "The microarray data that support the findings of this study have been deposited at NCBI GEO with accession number GSE99838. Processed data are presented in the Supplementary Material online. All other relevant data are available from the corresponding author on request." ] },{ "paper_id": "f6e985e472df7bba7a7ef1568336c0443b919639", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sequence loss is inherently an evolutionary process, at a minimum involving mutation and selection, and therefore needs to be framed in an evolutionary context. Here, we consider how theory might help to better understand and ultimately predict this process. First, inspired by empirical results we consider the effects of virus population and bottleneck sizes on sequence loss. Second, we consider whether there are different evolutionary trajectories that lead to a restoration of fitness following insertion of a sequence, and their implications for sequence stability.", "Alphabaculovirus, Lambdavirus, Mastadenovirus, Orthopoxvirus, T7likevirus, Varicellovirus", "When considering host species jumps using the same TEV-eGFP vector, we show that host switches can radically change evolutionary dynamics (Willemsen, Zwart, and Elena 2017)." ] },{ "paper_id": "f709c57759c73d92079f99c26fade99a13384f78", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dot signal intensities were analyzed using Two Way Analysis of Variance (ANOVA) with the Holm-Sidak method for pairwise multiple comparisons. A P \u2264 0.05 was considered statistically significant. SigmaPlot version 10.0.1 was used for performing all statistical analyses (Systat Software, Inc., San Jose, CA).", "Polyclonal IgG rabbit anti-chicken IgY-H+L (anti-chicken IgY secondary antibody), conjugated with alkaline phosphatase, ", "Mean dot signal intensity obtained using the negative plasma samples did not differ significantly within each bird species." ] },{ "paper_id": "f74a10293a7a838fc90185edecb37771cf6cd037", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Several similar models with different knots places, variable df and other parameter settings have been fitted for comparison. The result of the Akaike information criteria (AIC) analysis supports our current selection and parameter settings of the proposed model.", "Author Manuscript" ] },{ "paper_id": "f762eef06ad6975bb55dc425f10e33101d378379", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A single-chain HLA mutant enhances CTL priming M Matsui et al.", "Statistical analyses between two groups were performed with Student's t-test. One-way analysis of variance followed by post hoc tests was carried out for statistical analyses between multiple groups using Graph Pad Prism 5 software (GraphPad software, San Diego, CA) . A value of P < 0.05 was considered statistically significant." ] },{ "paper_id": "f7748ce96d52eeafe6b08a42b2f9f1774b373f78", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f774e52f2267ee839ba5b026e12dfef588e15bfa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Total RNA was extracted by Trizol reagent and reverse transcription was conducted by using Superscript III RT (Invitrogen) and random primers. Real-time PCR was performed with SYBR Green PCR Master Mix (Applied TaKaRa, Otsu, Shiga, Japan). The nucleotide sequences of the primers were as follows: GAPDH, 5'-ATGGGGAAGGTGAAGGTCG-3' and 5'-GGGGTCATTGATGGCAACAATA-3'; TRIM55, 5'-GGTTTT GGATAGACATGGGGT-3', and 5'-TTCTCCTCTTGGGTTCGGGT-3'. The results were analyzed by 2 -DDCT method with GAPDH as the internal control. Each sample was analyzed in triplicate." ] },{ "paper_id": "f77d9d6d6d7730a6a554319266051a8b1e36970b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical Analysis. The statistical analyses are indicated in figure legends and are detailed in Supporting Information. Statistical significance was defined as P < 0.05.", "Biosafety and Ethics. Experiments with live MERS-CoV were carried out in biosafety level 3 biocontainment facilities at the University of Hong Kong and the University of Iowa. Studies on the ex vivo cultures of human bronchus and lung were approved by the Institutional Review Board of The University of Hong Kong/Hospital Authority Hong Kong West Cluster (UW-13-104). All animal studies were approved by the Institutional Animal Care and Utilization Committee at the University of Iowa.", "research; C.D. contributed new reagents/analytic tools; G.D., A.R., and M.P. analyzed data; and L.L.M.P., S.P., and M.P. wrote the paper. Reviewers: S.S.M., Columbia University; and V.J.M., National Institutes of Health. The authors declare no conflict of interest. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND)." ] },{ "paper_id": "f7bbdd316b8d64ca1001b67b96c06efd531893b6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f7c0f747be302193f876a3d3ddf1e14098090e75", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "installation are provided through our ftp website or by simple request.", "In conclusion, PhEVER aims at being a comprehensive tool for the analysis of virus-virus and virus-host relationships from an evolutionary point of view, namely through the analysis of genomic interchanges. It should become a valuable tool for anyone working on viral evolution, but also to understand the general mechanisms behind protein evolution and functional innovation.", "The major drawback of currently available databases of homologous families to the study of viral homologies and lateral gene transfer in viruses is their taxonomic compartimentalization. Indeed, current databases present families of homologies either restricted to viruses only [Protein Clusters (8) , GeneTree (9) ] or to viral taxonomic groups [Viral Orthologous Cluster (10) ], some also not presenting viral information [HomoloGene (11) ]. The few databases that do present viral and non-viral sequences, such as Pfam (12) or the Conserved Domain Database (13) do not provide complete phylogenetic trees. This translates into the fact that it is not currently possible to have a global view on viral-host lateral gene transfers due to the difficulty of obtaining global information on cross-taxa transfers at the viral level." ] },{ "paper_id": "f7ef8b5d989ac724f2520aa8a0a83e60f8851e91", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CPMG relaxation dispersion measurements facilitate the extraction of information about exchange phenomenon occurring on the s-ms timescale (83) (84) (85) (86) (87) (88) (89) . Previously, others have used similar approaches to measure CPMG experiments for RNAs smaller than 50 nucleotides with specifically labeled pyrimidine bases (35, 36) . Here, we present data that illustrates the effect of creating an isolated, labeled C8 and C2 positions in our nucleotides, and show that measurements of CPMG parameters are readily accessible without the problem of J-coupled induced oscillations (28, 90) .", "The resulting assignment matched those previously determined (8) . In situations where there is significant overlap in the base region, samples in which certain bases are unlabeled or even deuterated can be made allowing for the assignment bottleneck to be quickly circumvented.", "Supplementary Data are available at NAR Online. ", "NMR spectral processing was done in Topspin (Bruker Biospin) and NVFx (One Moon Scientific). Peak intensities were selected using in-house software by David Fushman. CPMG data were fit to a two-state exchange model using the full Bloch-McConnell matrix. The time-dependent evolution of magnetization during the CPMG period was solved numerically by non-linear least squares fitting using in-house Matlab software. Errors in fits were calculated using Jacobian or 200 Monte Carlo simulations (33) , and the larger of the two errors was reported for CPMG and CEST relaxation dispersion analysis.", "However, in spite of this importance, directly establishing how dynamics modulates the structure and function of RNAs has been difficult because X-ray crystallography and nuclear magnetic resonance spectroscopy are plagued by distinct but equally challenging problems. In crystallography, motions can only be observed in the ps-ns timescales and the strain imposed by crystal packing can obscure and distort structural data (9, 10) ." ] },{ "paper_id": "f83b2d3bcbf4f5da7dbb22a53a5b2cb942d08a5e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f8540b3d4f17c2c73a9f6bf6f76b2d9350f85c46", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The author would also like to thank her graduate students not only for actually doing great science but also for their help editing this paper.", "The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.", "Katherine Seley-Radtke http://orcid.org/0000-0002-0154-3459." ] },{ "paper_id": "f866dfaccbc646719c85b4103b05ded741a30bee", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Where F(t) is fraction unwound at time t, A is the amplitude, k 1 is the observed rate constant of the burst phase.", "The chemical cross-linking reagent dimethylsuberimidate (DMS) was used to study the oligomerization of nsP13. A 300 mg/ml DMS stock solution was prepared immediately before use in ice-cold triethanolamine (TEA) buffer (TEA/ HCl, 0.15 M, pH 8.2) and the pH was readjusted to 8.2 with 1 N NaOH. The nsP13 (4 mM) was preincubated in 50 mM TEA buffer (pH 8.2) containing 50 mM NaCl and 5 mM EDTA for 10 min at 22 C and cross-linking was initiated by adding DMS (10 mg/ml). After incubation for 1 min at 22 C, the cross-linking reactions were quenched by adding an equal volume of 1 M glycine. The quenched samples were analyzed by SDS-PAGE (4-12% gradient) and proteins were detected by Coomassie Brilliant Blue R-250 staining.", "Single-turnover kinetics of duplex DNA unwinding by nsP13" ] },{ "paper_id": "f86a27f248abc89aef420f88323538086c8b9f8f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We note that sequence divergence does exist in a key region of the SPRY domain thought to be important for capsid binding. 42 We are currently investigating this in more detail.", "Electron microscopy. Scanning electron microscopy was used to examine cell morphology after fixation in 2.5% glutaraldehyde (0.1 mol/l sodium cacodylate buffer, pH 7.4) for 30 minutes. After serial alcohol dehydration, samples were treated with hexamethyldisilazane (Polysiences, Warrington PA) and mounted on stubs. Samples were examined under a Hitachi S-4800 electron microscope (Hitachi, Dallas, TX).", "Sinn et al." ] },{ "paper_id": "f87d2665175ce7e1c6ffd14e0da7bfc21b784e2e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f8da6bc56b3d7a64f5f0ba9a7928264dc986e43f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Toxin expression and purification. A 400-ml LB culture at 30\u00b0C was inoculated with a 1/8 volume of an overnight culture with appropriate antibiotic selection (Sp and Ap at 100 g/ml and Cm at 25 g/ml) and grown to an A 600 of 1.2, when it was induced with 400 M IPTG and 0.0005% l-arabinose with incubation continued overnight. Cells were collected by centrifugation, resuspended in 20 ml phosphate-buffered saline (PBS), and lysed by mixing for 20 min at room temperature with 0.5 mg/ml lysozyme and Elugent detergent (EMD Biosciences, Inc., La Jolla, CA) to 2%. Viscosity was reduced by sonication four times (10 s each) on ice, and the lysate was cleared by centrifugation at 15,000 rpm for 20 min in an SS34 rotor. Toxin was purified from the supernatants by Talon chromatography as detailed by the manufacturer (Clontech Laboratories, Inc., Mountain View, CA). Imidazole eluates were dialyzed against 50 mM Tris-HCl (pH 8.0) (buffer A). All chromatographic separations were conducted on an Akta purifier (GE Healthcare Biosciences, Pittsburgh, PA) in 4.6-mm by 100-mm Poros perfusion chromatography columns packed with Poros HS 20 cation exchange medium or Poros HQ 20 anion exchange medium. For cation exchange, the column was equilibrated with 5 column volumes (CV) buffer A and washed with 5 CV buffer A after sample loading. Bound material was eluted with 10 CV of a linear gradient of 0 to 100% buffer B (50 mM Tris-HCl, pH 8.0, 1M NaCl). For anion exchange, the column was equilibrated with 5 CV buffer A, washed with 5 CV of buffer A after sample loading, and was eluted with a 40-CV (initial separation) or 10-CV (second purification) linear gradient of 0 to 100% buffer B. Anion exchange fractions were pooled and concentrated using Microcon Ultracel YM-10 filter devices (EMD Millipore, Billerica, MA).", "T84 cells and electrophysiology. Measurements of short-circuit current (I sc ) on monolayers (0.33-cm 2 inserts) of the polarized human intestinal cell line T84 were performed as previously described (41) ." ] },{ "paper_id": "f901f9949a8c6e53727335e92a39707e89965422", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For nsp12 expression, the pASK3-Ub-nsp12-CHis 6 plasmid was transformed to Escherichia coli C2523 cells (New England Biolabs) together with the Ubp1 protease expression plasmid pCGI (26) , unless indicated otherwise for particular experiments. Routinely, 250 ml of Luria Broth, containing ampicillin (50 mg/ml) and chloramphenicol (34 mg/ml), was inoculated 1:1000 with 3 ml o/n precultures and cells were grown at 37 C to OD 600 >0.7. Subsequently, the cells were slowly cooled to room temperature, tetracycline was added to a final concentration of 200 mg/ml and the cells were further grown at 20 C for another 16 h. Cells were harvested by centrifugation, washed once with ice-cold phosphate-buffered saline (PBS) and stored at \u00c020 C until protein purification.", "Dr. Susanne Pfefferle, Dr. Christian Drosten, Dr. Isabelle Imbert and Dr. Bruno Canard for helpful discussions or providing reagents.", "Funding for open access charge: The Netherlands Organization for Scientific Research (NWO; Top talent grant 021.001.037); the Council for Chemical Sciences (NWO-CW; ECHO grant 700.55.002); and by grant AI45818 from NIAID/NIH (to J.A. and C.C.)." ] },{ "paper_id": "f90706bbb06cb2fa2992200bddfa2a3305f52b67", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "On hospital admission, clinical parameters and severity of the disease including wheezing, retraction, respiratory rate, and general situation were evaluated and assessed with Wang respiratory score. 16 Each parameter was given points from 0 to 3 and then the child's points were added up to describe the severity of AB; points between 0 and 3 showed mild bronchiolitis, between 4 and 8 moderate, and points between 9 and 12 indicated severe bronchiolitis. Complete blood count (white blood cell count and percentage of lymphocytes) and C-reactive protein were measured at admission.", "Data analyses were performed using SPSS version 21.0. The quantitative data including percentage, mean, and standard deviations were calculated by simple descriptive analyses. Means \u00b1 SD were used to summarize the demographic data and the baseline characteristics of the cases. All analyses were conducted using SPSS (SPSS Inc, Chicago, IL).", "A nasal smear was obtained from each infant and tested for the presence of RSV, influenza virus types A and B, adenovirus, parainfluenza viruses, human rhinovirus, human coronavirus, human metapneumovirus, and human bocavirus with multiplex reverse-transcription PCR methods (RealAccurate, Respiratory RT PCR, PathoFinder, Netherlands, and Seeplex RV15 ACE Detection, Seegene, South Korea). Nasal samples were obtained more commonly by a nurse or sometimes a research assistant on all subjects within 48 hours of admission using a standardized protocol. 17 Samples were frozen at \u221220\u00b0C and transported on ice to the Department of Clinical Microbiology and Virology Laboratory of our university for viral nucleic acid amplification." ] },{ "paper_id": "f91911b6a25c970324854df7b87c550ae7fb878f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f92cd3c86281eee402ab60a75990ae6bb57b3c35", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Although commercial rRT-PCR assays for MERS-CoV detection have been developed by several manufacturers, including Altona Diagnostics, Fast Track Diagnostics, and Primerdesign Ltd., studies validating diagnostic performance using authentic specimens are lacking [5, 6] ." ] },{ "paper_id": "f9476a333c17961ff4cc34b45f4b2da5ed29457f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Editor: Barry Margulies. \u00c3 x 2 test or Fisher exact tests for variables with any cell <5. Values are numbers (percentages) of respondents unless stated otherwise. The values in bold represented those with P < 0.10, which were selected as variables in the multivariate regression analysis.", "We recommend future qualitative studies to explore indepth reasons of the low uptake rate, the attitude and perception of the significance of antigenic drift, and interventional strategies which could enhance vaccine acceptability should be devised and evaluated in the future.", "Abbreviations: AOR = adjusted odds ratios, WHO = world health organization." ] },{ "paper_id": "f94c7a970b81de90b8594683b77db556e15ebd9f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u00a7 Range for the ratio of PtlKi to CV-I nuclei.", "Brefeldin A (BFA) was shown in earlier studies of numerous cell types to inhibit secretion, in-", "1. Abbreviations used in this paper: BFA, brefeldin A; endo H, endoglycosidase H; G Protein, glycoprotein; Gai T, galactosyltransferase; VSV, vesicular stomatitis virus." ] },{ "paper_id": "f956e0b68eaf7bac8fa50f0d1a9859938a96f8ad", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Prions, which were first proposed by Dr Prusiner at the University of California, San Francisco, became a hot topic since they do not have genes, unlike bacteria or viruses, and are able to replicate, unlike toxic elements [4] . Eventually, he scientifically answered a number of questions and suggested that these gene-less proteins can replicate in the body, induce the disease, and be subsequently transmitted to other animals; he received a Nobel Prize for his work in 1997. This type of prion-only hypothesis is recognized as a new pathogenic mechanism of neurodegenerative disorders [12] .", "Formalin-fixed brain tissue PrP Sc antigen Western blot Fresh brain tissue PrP Sc antigen Electron microscopy Fresh brain tissue Scrapie-associated fibril Bioassay", "Therefore, the EU places much emphasis on active monitoring and surveillance systems, such as total inspection, thorough removal of SRM (where 99% of the pathogenic prions exist), banning MBM, and monitoring animal feed. Through such actions, BSE has become manageable, but it is still not eradicated. The USA also started to emphasize the development of an effective animal-monitoring system over concerns for human health [42] .", "Clinical symptoms similar to those of CJD that were reported in the 1920s were displayed in a patient who consumed contaminated beef (affected with BSE); the disease was called vCJD, which was first described in 1996. There are four types of CJDs: two nontransmittable CJDs, including sporadic CJD (sCJD) and familial or genetic CJD (implying a genetic cause), and two transmittable CJDs, including iatrogenic CJD and vCJD ( Table 2 )." ] },{ "paper_id": "f9738261ac322d052e519fb1f1297eedc917a939", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data such as age, gender, clinical presentation and current medications were collected using an objectively prepared questionnaire. Informed consent was obtained from the parents/guardians of all patients before sample collection.", "The study was conducted after obtaining approval from the Ethical Committee of College of Medicine, King Khalid University, Saudi Arabia (KKU Research Ethics Committee Meeting No. REC # 2014-01-08; dated January 5, 2014)" ] },{ "paper_id": "f98e165a9cb60bc2e32686ceb4ed188425fbc318", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "It was concluded that Saudi pilgrims possess good knowledge about the MERS-CoV although more orientation is still required.", "The current study was intended to evaluate the knowledge and awareness toward Middle East respiratory syndrome coronavirus (MERS-CoV) of pilgrims from Saudi Arabia and from different Arabian countries.", "Currently, there is neither a commercially available protective vaccine nor a specific antiviral treatment for MERS-CoV. 23 There was a relatively insufficient awareness about the availability of effective vaccine and antiviral agents for MERS-CoV among Saudi and non-Saudi pilgrims; however, the awareness level was higher in Saudi pilgrims in comparison to no Saudi ones." ] },{ "paper_id": "f98ea77d586b02146fe03a209e44a0c1e8883ea5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The DBT-RGYI grant and Ramalingswamy fellowship to MS is gratefully acknowledged. SA and NK are supported by senior research fellowships from the Department of Science & Technology and the University Grants Commission, Government of India, respectively.", "In summary, recent studies have identified multiple leads, which should be pursued further to develop a potent antiviral against HEV.", "The authors have no conflict of interests related to this publication.", "Wrote all sections of the manuscript except the zinc section, and generated the figure and the table (SA), wrote the zinc section of the manuscript (NK), edited the manuscript (MS). All authors read and approved the manuscript. " ] },{ "paper_id": "f9a3b2b8a17beb5d81c2111277d9645dc137dd32", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The outbreaks of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) were caused by emerging coronaviruses.", "3C-like protease Benzotriazole esters CE-5 [284] Papain-like protease Thiopurines 6-thioguanine, 6-mercaptopurine [113] Helicase Triazole SSYA10-001 [162] RNA-dependent RNA polymerase Nucleotide prodrug GS-5734 [159] RNA-dependent RNA polymerase Nucleoside analog BCX4430 [160] Membrane-bound RNA synthesis Small molecule inhibitor K22 [285] Furin inhibitior Small molecule inhibitor Decanoyl-RVKR [286] SARS-CoV Viral/cellular target Drug class Drug 3C-like protease Benzotriazole esters CE-5 [284] 3C-like protease Anilides Peptide nitroanilides [287] 3C-like protease C 2 -symmetric inhibitors containing diol cores TL-3 [288] 3C-like protease Pyrazole analogs Pyrazolones [289] 3C-like protease Serine inhibitor Trifluoromethyl ketones [290] 3C-like protease Serotonin receptor antagonist Cinanserin [291] 3C-like protease Zinc-conjugated inhibitor JMF 1586 [292] Papain-like protease Thiopurines 6-thioguanine, 6-mercaptopurine [113] Helicase Triazole SSYA10-001 [162] Helicase Bananin derivatives Vanillinbananin, Idobananin [163] NTPase/Helicase Aryl diketoacids Dihydroxychromone and hydroxychromone derivatives", "An alternative is de-speciating the antibodies by using only the Fab antibody fragment; however, cost and sufficient material may make mass production of Fab fragments difficult. The use of sera from humanized mice or other small laboratory animals is complicated by sample acquisition/volume restraints. Larger laboratory animals may provide a potential alternative. SAB Biotherapeutics has developed a transchromosomic bovine platform for the generation of human IgG antibodies [201] . Vaccination of transchromosomic cattle with S protein nanoparticles or inactivated, whole virus generated fully humanized polyclonal antibodies that demonstrated efficacy in the Ad-DPP4 murine model of MERS.", "Influenza viruses are characterized by a high mutation rate of the RNA genome. As available vaccines may not be protective against a novel pandemic strain, antiviral agents are considered an essential component for preparedness. Combinations of direct-acting antivirals are under evaluation for additive or synergistic effects and prevention of resistance [208, 209] . One triple combination (oseltamivir, amantadine and ribavirin) is synergistic and prevents resistance in vivo [210, 211] , highlighting the potential of combinatorial therapy." ] },{ "paper_id": "f9ec0fcbc2df8fea3210c7db618e70145323c81b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fa021bfcf95acdbde556098bfd84e8a84c7948c9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ ", where biotinylated nucleotides are designated with a superscript b. Blots were hybridized overnight and washed with low-and highstringency buffers. Filters were incubated with streptavidin-AP, washed and then developed using the chemiluminescent substrate CDP-STAR (New England Biolabs).", "VeroE6 cells inoculated with SARS-CoV or S3L2-ACU ucc pk (multiplicity of infection of 1) or were mockinfected and incubated at 37 C. Media were harvested at 0, 5, 8 or 12 h post-infection (pi) and titers assessed by plaque assay as previously published (27) . Viral detection limit was 50 pfu/ml. Error bars are the standard deviation of three measurements.", "All CoV genome sequences were obtained from Gen Bank (http://www.ncbi.nlm.nih.gov/genbank/). Accession numbers for sequences discussed are summarized in Supplementary Table S1. Multiple sequence alignments were performed using ClustalW2 (version 2.0.12) (http:// www.ebi.ac.uk/Tools/msa/clustalw2/) (29) . Free energies of the proposed S3L2 structures at 37 C in 1 M NaCl were calculated with Mfold (30) .", "A novel coronavirus was responsible for the sudden epidemic, severe acute respiratory syndrome (SARS) outbreak, in 2003. Coronaviruses are positive-strand RNA viruses with large genomes [$30 000 nucleotides (nt)] that serve as templates for translation of viral proteins and for replication. The production of proteins from these viral RNAs does not follow the usual rules governing translation. The first polyprotein encoded by open reading frame (ORF)1a, which encodes non-structural proteins, is defined by initiation and termination codons and is translated normally. Signals embedded within the RNA just before the termination codon of ORF1a redirect a fraction of translating ribosomes to bypass the stop codon and continue translation in the -1 reading frame, thus creating the larger ORF1ab polyprotein (1-3). These programmed -1 ribosomal frameshift (-1 PRF) stimulating signals are typically composed of a heptameric slippery site, on which the ribosome can change register by 1 nt in the 5 0 direction, followed by a pseudoknot. Slippery site sequence requirements have been characterized for several cell types (4) but the range and diversity of frameshift-stimulating pseudoknots continues to grow (5) ." ] },{ "paper_id": "fa0eaef225e1bfa0aa470be4c089ae0689193fec", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As predicted in 1992 (1), previously unrecognized infectious diseases have continued to emerge, including variable Creutzfeldt-Jakob disease/bovine spongiform encephalopathy (vCJD/BSE), severe acute respiratory syndrome (SARS), and 2009 pandemic H1N1 influenza, and others have reemerged, e.g., disease caused by multiple-drug-resistant Staphylococcus aureus (MRSA), multiple-drug-resistant and extensively drug-resistant (MDR and XDR) tuberculosis, cholera, and dengue.", "Additional conceptual advances in EIDs include the realization that many chronic diseases have a direct or indirect infectious basis, e.g., cervical, hepatic, and gastric cancers; gastroduodenal ulcers; hemolytic-uremic syndrome; and possibly some types of tics and obsessive-compulsive disorders (6, 12) . We also have become aware of the critical role of microbial coinfections in the pathogenesis of certain infectious diseases (e.g., HIV and numerous opportunistic infections; influenza and measles in association with secondary bacterial pneumonias) and of nutrition, e.g., the link between vitamin A and measles (20, 21) .", "Genomics techniques, like PCR and high-throughput deep and whole-genome sequencing, that now greatly facilitate the discovery of EIDs (e.g., the etiologic agents of hantavirus pulmonary syndrome and Kaposi sarcoma) also reveal previously unimagined genomic diversity among microbes. This diversity includes complex and evolving viral quasispecies and microbes that have undergone considerable interbacterial horizontal gene transfer, creating new phenotypic properties of virulence and drug resistance." ] },{ "paper_id": "fa2ab10f1041d2bdf77688448044ce72dfc74eca", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Each PCR amplification was performed using 5 \u03bcL of isolated nucleic acid solution, 2 \u03bcL of 10 \u00d7 primer mixture, and 10 \u03bcL of 2 \u00d7 Multiplex Master Mix (Seegene Inc.) in a total volume of 20 \u03bcL." ] },{ "paper_id": "fa3906f048a58d703a5baff91a6545518cbcf4b7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Citation Furmanski M. 2015. The 1977 H1N1 influenza virus reemergence demonstrated gain-of-function hazards. mBio 6(5):e01434-15.", "My review of 11 relevant events (2) found that escapes of highconsequence pathogens causing community infections typically occur from state-of-the-art laboratories, including six outbreaks of severe acute respiratory syndrome and one of foot-and-mouth disease since 2003.", "Rozo and Gronvall also stated that, \"in 1977, influenza research was performed without modern biosafety regulations and protective equipment, making the lab accident hypothesis much less relevant to the modern GoF debate.\" However, the current record of containment of high-consequence pathogens is hardly reassuring." ] },{ "paper_id": "fa46fb0587956a218b9b81d5aa6b2a6c7ec68126", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fa9460f462e92e3ccbecc0e9fe406b886b7c1e35", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplementary data are available at The EMBO Journal Online (http://www.embojournal.org).", "In summary, the mutagenesis data for both UspA1 (527-665) and N-CEACAM1 when combined with their respective crystal structures enabled us to locate their interacting surfaces.", "Moraxella catarrhalis (Mx) is a human-specific bacterium present in the nasopharynx of up to 75% of healthy individuals, but frequently causes childhood otitis media, sinusitis and exacerbation of lung conditions in patients with chronic obstructive pulmonary disease (Karalus and Campagnari, 2000) . As such, it is associated with widespread morbidity. However, there are no protective vaccines and antibiotic resistance is an increasing problem. Understanding the molecular events that facilitate the complex virulence mechanisms during Mx infection is key to the development of novel therapeutics and vaccines." ] },{ "paper_id": "fa994c4585ad68547b8a9fd973109d183fe8b71e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fab32444594a7c25009ffcd48e91c923f5f0316f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Proficiency in managing an emerging outbreak should not be acknowledged by way of unfortunate experience if the outbreak can be prevented first-hand. Guidelines for human vaccine development encompass principles of cost, efficacy, and safety (8) . Guidelines of animal vaccine development are less stringent (2, 6) . The development of a human HeV vaccine can be time-consuming and prohibitively costly at the current stage. This strategy, however, is much more feasible than the one concerning the containment of an emerging infection \u00c1 clearly evidenced after taking into account the responses to the recent emergence of bat-related zoonotic epidemics such as Ebola and MERS-CoV.", "T he Hendra virus (HeV) is an emerging zoonotic infection in Queensland, Australia (1\u00c13). First identified in 1994, it is associated with a human fatality rate of 60% (4) . Traditionally infecting fruit bats, recent host amplification of HeV in infected equines is purported to underlie the spate of fatal outbreaks of HeV infection among exposed humans in Queensland, Australia (5). To prevent further outbreaks, Biosecurity Australia (the chief health surveillance agency in Australia) commissioned the successful and rapid development of an equine vaccine against HeV to preclude the incidence of additional human cases (6) .", "Effective initially, the HeV vaccine is slowly losing its efficacy. In 2013 alone, over a span of 6 months, eight equines and a canine died of an HeV infection. In 2014, over a similar time frame, three instances of HeV infection were reported in Queensland alone. An equine death resulting from an HeV infection in Murwillumbah, New South Wales, Australia, is the most recent incident, demonstrating that HeV remains a matter of grave concern despite the development of an equine vaccine.", "HeV is a Henipavirus that commonly infects Pteropid fruit bats (1, 4, 7) . Because of the novelty of the disease, there is very little information regarding the exact pathogenesis of HeV or its modes of transmission. The currently accepted model describes the excreta of bats \u00c1 urine \u00c1 containing HeV particles to be the mode of transmission, as is directly taken up by an intermediate host. In both equines and humans, HeV is purported to infect nervous and respiratory epithelial tissues, which can further disseminate, ultimately resulting in death (5, 3) . Apart from an outlier case comprising an infected canine, HeV has only been verifiably detected among fruit bats, equines, and humans. No human-to-human transmission has been documented, as of yet (4, 7) ." ] },{ "paper_id": "fac2661e813598348dbb6d0370ed1818895c9f53", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fac313563bd7a9ff7bb33495d81086ca75615951", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fac6a0008107bdbd3d6e609f613ea7b59288e36c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data between and (n = , ) TB before dialysis (n = , )", "Loss of data after matching (n = , , )", "Loss of data after matching (n = ) " ] },{ "paper_id": "faec4bca24cb275ebc6c55e7cba3bd6a3b74df32", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Transmembrane domain prediction. The transmembrane domain of HEPIS was predicted by Transmembrane Hidden Markov Model (TMHMM) Server v.2.0 (http://www.cbs.dtu. dk/services/TMHMM/).", "Cell culture. HeLa and MCF-7 cells (ATCC) were maintained in high glucose DMEM (Gibco; Thermo Fisher Scientific, Inc.) supplemented with 10% fetal bovine serum (FBS; HyClone; GE Healthcare Life Sciences), penicillin (100 U/ml) and streptomycin (100 U/ml) and incubated at 37\u02daC with 5% CO 2 .", "Statistical analysis. Data are presented as the mean \u00b1 standard deviation. SPSS v9.0 software (SPSS, Inc.) was used for statistical analysis. The data of RT-qPCR and EdU cell proliferation assay were analyzed using Student's t-test, the CCK-8 data were analyzed using one-way ANOVA followed by a Dunnett's post hoc test. Optical density or integrated optical density of breast cancer or normal breast tissue was analyzed using Student's t-test. P<0.05 was considered to indicate a statistically significant difference. Data represent three independent experiments.", "The partial human HEPIS CDS was amplified from MCF-7 cDNA using PCR with the following primers: Forward, 5'-ATA CTC GAG GAA GTG GAG CAG GAT GTA-3' and reverse, 5'-ATA GCG GCC GCT CAG TCA CAG GAT TTC TC-3' , and the PCR fragments were cloned into the psiCHECK\u2122-2 (Promega Corporation) vector using XhoI (CTCGAG) and NotI (GCGGCCGC) restriction sites. This partial human HEPIS CDS sequence contained the targeting site of the small interfering (si)RNAs described below." ] },{ "paper_id": "fb02396b27e7eba6cd6e52fec15c040a98cc0d48", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fb4f03ec469640093e45b1bf924456d1cf05c07b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Mice. Most experiments used 5-10-wk-old C57BL/6J (H2 b ) male mice; some experiments used Balb/cByJ (H2 d ) mice or C57BL/6 mice lacking all T cells as a consequence of genetic recombination deleting the TCR-\u00e2 and \u00e4 genes (T cell knockout [KO] mice). All mice were purchased from The Jackson Laboratory.", "Isolation of Leukocytes. Spleens were ground between glass microscope slides, and spleen leukocytes were isolated by treatment with 0.84% NH 4 Cl to lyse erythrocytes. Peritoneal cells were isolated by lavaging the peritoneal cavity with 10 ml of RPMI 1640 (Life Technologies). Liver leukocytes were isolated by flushing blood from the liver by injecting media through the portal vein, crushing the liver in a tissue grinder, treating with type II collagenase (Sigma-Aldrich) and type I DNase (Sigma-31 Daniels et al.", "Aldrich), and harvesting the leukocyte layer from a metrizamide (Sigma-Aldrich) density gradient, as described previously (28) ." ] },{ "paper_id": "fb776803a925865af38ca4de4f23e94668455a02", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "150-raM dishes of NRK cells were washed three times with ice-cold phosphate buffered saline (PBS) and scraped with a rubber policeman in a buffer containing 10 mM Hepes-KOH (pH 7.2) and 250 mM mannitol (buffer A). The cells were pelleted, resuspended in buffer A, and homogenized by passing the cell suspension six times through a ball-bearing homogenizer (Balch and Rothman, 1985) . A postnuclear supernatant (PNS) was prepared by centrifuging the homogenate at 1,000 g for 10 min at 4\u00b0C.", "Mutant ARFl(Q71L) and ARF1(T31N) in a pET3a vector were either expressed or coexpressed with N-myristoyltransferase in E. coli strain BL21 (DE3) (Novagen), and purified by DEAE-Sephacel (Pharmacia LKB Biotechnology, Piscataway, NJ) and UItrogel AcA54 (Sepracor, Marlborough, MA) chromatography as described (Weiss et al., 1989) . The Sarla(H79G) mutation was introduced into the wild-type Sarla using 4-primer PCR site-directed mutagenesis. His6tagged pETlld-Sarla(T39N) (Kuge et al., 1994) and pET11d-Sarla(H79G) were expressed in BL21 (DE3) E. coli and purified over nickel-nitrolotriacetic acid (Ni-NTA)-agarose (Quiagen) column and $100 Sepharcyl column (Pharmacia) as described (Rowe, 1995) . All proteins were dialyzed against a buffer containing 25 mM Hepes-KOH (pH 7.2), 125 mM KOAc and 1 mM MgOAc before use in the in vitro assay. Protein concentration was determined by the Coomassie blue method (Bio-Rad Labs. Inc.) using bovine serum albumin (BSA) as a standard.", "For both biochemical and morphological transport assays, as well as for membrane-binding assays, representative experiments carried out in duplicate are presented. All experiments were repeated independently at least twice." ] },{ "paper_id": "fbb2b307ad6be9561286c3b8a9114d283fb2e224", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Anthropometrics (including but not restricted to height, weight, waist and mid-arm circumference and triceps skin-fold circumference) are measured quarterly. Grip strength and fatigability are measured using standard techniques. Anthropometric data are used to compute the Malnutrition Universal Screening Tool (MUST) score. 30 Nutritional information (including planned/unplanned weight loss and history and changes in food intake patterns) is collected quarterly according to MUST guidelines.", "A posteroanterior chest X-ray (and lateral if required) is performed at all exacerbation visits, as per standard clinical practice, in order to rule out pneumonia.", "All participants must provide written informed consent to participate.", "Questionnaires and patient-reported outcome instruments Various outcomes are assessed quarterly and at exacerbation using a series of questionnaires and patientreported outcome instruments, such as the COPD Assessment Test (CAT), 31 the Nottingham Extended Activities of Daily Living (NEADL) Scale, 32 the Council on Nutrition Appetite Questionnaire (CNAQ) 33 and the EQ-5D. 34 The five items included in the EQ-5D index are mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The BODE index (Body-Mass Index, Degree of Airflow Obstruction, Level of Functional Dyspnoea, Exercise Capacity) 35 will also be calculated." ] },{ "paper_id": "fbcdafa6bac2c69c1f5afafc5338f777f234d592", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "1796 Classical vaccinology Growing microorganisms: Growth of microorganisms allows making killed and live-attenuated vaccines or to discover antigens used for subunit vaccines.", "Approach to discover and design vaccines" ] },{ "paper_id": "fbdc0117c66b252ed77172829bf245b090ca83f7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Triple-shots 0 P v3 (3-8) *(1-P i3f )*(1-P mi3 ) P v3 (9-14) *(1-P i3s )+ (1-P v3 (9-14) )*P v3 (3-8) *(1-P i3f ) P v3 (15-18) *(1-P i3t )+ (1-P v3 (15) (16) (17) (18) )*P v3 (9-14) *(1-P i3s ) P v3 (19-) *(1-P i3t )", "Transient infection: Cattle which did not receive any vaccine administrations or those that had insufficient immunity for protection against BVDV infection, even after receiving vaccine administrations, were considered as potential targets to become Table 1 ." ] },{ "paper_id": "fbf3cc84b1d412693330fffee86bef8fbdda3b07", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Enforced microglia depletion and repopulation with fully differentiated cells, termed microglia-replacement therapy, has great potential as an intervention in many neurological disease states. Optimization of timing between depletion and repopulation, long-term effects on CNS homeostasis and long-term therapeutic efficacy in preclinical models will provide a solid rationale for clinical translation. BarnCancerFonden.", "The authors declare that there are no conflicts of interest.", "Xing-Mei Zhang https://orcid.org/0000-0002-8728-8849" ] },{ "paper_id": "fbf7b36a98caf3fa41ff9f011dbc9eec0d02609d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "El caso del Coronavirus novel 2019 (2019-nCoV)", "La comunicaci\u00f3n cient\u00edfica es un aspecto fundamental en el proceso de investigaci\u00f3n, tanto que, algunos cient\u00edficos indican que la investigaci\u00f3n que no se publica simplemente no existe.", "EDITORIAL 07 La comunicaci\u00f3n cient\u00edfica y el acceso abierto en la contenci\u00f3n de enfermedades:" ] },{ "paper_id": "fc1d9acb5bb63e3a7898b27d287ff5862b4f2b09", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Wildlife Human activities and their impacts, such as hunting and wildlife trade, the introduction of foreign species, urbanization, ecological tourism, construction of transportation infrastructure, climate change, pollution, and habitat destruction (5, 21\u00c123), have direct or indirect impacts on wildlife. These impacts include changes in behavior, population, distribution, community structure, reproductive capacity, biodiversity, and so on.", "JYW and LLL contributed to the literature review and manuscript writing. JHL guided writing of the manuscript and provided the final approval of this version for publication.", "To meet the demand for meat, the animal husbandry industry has been unprecedentedly developed in China." ] },{ "paper_id": "fc1f4b62e7c63ec2a3536401ce6aea880dca8512", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "No potential conflict of interest was reported by the authors.", "Aymn Talat Abbas http://orcid.org/0000-0001-7372-370X Sherif Aly El-Kafrawy http://orcid.org/0000-0002-3667-7529", "ARTICLE HISTORY" ] },{ "paper_id": "fc363739ad7ec8d796aba6af478d986a4c0f5f3f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Babies were clinically examined during their stay in the NICU. Once sepsis was confirmed, blood samples were taken within 12-50 hours after birth. Babies suspected of having sepsis infection, before proven positive culture, were treated by clinicians (neonatologist) with double antibiotics (Ampicilin and Gentamicin) until the baby became symptom free or finished their course of antibiotic. Full blood count was routinely taken. All investigations and treatments were provided free of charge.", "Before pharmacological treatment was started, 50 \u03bcl of blood were collected on filter paper (Schleicher & Schuell; n\u00b0 903TM) for DNA amplification and quantification of cytokines. Two mls of venous blood was collected in EDTA Vacutainer \u00ae tubes (Becton Dickinson, Meylan, France) for bacterial culture.", "A prospective cohort (cross-sectional) study was carried out over six months, from March to August 2012, in the Neonatal Intensive Care Unit (NICU), King Abdel Aziz Specialist Hospital (KAASH), Taif City, Kingdom of Saudi Arabia (KSA).", "DNA was extracted from filter papers using Chelex-100, which was stored at -80\u00b0C. 25 \u03bcl from peripheral blood or discs of the same size from filter paper were incubated overnight in 1 ml of 0.5% saponin in PBS at 4\u00b0C, and they were then washed for 15-30 minutes in 1 ml PBS at 4\u00b0C. The discs or the pellets, were boiled in 200 \u03bcl of 5% Chelex-100 in water for 15 minutes, and the DNA was collected in supernatants after centrifugation at 250 \u00d7 g for 10 minutes [39] ." ] },{ "paper_id": "fc3bce122003ef28564d0dfaec7bd5771cfa4bff", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Key words: canine parvovirus type 2c, sequence analysis, Brazil.", "The canine parvovirus type 2 (CPV-2) emerged as a novel pathogen in the late 70`s (1) and rapidly spread worldwide. Within few years, the virus underwent a rapid evolution and, new antigenic types, termed CPV-2a and 17) , completely replaced the original type 2 (21,", ". In 2001, an antigenic variant was reported in Italy (3, 4) ." ] },{ "paper_id": "fc6489e42c4a336fd64bd4b82639037087aa60fe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nucleotide sequence accession numbers. Genome sequences were entered into GenBank under accession numbers KF425652 to KF425658 (C/628), KF425659 to KF425665 (C/660), and KF425666 to KF425672 (C/729).", "Text S1, DOC file, 0.1 MB. Figure S1 , PDF file, 2.3 MB. Figure S2 , PDF file, 1.5 MB. Figure S3 , DOC file, 0.1 MB. Figure S4 , DOC file, 0.1 MB. Figure S5 , PDF file, 0.2 MB. " ] },{ "paper_id": "fc7c462f4b3c1a7e4ab9cf9d7be29353a8595a8c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Citation Perlman S, Zhao J. 2013. Human coronavirus EMC is not the same as severe acute respiratory syndrome coronavirus. mBio 4(1):e00002-13.", "A newly identified betacoronavirus, human coronavirus EMC (HCoV-EMC), has been isolated from several patients with respiratory and renal disease in the Middle East. While only a few infected patients have been identified, the mortality of the infection is greater than 50%. Like its better-known cousin severe acute respiratory syndrome coronavirus (SARS-CoV), HCoV-EMC appears to have originated from bats. In a recent article in mBio, M\u00fcller et al. described several important differences between the two viruses [M. A. M\u00fcller et al., mBio 3(6):e00515-12, 2012, doi:10.1128/mBio.00515-12]. Unlike SARS-CoV, HCoV-EMC can directly infect bat cells. As important, HCoV-EMC does not enter cells using the SARS-CoV receptor, human angiotensin-converting receptor -2 (hACE2) . These results provide a strong incentive for identifying the host cell receptor used by HCoV-EMC. Identification of the receptor will provide insight into the pathogenesis of pulmonary and renal disease and may also suggest novel therapeutic interventions.", "If the receptor for HCoV-EMC is a protein, it is predicted to have a distribution similar to that of ACE2 or an even more pronounced localization to the lower respiratory tract, given its apparent lack of human-to-human spread. It will also be interesting to determine whether the receptor is an ectopeptidase. Several alphacoronaviruses, including HCoV-229E and transmissible gastroenteritis virus, a pathogenic porcine coronavirus, use aminopeptidase N (APN). Both APN and hACE2 are ectopeptidases and cleave N-terminal amino acids from small peptides. However, in neither instance is the enzymatic activity of the protein required for receptor function, suggesting that the structure of the ectodomain of each molecule is especially amenable to coronavirus binding. In addition to serving as the receptor for SARS-CoV, ACE2 has lung-protective properties. Downregulation of ACE2, as occurs during SARS-CoV infection, is believed to contribute to pathological changes in the lung (7) . It will be of interest to determine if the receptor for HCoV-EMC has similar properties." ] },{ "paper_id": "fc9566ce58963eeecb60b3dd52a9e03712045a38", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fc97aeb066cf1151c61d37d9bdce776463d9fbc4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The PCR product was electrophoresed at 100 V for 35 min in a 2% agarose gel. Then, the gel was stained with ethidium bromide and was visualized under UV illumination.", "Further detailed epidemiological investigations including rearing environments and symptoms, as well as experimental infections, are considered necessary to clarify the pathogenicity of CaKoV.", "For the purpose of determining evidence for the circulation of CaKoV among domestic dogs in Japan, we attempted to isolate the CaKoV gene from fecal samples of household dogs and dogs being kept in pet shops." ] },{ "paper_id": "fca7adbc5fdaeba0fedd1201e496704b1a888556", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Several fatal infectious diseases, such as Middle East respiratory syndrome coronavirus (MERS), Ebola and Zika virus, have recently emerged around the world, and mortality rates are very high in patients who contract these illnesses (1) . Many infectious diseases are caused by viral infections, and in particular by RNA viruses. Detection and identification of these viruses are essential for understanding viral disease, and the accuracy and availability of tools designed for this purpose are crucial for effective and efficient virological studies.", "The MRPrimerV database consists of nine key-value tables: one table for PCR primers, one table for TaqMan probes, five partial annotation tables for five query types, one full annotation table for viral genomes, and one full annotation table for viral CDSs. The partial annotation tables are used to identify user input for each query type. The full annotation tables are used to generate the output page. The database is physically stored using Redis (http://redis.io/), an in-memory key-value store that supports various kinds of data structures for various types of values, including string, hash, list, set and sorted set.", "Supplementary Data are available at NAR Online." ] },{ "paper_id": "fcbb20fc325656ad86d5ed3e810cd0f4639ada77", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Yeast strains and plasmids used in this work are listed in Supplementary Table S1 . The transformation procedure was as described (28) . Strains were grown at 308C either in YPD, YPGal or YPGly medium (1% yeast extract, 2% Bacto-peptone, 2% glucose or 2% galactose or 2% glycerol, respectively) or in synthetic complete medium (SC, 0.67% yeast nitrogen base, 2% glucose or 2% galactose, supplemented with required amount of amino acids and nucleotide bases). Strains W303-1A-Bax, W303-1A-Bcl-x L , W303-rDNA were grown in SC media without leucine, tryptophan or uracil, respectively.", "Preparation of samples and analysis of chromosomal DNA fragmentation by pulsed field gel electrophoresis (PFGE) was performed exactly as described (30) . PFGE was conducted in a CHEF-DRIII Chiller System (Bio-Rad). One percent agarose gels were run in 0.5% Tris borate-EDTA buffer at 148C with an angle of 1208 with a voltage of 6 V/cm and switch times of 60-90 s for 24 h. Gels stained in ethidium bromide were analysed after destaining using Syngene Gene Genius Bioimaging System.", "RNase H cleavage was performed essentially as described (35) . Samples of 10 mg of total RNA were annealed with 40 ng of oligonucleotide complementary to the specific regions within rRNA at 688C for 10 min and digested with 1.5 U RNase H at 308C for 1 h. For detection, samples were separated on polyacrylamide gels and analysed by northern hybridization using probes located upstream of RHase H cleavage." ] },{ "paper_id": "fce3506fcb7fa163babc7f4e959283ecbe346bc9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As the ER did not have private rooms with toilet, the patient walked through the ER to go to the public toilet several times a day. The social tradition of many visitors or family members staying with patients created an environment conducive to superspreading events because of allowing close contact. Thus, the behavior of the patient, the environment of ER, and social tradition contributed a large number of close contacts, leading to this superspreading event.", "On May 21, he was readmitted to Hospital A with fever of 38.3\u00b0C. Computed tomography performed on readmission revealed slight improvement of consolidation in left lung but newly appearing small ground glass nodules in multiple lung fields (Fig. 1A , B, and C). His symptoms did not improve despite changing the antibiotics. As his fever continued and diarrhea developed, he sought another hospital (Hospital B) for treatment on May 25. Chest radiography showed faint infiltrates in both lung fields (Fig. 1D) . On May 27, chest infiltrates became more prominent and intermittent tachypnea developed. The attending phy- sician of Hospital B recommended that he visited a tertiary referral hospital.", "We found the shortest incubation period was 2 days, and half of the 81 cases developed symptoms within 7 days after the exposure. Therefore, it is of paramount importance that case identification, laboratory confirmation, and contact tracing should be done within a few days. As contact tracing would be the most time-consuming task, public disclosure of the information on the possible exposure (time and place of the index case) could facilitate a more rapid and comprehensive contact tracing. Our report highlights that all persons staying in the same ER or perhaps using the same toilet, should be considered and evaluated as having been potentially exposed to MERS-CoV. It is not always possible to early identify patients with MERS. Therefore, all health care facilities should have infection prevention and control practices in place." ] },{ "paper_id": "fce74c6d77b50d5f596c327529665bf89087097c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fcf83e742399308d0bd2e6c735ec2d46ecb03b9d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The Human Research Ethics Committees of the Children's Health Queensland Hospital and Health Service, the Royal Brisbane and Women's Hospital and The University of Queensland approved the study.", "Sample size and data analysis plan As respiratory syncytial virus (RSV) is the most widely recognised respiratory agent associated with severe disease in this age group, we chose it to use for sample size calculations. To calculate the proportion of pathogens detected that are RSV to within \u00b12.5%, we assumed the current proportion to be approximately 12.5%, that conservatively each participant will have an average of eight episodes of ARI over the course of the study, 13 20 62 the intraclass correlation coefficient within individuals is 0.07 (calculated from Lambert et al 13 ) and that 90% of subjects will remain enrolled at study completion ( previous large cohort studies conducted by the investigators had retention rates of 97-98%). 13 63 Consequently, with \u03b1=0.05 and power of 80%, we were required to enrol 138 infants. Similarly, if each subject returns 80% of their weekly nasal swabs, 13 we will be able to estimate the proportion of all swabs positive for RSV to within \u00b10.5%.", "Strengths and limitations of this study \u25aa As study procedures, including specimen collection and return, are conducted by parents, findings will be free from Hawthorne effects due to frequent interactions with study staff. \u25aa Systematic weekly sampling will provide a control set of specimens for the individual and the cohort, allowing quantification of virusspecific attributable risk to illness. \u25aa Non-random recruitment and enrolment requires awareness and assessment of potential bias and confounding prior to broad-based generalisation. \u25aa Similar studies in the past have oversampled from higher socioeconomic households, and we attempt to avoid this by using a recruitment strategy that targets pregnant women in both public and private hospital settings." ] },{ "paper_id": "fd90269a5594e3c1c8d7c98e497070eedef35213", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Multiple stockpiles and releasing models were adopted in the SNS system, including self-managed inventory, vendormanaged inventory, and just-in-time procurement and supply. 12 The stockpile includes vaccines, antiviral drugs, and PPE. The SNS serves as a national repository for state and local public health authorities to support and resupply materials. It also supports multi-state and national emergencies, such as large-scale pandemics and natural disasters.", "To counter potential biological and chemical threats, some countries formulate and provide funds for medical countermeasure (MCM) stockpiles, such as the Strategic National Stockpile (SNS) in the United States, 8 the National Emergency Stockpile System (NESS) in Canada, 9 the National Medicine Stockpile (NMS) in Australia, 10 and the rotation system in Singapore. 11 These systems are prepared to provide medicine (antiviral drugs, chemical antidotes, and antibiotics), vaccines, medical materials, PPE, and lifemaintaining equipment.", "After the SARS outbreak, the Canadian government established a surge supply system of antiviral agents, antibiotics, and PPE (masks, face shields, gloves, gowns). However, at present, a significant proportion of the supplies and equipment in the stockpile is nearly out-of-date and not in accordance with current medical standards or practices. Therefore, the Canadian government is working on new strategies to solve the issue of the high maintenance cost. For instance, the ''mini-clinics'' program was designed as a concept of portable, modular, and flexible medical emergency response delivery. This pre-positioning of ''mini-clinics'' aims to supplement existing medical care facilities that might be overwhelmed in a disaster." ] },{ "paper_id": "fe2b70a4317057c021120d2281f2d7796c742e86", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The murine macrophage J774A.1 cell line was purchased from ATCC (Manassas, VA). Cytochalasin D was purchased from MP Biomedicals (Solon, OH). Blocker of lipid transport 1 (BLT-1) was purchased from Calbiochem (Torrey Pines, CA). Sodium cholate, cholesteryl oleate, fucoidan, and other chemicals were purchased from Sigma-Aldrich (St. Louis, MO). 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-(lissamine rhodamine B sulfonyl) (rho B), and cholesterol were purchased from Avanti Polar Lipids (Alabaster, AL).", "The following synthetic peptides were ordered from Bachem (Torrance, CA): one 9-mer peptide, GFLSKSLVF (human TREM-1 213-221 , GF9); two 22-mer methionine sulfoxidized peptides, PYLDDFQKKWQEEM(O)ELYRQKVE (H4) and PLGEEM(O)RDRARAHVDALRTHLA (H6), which correspond to human apo A-I helices 4 (apo A-I 123-144 ) and 6 (apo A-I 167-188 ), respectively; and two 31-mer methionine sulfoxidized peptides, GFLSKSLVFPYLDDFQKKWQEEM(O) ELYRQKVE (GE31) and GFLSKSLVFPLG-EEM(O)RDRARAHVDALRTHLA (GA31).", "Total protein was extracted from liver samples using radio immunoprecipitation assay buffer (BP-115; Boston BioProducts) supplemented with protease inhibitor cocktail tablets (11836153001; Roche) and Phospho Stop phosphatase inhibitor (04906837001; Roche). Cell debris was removed from cell lysates by 10 minutes centrifugation at 12,000 rpm." ] },{ "paper_id": "fef0bb9eaac69559d0ff2f92ff83e0affd4435f0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplemental material for this article may be found at http://mbio.asm.org/ lookup/suppl/doi:10.1128/mBio.01174-14/-/DCSupplemental. Text S1, DOCX file, 0.1 MB. Figure S1 , DOCX file, 0.7 MB. Figure S2 , DOCX file, 0.6 MB. Figure S3 , DOCX file, 0.1 MB. Figure S4 , DOCX file, 0.1 MB. Figure S5 , DOCX file, 0.4 MB. Table S1 , DOCX file, 0.1 MB.", "stimulation, and overall lethality (4) . Together, the similarities and differences offer an opportunity to identify both conserved and pathogen-specific host responses important during respiratory virus infection." ] },{ "paper_id": "fef7a8f796c4068d359d7b65f03ddba1841d1738", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The database will expand in accordance with the growth of available sequence information that will be scanned by one of the existing programs for recode annotation.", "The data in the database may be explored in two ways. They may be browsed by one of the three categories: kingdom (archaea, bacteria, eukaryotes and viruses), organism and type of recoding. The data may also be searched directly by key words that can be inserted into the search field. Searches that use regular expressions are allowed. The output of a database search is a list of Recode-2 entries in a short format that includes organism name, kingdom, genus, type of recoding event, status of Figure 2 shows an example of sequence annotation for the human oaz1 gene, alongside a diagram of a stimulatory RNA secondary structure, and the Recode-1 logo.", "We also plan to continue developing tools for the automatic identification of recoding events from nucleotide sequences. As the field grows and the number of recoded genes progressively increases, it becomes harder to extract data from the relevant literature and a number of novel recoded genes may escape the database. Therefore, we encourage users and researchers in the field to submit their data directly to the Recode-2 database. We are also willing to provide help with the analysis of potential new recoding events." ] },{ "paper_id": "ff2461416a15e35f6befb112accdc1301f5a7724", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ff292a9fce88c9c34f9ffe636729dc31c20cf300", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Beta-hydroxybutyrate concentrations were analyzed in whole blood samples using an automatic analyzer (Precision Xceed, Abbott Lab.); hematocrit (Hct), Hb and BE were measured using an automatic gas analyzer (i-STAT 1, Abbott Lab.). Changes in relative plasma volume (rPV) were calculated from Hb and Hct, using accepted formulas [10] .", "Neonatal diarrhea remains the most common cause of death in beef and dairy calves, and is a major source of economic loss in the cattle industry [18] . Enterotoxigenic Escherichia coli (ETEC), and Cryptosporidium parvum, rotavirus and coronavirus appear to be the most important causes of infectious calf diarrhea. Calves are more sensitive to fluid loss than adult cattle, because of their higher total body water content and higher extracellular fluid volume. In addition, metabolic acidosis can occur secondary to diarrhea contingent on its severity and duration [22] . Intravenous (IV) fluid therapy is important for decreasing mortality associated with diarrhea in calves.", "All procedures were performed in accordance with the National Research Council Guidelines for the Care and Use of Laboratory Animals (National Academy Press, 1996). The following fluids were used: isotonic saline (ISS; Doubutuyou seisyoku-V injection: Nippon Zenyaku Kogyo Co., Ltd., Fukushima, Japan), acetated Ringer ' s (AR; Sakusan Ringer ' s-V injection: Nippon Zenyaku Kogyo Co., Ltd.) and acetated Ringer ' s with 5% dextrose (ARD; Prototype: Nippon Zenyaku Kogyo Co., Ltd.). Table 1 shows the composition of the different fluids used." ] },{ "paper_id": "ff2ac3737c6edf81ff29b8d72c3abc2b3df5b344", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ff34c772e37156609477e7f0fa4aba793171f806", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ff368c9be888417304869b18575ea6521dcc95b6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dynasore, bafilomycin A1, cathepsin B inhibitor (catalog no. 205531), and cathepsin L inhibitor (catalog no. 219427) were obtained from Calbiochem. Chlorpromazine (CPZ), methyl-beta-cyclodextrin (M\u2424CD), and NH 4 Cl were from Sigma. Compound R78206 was provided by Janssen Pharmaceuticals.", "Analysis of experimental variation. In all figures, error bars indicate the means \u03ee standard deviations for 4 or more independent samples. Single asterisks indicate P values of \u03fd0.05, as determined by Student's t test; double asterisks indicate P values of \u03fd0.01." ] },{ "paper_id": "ff3786e07cdc8f41bc8347c875b84813cbb8d3eb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Final diagnoses in 20 patients of the extrathoracic fever focus group were eight urinary tract infections, ten catheter-related infections, and two pseudomembranous colitis.", "Conflict of interest relevant to this article was not reported." ] },{ "paper_id": "ff3db609dbf2669d8d528279ef32280c2646ba85", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "View/request a protocol for this paper from Bio-protocol.", "DMSO and rupintrivir were purchased from Sigma Chemical Co. (St. Louis, MO, USA). 2\u2032-C-Me-A was obtained from Carbosynth Limited (Compton, Berkshire, UK). Solutions of GA and GS in DMSO were provided by X. Zhang (Department of Chemistry, Pennsylvania State University) and J. Frydman (Department of Biology, Stanford University), respectively. All the antiviral compounds were prediluted in DMSO for use. For no drug groups, same volumes of DMSO were spiked into the culture medium.", "The device was placed in the chamber of a stage top WSKM GM2000 incubation system (Tokai, Japan) adapted to a Nikon Eclipse Ti inverted microscope (Nikon, Japan) equipped with a ProScan II motorized flat top stage (Prior Scientific, USA). With this setup, bright-field and fluorescence images of the microwells were automatically acquired every 30 min from 2.5 to 24 hours postinfection. In each image, 36 (6 \u00d7 6) microwells were included with a CFI60 Plan Apochromat Lambda 10\u00d7 objective and a Hamamatsu C11440 camera." ] },{ "paper_id": "ff5a79ed22ea416e6d89caad1cf0d83dbc741a4b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Coronaviruses (CoVs) belong to the family Coronaviridae in the order nidovirales. Members of the Coronavirus family are positive-strand RNA viruses with large genomes ranging in size from 27-33 kb. The coronavirus genome encodes for a 5 replicase polyprotein (ORF1a and ORF1b) that, in turn, encodes for all the enzymes required for viral RNA replication. The genome also encodes for the 3 structural proteins, including spike (S), envelope (E), membrane (M) and nucleocapsid (N), which are common to all coronaviruses. The structural proteins are involved in various viral processes, including virus particle formation [4] . Additional subgroup-specific accessory genes are found interspersed among the structural genes, which vary in number and location. Recent studies have shown that the proteins encoded by these genes could be modulators of pathogenicity in the natural host [5] [6] [7] . \u00a7 These authors made equal contribution.", "It is noteworthy to say that the report of symptoms in young children, who represent the majority of patients, is based mainly on parental observations, where other possible subjective signs and symptoms fail to be recognized by the parents. Moreover, most of the studies were conducted on patients reporting to hospitals suffering from acute respiratory tract infection. To date, there are only few population-based studies and the question arises whether larger numbers of such studies might reveal the involvement of other body systems.", "Nevertheless, high pathogenicity is expected to evolve with coronaviruses. As for HCoV-NL63, the possibility of the development of a recombinant virus variant is high because of its high prevalence and the possibility of a recombination event through co-infection [24] . Moreover, the virus is able to survive for up to seven days in an aqueous solution and respiratory secretions and remains infective at room temperature. In heavily populated regions, direct person-to-person transmission is considered the major route of HCoV-NL63 spread [42, 44] .", "It is difficult to distinguish clinical symptoms caused by HCoV-NL63 from those caused by many of the other human viruses, which could make diagnosis and detection of the virus complex. Treatment of patients without a clear diagnosis could result in implementation of expensive and disruptive public health measures, as well as to an increased spread of the disease [68] . Therefore, improved surveillance and diagnosis of respiratory illness could reduce health-care costs drastically [68] [69] [70] ." ] },{ "paper_id": "ff6d57f2aad99be129432058665b361dc18747e8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Macrophage Cultures. Methods of harvesting and preparing cultures of mouse peritoneal macrophages have been previously described (5). In the present experiments, macrophages were seeded in 13 x 100-ram Wassermann tubes and incubated at 37\u00b0C in a roller drum.", "MLC. Individual spleens from PRI, C3H, and C3Hss mice were removed and passed through a 60-mesh stainless steel wire cloth (Small Parts, Inc.). Cells were counted and suspended in a medium consisting of 80% RPMI-1640 (Grand Island Biological Co.), 20% Chang's medium (6) (90% horse serum, 8% Hanks' BSS and 2% beef embryo extract), and 100 U/rag per ml of penicillin and streptomycin. Equal amounts of PRI and C3Hss or C3H lymphocytes were mixed and cultivated in glass Petri dishes in a 37\u00b0C incubator maintained with 5% CO2. C57 black/6 and DBA/2 spleens were processed and cultivated in the same manner.", "The plus signs indicate that the virus and the host are compatible." ] },{ "paper_id": "ff83907653a4c4500e8c509ca28169e924742b40", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In humans, only a single heterochromatin protein has been identified to date. This protein, CENP-B, was originally discovered when centromeric autoantigens (termed CENP antigens) recognized by sera of patients with scleroderma spectrum disease were identified by immunoblotting (Earnshaw", "of the chromosome scaffold are widely thought to have a structural role in mitotic chromosomes (Laemmli et al., 1978) ." ] },{ "paper_id": "ffe718db1820f27bf274e3fc519ab78e450de288", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Flavivirus virions are $50-nm particles with a nucleocapsid composed of capsid (C) protein surrounding a positive-sense single-stranded RNA genome of $11 kb. The capsid is enclosed in a lipid membrane within which the viral membrane (M) and envelope (E) proteins are embedded. The genome encodes a single polyprotein of approximately 3400 amino acids from which the three structural (C, M and E) and seven non-structural (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) proteins are processed by cellular and viral proteases (8) .", "Porcine embryo kidney cells (PS) have been used in experiments with TBEV strain Vasilchenko (Vs) and its infectious clone (pGGVs) as described previously (33) (34) (35) .", "The construction of the infectious clone pGGVs for Vs virus and methods of mutagenesis have been described (34, 36) . Briefly, the pGGVs was subcloned into two plasmids; one, pGGVs 660 contained the first 660 nt of the virus genome and the second pGGVs 660-10927 included the remainder. Site-directed mutagenesis was accomplished by PCR (details of primers are available on request). Mutated PCR products were cloned into the pGGVs 660 between MluI and EcoRI sites followed by sequencing.", "For growth curves, monolayers of PS cells in 96-well plates were infected with viruses at a multiplicity of infection (moi) of 1 PFU/cell, in quadruplicates. The inoculum (30 ml) was removed after 1 h, the monolayer washed thoroughly and replaced with 200 ml of media containing 2% serum. Media (10 ml) was collected at different time-points (8, 12, 16 and 24 h post-infection) and stored frozen at \u00c070 C, before virus quantification by plaque assay. For cytopathic effect (cpe), PS cell monolayers were infected in 96-well plates at an moi of 1 PFU/cell, in quadruplicates, and stained with naphthalene black after 72 h." ] },{ "paper_id": "ffed5d2a31a0c1a0db11905fe378e7735b6d70ca", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Israel. *Corresponding author (TT): tamirtul@post.tau.ac.il", "Ribosome profiling data normalization. We began the analysis by reconstructing ribosome profiles for E. " ] }]