[{ "paper_id": "002f09dfc9a1323a15bf72e349d8b733ac97a2aa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0036e8891c93ae63611bde179ada1e03e8577dea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "to Western Europe with the assistance of migratory birds carrying infected ticks over long distances (4, 5) .", "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .01065-19.", "FIG S1, TIF file, 0.2 MB. " ] },{ "paper_id": "00573277e6be50669016f770bc28ec2da0639a8f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "00683d59d56123ae85e080d00ef1b3edd3f7405d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "by infection with a phlebovirus (family Bunyaviridae, genus Phlebovirus). The main vectors are specific Aedes and Culex spp. mosquitoes, and primary hosts are sheep, goats, and cattle (1, 2) . RVF epidemics usually occur after heavy rainfalls, which inundate ephemeral wetlands and enable large numbers of Aedes spp. mosquito eggs to hatch; it has been hypothesized that these mosquitoes harbor RFV virus (3) (4) (5) . Virus transmission is sustained in locations with more persistent surface water, which provides suitable breeding conditions for other vectors, such as Culex sp. mosquitoes (6) . RVF epidemics among animal herds cause abortion storms, affecting all stages of pregnancy, and high death rates among neonates. Epidemics among humans often cause influenza-like illness, although severe conditions (e.g., hemorrhagic fever and death) have been reported (1, 2) .", "In early February, the highest R e value was 4.3 (95% CI 2.0-6.5). The HIT at that time was therefore estimated at \u224878.9%, varying between 50.0% and 84.6%.", "Herd immunity threshold (HIT) is defined as the proportion of animals that needs to be immune to a pathogen to control transmission (15):", "In the equation, R 0 , the basic reproduction number, is the expected number of secondary cases generated by a primary case in a totally susceptible population and measures the potential for an infectious agent to start an outbreak." ] },{ "paper_id": "0104f6ceccf92ae8567a0102f89cbb976969a774", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Fourteen cases were also tested for HBsAg, all showed negative results." ] },{ "paper_id": "01363927a2d74245f78e5850a085caf62836f9b8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A total of 538 (97%) participants agreed to put on an N95 FF respirator. Most of these (n = 489, 91%) used 1 of the 2 models offered by the interviewers. Twelve (2%) referred to the manufacturer's directions.", "Using geographic information system mapping software, we randomly selected homes in Orleans Parish (city of New Orleans). To focus on residential areas, we eliminated 6,345 of the parish's 10,181 census blocks (US Census, 2000) . The eliminated blocks were likely to be sparsely populated or to contain industrial buildings, commercial centers, or parks (blocks with <20 housing units and blocks in the lower 2.5% of housing unit density); to contain mostly high-rise apartment buildings or public housing units that would be diffi cult to access or remain uninhabited (blocks in the upper 2.5% of housing unit density); and to be in uninhabited neighborhoods (blocks in the Lower Ninth Ward). We randomly generated 600 waypoints (unique locations based on latitude and longitude) across the remaining 3,836 census blocks.", "We conducted analyses with SAS (version 9.1) and JMP (version 5.1) software packages (SAS Institute, Cary, NC, USA)." ] },{ "paper_id": "01732214b0e66594afaceb2f641102b42e1b4685", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "T oday's abundance of publicly available data from Internet-based sources has inspired ambitious disease surveillance efforts. Online news articles, Internet search terms, and user-generated content provide a wealth of information that can indicate disease occurrence, syndromes, and transmission patterns. Scientists can now collect and translate these data sources into useable surveillance platforms (1, 2) .", "Since that time, the world has seen several large outbreaks (e.g., cholera in Haiti and Ebola in West Africa), several emergences of new pathogens (e.g., Middle East respiratory syndrome and avian influenza H7N9), and some reemergence of established pathogens (e.g., poliomyelitis in the Middle East and Africa). The past few years have also seen further development of digital surveillance tools, with increased data volume on social media sites (e.g., Twitter and Facebook), more timely updating of news sources, and increased citizen science reporting.", "Additionally, we searched Google, Google Scholar, and PubMed to fill in missing outbreak start and discovery milestones, which was not done in the 2010 study. We did not expand our search for date of public communication because we were primarily interested in communications identified by the 3 informal disease reporting systems." ] },{ "paper_id": "017ca5bdac589a37196df7b8e077c4c371ab32da", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "019ede0c6f1c02b64dea8e05e3bc8c7cb5811fae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "01cfb2699f116b6a9e107c5eb20b1c5327d554f0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "022c31717b2ad8e7c25aab342d27c203d7e32527", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "026195c31c1b5e03c8b24560de008bce009e6ada", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This approach can be extended to other viral, bacterial, fungal, or protozoal pathogen groups and is a powerful new paradigm for timely identification of previously unknown organisms that cause disease in humans or animals and for monitoring the progress of epidemics.", "This study used platform technology that was funded in part by the Department of Defense through its DARPA Special Projects Office for the development of TIGER Technology, under contract MDA972-00-C-0053; patents are currently pending in the United States and internationally. Additional funding and support was provided by grants from the National Institutes of Health, AI 25913 to M.B., and T32 NS 41219 to B.N. All authors, with the exception of M.B. and B.N., are employees and stockholders of Isis Pharmaceuticals, Inc.", "We have described a novel approach using base composition analysis for viral identification. However, since RNA virus nucleotide sequences mutate over time within the functional constraints allowed by selection pressure (29) , the utility of this method to correctly classify RNA viruses depends on the resolution needed for a particular application. We considered 2 specific applications. The first was to distinguish SARS-CoV from other species of CoV that infect humans, namely HCoV-OC43 and HCoV-229E. The second application was the utility of the technique for exploration of animal reservoirs for the discovery of SARS-related CoV species.", "N ucleic acid tests for infectious diseases are primarily based on amplification methods that use primers and probes designed to detect specific organisms. Because prior knowledge of nucleic acid sequence information is required to develop these tests, they are not able to identify unanticipated, newly emergent, or previously unknown infectious organisms. Thus, the discovery of new infectious organisms still relies largely on culture methods and microscopy, which were as important in the recent identification of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) as they were in the discovery of HIV 2 decades ago (1) (2) (3) (4) ." ] },{ "paper_id": "02db9273596bf34a72c596189ed95dab16e683e4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For these 2 cameras, operators recorded the highest temperature displayed for each person. Measurements recorded by the FLIR during periods when the camera was not properly focused were excluded from the analysis.", "The 3 ITDS were positioned at the optimal distance (2-3 m) from each participant as recommended by the manufacturers. Each ITDS camera fi eld of view was preset to capture the patient's face and neck. Participants were asked to remove eyeglasses and hats and instructed to stand facing the cameras until temperature measurements from all 3 devices had been recorded.", "The study was approved by the Institutional Review Board (IRB) of the Centers for Disease Control and Prevention (CDC) and the IRBs of the hospitals in Atlanta and Chicago. The Albuquerque hospital's IRB reviewed the protocol but deferred to CDC's IRB for approval." ] },{ "paper_id": "0312582594429d880453377773c1925f5b65682b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "2. Gorbalenya AE. Genomics and evolution of the Nidovirales. In: Per-", "Specimens were homogenized (10% wt/vol) in Dulbecco modifi ed Eagle medium and subsequently clarifi ed by centrifuging at 2,500 \u00d7 g for 10 min. For RNA extraction, 140 \u03bcL of the supernatants were then used by means of QIAamp Viral RNA Mini Kit (QIAGEN S.p.A., Milan, Italy); according to the manufacturer's protocol, RNA templates were stored at -70\u00b0C until use.", "Step RT-PCR for Long Templates (Invitrogen S.R.L.), according to the manufacturer's instructions. The following thermal protocol was used: reverse transcription at 50\u00b0C for 30 min, inactivation of Superscript II RT at 94\u00b0C for 2 min, 40 cycles of 94\u00b0C for 30 s, 55\u00b0C for 30 s, 68\u00b0C for 30 s, and fi nal extension at 68\u00b0C for 10 min. The PCR products were detected by using electrophoresis through a 1.5% agarose gel and examination under UV light after ethidium bromide staining.", "GQ130243-GQ130268 and GQ148749-GQ148774 for 5\u2032 and 3\u2032 ends of the spike gene, respectively." ] },{ "paper_id": "038f7612653a0732ece011b4cc49e29d305d345b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "03e352c35635f746ff112e5a766eefe10efb59b4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "041827953afeda8e10e25ae78437e37f8a453578", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In summary, we generated specific mAbs directed against the human IRAS N-terminal. The mAb DA041 exhibited the best performance in a variety of assays including immunoblotting, immunoprecipitation, indirect immunofluorescence stainning, and flow cytometry. Specific mAbs may provide an ideal reagent for further investigation of the function of IRAS proteins.", "Imidazoline receptors were first proposed by Bousquet et al., when they studied antihypertensive effect of clonidine [1] . Based on their physiologic and pharmacological properties, imidazoline receptors are classified into three main types: I1R, I2R, and I3R [2] [3] [4] . I1R and I2R have been implicated in hypertension and psychiatric disorder regulation, respectively, while I3R may be involved in insulin secretion [5] [6] [7] [8] [9] . Compared with mitochondrial I2R, which resides within the monoamine oxidase protein [10] , the clonidine-preferring imidazoline binding sites (known as I1R) are localized to plasma membrane fractions [11, 12] and specifically to synaptic plasma membranes [13] .", "Transfected cells were harvested 48 hours after transfection. Total cell lysate preparation and western blot analysis were performed according to previously described procedures [26] . In brief, cell lysates were prepared, electrophoresed on SDS-PAGE gels, and transferred to polyvinylidene difluoride (PVDF) membranes. Membranes were blocked with 5% nonfat milk in TBST (20 mM Tris-HCl [pH 7.5], 150 mM NaCl, and 0.05% [v/v] Tween 20) and incubated with IRAS or GFP mAbs (Cell Signaling Technology Inc). Blots were incubated with horseradish peroxidase (HRP) conjugated goat antimouse antibodies (Santa Cruz) after primary antibody incubation, and blots were developed with enhanced electrochemiluminescence (ECL, Cell Signaling Technology Inc).", "The cellular localization of the IRAS protein was identified according to previously described procedures [27] . Cells on glass cover slips were rinsed with PBS, fixed with 3% paraformaldehyde for 30 minutes, and permeabilized with 0.2% [v/v] Triton X-100/PBS. Permeabilized cells were incubated with IRAS mAbs and TRITC-conjugated affinipure goat antimouse by PCR amplification of the human IRAS cDNA (AF082516) using the following oligomers: sense, 5 -CGGGATCCA-TGGAGCGGGAAGCCGAGCCG-3 , and antisense, 5 -CGGAATTCATAGAAGTGAAAATGCAAGAAGTG-3 . The full-length human IRAS was obtained by PCR amplification of the entire coding region, and the resulting 4512-bp PCR product was ligated into the pEGPC1 and PCMV-myc vectors in a similar fashion using the following oligomers, respectively: sense, 5 -CGCGAATTCTATGGCGACCGC-GCGCACCTTCG-3 , and antisense, 5 -CGGGATCCTAGC-CGGTGAGCTCGACAGGC-3 , sense, 5 -CGCGAATTC-GGATGGCGACCGCGCGCACCTTC-3 , and antisense, 5 -CCGCTCGAGCTAGCCGGTGAGCTCGACAGGC-3 . All plasmid sequences were confirmed by sequencing analysis." ] },{ "paper_id": "04733d9b91b1744e046dddef8b3253aa13a3c717", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "04f9e08f4eb5091105c2cca3133719d1bd10b1dc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Wuxi is a prefecture-level city of Jiangsu province, located in eastern China, with a population of 6AE2 million. Wuxi has seven districts and two county-level cities (Jiangyin and Yixing). Wuxi has a typical subtropical monsoon climate and seasonal influenza usually peaks once a year. 4" ] },{ "paper_id": "04fb1656b773a1db9bc2b340aa503fe12132c670", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "substrate scanning form complex in the entire asymmetric unit of the crystal. Table 1 , 2) were resolved in a 18% polyacrylamide denaturing gel 36 running for 3 hours. (c) 0.5, 2, 5 nM of FAN1 373-1017 wild type or 5 nM of D960A mutant 37 was incubated with 5' 32 P-radiolabeled 5' flap (10-1-10) substrate (5 nM) at 37 \u00b0C for 5 38 minutes, and the reaction mixtures were resolved in a 18% polyacrylamide denaturing 39 gel. dT 5 and dT 10 were loaded as size markers. TTGATAAGAGGTCATTTGAATTCATGGCTTAGAG M36 TTGATAAGAGGTCATTTGAATTCATGGCTTAGAGCT M38 TTGATAAGAGGTCATTTGAATTCATGGCTTAGAGCTTA M40 TTGATAAGAGGTCATTTGAATTCATGGCTTAGAGCTTAAT M42 TTGATAAGAGGTCATTTGAATTCATGGCTTAGAGCTTAATTG M44 TTGATAAGAGGTCATTTGAATTCATGGCTTAGAGCTTAATTGCT M46 TTGATAAGAGGTCATTTGAATTCATGGCTTAGAGCTTAATTGCTGA X0F TTGATCAGAG GTCATTTGAA TTCATGGCTT CGAGCTTCAT GTAGAGTCGAC GGTGCTGGGA TCCAACATGT TTTCAATCTG X0R CAGATTGAAA ACATGTTGGA TCCCAGCACC GTCGACTCTAC TCCGTTTCCG ATCGTCCGTT CGATGCTGGC TCCTGCTTGC X2F TTGATCAGAG GTCATTTGAA TTCATGGCTT CGAGCTTCAT GGATAGTCGAC GGTGCTGGGA TCCAACATGT TTTCAATCTG X2R CAGATTGAAA ACATGTTGGA TCCCAGCACC GTCGACTATCC TCCGTTTCCG ATCGTCCGTT CGATGCTGGC TCCTGCTTGC X6F TTGATCAGAG GTCATTTGAA TTCATGGCTT CGAGCTTCAT GGAGTCGTAAC GGTGCTGGGA TCCAACATGT TTTCAATCTG X6R CAGATTGAAA ACATGTTGGA TCCCAGCACC GTTACGACTCC TCCGTTTCCG ATCGTCCGTT CGATGCTGGC TCCTGCTTGC X12F TTGATCAGAG GTCATTTGAA TTCATGGCTT CGAGCTTCAT GGAGTCGACGG TGTACTGGGA TCCAACATGT TTTCAATCTG X12R CAGATTGAAA ACATGTTGGA TCCCAGTACACC GTCGACTCC TCCGTTTCCG ATCGTCCGTT CGATGCTGGC TCCTGCTTGC X16F TTGATCAGAG GTCATTTGAA TTCATGGCTT CGAGCTTCAT GGAGTCGACGG TGCTGGTAGA TCCAACATGT TTTCAATCTG X16R CAGATTGAAA H3, H4 5'-flap (10-1-10) a3-10-1, c10, b22 5'-flap (AT)(10-1-10) a3-10-1, c10, b22(AT) 5'Flap (crosslink at fork, \"0\") X0F, X0R, X40 5'Flap (crosslink at -2 bp from fork, \"-2\") X2F, X2R, X40 5'Flap (crosslink at -6 bp from fork, \"-6\") X6F, X6R, X40 5'Flap (crosslink at -12 bp from fork, \"-12\") X12F, X12R, X40 5'Flap (crosslink at -16 bp from fork, \"-16\") X16F, X16R, X40 ", "3 4 Supplementary Figure 1. Electron density for the FAN1-DNA complexes. (a) The 5 substrate scanning form ( P FAN1 shown as orange coils and A FAN1 as grey coils). 6 Example experimental electron density (blue meshes, 2.8 \u00c5 resolution, contoured at 1.5 7 \u03c3) is shown in the left panels. Right panel: Example electron density (blue meshes, 2.2 \u00c5 8 resolution, contoured at 1.5\u03c3) of DNA (yellow sticks) in the unbiased 2Fo-Fc simulated-9 annealing composite-omit map (torsion angle dynamics at 1000K using CNS 1 ). (b) The 10 substrate-unwinding form ( P FAN1 shown as orange coils and A FAN1 shown as cyan 11 coils). Top panel: Example electron density (blue meshes, contoured at 1\u03c3) of DNA 12 (green coils) in the unbiased 2Fo-Fc simulated-annealing composite-omit map (torsion 13 angle dynamics at 1000K using CNS). Bottom panel: Simulated annealing (torsion angle 14 dynamics at 3000K using Phenix) 2mFo-DFc map is contoured at 1.0\u03c3 as blue meshes 15 around 4\u00c5 radius of the complex. (c) The substrate-latching form. Top panel: Example 16 electron density (blue meshes, contoured at 1.7 \u03c3) of DNA (green coils) in the unbiased 17 mFo-DFc simulated-annealing composite-omit map (torsion angle dynamics at 1000K 18 using Phenix). Bottom panel: Simulated annealing (torsion angle dynamics at 2500K 19 using Phenix) 2mFo-DFc map is contoured at 1.0\u03c3 as grey meshes around 4\u00c5 radius of 20 the complex. (d) The stereo view of the experimental electron density map of the 21 105 106 107 108 109 110 111 112 Supplementary Figure 8. Twinning analysis of the substrate-unwinding form (a) 113 and the substrate-latching form (b) data. The left plots are the L tests 5 and right plots 114 are the maximum likelihood estimation of the twinning fractions 6 for the twinning 115 operator (h, -k-h, -l)." ] },{ "paper_id": "05326cc45fa2898c5850df85d30dad3d2c82acef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "057e31ee37a66543d6cf7f189356b43deb91a31a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "05fbc9a48ec571d9292767d0ac0e54d318a6eadc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Waterfowl are primary hosts for influenza A viruses (IAVs); however, there is sporadic infection of swine and other species that pose a risk of zoonotic spread. Yellow-shouldered bats were shown to be hosts of an IAV, thereby constituting a potential novel reservoir. We show that Pteropus alecto kidney cells (PaKi) are susceptible to infection and sustain replication of A/WSN/33 (H1N1) and A/Vietnam/1203/04 (H5N1). Importantly, we show that co-infection of PaKi cells results in novel reassortants. Please cite this paper as: Dlugolenski et al. (2013) Bat cells from Pteropus alecto are susceptible to influenza A virus infection and reassortment. Influenza and Other Respiratory Viruses 7(6), 900-903.", "In this study, the susceptibility of Pteropus alecto kidney (PaKi) cells 9 to infection with IAVs was investigated. Initially, a human strain of IAV, that is, A/WSN/33 (H1N1), was investigated for its ability to infect PaKi cells. Cells were infected with A/WSN/33 H1N1 at an MOI of 0\u00c101 in DMEM supplemented with 5% fetal bovine serum (FBS) without the addition of exogenous trypsin for 24 hours at 37\u00b0C. Infected cells were then examined by immunofluorescence using a mouse anti-NP primary antibody and a goat anti-mouse Alexa Flour 488-conjugated secondary antibody and visualized using confocal microscopy. As shown in Figure 1A , NP staining was observed in the nucleus and cytoplasm of PaKi cells indicating that bat cells are susceptible to infection with IAV.", "From these findings, the propensity for the generation of reassortant viruses was examined following co-infection of PaKi cells with A/California/04/09 and A/Swine/Illinois/ 02860/08 at an MOI of 3 per virus in DMEM supplemented with 0\u00c15% L-glutamine. Because these viruses require the presence of trypsin for multiple rounds of replication, infections were limited to one round of replication. Supernatants were collected at 24 hpi and plaqued on MDCK cells. Individual plaques were picked and amplified in MDCK cells. Supernatants were collected at 72 hpi, and RNA was isolated using the RNeasy kit (Qiagen). cDNA was synthesized from the purified RNA using the Verso cDNA synthesis kit (Thermo Scientific). The residual RNA was precipitated as described previously, 12 and cDNAs were further purified using the QiaQuick PCR Purification kit (Qiagen). cDNA from individual plaques was then screened using triplex TaqMan qPCR specific for each virus with primers and probes specifically targeting the HA, NA, and PB2 gene segments (Table 1) . Reactions were performed using the Quantifast Multiplex qPCR kit (Qiagen)." ] },{ "paper_id": "06559dd625491d6474ee88f08c12fc17c1830995", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "GIS are potentially powerful resources for community health for many reasons including their ability to integrate data from disparate sources to produce new information, and their inherent visualisation (mapping) functions, which can promote creative problem solving and sound decisions with lasting, positive impacts on people's lives [8, 9] ." ] },{ "paper_id": "0676519ecc7cd61639721c0d062615707f044506", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "06896d4cce2f5c7acef18238c110efec0865c2a7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "06d7c3e1e46a199332798bd18e31d49787b39f99", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "U cakar et al." ] },{ "paper_id": "0746647069ab1d117996a1f4468e4068629e6da6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0758be46dc2f4ada2905d557959a82ed31f0b93c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dr. Stone is an assistant professor at Columbia University School of Nursing. Her research interests include the assessment of cost and quality outcomes related to nursing care delivery.", "Nearly 3 million registered nurses (RNs) work in the United States. Ninety-five percent of these nurses are women, as are most of the 700,000 licensed practical nurses and >2 million unlicensed nurse assistants. Internationally, occupational distributions are similar.", "Policy solutions for nurse staffing fall into two general categories: 1) incentives and funding for various parties to increase the supply of nurses and 2) employer and hospital regulatory approaches. Although scholarships, loan forgiveness schemes, and funding of new nursing school student slots may be helpful, these policies are unlikely to overcome the long-standing, complex nature of the difficulties in recruiting sufficient newcomers to the nursing profession and then retaining a qualified workforce." ] },{ "paper_id": "078025b470595541bbb492b1aaed90862cdca287", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Antimicrobial use is affected by reimbursement policies, financial incentives, and healthcare regulation (19) . Forecasting the political and regulatory development in this area presents a major challenge. There is always a short-term lack of predictability with regard to political decision-making after unexpected epidemiologic situations, such as the bioterrorist attacks in 2001 and severe acute respiratory syndrome in 2003, which quickly influenced perceived medical needs (30) .", "New resistance mechanisms will emerge and disseminate. Multiresistant group A streptococci will render penicillin and macrolides useless in the treatment of pharyngitis. Salmonella spp. infections can no longer be treated with advanced cephalosporins, fluorquinolones, or carbapenems.", "\"Antibiotic therapy, if indiscriminately used, may turn out to be a medicinal flood that temporarily cleans and heals, but ultimately destroys life itself.\"" ] },{ "paper_id": "07fe504a3b64db4dd23da77929893eb89215f3be", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data analysis was performed using SPSS, version 11.5 (SPSS Inc., Chicago, IL, USA). Categorical data were compared by Pearson's chi-squared or Fisher's exact test, where appropriate. Normal distribution in continuous variables was determined with the Kolmogorov-Smirnov test and differences were subsequently determined either with student's t-test or Mann-Whitney U test. All p values reported were calculated two-sided with statistical signifi cance set to p \u0545 0.05.", "The study protocol was approved by the ethics committee of the Ruhr University, Bochum, Germany. All study participants gave their written informed consent prior to study inclusion.", "PCR products were visualized by staining with ethidium bromide by agarose gel electrophoresis considering a positive PCR reaction when a band of the expected size of 354 base pairs (bp) was detected. Sequence specifi city was confi rmed by sequencing all positive PCR products in both directions using Big Dye terminator chemistry and the ABI Prism 3100 (Applied Biosystems, Darmstadt, Germany).", "The laboratory team was blinded to the patient's COPD status. Strict laboratory procedures were implemented to prevent PCR contamination. One negative control was amplifi ed for every fi ve samples. A plasmid containing 5182 bp of HBoV DNA, isolate Stockholm 2 (ST2) [GenBank: DQ000496] cloned in the vector pCR4-TOPO \u00ae (Invitrogen, Paisley, UK) was used as positive control. Sensitivity of the HBoV PCR assay was assessed by dilution series and was determined to a single copy of viral genome per reaction." ] },{ "paper_id": "080315372a3c246497a2f111b90af0c956032487", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "One output of these surveillance systems is an indication of unusual events that require additional investigation. This investigation might include communication with other veterinarians to find additional cases, targeted epidemiologic studies, research projects, or control programs.", "Economic consideration leaves few alternatives to clinical detection of farm animal diseases. Laboratory analyses are infrequently performed and generally more basic compared to human medicine (32). However, slaughterhouses and other assembly points do provide surveillance opportunities.", "In all these systems, routine data recording is simplified by the use of pick-up lists. However, free text fields are also available, as the unexpected often does not fit in predefined fields. VetPAD and RSVP-A use mobile telephones or personal data assistants for data capture. \"\u00e9mergences\" primarily uses the Internet." ] },{ "paper_id": "08339aa5e21ebd96be7ad261cbff35cc29466329", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "08432fbe941b440c394214311d01a0dd2a29acd6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Diagnosis of ARI and assessment of its severity was made by using World Health Organization (WHO) standard protocol for ARI based on the presence of cough, tachypnea, chest indrawing, and wheezing for <7 days (9) . Severe disease was defined in children with a respiratory rate >60/minute and chest indrawing. Oxygen saturation (pO 2 ) was measured by using pulse oximetry (Nellor, Puritan Bennet, UK), and a pO 2 <85% was used as the cutoff for giving supplementary oxygen. Nasopharyngeal aspirates (NPAs) were collected by instilling 1 mL sterile phosphate-buffered saline through a nasopharyngeal mucous extractor. The aspirate was frozen at \u221280\u00b0C and transported frozen to Liverpool for analysis.", "From December 2003 to May 2004, all children <5 years of age admitted to the pediatric wards of King Hussein Medical Centre (KHMC) and Queen Alia Hospital (QAH) in Amman, Jordan, were enrolled into the study after informed consent was obtained from parents or guardians. The study, which determined the etiology, inflammatory responses, and clinical effects of ARI was approved by the research ethical approval committee of the Royal Medical Services, Amman, Jordan. KHMC and QAH provide all hospital pediatric care for Amman and its surroundings.", "This study was conducted during the peak period of ARI in Jordan, and the prevalence of detection of HBoV ranged from 12.9% in March to 37% in April. However, larger cross-sectional studies and longitudinal studies of HBoV-infected children are needed to determine whether HBoV causes ARI, its effect on children, and its seasonality. In addition, HBoV, similar to some adenoviruses (14) and other human parvoviruses, may show persistent shedding after an initial acute infection.", "Finally, we have also obtained evidence for variations in the HBoV NP-1 gene. In addition to the original Swedish strain, we found 5 variants with point mutations in the gene causing amino acid substitution in the deduced protein. What role this might play in HBoV pathogenesis and whether other genes encoding nonstructural protein 1 (NS-1) and virion proteins 1/2 (VP1/2) show similar variability are unclear. However, 2 CPV-1 strains showed 96.5%, 92.5%, and 97.5% homology in their NS-1-, NP-1-, and VP1/2-deduced proteins (15) .", "A total of 326 children were enrolled in the study, but sufficient nucleic acid was extractable from 312 NPAs for detection of each potential respiratory pathogen. For the remainder, the volume of NPA was too small for extraction of both DNA and RNA Of these, 57 (18.3%) children were infected with HBoV (Table) . The median age of HBoVinfected patients was 8 months and 29 (51%) were male, compared with a median age of 6 months and 156 (61%) male patients in the HBoV-negative patients (p>0. (1 patient) and adenovirus (6 patients). The median age was 3.5 months for those infected only with HBoV and 10 months (p = 0.012) for those co-infected with HBoV and other potential pathogens." ] },{ "paper_id": "0843b669142963c77ba252334d8bba1d78abbc12", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "085d7daf789f97c9886b9b8ab08bbf416d3128d2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "08a5baead4b645020cadeb031cd31220322b734c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "08ac8987e585268b0664efc52bc4abbfda31249d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "SUPPLEMENTARY FIG. S2. Expression of SMN protein in cortex, spinal cord, and kidney in adult SMA mice with 6 weekly doses of 10 mg/kg. Westerns were quantified on a LI-COR Odyssey \u00d2 FC imager and analyzed with Image Studio \u00d4 software. SMA, spinal muscular atrophy; SMN, survival motor neuron. The asterick indicates a p value of < 5 \u00b7 10-4. ", "Supplementary Data SUPPLEMENTARY FIG. S1. High Performance Liquid Chromatography trace of branched PepC7 cyclized product. (Top Panel) Branched PepC7 with first disulfide bond formed by dissolving the linear peptide in 0.1 M NH 4 HCO 3 (1 mg/ 3 mL, pH 8) followed by the addition of 2,2\u00a2-dipyridyldisulfide (1 mM) in methanol (0.2 mL/1 mg). (Middle Panel) Iodine oxidation of the Acm-protected Cys residues using a 10-fold excess of I2 per Acm as 20 mM I2 solution in acetic acid, 60 min at room temperature. (Bottom Panel) Iodine oxidation using a 20-fold excess of I2 per Acm, 30 min at room temperature." ] },{ "paper_id": "09fc4c5e368a43d21f5130cb8474d61d65191dd9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cell lines used were human HEK 293, rat PC12 and monkey Vero. HEK 293 cells were maintained in DMEM supplemented with 10% foetal bovine serum, penicillin, streptomycin and glutamine. PC12 were maintained in DMEM supplemented with 10% horse serum, 5% foetal bovine serum, penicillin, streptomycin and glutamine. Vero cells were maintained in Eagle's MEM supplemented with 5% foetal bovine serum, penicillin, streptomycin and glutamine (Invitrogen). SARS-CoV, Frankfurt 1 isolate (GenBank AY291315) was amplified as previously described (25) .", "Inhibition of SARS-CoV-induced cytotoxicity followed a similar procedure. SARS-CoV infections and siRNA transfections of Vero cells were performed as described previously (25) . Vero cells were seeded in 96-well plates, transfected with 85 nM siRNA using Lipofectamine 2000 and thereafter infected with 6000 TCID50 of SARS-CoV. The cytotoxicity was quantified with an LDH Cytotoxicity Detection Kit (Roche, Penzberg, Germany) 50 h later.", "\u00aa 2005, the authors" ] },{ "paper_id": "0a3a221e70ed8497ac197567fe69e7d384759826", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Methods: Retrospective study describing the epidemiological findings, clinicopathological findings, and fecal viral load from affected horses.", "Complete blood cell count and biochemical panels were performed on 8 horses. Blood ammonium concentration was measured in 6 ECoV-infected horses with clinical signs. For a complete list of variables that were evaluated refer to Table 1 ." ] },{ "paper_id": "0a3d78fb4b228cdc20e48fcc96f9da3f92ce1207", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0a492457fae69095f62bea0f3394665a4d83285c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "2 rare human enterovirus serotypes, coxsackievirus A21 and enterovirus 68, were detected most frequently in human enterovirus-positive adults with acute respiratory tract infections. Thus, during some years, these 2 viruses cause a substantial proportion of enterovirus-associated adult acute respiratory tract infections.", "The frequency of detecting CVA21 and EV68 among HEV-positive adults with ARTIs in Beijing, China, was high. The difference in the HEV serotypes we detected compared with serotypes detected by others (2, 3) suggests that the spectrum of HEV serotypes associated with ARTIs differs among geographic regions.", "H uman enteroviruses (HEVs) are small, nonenveloped RNA viruses belonging to the family Picornaviridae. HEVs are classifi ed into 4 species (HEV-A to -D) according to their molecular and antigenic properties (1) . HEVs are associated with diverse clinical syndromes, ranging from mild upper respiratory tract illnesses to severe and potentially fatal conditions, such as aseptic meningitis, encephalitis, myocarditis, acute fl accid paralysis, and handfoot-and-mouth disease (1) ." ] },{ "paper_id": "0a6e9aa35d1320355bf071879e98aabcacfe2b85", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This article presents a systematic framework of 12 essentials, or basic elements, of science-based policy. The 12 essentials are grouped into three categories, or areas, as follows: 1) knowledge generation, which includes credible design, accurate data, sound analysis, and comprehensive synthesis; 2) knowledge exchange, which includes relevant content, appropriate translation, timely dissemination, and modulated release; and 3) knowledge uptake, which includes accessible information, readable message, motivated user, and rewarding outcome.", "The science-based policy framework of knowledge generation, knowledge exchange, and knowledge uptake has similarities to Boyer's research (65) . Boyer studied the concept of scholarship and distinguished four kinds of scholarly pursuits: discovery, integration, application, and teaching (65) . Many parallels exist between Boyer's work and the framework described in this article: Boyer's discovery category parallels the framework's knowledge generation area, his integration category parallels the knowledge exchange area, and his application category parallels the knowledge uptake area. Overall, education is important in all three areas of the framework.", "where C ti indicates the predicted number of incident cases on day ti, and t is time expressed in the number of incubation periods; C, the predicted total number of cases; D ti + d , the predicted number of deaths on day ti + d, and t is time expressed in the number of incubation periods; D, the predicted total number of deaths; R 0 , the basic reproductive number (i.e., the expected number of new infectious cases per infectious case); F, the case-fatality rate (i.e., the proportion of cases who die within the symptomatic period); i, the incubation period (i.e., the time from infection to symptoms); and d, duration of disease (i.e., the time from symptoms to recovery or death).", "Apply existing methods and develop new methods for reducing bias and increasing data accuracy obtained from scientific research." ] },{ "paper_id": "0a89f0c083b2766075f2e8f8cdfaeccf6c43e406", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0aa9c6e5d23acccfae9077750071e2768bdeefe6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Since the pioneering work of the Ahlquist laboratory, a growing list of viruses has been reported to undergo replication in yeast. These include RNA and DNA viruses that infect plants, insects, mammals, and humans (Table 1 ) [17] [18] [19] [20] [21] [22] .", "The yeast Saccharomyces cerevisiae is a simple eukaryotic organism with approximately 6,000 genes. It is inexpensive to cultivate, can exist in either haploid or diploid states, and is extremely simple for genetic manipulations. The complete sequence of this yeast genome, the fruit of a worldwide collaboration of more than 100 laboratories from 1989 to 1996, was the first determined for a eukaryote cell. More than 75% of the genes have an assigned function, while more than 40% share conserved sequences with at least one known or predicted human gene ( [1] ; http://www.yeastgenome.org/).", "Since the genetics and cell biology of higher eukaryotes are extremely complex, scientists looking for a good model have turned to the use of yeast as a simpler system for the study of various pathologies including virus proliferation and assay new drugs against these pathogenic agents.", "In basic research in Virology, yeast has assisted the elucidation of the function of individual proteins from important pathogenic viruses such as Hepatitis C virus, and Epstein- Barr virus ([11, 12] ; for a review and further references see [13] ). Furthermore, studies of viruses that infect yeast have provided many important contributions to the dissection of the life cycle of many other higher eukaryotes RNA viruses and the host factors involved [14] ." ] },{ "paper_id": "0aca9344d369a4d450301ff2d727e4dd5219d45b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Moreover, their open-air storage may cause spontaneous combustion (Kheang et al. 2006) .", "Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.", "A weighted portion of SBE (5 g) was extracted with nhexane in a Soxhlet apparatus. Obtained solution has been concentrated in an evaporator until an oily substance was received, and its weight was determined.", "The emulsifying properties of betulin and its synthetic ester derivatives (tartrate, phthalates, tetrachlorophthalate) are being mainly used in the chemical industry, using them as emulsifiers and stabilisers of the oil/water systems or plasticisers in PCV production." ] },{ "paper_id": "0ad01da34afb0c735d7d9e50ca27610651b81d6e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0ae70ae84cc9052dedf214ca44a842f0f9edc161", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data were collected from respondents at the region, province, and district levels. Data from 73 (96%) provinces were made available through respondents in 765 districts (765/834, 92%). Full data from all province institutions were provided from 53 (70%) provinces. Data from Bangkok were provided solely by public hospitals.", "The survey instrument was sent to representatives of each of the 75 provinces and Bangkok in July 2007. These province representatives sent questionnaires to institutions at lower organizational levels. Duplication of data was avoided by coordinating data collection through designated institutional respondents. Those who did not respond were reminded by letter and phone calls 2 months after they had received the questionnaires.", "A survey instrument was developed from the resource list and pilot tested in Kanchanaburi Province among healthcare personnel from several public health and healthcare institutions at the local, district, and province levels. Minor modifi cations and clarifi cations were made to the survey instrument as a result." ] },{ "paper_id": "0b0cc43d86df1f781f1b37dc2e1a5d8e0b12f7ae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As an academic discipline, comparative medicine is not new; the first chair in it was established in 1862 in France (25) . The field has an illustrious history. In 1893, Theobald Smith, a physician, and F.L. Kilbourne, a veterinarian, published a paper establishing that an infectious agent, Babesia bigemina, the cause of cattle fever, was transmitted by an arthropod vector (25) . Their seminal work helped set the stage for Walter Reed's discovery of yellow fever transmission (25) . Another physician-veterinarian team, Drs. Rolf Zinkernagel and Peter C. Doherty, won the 1996 Nobel Prize in physiology or medicine for their discovery of how the immune system distinguishes normal cells from virus-infected cells (26) .", "Emerging Infectious Diseases \u2022 www.cdc.gov/eid \u2022 Vol. 12, No. 4,", "At the population level, zoonotic pathogens cause foodborne, waterborne, and arthropodborne disease outbreaks. These pathogens include Salmonella, Escherichia coli O157:H7, Cryptosporidium, yellow fever virus, and Borrelia burgdorferi (15) . Many of the category A, B, and C bioterrorist agents, such as Bacillus anthracis, Yersinia pestis, Francisella tularensis, Coxiella burnetii, and Nipah virus, cause zoonoses (16, 17) ." ] },{ "paper_id": "0b3d08dea77cc6eb97d674682c1a4eb6145940a1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "cDNA was generated from RNA using random hexamers and Multiscribe reverse transcriptase (Applied Biosystems). Transcripts were quantified on a 7500 Fast Real-time PCR system (Applied Biosystems) with Taqman primers and probe sets (Integrated DNA Technologies). Cellular levels of 18S ribosomal RNA were quantified in parallel by TaqMan analysis and used for normalization.", "Parametric and non-parametric data were analyzed by a two-tailed Student's t test and Mann-Whitney test, respectively using Prism software (GraphPad Software). Microarray data were analyzed by ANOVA and the Benjamini and Hochberg algorithm was used to control the false discovery rate (FDR) of multiple testing (Partek Genomic Suite; Partek Incorporated).", "Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:" ] },{ "paper_id": "0b746643e6aba929cdb7b709d0af00d39f09cb79", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In total 230 samples of symptomatic and asymptomatic samples were collected and tested for WUPyV and KIPyV by real-time PCR using an ABI 7500 System (Applied Biosystems, Foster City, CA, USA) (10) and for other respiratory pathogens by PCR (11) (Figure 1 ). In 119 samples (52%), the following nonpolyomavirus respiratory pathogens were detected: rhinovirus (32%); enterovirus (3%); respiratory syncytial viruses A and B (2%); coronaviruses OC43, 229E, and NL63 (17%); infl uenza viruses A and B (1%); human metapneumovirus (1%); adenovirus (<1%); Mycoplasma pneumoniae (3%); and Chlamydophila pneumoniae (5%).", "To track possible reinfections and/or prolonged infections of WUPyV and KIPyV during the observation period, we constructed Figure 2 . For pediatric patients 1, 2, 3, and 6, WUPyV was found in >1 positive sample. In addition, prolonged presence of WUPyV (in >2 successive samples, equal to >2 weeks) was detected in 3 children (1, 2, and 6). ", "Our overall percentages of WUPyV and KIPyV are somewhat higher than percentages reported in most other studies (1) (2) (3) (4) (5) (6) (7) (8) . This fi nding may partially be explained by the fact that samples were collected during the respiratory disease season. In addition, our study had a longitudinal design, and, therefore, our prevalences cannot be compared with those of other studies. In our study WUPyV was the third most prevalent pathogen (9%) after rhinoviruses (32%) and coronaviruses (17%). KIPyV was the fi fth most prevalent pathogen (3%), comparable with enteroviruses." ] },{ "paper_id": "0b94596064704e2646533ca450403c1ee7ce4ef2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0bef65699098fb63e5091c44004b59bcdb52858f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A surveillance program for infl uenza A viruses (H5N1) was conducted in live bird and food markets in central Thailand during July 2006-August 2007. Twelve subtype H5N1 viruses were isolated. The subtype H5N1 viruses circulating in the markets were genetically related to those that circu-", "Phylogenetic analysis of the virus HA and NA genes indicated that all 12 subtype H5N1 isolates were part of the Vietnam and Thailand lineage (clade 1). The viruses were closely related to those investigated in Thailand (2004) (2005) as well as to other subtype H5N1 isolates in clade 1. In contrast, they differed from infl uenza subtype H5N1 viruses of the south China and Indonesia lineages (clade 2) (Figure 2) . In this study, we did not discern any Thailand isolates closely related to the south China lineage, as previously established in Lao and Cambodia (5) . Phylogenetic analysis of 6 remaining genes showed them to be also closely related to the Vietnam and Thailand isolates.", "Emerging Infectious Diseases \u2022 www.cdc.gov/eid \u2022 Vol. 14, No. 11, November 2008 (H), 293 (R), and 295 (N) of the NA protein. In summary, the 12 viruses isolated from this study were similar to the viruses from other sources in Thailand, which indicates that the viruses are endemic to Thailand, are circulating in the country, and can be found in any exposed species. The route of infl uenza virus (H5N1) introduction into the markets remains to be established. We suspect that this contamination might have occurred as a consequence of animal movement from outbreak areas or from viruscontaminated cages, trucks, and equipment. Unfortunately, the original sources of animals in the markets could not be identifi ed because birds from different sources were housed in 1 or several cages. Fortunately, no human infection was found during 2007-2008 in those provinces where the viruses were isolated." ] },{ "paper_id": "0c3220694f8a18b6dcd64afae28c4784190e4ee6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A minimum of 1 \u00b7 10 4 events were collected for each sample (flow cytometry conditions for the FACSCalibur machine are listed in Supplemental Table 3 ). The data were analyzed using CellQuest 3.3 (BD Biosciences, San Jose, CA). A positive threshold was set for each BeadCon, based upon the highest fluorescent point seen in the negative control sequence (for all BeadCons, an HIV complementary sequence was used; the sequence is listed in Supplementary Table 2 ). Mean fluorescence intensities (MFIs) were recorded for the FL1 (6-FAM) and FL3 (Cy5) channels on gated BeadCons populations.", "Flow cytometers are common diagnostic tools used in the immunophenotyping of immune system cells or in the characterization of blood malignancies. With a routine configuration, they allow for the contemporary measurement of four different fluorescent wavelengths, in addition to two signals related to cell size and internal complexity. As such, their application is possible only when the fluorescent signal is associated with discrete particles, such as cells in suspension or microparticles. The flow cytometer has recently been used to detect nucleic acids in a multiplexed format using secondary reagents for signal detection (16) .", "In assay development for each group of targets, it will be necessary to consider whether single nucleotide polymorphism detection will be developed through these means, or if it is better for the system to be tolerant for small nucleotide changes that would allow detection even as the target sequence contains mutations. Unique sequences can be selected for each target, allowing specific detection. In addition, redundancy can be included within the assay by conjugating molecular beacons for multiple sequences of the same pathogen or gene onto a single type of bead. The further development of this assay to detect a single target from a complex mixture may be important in several fields of use. We hope to facilitate differential diagnosis, genetic testing, genotyping and gene expression studies through the use of this technology." ] },{ "paper_id": "0c4b19d02fd4fad087f3571c64cc5c33dcb5a3fb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0c4bfbf56443b6d80e018f40564789037ce69418", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0cb9fd10d6764d4a7400fe3efb76ee44955eba4c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ ", mostly from countries in the Arabian Peninsula. Travel-related cases have been reported in Europe, Asia, and the United States, with limited, local, person-to-person secondary transmission (3) .", "Although dromedary camels are considered to be the probable source for zoonotic infections in humans, the mode of transmission from animals to humans is not understood (4) . In 2014, Saudi Arabia experienced an outbreak due to increased zoonotic transmission and amplification by health care-related human-to-human transmission (3) ; the risk for secondary transmission from patients to household contacts was estimated at \u22485% (5) . To prevent secondary cases and local transmission, the World Health Organization recommends monitoring all contacts of confirmed patients (6) .", "We monitored 131 contacts of 2 case-patients with imported MERS-CoV infections in the Netherlands. Laboratory testing did not indicate transmission of the virus, including among contacts with high-risk exposures or those who developed respiratory symptoms. We also found no infections among travelers from the same group. Our findings agree with reports from Greece and Italy, in which no and limited secondary transmission, respectively, was found among close contacts of MERS-CoV patients (12, 13) ." ] },{ "paper_id": "0cf35bb67d4a9d57d3482d3acc790525eab934eb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "HIV-1 Virion Production. HIV-1 virion particles were prepared as described. 23 Briefly, HIV-1 NL4-3 (group M, subtype B) derived by the transfection of 293T cells with pNL4-3 (obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: pNL4-3 from Dr. Malcolm Martin 24 ) was used to infect cells from a non-Hodgkin's T cell lymphoma line (SupT1-CCR5). 25 Purified HIV-1 preparations (1000\u00d7 concentrates) were stored frozen at \u221280\u00b0C until used.", "Plasmid Construction. Complementary synthetic oligonucleotides (IDT) with BamH I and Sac I compatible ends were phosphorylated, annealed, and ligated into the p2luc vector using the BamH I and Sac I sites between the rluc and fluc reporter genes. 22 Plasmid DNA was purified from cell cultures (Qiagen), and the sequences of all constructs were verified by sequencing.", "RNA Synthesis, Purification, and the Frameshift Assay. RNAs for the frameshift assay were transcribed in vitro from p2luc plasmid DNA linearized with PmlI, purified His6-tagged T7 RNA polymerase (10\u00d7), 11.25 mM NTPs, and 2 units of RNase inhibitor (RNasin Plus; Promega, N2615) in 200 \u03bcL for 2 h at 37\u00b0C. Pyrophosphate was pelleted by centrifugation (10 min, 13,200 rpm), and RNA was extracted with phenol/chloroform. Unincorporated NTPs and salt were separated from the RNA by gel filtration (Ilustra MicroSpin G-25 Columns; GE Healthcare). RNAs were heated at 95\u00b0C for 5 min followed by incubation on ice for 30 min. Samples were lyophilized to dryness and resuspended in water at 1 \u03bcg/\u03bcL. RNA integrity and purity were confirmed with 1% agarose gel electrophoresis." ] },{ "paper_id": "0d8f8313ebf345a47ae755d7f470b393a79893fe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The ORF6A49-52 mutant did not show as high a level of significance.", "The ORF6 protein localizes to intracellular vesicles positive for Lamp1 and CD63" ] },{ "paper_id": "0de11ee7d10c90212661c1a3822244833f2465a0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All organisms, including plants, have developed mechanisms of defense against pathogenic and other challenges, thus solving a key biological problem: survival. A stunning example of this in human is the development of learned, or acquired, immunity, which is composed of both humoral and cell-mediated components. Adaptive immunity involves the production of Reprints and permission information is available at www.nature.com/reprints.", "A 7.2 \u00b5L sample of 20 \u00b5M CT (with phosphate group on its 5 prime end) was placed in 4 \u00b5L CircLigase II 10\u00d7 Reaction Buffer containing 330 mM Tris-acetate (pH 7.5), 0.66 M KAc, 5 mM DTT and 2.5 mM MnCl 2 . Afterwards, 2.8 \u00b5L CircLigase II (Epicentre, Madison, WI) was mixed with the buffer and diluted to 40 \u00b5L with water. The mixture was incubated at 60\u00b0C for 3 hours. Then 20 U Exonuclease I and 200 U Exonuclease III (New England Biotech, Ipswich, MA) were added to the mixture and incubated at 37\u00b0C for 1 hour. The enzyme was denatured by heating up the solution to 90\u00b0C for 20 minutes. Finally, the CT product was purified by denatured PAGE and desalted with NAP-5 columns." ] },{ "paper_id": "0e547f3723a50ef4f55c873f2a65dfbee42cd655", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0f3ba0147ba55673ad30d983c9c850e0e327d1cd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Age-and serogroup-specific ABCs data highlighted the increased risk for vaccine-preventable meningococcal disease among college students, adolescents, and young adults. These findings contributed to the Advisory Committee on Immunization Practices policy recommendation for routine use of meningococcal conjugate vaccines in all persons 11-18 years of age and subsequent recommendations for a booster dose during late adolescence.", "With the exception of surveillance for pertussis and legionellosis, the current ABCs case definition includes only culture-proven disease. Although culture remains the standard for diagnosing invasive infections, the use of culture-independent diagnostic tests will probably increase. Validation of culture-independent diagnostics will remain a major consideration for determining whether culture-independent tests are added to the ABCs case definition.", "When ABCs began, most cases were identified by reviewing paper laboratory log sheets and computer printouts and most case report forms were abstracted from paper records. The increasing availability of electronic laboratory and medical records may improve timeliness, completeness, and accuracy of reporting (34) . Ensuring that cases are appropriately captured requires an understanding of laboratory information system codes and periodic reviews of how data are imported. Extracting information and transferring it into usable formats remains a challenge (35) .", "ABCs and other EIP activities are collaborations between CDC, state and local health departments, and academic institutions. Originally established at 4 sites (California, Connecticut, Oregon, and Minnesota), by 2003 ABCs added Georgia, Maryland, New York, Tennessee, Colorado, and New Mexico, for a total of 10 sites. The sites represent geographic diversity and approximate the racial composition of the US population (2) . Currently, the population under surveillance ranges from 19 to 42 million (up to 12% of the US population), depending on the pathogen.", "For routine surveillance, a case of invasive bacterial disease is defined as isolation of H. influenzae, N. meningitidis, GAS, GBS, S. pneumoniae, or MRSA from a normally sterile body site (e.g., blood, joint, pleural, or cerebrospinal fluid) in a resident of the surveillance area. Additionally, cases include ill persons from whom GAS is isolated from a wound or other tissue in the presence of necrotizing fasciitis or streptococcal toxic shock syndrome. Cases of GBS in a mother are also included if GBS has been isolated from the placenta or amniotic fluid in the event of fetal death." ] },{ "paper_id": "0f82974698355743046b60766dc767f02c357ad0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Emerging Infectious Diseases \u2022 www.cdc.gov/eid \u2022 Vol. 22, No. 7, July 2016 MedicalDevices/ProductsandMedicalProcedures/DeviceAp provalsandClearances/510kClearances/default.htm).", "One promising approach has been to investigate libraries of drugs approved by the FDA and the European Medicines Agency. Considering development times and manufacturing requirements for new products, repurposing of existing drugs might potentially facilitate a rapid response to outbreaks of emerging viruses (see Regulatory section for a discussion on repurposing). Other early-stage work on MERS-CoV therapeutics includes studies focusing on the essential viral replication steps of fusion, proteolysis, and RNA polymerization (Table 3 ) (54) .", "For diagnostic devices, the current emergency use authorization pathway serves as a fast approach to make products available for emergency public health purposes. After an emergency has been terminated, Premarket Notifications for these products should be submitted to FDA for a more thorough evaluation as 510(k)s (http://www.fda.gov/ e6" ] },{ "paper_id": "0f9a9bcd7f82dc2e386aa78be1dc311be95e314b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "device reduces the mean IOP measurement variation compared to conventional rebound tonometry without signs of inflammation.", "Imaging for in vivo biocompatibility analysis was performed using a laser scanning confocal microscope (LSM 880 with Airyscan, Carl Zeiss AG). Z-stack images (step size: 2.5 \u00b5m, range: 500 \u00b5m) were captured using a 25\u00d7 EPI objective with immersion oil, and controlled by Zeiss ZEN 2.1 software. A 2\u00d72 tiling with 10% overlap section of each sensor field of view was captured and then stitched together using an imaging software (Zeiss ZEN, Carl Zeiss AG). All subsequent image analyses were performed with ImageJ/FIJI software.", "Dried wings of C. faunus, bought from Bicbugs LLC were coated with a 15 nm gold layer (Lesker Labline E-beam Evaporator, Kurt J. Lesker Company\u00ae, USA) before examination by scanning electron microscopy (SEM) (FEI Nova 200 NanoLab Dualbeam, USA) operated at 5 kV.", "Once harvested, the sensors were rinsed in 1\u00d7 PBS with 0.02% NaN 3 and incubated in 4% paraformaldehyde (PFA) for 30 minutes at room temperature (RT) followed by O/N incubation at 4\u00b0C. Then, the sensors were rinsed in 1\u00d7 PBS with 0.02% NaN 3 followed by incubation in freshly prepared quenching buffer (1\u00d7 PBS with 0.02% NaN 3 and 50 mM NH 4 Cl) for 15 minutes at RT. Following quenching, the sensors were rinsed again in 1\u00d7 PBS with 0.02% NaN 3 . The sensors were then incubated in blocking buffer (1\u00d7 PBS with 0.02% NaN 3 , 2% BSA and 0.25% Triton\u2122 X-100) O/N at RT with gentle shaking (20 rpm). For staining, the sensors were incubated in 1 mL staining reagent containing blocking buffer with 1:1000 DAPI 405 (cell nucleus marker), 1:500 Phalloidin 488 (cell F-actin marker), and 1:500 MMP-2 594 (matrix metalloproteinases marker)) O/N at RT with gentle shaking (20 rpm) followed by 37\u00b0C for 1 hour. Following staining, the sensors were washed in blocking buffer several times followed by incubation O/N at RT with gentle shaking (20 rpm). All confocal imaging was performed with the sensors fully immersed in blocking buffer to retain the morphology of the tissue.", "To demonstrate the multifunctionality of bio-inspired nanostructures in medical use, we combined the bottom-up nanofabrication approach with top-down microfabrication processes and made a nanostructured micro-optical implant that senses intraocular pressure (IOP) for diagnosis and management of glaucoma, which is a leading cause of irreversible blindness globally [19] [20] [21] . We confirmed significant improvement in the bio-inspired nanostructured sensor's optical readout angle, pressure-sensing performance, and biocompatibility during a one-month in vivo study conducted in rabbits." ] },{ "paper_id": "0faea8445e96457c63aa5ac80ed6b13b08c2e992", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0fe7366fd2acdb22f69d45c7373adf169a4636db", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Children with the diagnosis of CF between 6 and 18 years of age who attended clinics at Seattle Children's Hospital were eligible for enrollment. Lung transplant recipients were excluded. This study was approved by the Institutional Review Board at Seattle Children's Hospital." ] },{ "paper_id": "10243aff722d36cdd14970ce1fd5d4ac737430d5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "105aab8d21e803d2b363183c263a90ce47a9c5ae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Whether early viral suppression by antivirals can lead to attenuation of these cytokine responses and better outcomes warrants further study (7) .", "We report acute encephalopathy associated with infl uenza A infection in 3 adults. We detected high cerebrospinal fl uid (CSF) and plasma concentrations of CXCL8/IL-8 and CCL2/MCP-1 (CSF/plasma ratios >3), and interleukin-6, CXCL10/IP-10, but no evidence of viral neuroinvasion. Patients recovered without sequelae. Hyperactivated cytokine response may play a role in pathogenesis.", "Simultaneous CSF and plasma OC and OP concentrations were determined for patient 3, as symptoms progressed at 18 h after oseltamivir. The concentrations (mean \u00b1 SD) of OC in duplicate CSF and plasma samples were 18.3 \u00b1 0.9 ng/mL and 143.8 \u00b1 3.3 ng/mL, respectively; the CSF/plasma concentration ratio was 12%-13%. The OP plasma concentration was 1.05 \u00b1 0.03 ng/mL; it was not detectable in the CSF." ] },{ "paper_id": "109ac576c495ec3c3f4366c6f0f31d69e9b60dee", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "On October 21, 2010, cholera was confirmed for the first time in Haiti in over a century. The outbreak spread rapidly through an earthquake-devastated country; in less than one month after initial detection (from October 19 to November 15 of 2010), cholera had spread throughout the ten departments of Haiti and into neighboring Dominican Republic.", "Actions that were taken in response to alerts included (1) field investigation of outbreaks and alerts; (2) rapid set-up of a CTC/CTU or ORP; (3) WASH response: chlorination of water, distribution of Aquatabs, access to latrines, waste management, dead body management, and household decontamination; (4) provision of supplies (medical and non-medical) and equipment; (5) provision of human resources for health facilities and community mobilization activities; (6) training on case management, cholera prevention, and control; and (7) training for community workers (brigadiers and health agents).", "Received May 16, 2013 . Accepted for publication August 27, 2013. ", "The majority of the alerts (89.6%) were related to cholera. Nevertheless, the system also detected 76 non-cholera alerts, including threats such as rabies (canine and human), acute flaccid paralysis, diphtheria, varicella, suspected cases of measles, anthrax, intoxications, and other hazards, like riots, strikes, and others." ] },{ "paper_id": "10d5a17a8cfc4407042a218f9d7acb53c41056e2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Page 24", "Mol Immunol. Author manuscript; available in PMC 2019 September 30." ] },{ "paper_id": "10ec2c11f19caa55906670f42b14fa28ded3a926", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "10f76405b60d19a29ab68f2b476a870d91d5ea7d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1113bc8b42aace6654dc131243f78f2302bd63ba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The International Committee for the Taxonomy of Viruses has suggested criteria for circovirus species demarcation: genome nucleotide identities of <75 % and capsid protein amino acid identities of <70 % (1). The MiCV reported here therefore represents a new circovirus species.", "A long-established epidemic of enteritis, caused by an unidentified pathogen distinct from parvovirus, has now been recognized in mink. In 2013, we identified a novel circovirus by degenerate PCR and fully sequenced its genome. This virus differs substantially from currently known members of the genus Circovirus and represents a new species.", "To obtain the complete genome sequence of MiCV, we used primers CV-F3, CV-R3, CV-F4, and CV-R4 (Table 1) for inverse PCR, together with Premix PrimeSTAR HS DNA polymerase (Takara Bio, Inc., Dalian, China). The product was sequenced in duplicate. The complete The deduced capsid protein is 227 aa; highest similarity is 47.3% with porcine circovirus 2 (EU-RO-WB2006-38, JN382157) from wild boars in Romania (12) ." ] },{ "paper_id": "11618b8e0169b98b7c4f0b06f900d3fe4c853ab3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "118d16b3829c6880298058627442bdc06591be6e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Genome sequencing and virulence studies of 2 Japanese encephalitis viruses (JEVs) from bats in Yunnan, China, showed a close relationship with JEVs isolated from mosquitoes and humans in the same region over 2 decades. These results indicate that bats may play a role in human Japanese encephalitis outbreaks in this region.", "Phylogenetic trees derived from nucleotide sequences of the complete genome or the most variable envelope protein gene of selected JEV strains (Table 1) indicated that both JEV isolates from bats are members of genotype III as defined by Solomon et al. (3) . A more detailed analysis indicated that the bat JEVs are most closely related to human isolate LiYujie and mosquito isolate BN19 within cluster 6 ( Figure) . Similar phylogenetic trees were obtained based on other gene sequences, such as PrM (data not shown).", "Neurovirulence of the 2 bat JEV isolates was determined as described above, and the LD 50 for suckling mice was 8.0 log 10 /0.02 mL, compared with 3.5 log 10 /0.02 mL for the mosquito strain M10. Neurovirulence of these 2 bat isolates also was predicted from aa sequence comparison to those known to have high neurovirulence (13, 14) . As shown in Table 2 , all residues important for virulence and neurotropism were conserved between the bat JEV isolates and the Nakayama strain." ] },{ "paper_id": "11a21be0569b11edf62c871f9e2561a2a5389006", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "11e29fd44b612542dcb4724e582ed38d68cd93ae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A detailed description of how age-specific mortality was estimated for each sex, country, and year is published elsewhere (15) . Data on mortality come from various sources depending on the availability of data. For countries with abundant resources, information on deaths is from official vital registration systems (15) . In low-and middle-income countries, multiple sources of data may be used in an attempt to achieve as complete all-cause mortality estimates as possible (12) (13) (14) (15) (16) (17) (18) ." ] },{ "paper_id": "11e93497dd9355cd46dadf58d09c331585f0b6cf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We obtained informed consent from each child's parents or guardians before enrollment. The study protocol was approved by the ethics review committee at the Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China.", "We transferred the nasopharyngeal aspirates of each enrolled patient into Universal Transport Medium (Copan Group, https://www.copangroup.com), distributed them into aliquots, and stored them at -80\u00b0C. We screened for RSV subgroups A (RSV-A) and B (RSV-B) and other common respiratory viruses, including influenza virus (A and B), human rhinovirus, human parainfluenza viruses 1-4, human adenovirus, human enterovirus, human bocavirus, human metapneumovirus, and human coronavirus (229E, OC43, NL63, and HKU1), using multiplex reverse transcription PCR and PCR assays as described (18) .", "Considering no international RSV case definition exists (13), we encourage researchers in future studies to determine a working case definition that can balance the many attributes (e.g., accuracy, feasibility, flexibility, and usefulness) of the various definitions that have been used to conduct RSV surveillance or study disease burden." ] },{ "paper_id": "1227edfb87826c52b770b469aaa2f41f5276cc84", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "123c9d8da7648c728ebc6bfcd0e3b57cdc9cc8b7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Autopsy studies are essential to characterize newly emerging diseases. The recent severe acute respiratory syndrome (SARS) epidemic illustrates this point. It was hypothesized that the corona virus-induced pneumonia was associated with acute lung injury but pathological information was required to confirm this. Autopsy data suggest that lung injury in SARS patients is diffuse alveolar damage and is histopathologically consistent with that of the acute respiratory distress syndrome (ARDS) [3] .", "In the present issue of Critical Care, Perkins and colleagues revisit the role of autopsy in critically ill patients [1] . These authors evaluated 38 of 49 available autopsy reports in a population of 636 patients (6%). They found that premortem and postmortem findings were in complete agreement in less than one-half of these cases and that major missed diagnoses that might impact on treatment and outcome were present in 39% of the cases reviewed. The most frequently missed diagnoses included myocardial infarction, carcinoma and pulmonary embolism.", "Findings on autopsy may reflect systematic shifts in the prevalence of disease states over time and may serve to highlight the limitations of current medical imaging and other diagnostic procedures. In 1983, Goldman and colleagues analyzed 100 randomly selected autopsies from each of the academic years 1960, 1970 and 1980 at one university teaching hospital [2] . In each of these three decades, approximately 10% of autopsies revealed a diagnosis that might have lead to a change in therapy or outcome had it been known prior to the patient's death. In the 1980 autopsy series, there were fewer cases of renal disease and pulmonary embolism but a dramatic increase in systemic bacterial, viral and fungal infections. Renal disease became a less prevalent cause of death because of the introduction of long-term renal replacement therapy. Pulmonary embolus was better diagnosed by improved imaging modalities, and infectious complications increased because newer chemotherapy practices resulted in a greater population of immunocompromised patients. Autopsy findings helped to highlight shifts in clinical practice and to inform the clinician of new sequelae of emerging treatments." ] },{ "paper_id": "123d3406f2ad2c3c7f1595a4c4491aaf3a570931", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "125d62b8501fb7db5ffe3d173e9f805c568df5b4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "From September 20 through November 22, 2005, interviews were conducted in native languages by native speakers of each region, who used computer-assisted telephone interviewing and random-digit dialing. Unanswered numbers were tried again as many as 5 times; when possible, call-back appointments were made. Persons 18-75 years of age were eligible for participation, and the member of the household with the most recent birthday was invited to participate." ] },{ "paper_id": "12627b91b3942f3727458c1bd4653be6fe30600f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Bacteriology failed to grow organisms in cultures inoculated with liver and spleen after 48 h culture.", "Here we report a strain of CCV isolated from the livers and spleens of diseased pandas.", "The giant panda (Ailuropoda melanoleuca) is an endangered animal that is treasured by humans and strictly protected by law. Currently, pandas face the threat of infectious diseases [3, 10] . It has been reported that antibodies against multiple species of viruses such as canine distemper virus, canine coronavirus (CCV) [3, 4] . However, little information is available regarding the clinical relevance and epidemiology of these pathogens in giant pandas.", "Further characterization of the GPV gene, such as cloning of the entire S gene or other viral structure, may provide additional information on the virus." ] },{ "paper_id": "128fc4c67ef01890625e271452e1b9c7a4ac7984", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "in immunostimulatory strategies by blocking the interaction of the inhibitory programmed death receptor 1 with its ligand in this animal model.", "Important woodchuck immune cell surface molecules which have been cloned so far can be divided into two categories based on their function: molecules involved in innate immunity and molecules involved in adaptive immunity.", "The aim of a study in Vietnam was to evaluate viral suppression following combined treatment with a new vaccine containing all three envelope proteins of HBV (pre-S1/pre-S2/S) and lamivudine in CHB patients. The enhanced suppression of viremia in the combination group was reversed after the discontinuation of vaccine treatment, suggesting that booster doses are required for a sustained viral response. Anti-HBs was detected in 55/120 vaccine recipients, but only three patients demonstrated HBsAg loss, indicating that the vaccine-induced anti-HBs was unable to completely neutralize HBsAg in the serum [28].", "Development of the 2[ 3 H]-adenine-based proliferation assay enabled to detect the T-helper lymphocyte responses after stimulation of woodchuck PBMCs [39, 41] . In addition, several T-helper epitopes within WHcAg [39, 41] were identified in PBMCs from acutely WHV-infected animals. Significant progress in studying the T cell response of woodchucks was achieved by introduction of the flow cytometric CD107a degranulation assay that enables the detection of WHV-specific cytotoxic T cells (CTLs) in woodchuck PBMCs and splenocytes [38] . Several studies demonstrated that detection of CD107a, as a degranulation marker, is a suitable method for determination of antigenspecific cytotoxic T lymphocytes [71, 72] ." ] },{ "paper_id": "129385d837be59df19fab81b392563d1202ae5d1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "12c156dc659a9b4c3008ce4d6d10f464d60b5b65", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The approach smoothed the temporal pattern of the reproduction number, leading to overestimation of R in the week after control measures were implemented. We are trying to find a correction factor for this bias in ongoing research.", "The method has a natural real-time implementation in which 1) a first estimate of the reproduction number is available after a lag that depends on the generation interval, and 2) while the epidemic goes on, the estimate is consolidated, and its credible interval narrows. Incorporation of such a statistical estimation framework into real-time surveillance of future infectious disease outbreaks would enhance the ability of epidemiologists to provide timely advice to public health policymakers.", "Assume that we would like to compute the daily values R t from day 0 to present day T, before the epidemic has ended. Although daily incident case counts can be known up to day T, provided no delay in reporting occurs, the corresponding counts of secondary cases X t cannot. Secondary case-patients infected before day T, whose illness had a long incubation time, may have clinical onset only after day T. Furthermore, since the exact chain of transmission is seldom observed in practice, attributing secondary cases to previous cases is difficult. Focusing on these 2 issues, we show that the daily counts of symptom onset available until day T are sufficient to estimate R t .", "The method was retrospectively used to analyze the SARS outbreak in Hong Kong. The data consisted of the dates of symptom onset of the 1,755 case-patients who were detected in Hong Kong in 2003 (4)." ] },{ "paper_id": "12e736a64e6f0562c5360b81802cb2641033a769", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "13157beaef7cf1c5fd5a90b3a77bf3917409cdb4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Recently discovered respiratory viruses were detected in 19 (9.2%) of 205 nasal swab specimens from children in Brazil with respiratory illnesses. Five each were positive for human metapneumovirus (HMPV) alone and human bocavirus (HBoV) alone, 3 for human coronaviruses (HCoV-HKU1 or -NL63) alone, and 6 for more than 1 recently discovered virus.", "The diagnosis for most patients infected with HCoV-NL63 or HCoV-HKU1 was pneumonia. Of the 3 patients with single infections, 2 were hospitalized and 1 was treated at the emergency department; the 2 patients with mixed Novel Respiratory Viruses, Brazil infection of HCoV-NL63 and HMPV or RV were treated at walk-in clinics.", "The study protocol was reviewed and approved by the research ethics committees of the Institute of Puericulture and Pediatrics Martag\u00e3o Gesteira of the Federal University of Rio de Janeiro and the Educational Foundation of Serra dos \u00d3rg\u00e3os of Teres\u00f3polis. The parents of all children involved in the study gave informed consent for their chil-dren's participation in accordance with Resolution 196/96 of the Brazilian Ministry of Health." ] },{ "paper_id": "134953face0c7475092ed130a40ebd194b99358b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical Analyses of Distance Measurements. The determined initial contact position D C , equilibrium separation D eq , position of maximum adhesion D Adh , and thickness in the absence of ligand D T are averages of 7\u00c020 measurements from 2\u00c03 independent experiments. Standard deviations are the pooled standard deviations from separate sets of measurements. Averages were compared using the student's t test, and p-values <0.05 indicate a statistically significant difference, at the 95% confidence level. The standard deviation of the difference between pairs of values was determined by propagation of errors.", "' ASSOCIATED CONTENT b S Supporting Information. Details of the protein surface coverage determinations from SPR data and the force\u00c0distance measurements between protein monolayers and bare lipid membranes without neoglycolipid. This material is available free of charge via the Internet at http://pubs.acs.org. ", "Because the pull-off forces can depend on the rate of separation, preliminary measurements were done at different separation Biochemistry ARTICLE rates to establish conditions where the pull-off forces were rate independent and would therefore report the equilibrium adhesion energy per area. In the present study, at typical separation rates of \u223c20\u00c040 \u00c5/min, the pull-off forces were in the rate-independent regime." ] },{ "paper_id": "1373fc003367712c4d7def8811c096e4d270274b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dr. Aliabadi is an Epidemic Intelligence Service officer in the National Center for Immunization and Respiratory Diseases at CDC and a board-certified physician specialized in internal medicine. In addition to acute flaccid myelitis, her research interests include surveillance for rotavirus before and after rotavirus vaccine introduction in resource-poor settings and epidemiologic and infection control support for the Ebola response in West Africa. ", "Samples from PICU patients were tested first with the FilmArray panel at CHCO; positive samples were sent to CDC, where they underwent the same series of testing as controls.", "We also analyzed results of FilmArray testing for all patients admitted to the pediatric intensive care unit (PICU) at CHCO during July-November 2014. We chose this population because all patients admitted with respiratory symptoms routinely undergo FilmArray testing and results would provide a representative view of pathogens circulating in the community and resulting in severe respiratory illness at the time of the outbreak." ] },{ "paper_id": "13aaa954a9640c1432ca19b75e00c021ab63871b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "13b2340ab0e81bc4d29b8c0fb0a6894490c003b1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Vertebrate cell surface glycans consist mainly of five-and six-carbon monosaccharides. One remarkable exception is the family of sialic acids, whose members have nine-carbon backbones. 10 Other important features of sialic acids are: (i) the high level of diversity -currently the family comprises over 50 different members, with neuraminic acid considered as the prototype, and includes important variants such as N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) (Figure 1 ), (ii) their presence mainly in higher animals and in certain bacteria, and (iii) their location, typically at the termini of glycan chains, and usually linked to galactose via a2,3-or a2,6glycosidic bonds, or to sialic acid via a2,8-glycosidic bonds. Not surprisingly, their expression on the surface of cells makes sialic acids easily accessible as attachment molecules for a wide variety of microbial pathogens, including many viruses.", "Recently it become evident that other pathogenic viruses, including adenovirus type 37 (Ad37, family Adenoviridae), enterovirus type 70 (EV70, family Picornaviridae) and Newcastle disease virus (NDV, family Paramyxoviridae), all with a pronounced tropism for the human eye, share receptor preference with avian influenza A viruses for glycans terminating with a2,3-linked sialic acid (SAa2,3), [5] [6] [7] [8] [9] which is distinct from the SAa2,6-terminated receptor preferred by human influenza A viruses. Here, we review differences in sialic acid preferences of viruses that cause disease in humans and in the distribution of different sialic acids in tissues. Given the ocular tropism of Ad37, EV70 and NDV, and their preference for SAa2,3, we also discuss the human eye as a potential portal of entry for viruses such as the avian influenza A viruses.", "Avian influenza A viruses exhibit a strong preference for using a2,3-linked sialic acid as a receptor. Until recently, the presumed lack of this receptor in human airways was believed to constitute an efficient barrier to avian influenza A virus infection of humans. Recent zoonotic outbreaks of avian influenza A virus have triggered researchers to analyse tissue distribution of sialic acid in further detail. Here, we review and extend the current knowledge about sialic acid distribution in human tissues, and discuss viruses with ocular tropism and their preference for a2,3linked sialic acid." ] },{ "paper_id": "13b6abc1061e1cb04624b733ae472952f741e17f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Emerging Infectious Diseases \u2022 www.", "identified 40 confirmed dengue cases. Results obtained by capture immunoglobulin (Ig) M and IgG enzyme-linked immunoassay, real time 1-step polymerase chain reaction, and virus isolation showed that 33 (82.5%) of 40 patients were viremic. Airport fever screening can thus quickly identify imported dengue cases.", "Our results demonstrated that fever screening at airports is an effective means of identifying imported dengue cases, whereas the health statements of inbound passengers, which have been required for years, are ineffective. Although fever screening with infrared temperature screening was implemented in an attempt to avoid SARS transmission, it proved to be effective in active surveillance of dengue. This approach seems promising for dengue and perhaps for other diseases and should be further evaluated.", "Most of the confirmed cases (33 of 40) identified by airport fever screening were viremic (real-time PCR positive, IgM and IgG negative). The other 7 case-patients tested positive for dengue-specific IgM or IgG antibody, although they were febrile at the time of testing (data not shown). Estimating how many patients might have been viremic but were not picked up by the system is difficult, since persons infected with dengue virus are usually viremic from 2 to 3 days before onset of symptoms until defervescence." ] },{ "paper_id": "13cc0633cce64b71718f50ff5276ff5181a8e4fd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "14180d7522cd39919afbfe4a6725e1cfc51229bc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Background", "where is a constant factor." ] },{ "paper_id": "1447cbaffd1c03718da0534b7bfa97435cd3c78d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "144a42d199c75de765dbf0d0ec7b32a0f9b30dc4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In 2011, porcine epidemic diarrhea virus (PEDV) infection rates rose substantially in vaccinated swine herds.", "To determine the distribution profi le of PEDV outbreak strains, we sequenced the full-length spike gene from samples from 9 farms where animals exhibited severe diarrhea and mortality rates were high. Three new PEDV variants were identifi ed.", "F). The disease progressed to death within a few days. Pigs of all ages were affected and exhibited diarrhea and loss of appetite with different degrees of severity, which were determined to be age dependent; 100% of suckling piglets became ill. Pigs >2 weeks of age experienced mild diarrhea and anorexia, which completely resolved within a few days (5) . Morbidity and mortality rates were lower for vaccinated herds than for nonvaccinated herds, which suggests the emergence of a new PEDV fi eld strain(s) for which the current vaccine, based on the CV777 strain, was partially protective. To identify the PEDV strain(s) responsible for the recent outbreak in China, we sequenced the full-length S gene of isolates obtained from diarrhea samples collected from pigs at 9 affected pig farms. " ] },{ "paper_id": "145f37b63789de6209b2d69b56ea22f8755d76f1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Coronaviridae family causes various diseases including bronchitis, gastroenteritis, hepatitis systemic diseases and etc. on humans, animal and birds [12, 13] . Both host and viral factors affect the coronavirus virulence and the disease severity in animals. The disease is generally most severe in newborns [14] .", "Fold-change values greater than 1 indicate an up-regulation and fold-change values less than 1 indicate downregulation. However fold-change values more than 2 and less than 0.5 are considered significant." ] },{ "paper_id": "147048173a533a2503ddabbd4aedadd921ecb82c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1489b6508e4fd548cb93f4638e640de5f2741634", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Optimization of RPA and multiplex RPA development", "where SD Bg is the standard deviation of the background signal.", "As a solid support, in-house produced epoxy-silanated glass slides were used. Amino-modified oligonucleotide probes were spotted at a concentration of 15 \u03bcM in 3xSSC buffer with a Topspot Microarray Printer (BioFluidix GmbH, Freiburg, Germany, www.biofluidix.com). In total nine 6\u00d74 subarrays were spotted on each slide ( Fig. 1) with an approximate distance of 500 \u03bcM between individual spots. Several controls were incorporated in the assay including a specificity control (35 mer oligonucleotide with no sequence homologies), an immobilization control (15mer oligonucleotide with 5\u2032-Cy5-modification) and spotting controls (spotting buffer). The biochips were incubated over night at 25\u00b0C and 75 % air humidity in a climate chamber (Binder, Tuttlingen, Germany, www.binder-world.com). Before on-chip RPA reactions the glass slides were blocked in Thermo Scientific SuperBlock Blocking Buffer (Waltham, USA, www.thermoscientificbio.com) at room temperature for 1 h.", "Where C is the contrast value (in %), S is the primary fluorescence signal and Bg is the average fluorescence signal of the specificity and the negative controls of the individual " ] },{ "paper_id": "149587a47192b3b0d086c8fa649c00ed2e3a4bcf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "149fee3f610ddebf8ad1045779c8af5fb1f40940", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "14b39f322085ccc2513a1180bb7c5fa9ca9002e0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "14d04f36cb13550aa7769b61a079fa54031a21eb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All responses were coded on a fi ve-point Likert-scale. Response options for all questions were 'not at all willing,' 'a little willing,' 'moderately willing,' 'very willing,' and 'extremely willing'. In addition, 'don't know' and 'refused' responses were coded.", "Tables 1A-D present results of the survey logistic regression modeling, showing the unadjusted and adjusted odds ratio (OR) for the associations between the three health protective behavior questions and the composite (All) indicator.", "The survey data were weighted to adjust for probability of selection and for differing response rates among males and females and different age groups. 21 Data analysis was performed using the \"SVY\" commands of Stata version 9.2 (Stata Corp, College Station, TX, USA), which allowed for adjustments for sampling weights." ] },{ "paper_id": "14ec024c18ac73f9f5c859853acf801887aa9ef0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Page 6 of 7 ", "Pseudotyped lentiviruses with wild type or mutant spikes of MERS-CoV were generated from 293T cells (Invitrogen) by cotransfection of human immunodeficiency virus backbone plasmids expressing firefly luciferase as previously described (1). We used the packaging plasmids, pLP1, pLP2, and pLP/VSV-G (Invitrogen) and pLVX-Luc-IRES-ZsGreen1 (Clontech; https://www.takarabio.com). For spike protein pseudotyping, condon-optimized cDNA of the" ] },{ "paper_id": "156e1cb11da156eec419079bd54c3b78ab65d6f7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To detect SARS early, health professionals need to look not only for epidemiologic links but also clusters of unexplained respiratory infection. A cluster of respiratory infec-tions among families and visitors may not be evident initially because hospitals do not normally track infections in inpatients' families and visitors. In addition, infected patients may be asymptomatic before they are transferred to another healthcare facility.", "The SARS outbreak involved 88 case-patients whose exposure setting was hospital X (Figure) . SARS occurred in 50 patients, family members, or visitors. Thirty-three of these 50 persons were admitted to hospital X, and all 33 were included in this analysis.", "Although our results highlight the challenge of recognizing SARS among hospitalized patients, the occurrence of seasonal respiratory infections such as influenza may further compound the difficulty in identifying a SARS case. In places where recent SARS transmission has occurred, SARS should be considered during the evaluation of nosocomial as well as community-acquired pneumonia. This recommendation is particularly important if the hospital housed SARS patients within the previous 20 days or if unexplained febrile respiratory clusters had been noticed within the institution." ] },{ "paper_id": "1578499cbeda9a2abea8e444aab66575e8618b8c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Most (>80%) states reported having 1 POC for reporting chemical, radiologic, foodborne, infectious, and zoonotic events. All states should have a POC to facilitate prompt assessment and appropriate reporting. Such contacts also can assist in assessing events outside their areas of expertise or with unknown cause.", "Internal and external relationships of each state can play a role in reporting. Most states have formal information-sharing systems with other agencies within their state. Such dissemination of information within a state increases the likelihood that IHR reportable events are appropriately evaluated and reported. Other agencies may have knowledge that could be incorporated into a risk assessment.", "The CSTE State Reportable Conditions Assessment, completed by state epidemiologists, also was used to assess state reporting practices. Information was obtained from the 2007 Assessment, which is available for review by all states and territories (10) ." ] },{ "paper_id": "16519fe598d255bb46c40f7f08d79bf21b3a7ff2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "16692bb9b2915fbac5398b1171076aeeb4397528", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "166b70bab11b13953f7a074daa76bbe53d7300b7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "3 \u00d7 10 9 vector genome/well of AAV6 and AAV2 and 10 \u03bcl/well of parvovirus vaccine at 1:10 dilution were loaded onto a 4-12% NuPAGE Bis-Tris gel (Bio-Rad, USA). The gel was transferred onto nitrocellulose membrane (Bio-Rad, USA). Membranes were blocked with 5% non-fat milk, 0.1% Tween-PBS (w/v) overnight at 4\u02daC and then incubated with serum at 1:200 dilution. Horseradish peroxidase (HRP)-labeled rabbit anti-dog Ig was used as secondary antibody at 1:25,000 (Jackson ImmunoResearch, USA). Immunoreactive proteins were visualized using the ECL system (Amersham, USA).", "Muscle tissue was frozen in liquid nitrogen-cooled isopentane embedded in Tissue-Tek OCT medium (Sakura Finetek USA, Torrance, CA, USA) and sectioned transversely in cryostat at www.frontiersin.org 10 \u03bcm. For hPLAP staining, sections were fixed with ice cold 4% paraformaldehyde, washed three times in cold phosphate-buffered saline, placed in 65\u02daC phosphate-buffered saline for 90 min, rinsed in room temperature phosphate-buffered saline, and washed in alkaline phosphatase buffer (0.1 mol/l Tris-HCl pH 9.5, 0.1 mol/l NaCl, 0.01 mol/l MgCl 2 ) for 10 min. Excess liquid was removed from the sections, and Sigma FAST BCIP/NBT substrate solution (Sigma, St Louis, MO, USA) was applied to each section for 30 min at room temperature, in the dark. Slides were rinsed three times in room temperature phosphate-buffered saline, dehydrated in 70% EtOH for 5 min, 2\u00d7 (95% EtOH for 2 min), 2\u00d7 (100% EtOH for 2 min), 2\u00d7 (xylene for 3 min), and coverslipped with Permount mounting media (Fisher Scientific, Fair Lawn, NJ, USA). Images were captured using QIcam or Olympus digital cameras and processed using QCapture Pro (QImaging, BC, Canada). For hematoxylin and eosin m thickness were briefly fixed in methanol and staining, cryosections of 10 stained with Gill's hematoxylin and eosin-phyloxine. The sections were washed, dehydrated, and cleared in xylene before mounting with Permount.", "The 293 human embryonic kidney cells and HT-1080 human fibrosarcoma cells were maintained in Dulbecco's modified Eagle medium supplemented with 10% fetal bovine serum supplemented with penicillin and streptomycin. Cells were cultured at 37\u02daC in an atmosphere of 5% CO 2 ." ] },{ "paper_id": "16715be315ab1392947070e15252a60ae2b745f8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Prophylactic vaccine for Hiv-1 and 6 months. The placebo or AIDSVAX B/E vaccine was given to participants at 3 and 6 months. Participants were tested for HIV-1 infection every 6 months for 3 years. During each clinic visit, study participants were counseled on how to prevent HIV-1 infection.", "Recently, there have been encouraging developments regarding HIV vaccination. In the 1980s, in Thailand, there was a substantial increase in the prevalence of infection with HIV-1. [254] [255] [256] By first observation, these groups consisted of intravenous-drug users and commercial sex workers; this infected group then expanded to the general population. 101 By the mid 1990s, the overall seroprevalence of HIV-1 reached a peak of 3.7% among members of the Royal Thai Army and of 12.5% among people from Northern Thailand. 255, 257 The Thai Ministry of Public Health acted by starting an effective HIV-prevention campaign. With this effort, the number of new HIV-1 infections per year decreased from an estimated 143,000 in 1990 to 14,000 in 2007. 255, [258] [259] [260] Although this decrease was promising, there was still a desire to do more to prevent HIV infection. To achieve this goal, an HIV Phase III study was begun.", "As mentioned in the previous section, there are several daunting problems facing scientists who are attempting to create an HIV-1 vaccine. In hopes of creating a vaccine which elicits sterilizing immunity to HIV-1, researchers have focused their efforts on (1) the use of plasmid DNA vaccines, (2) live recombinant vectors for vaccine development (expressing or presenting HIV antigens), and (3) mucosal immunity. These critical topics will be discussed in more detail below.", "While several problems face scientists who are attempting to create an HIV-1 vaccine, three problems in particular have posed extremely daunting challenges. These three problems are 1) degree of diversity of the virus, 2) ability of the virus to evade the hosts' immunity, and 3) lack of appropriate animal models in which to test vaccine candidates. These three major problems will be discussed in more detail below." ] },{ "paper_id": "169edebe1c7c37c530c58a25683bdae4cc4eb14e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Replicative capacity of Middle East respiratory syndrome coronavirus (MERS-CoV) was assessed in cell lines derived from livestock and peridomestic small mammals on the Arabian Peninsula. Only cell lines originating from goats and camels showed efficient replication of MERS-CoV. These results provide direction in the search for the intermediate host of MERS-CoV.", "and representative peridomestic small mammals on the Arabian Peninsula. To estimate MERS-CoV permissiveness of cell cultures derived from these animals, we compared MERS-CoV replication and infectious virus production with that in bat-and primate-derived cells known to be permissive for MERS-CoV. The MERS-CoV receptor dipeptidyl peptidase 4 (DPP-4) is expressed in epithelial cells of the lung and kidney, and patients with MERS-CoV consistently show severe involvement of both organs; thus, we focused on lung and kidney cells in potential animal hosts (10, 11) .", "After following virus growth in all permissive cells for another 20 h, we harvested supernatants and, to confirm the production of infectious virus particles, we titrated the supernatants by using a plaque assay in Vero cells. MERS-CoV replication was seen in all permissive cells except TT-R.B (Figure 2 , panel D), and all permissive cells showed cytopathic effects. The highest production of virus particles was in goat lung and kidney cells (1.0 \u00d7 10 7 and 2.7 \u00d7 10 6 PFU/mL, respectively). This level of replication was comparable to that in human lung cells (A549) and Vero E6 (Figure 2, panel D) ." ] },{ "paper_id": "16b0744424f02e01fe2f01b3ea03e2862f1359fc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Bacterial and Archaeal 16S rRNA datasets are available from BioProject (PRJNA33175 and PRJNA33317, respectively). A custom BLAST database is also available ('16S ribosomal RNA sequences (Bacteria and Archaea)').", "The new prokaryotic data model offers a significant advantage to name management as the protein name is carried with the protein sequence record; updating the name on that protein record results in automatically propagating the update to all genomes that are annotated with that accession number.", "In recent years advanced sequencing techniques have facilitated a substantial increase in whole genome assembly submissions to the public databases. As a result, the RefSeq project has concordantly expanded the depth and breadth of taxa included in the dataset primarily through improvements to several in-house annotation pipelines. All taxa are in scope for RefSeq inclusion; however, annotation is often limited to those organisms for which a high quality primary genome assembly is available with uncontested organism information. Thus, we may exclude some categories of data that don't meet our quality standards. Excluded datasets include: metagenomes, assemblies with low contig N50 values or especially high number of unplaced scaffolds/contigs (i.e. high fragmentation), or genomes that have significant mismatch or indel variation compared to other closely related genomes for the species (e.g. some prokaryotes).", "In 2015, we released a comprehensive annotation update for RefSeq prokaryotic genomes in order to harmonize genome annotation and complete the transition to the new protein data model. A new prokaryotic protein name database, name specifications, and an evidence-based strategy were developed and are currently in the process of being deployed. Thus far, over 3 million protein records have updated names in an initial demonstration of the approach." ] },{ "paper_id": "16b7f68551e24898021ef6f3ba87149381fb0dd0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "16f9fa5dc35b07c217016a843dff05fa7d9874bf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "H epatitis E virus (HEV) belongs to the family Hepeviridae and genus Hepevirus. Among humans worldwide, HEV is the most common cause of acute viral hepatitis. The disease is generally self-limiting, but mortality rates are high among pregnant women and young infants. Chronic HEV infection is a problem for immunocompromised patients, such as those who have received a solid organ transplant and those with HIV infection. In addition to humans, HEV has been found in the other mammals: pigs, boar, deer, rodents, ferrets, rabbits, mongoose, bats, cattle, sheep, foxes, minks, and horses (1-3). Among the 4 known HEV genotypes, HEV1 and HEV2 infect only humans; whereas, HEV3 and HEV4 can infect humans, pigs, and other mammals. Human infections with HEV3 and HEV4 have been associated with consumption of raw or undercooked pork or game meat (4). Traditionally, HEV infection is mainly transmitted through water contaminated with infected feces. Since water supplies and sanitary infrastructures have been improved, animals have become a major source of human HEV infection. We detected HEV in fecal samples from dromedary camels in the Middle East.", "In a molecular epidemiology study of hepatitis E virus (HEV) in dromedaries in Dubai, United Arab Emirates, HEV was detected in fecal samples from 3 camels. Complete genome sequencing of 2 strains showed >20% overall nucleotide difference to known HEVs. Comparative genomic and phylogenetic analyses revealed a previously unrecognized HEV genotype.", "Reverse transcription PCR for a 284-bp fragment in ORF2 of this HEV, which we named dromedary camel HEV (DcHEV), was positive for 3 fecal samples; viral loads were 3.7 \u00d7 10 5 , 4.5 \u00d7 10 5 , and 3.2 \u00d7 10 7 copies/mL. Complete-genome sequence data for 2 DcHEV strains (GenBank accession nos. KJ496143-KJ496144) revealed that the genome size was 7,220 bases and had a G+C content of 55% (Table) . Overall, the DcHEV genomes differed from all other HEVs by >20% nt (online Technical Appendix Table, wwwnc.cdc.gov/EID/article/20/6/14-0140-Techapp1.pdf)." ] },{ "paper_id": "170447c8d130a81bb16cd4232cb1332bcc8a1863", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Herein, I overview current understanding of the biological aspects of various PLA 2 enzymes in the context of lipoquality.", "By applying lipidomics approaches to knockout or transgenic mice for various PLA 2 s, it has become evident that individual enzymes regulate specific forms of lipid metabolism, perturbation of which can be eventually linked to distinct pathophysiological outcomes. Knowledge of lipoquality control by individual PLA 2 s acquired from studies using animal models should be translated to humans. Current knowledges on the relationship between PLA 2 gene mutations and human diseases are summarized in Table 2 . Nonetheless, future development of more comprehensive and highly sensitive lipidomics techniques will contribute to the discovery of novel PLA 2driven lipid pathways that could be biomarkers or druggable targets for particular diseases. Nakanishi, H., Ikeda, K., Taguchi, R., Kabashima ", "The iPLA 2 /PNPLA family.", "Unlike most PNPLA isoforms that are ubiquitously expressed in many tissues, PNPLA1 is localized predominantly in the upper layer of the epidermis. PNPLA1 acts as a unique transacylase, catalyzing the transfer of linoleic acid (LA; C18:2) in triglyceride to the B-hydroxy residue of ultra-longchain fatty acid in ceramide to form B-O-acylceramide, a lipid component essential for skin barrier function. 68),69) Accordingly, genetic deletion or mutation of PNPLA1 hampers epidermal B-O-acylceramide formation, thereby severely impairing skin barrier function and causing ichthyosis. The unique role of PNPLA1 in the acylceramide-metabolic pathway in the epidermis is depicted in Fig. 5 ." ] },{ "paper_id": "174406471afbd68d911a4e2f3033a40b7baa7765", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "and was observed to be stuck (yellow arrows) on the wall of the canister.", "In order to determine the minimum RNase A concentration to degrade siRNA completely, siRNA (300 ng) was incubated with different amounts of RNase A in TE 1X pH 8 buffer (0.02, 0.07, 0.162, 0.348, 0.7, and 3.3 \uf06dg RNase A per 1 \uf06dg siRNA) for 45 min at 37\uf0b0C, in presence or absence of RiboLock \u00ae RNase Inhibitor (RI, 1\uf06dL = 40U). The concentration of 0.35 \uf06dg RNase A per 1 \uf06dg siRNA has been reported in literature to be enough to degrade a large fraction of siRNA in polyplexes, 1, 2 and based on that, the amount of RNase A was varied in this experiment. Next, samples were frozen at -20\uf0b0C overnight, and loaded in the slots of casted agarose gel (1.5 % w/v in TAE 1X pH 8.2 buffer) stained with ethidium bromide (0.5 \uf06dg \uf0b4 mL -1 ). The electrophoresis was performed at 60V (E0160-VWR Mini Gel Electrophoresis) for 40 min, and the siRNA-dye migration was visualized under UV irradiation (FOTO/Analyst \u00ae Investigator/Eclipse with UV Transilluminator Fotodyne Inc.) and the images were recorded using the FOTO/Analyst \u00ae PC Image software (v.5). The result is shown in Figure S1 , and clearly indicates that free siRNA (not protected by RNase inhibitor) was completely degraded by RNAse A starting at concentration 0.162 \uf06dg RNase A per 1 \uf06dg siRNA, since no siRNA band was observed in lane 6 compared to lane 7 and lane 1.", ". RNase degradation assay (non-denaturing agarose gel electrophoresis) of the free siRNA as a function of the RNase A concentration. siRNA (300 ng) was incubated with increased concentrations of RNase A (0.02, 0.07, 0.162, 0.348, 0.7, and 3.3 \uf06dg / \uf06dg siRNA, in lanes 2 -3, 4-5, 6-7, 8-9, 10-11, 12-13, respectively) siRNA RNase A RiboLock\u00ae Lane + + + + + + + + + + + + + -+ + + + + + + + + + + + -+ -+ -+ -+ -+ -+ -S2. Heparin decomplexation assay. Heparin is known as a model polyanion competing agent with nucleic acids for electrostatic interactions with polycations, 3 and it has been used to dissociate siRNA from several polycationic carriers. [3] [4] [5] [6] [7] [8] [9] Thus, heparin was used in this work to dissociate siRNA from PAMAM G4NH2 dendrimer. In order to determine the most favorable condition of heparin treatment to release the highest siRNA content from the dendriplexes, siRNA-G4NH2 at N/P 10 were formed in 10 mM Tris-HCl pH 7.4 buffer, 10 as described in the Experimental Section, incubated with heparin in TE 1X pH 8 buffer at 37\uf0b0C for different time points, and frozen at -20\uf0b0C overnight. The final heparin concentration was 5 mg \uf0b4 mL -1 corresponding to 455 U per 1 \uf06dg siRNA calculated based on 1000 U per 1 mL. 4 The final siRNA concentration after dilution of the dendriplexes to 1 mL was 80 nM. siRNA-G4NH2 dendriplexes incubated in presence or absence of heparin (minimum of three independent batches, n = 3) were quantitatively analyzed using PicoGreen \u00ae assay 11 in Synergy 2 Microplate Reader (BioTek, VT) for the siRNA content released, which was calculated using a linear calibration curve (siRNA concentration vs. fluorescent units). Thus, siRNA released from the dendriplexes due to heparin treatment was determined based on the difference between the siRNA content truly complexed with G4NH2 (siRNA CE was applied in the calculations) and the free siRNA released and remaining in the dendriplexes dispersion. Appropriate control (PAMAM G4NH2 in presence of heparin, but no siRNA) was used as blank. The results are shown in Figure S2 , and indicate that the siRNA is released from G4NH2 dendrimer due to treatment of the dendriplexes with heparin. The incubation time of 30 min released the highest siRNA content -80% on average, and narrower standard deviation -out of the total siRNA complexed with G4NH2, and thus, it was chosen as standard time for all further heparin decomplexation assay experiments. constitutively express eGFP (enhanced green fluorescence protein) according to GenTarget protocol. 12 Briefly, A549 cells (passage 5) were seeded in 24-well microplate (25,000 cells per well) and cultured in 500 \uf06dL DMEM supplemented with 10% FBS and 1% AB (v/v) for 24 h at 37\uf0b0C and 5% CO 2 (Thermo Scientific Incubator, NAPCO 8000WJ). Cells were rinsed with PBS 1X buffer, and fresh culture medium (DMEM + 10% FBS + 1% AB, v/v) was added to them, following 50 \uf06dL per well of eGFP lentiviral particles. Cells were kept in incubator for 72 h at 37\uf0b0C and 5% CO 2 , and after that, they were rinsed with PBS 1X buffer, and the puromycin selective medium was added to them (DMEM + 10% FBS + 2.5 \uf06dg \uf0b4 mL -1 puromycin selective antibiotic; concentration was previously determined by a kill curve). Cells were cultured under this selective condition for 4 weeks, 13 dendriplexes alone were attempted to be formulated as pMDI. Dendriplexes at N/P 10 were prepared in RNase-free DI-water, the aqueous dispersion (siRNA and PAMAM G4NH2 at the same amount as what is loaded into CSLA and mannitol particles) was placed into the pressure proof glass vial, which was frozen (-20\uf0b0C) and lyophilized. The canister was crimp sealed with a 63 \uf06dL metering valve, and a known volume of propellant HFA-227 was filled into it so that the siRNA concentration was the same for pMDI formulations containing dendriplexes loaded into CSLA or mannitol particles. Then, the formulation was placed into sonication bath (30 min at 15 -20\uf0b0C) to disperse the dendriplexes in the propellant. As a result, the dendriplexes were observed getting stuck on the wall of the glass vial, and even after sonication for a long time, they did not disperse in the propellant as seen in Figure S5 . Thus, it was not possible to have pMDI formulations of free siRNA-G4NH2 dendriplexes for further comparison with those prepared with CSLA and mannitol particles. Therefore, this result presents the difficulty of formulating siRNA-based dendriplexes alone in propellant HFA, and strongly suggests that an appropriate micro-carrier is needed for the job -such as CSLA and mannitol which are being proposed in this work. Figure S5 . Free siRNA-G4NH2 dendriplexes at N/P 10 did not disperse in propellant HFA-227" ] },{ "paper_id": "177dc1a77c417696ac36875b7fc3cefec3ec8d55", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In conclusion, we confirmed HBoV infection in hospitalized children with acute LRTI in South Korea. Further prospective population-based studies are needed to confirm the role of HBoV in LRTI in children.", "Dr Chung is a researcher at the Sanggyepaik Hospital, Inje University College of Medicine, South Korea. His research interests include viruses that cause respiratory tract infections in children and the molecular epidemiology of HMPV and HCoV NL-63.", "This study presents the first evidence of human bocavirus infection in South Korean children. The virus was detected in 27 (8.0%) of 336 tested specimens, including 17 (7.5%) of 225 virus-negative specimens, collected from children with acute lower respiratory tract infection." ] },{ "paper_id": "17845fc831495c6ed20d436bbab6a7a0c77a48ec", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Treatment of OME: tympanostomy tubes?", "Watchful waiting for 3-6 months in the winter period seems advisable in children with mild hearing deficit.", "Children with cleft palate are particularly prone to otitis and should be treated by early tympanostomy tube insertion [60] .", "The recommendations by the American Academy of Pediatrics [1] are to insert tubes in conditions with persisting hearing loss of more than 40 dB particularly with posterosuperior retraction pockets, ossicular erosions and adhesive atelectasis because of the increase of structural damage with effusion duration." ] },{ "paper_id": "17ad982bf94d44ae2cc3e26362ec70d70cbc6c31", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "183dc10a5eac02c39b5c2b6151c6eb6fc6cf88a3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "184aded923f0ac3cbdbcf74d2a5b42cda0f414c2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The commercially available RNA samples were the 'Universal Human Reference' (N = 75) distributed by Stratagene (USA), and human brain (N = 2) and muscle (N = 2) RNAs supplied by Clontech (USA).", "Software and manual are freely available at http://www. dnaarrays.org/downloads.php. Degradometer version 1.4.1 (released in May 2004) of the software was used.", "The beta release of the software and manual are freely available at http://www.agilent.com/chem/RIN. Agilent 2100 expert version B.01.03.SI144 (released in November 2003) of the software was used." ] },{ "paper_id": "184daf3507a842a3231c6639f3adb05539afb2d2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The article complies with International Committee of Medical Journal Editor's uniform requirements for the manuscripts. ", "Methods" ] },{ "paper_id": "185a01541eeba3c18e5c68ee961fdabd6069564e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "18acb42cf96716cbb91dd26e491e253cc130cb78", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history 1", "CoVS931F-5\u2032-VWGADGTTGTKAGRTTYCCT-3\u2032 and CoVS1909R-5\u2032-TAARACAVCCWGCYTGWGT-3\u2032; second PCR primers:", "Extended" ] },{ "paper_id": "18d1ff1667652b4e383a0a1ea258db97ac74735c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Interacting residues tend to build clusters in protein sequences, so the support vector machine can easily be applied [83] . Ofran and Rost [68] proposed a simple neural network that can predict which protein fragments interact. The 94% high fidelity predictions for 34 of 333 proteins were confirmed experimentally. In the case of good predictions, almost 70% are confirmed experimentally, and at least one interaction patch is predicted correctly in 20% of cases, i.e. in 66 of 333 protein complexes. Those results show that effective prediction using only sequence information is possible. The inclusion of evolutionary information and structural descriptors improves those methods.", "The term Interactome describes the set of all molecular interactions in cells, especially in the context of protein-protein interactions. These interactions are crucial for most cellular processes, so the full representation of the interaction repertoire is needed to understand the cell molecular machinery at the system biology level. In this short review, we compare various methods for predicting protein-protein interactions using sequence and structure information. The ultimate goal of those approaches is to present the complete methodology for the automatic selection of interaction partners using their amino acid sequences and/or three dimensional structures, if known. Apart from a description of each method, details of the software or web interface needed for high throughput prediction on the whole genome scale are also provided. The proposed validation of the theoretical methods using experimental data would be a better assessment of their accuracy.", "Up to now, all the computational algorithms have only used single machine learning methods for the analysis and prediction of protein-protein interactions [156] [157] [158] [159] [160] , or the statistical analysis of interacting patches of protein surfaces [75, 149, 161, 162] . Our experience clearly supports the idea that each machine learning algorithm performs better for selected types of training data [163, 164] . Some have very high specificity, others focus more on sensitivity. Sometimes one can have a very large number of positives in training, but it is also common for some specific types of experiments with only a few confirmed instances known. In most cases, the proper selection of negatives is not trivial. In the case of protein-protein interactions, one should use a rich variety of input data for training, such as sequences, short sequence motifs, evolutionary information, genomic context, enzymatic classification, or the known or predicted local or global structure of interacting proteins. Using this data, one can apply various types of machine learning methods trained on the same set of positives and negatives, for example neural networks, the support vector machine, the random forest, decision trees, or rough sets. The crucial step of meta-prediction is building a consensus between those various prediction methods. Since systematic errors of multiple methods are usually randomly distributed, the consensus approach can be used to select a common prediction, probably the most accurate one [165] . Thanks to its easy parallelization, a consensus method can improve the accuracy of any single machine learning method without extending the time of prediction (the time needed is equal to the slowest used machine learning algorithm). The combination of various approaches done by Sen and Kloczkowski [166] provides the solid justification for this statement. They combine four different methods, such as data mining using Support Vector Machines, threading through protein structures, prediction of conserved residues on the protein surface by analysis of phylogenetic trees, and the Conservatism of Conservatism method of Mirny and Shakhnovich [167] [168] [169] . A consensus method predicts protein-protein interface residues by combining sequence and structure-based methods. Therefore, we hypothesize that consensus approaches are the main tools to handle the prediction of protein-protein interactions on the whole proteome level, the ultimate goal of system biology." ] },{ "paper_id": "18d51b527546f388651b7d1322d9a9538c333b61", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The Wilcoxon signed-rank test was used for statistical comparisons of pairs of data groups in rosetting experiments.", "The Plasmodium falciparum clone 3D7 and nine laboratory-adapted parasite isolates from severe and non-severe malaria patients in Kilifi, Kenya (sampled between 2009 and 2010), were cultured in vitro according to standard procedures 20 and cryopreserved at the late 21 . Adults in this area are clinically immune from febrile malaria, having acquired immunity during childhood. The two donors were P. falciparum-negative during sample collection.", "To identify individuals that may produce antibodies that broadly react with P. falciparuminfected erythrocytes (IE), we developed an improved mixed agglutination assay (Fig. 1a) . Plasma from adults (n = 557) living in a malaria-endemic region in Kilifi, Kenya, were initially tested in pools of five (Fig. 1b) and then individually for their capacity to agglutinate mixtures of erythrocytes infected with three culture-adapted Kenyan parasite isolates, each stained with a different DNA dye. Most plasma samples formed single-color agglutinates, but three were able to form mixed-color agglutinates with at least six isolates (Fig. 1c) ." ] },{ "paper_id": "190a3e95092a129b94052ac128ce9b690350d9af", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Forward RT (5 -CCAAGCTTGCCAATAGCAATTAAT-CATAGGAGTAGAGC-3 ) and Reverse E (5 -CCAAGC-TTCTCCAAAATCCCAAGCTGT-3 ) for construction of clone pRT, Forward (RT) TGG (5 -AAGCTTGGCAATAGC-AATTAATCATAGGAGTAGAGCCG-3 ) and Reverse Q (5 -CCAAGCTTGTCCAAAATCCCAAGCTGTGT-3 ) for clone pRG, and Forward SRT (5 -CCAAGCTTCCAAATAGCA-ATTAATCATAGGAGTAGAGCCG-3 ) and Reverse E (5 -CCAAGCTTCTCCAAAATCCCAAGCTGT-3 ) for clone pCG+FSRTRE.", "The 45 amino acid-long EB4 protein used in this study has been previously shown to react with the dengue-specific antibody 3H5-1 (S. Abu Bakar personal communication).", "Analyses of sequences of the amplified products were carried using BioEdit Sequence Alignment Editor Software (version 6.0.5) (http://www.mbio .ncsu.edu/BioEdit/bioedit.html). The pI and charge values of the coat protein were calculated using the protein calculator developed by Chris Putnam of The Scripps Research Institute (http://www. scripps.edu/\u223ccdputnam/protcalc.html)." ] },{ "paper_id": "191e007b37a6d065812478b235a03ec1ebb0202f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "191ff4c78c5ff376029d94493b54410fb6662ea6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Self-identifi cation of other health conditions that were considered potential concurrent conditions for purpose of this study included obesity, diabetes mellitus, immunosuppression, asthma, chronic lung disease, and pregnancy. Seat location, concurrent condition status, and contraction of disease were compared. Ethics approval was given by the Australian Government Department of Health and Ageing Ethics Committee and the Australian National University Human Research Ethics Committee.", "Twenty (83%) of 24 passengers in whom an ILI developed postfl ight sat in aisle seats ( Figure 2 ). This seat location increased the risk of contracting an ILI by 1.8\u00d7; however, it did not reach statistical signifi cance. Survey respondents were 1.3\u00d7 more likely to sit in an aisle seat.", "Vigilance by health authorities and cooperation by the public assisted in detecting many ILIs that were not associated with pandemic (H1N1) 2009. These ILIs could be caused by different viruses, as seen by Follin et al. (20) . Follin et al. reported that, although 5% of the 70 passengers examined in their study had pandemic (H1N1) 2009, rhinovirus, coronavirus, infl uenza B, and parainfl uenza were also detected." ] },{ "paper_id": "196744775d0812baf3fdb72bf700df2c99e36ac5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "19771e5bae9637f1f2d1c788e9089d17ebf37c42", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Fear of being socially marginalized and stigmatized as a result of a disease outbreak may cause people to deny early clinical symptoms and may contribute to their failure to seek timely medical care (5) . Such fear can ultimately increase stigmatization when cases are identified at a later date (11) . Stigmatization associated with discrimination often has social and economic ramifications that intensify internalized stigmatization and feelings of fear (13) .", "While persons, agencies, and governments sought to identify modes of transmission, strategies for disease containment, and treatment for SARS, fear spread unchecked throughout the global community. Fear of SARS arose from the underlying anxiety about a disease with an unknown cause and possible fatal outcome (5) . Stigmatization of potential SARS patients emerged early in the outbreak, as global media reported dramatic stories from Asia in print media, television, and the Internet. Headlines from the English-language press heightened the fear. \"Concern is mounting over the continuing spread of the deadly SARS virus. Some experts say it could have a similar impact to the 1918 flu epidemic that killed 50 million-or the current world HIV crisis,\" wrote the British Broadcasting Corporation from London, England (6) . \"China has threatened to execute or jail for life anyone who deliberately spreads the killer SARS virus,\" stated the Cable News Network from Beijing, China (7) .", "Five major recommendations were derived from the facilitated group discussions with key informants: 1) develop simple, tailored SARS prevention messages; 2) develop SARS information materials in various Asian languages; 3) disseminate SARS information through multiple and culturally appropriate channels, including (but not limited to) community visits, town hall meetings, and health education and communication channels to complement mass media messages; 4) establish partnerships with local Asian-American community-based organizations to educate the community; and 5) ensure that CDC would continue to provide leadership and coordination in preventing and controlling SARS. The relationships developed during these group discussions allowed team members to monitor and document ongoing stigmatizing situations related to the disease outbreak in real time and to deal more effectively with intentional and unintentional discrimination.", "Studies have shown that during serious disease outbreaks, when the general public requires immediate information, a subgroup of the population that is at potentially greater risk of experiencing fear, stigmatization, and discrimination will need special attention from public health professionals (8) (9) (10) . The recent SARS outbreak was a classic example of such an outbreak." ] },{ "paper_id": "19bc8e320b35b2a9a0304aa51b5db76460b82137", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We performed 2 separate univariate and multivariate analyses to delineate putative risk and protective factors (1 included all participants and the other included clinical participants only) to investigate any association between health care-specifi c risk factors and pandemic infl uenza. Multivariate analysis was performed by using forward and backward stepwise logistic regression, including all variables in the model initially and a p value for removal ", "Participants were instructed to provide nose swab specimens for viral testing if they experienced signs and symptoms, including cough, sore throat, rhinorrhea, laryngitis, fever, myalgias, or headache. All were asked to complete a weekly questionnaire regarding symptoms, infl uenza exposure, and use of NIs. If a participant reported respiratory illness, a second serum sample was requested for antibody testing to document possible seroconversion.", "HCWs need to know the transmission risks to make rational decisions about working during an infl uenza pandemic. Because HCWs are exposed in the community as well as the workplace, they should know about the additional risks for contracting infl uenza at work. This information is also imperative for pandemic workforce planning." ] },{ "paper_id": "1a537a4d664e3ee6f53bbb7566e4837f31945b8d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "MBP79-87-specific TCR transgenic 8.8 and 8.6 mice on the Mbp +/+ , Mbp \u2212/\u2212 and Rag2 \u2212/\u2212 background have been previously described11. Thy1.1 C3HeB/FeJ mice were generated by backcrossing the Thy1.1 allele onto the C3HeB/FeJ background for twelve generations. All mice were bred and maintained in a specific pathogen-free facility at the University of Washington (Seattle, Washington). Mice used for EAE induction were female mice between 8-12 weeks old. All procedures have been approved by the Institutional Animal Care and Use Committee at the University of Washington.", "All P values were calculated with a two-tailed Student's t-test." ] },{ "paper_id": "1a6dfebcc7315a03ee559aec809e9c7591833999", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The author(s) declare that they have no competing interests.", "The authors suggest that HCAP is a distinct entity from CAP and should be treated as a hospital-acquired type of infection from first presentation; the paper certainly supports the recently published guidelines from the American Thoracic Society [2] ." ] },{ "paper_id": "1af6f8be4db8c2fb39dccbc04ea21d8e263af56a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A case of SARS was defined by the presence of fever (temperature >38\u00b0C) and evidence of pneumonia on either a radiograph or computed tomographic image of the thorax, with or without respiratory symptoms (e.g., cough and shortness of breath).", "Data on ventilation, temperature, relative humidity, and heat sources were analyzed by computational fluid dynamics (CFD) simulations. The industry standard CFD package, Fluent, (Fluent USA, Lebanon, NH) was used to predict (reproduce) the average airflow pattern in the ward during the outbreak, taking into consideration the effect of thermal buoyancy.", "Epidemiologic data were entered into a predesigned database and analyzed by using SAS Version 6.12 software (SAS Institute Inc., Cary, NC). Attack rates among persons with and without specific exposures were calculated. Dose-response relationships were also evaluated with respect to the proximity to the index patient and duration of these exposures.", "Paired serum specimens were collected from 15 of the 16 students during their illnesses, and all had demonstrable IgG antibodies to SARS-CoV at a titer of >1:40 in the convalescent-phase serum. The antibody titer ranged from 1:80 to 1:1,280, with a geometric mean titer of 1:440. Antibodies to SARS-CoV were absent in the serum specimens obtained from all 50 healthy students." ] },{ "paper_id": "1afdb2fbad2a5cb21a3420d4af09352912633a8a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1b18bebba1cbb0fdf78888bf15d03ac44c1582af", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A total of 103 CF patients (49 girls, 54 boys; median age 8.9 years; age range 3.8 months-17.8 years) were enrolled in the study from September 6, 2006 through September 4, 2007. Nasopharyngeal aspirates or nasal mucus specimens for viral investigation, as well as sputum or oropharyngeal samples for microbiology culture, were collected during scheduled visits or unscheduled visits on 408 occasions, with a median \u00b1 SD of 4 \u00b1 1.74 visits per patient (range 1-9 visits).", "To account for correlations among samples from the same patient, we used binomial generalized linear models to identify the virologic variables associated with the main endpoints (respiratory exacerbation and hospital admission). Results were presented as odds ratios (ORs) and 95% confi dence intervals.", "C ystic fi brosis (CF) is an autosomal inherited disease characterized by recurrent and chronic respiratory infections that ultimately lead to the need for a lung transplant early in life or to death (1) . The role of bacterial infections in CF is well established, and most treatments focus on eradication or suppression of bacterial infections (mainly those caused by Pseudomonas aeruginosa) (1) .", "Clinical and lung function data were obtained at all visits. Exacerbation of respiratory disease was defi ned as the presence of >2 of the following signs or symptoms: fever, increase in the amount of secretion or cough intensity, change in sputum's color, worsening of dyspnea, loss of appetite, a decrease of forced expiratory volume in 1 s >10%, and weight loss." ] },{ "paper_id": "1b6616fe20c678e18915ea2b6fab8b22309b45b6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.", "Informed Consent: Informed consent was obtained from the patient prior to the study.", "Conflict of Interest: All authors declare that they have no conflict of interest.", "Human/Animal Rights: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008(5).", "Ethical Standards: This study was approved by the Medical Ethics Committee of St. Marianna University School of Medicine Yokohama City Seibu Hospital. The investigation conforms to the principles outlined in the Declaration of Helsinki." ] },{ "paper_id": "1b822763c007bb77798727490e95ee2bec342494", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Additional file 1: Infection Control Readiness Checklist -Ebola.", "This survey is an initiative of the International Society of Chemotherapy (ISC) -Infection Control Working Group, to better understand the infection control needs and preparedness levels of various ISC members found globally.", "The need for ameliorated global preparedness for emerging infectious diseases outbreaks has been identified here. In order to save lives and protect healthcare workers, it is vital for healthcare facilities to make available essential equipment in some countries and ensure that standardized training with regular competency assessments on use of PPE and the removal sequence is implemented on an international level.", "No responses were obtained from the three affected countries with widespread and intense EVD transmission. Moreover, 6 countries (Mali, Nigeria, Senegal, Spain, United Kingdom and USA) have previously reported a case or cases imported from a country with intense EVD transmission. Our survey reported on participating hospitals from Nigeria (n = 3), United Kingdom (n = 9) and USA (n = 3) only, with no respondents from other countries. As the number of respondents differed substantially with low numbers in Nigeria and USA, results should be interpreted with caution. Nonetheless, whilst UK and USA have many of the preparedness activities implemented, responses from Nigeria indicate lack of essential PPE and lack of periodical training to ensure staff competency and safety in use of PPE." ] },{ "paper_id": "1bb5464402133a23adce74998e5658cf9f3fa491", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In all screens, where there were multiple models of a distinct compound due to alternate tautomeric, stereoisomeric, or protonation states, the best-scoring model was selected, and all others were discarded.", "Real-world example of how scoring-function biases can affect screening results. This material is available free of charge via the Internet at http://pubs.acs.org.", "On the other hand, one must consider the possibility that at least a portion of these scoring-function \"biases\" in fact represent accurate characterizations of small-molecule binding.", "Because of the high cost and time requirements associated with traditional high-throughput screens, many researchers now use computational methods to prefilter candidate ligands prior to experimental testing. A number of ligand-based computational techniques for identifying likely binders have been utilized. These include 2D screening with fingerprints, 1\u22123 shape-based screening, 4, 5 and pharmacophore matching, 6 which identify potential actives by comparing their atomic connectivities, three-dimensional shapes, and three-dimensional pharmacophores to those of known ligands, respectively." ] },{ "paper_id": "1bc6ca895dc8218ab2d2a126ae92b1593637328c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Therefore, the importance of rapid classification as probable case-patients cannot be ignored.", "In the future, when facing newly emerging infectious diseases like SARS, in which the patient's infectivity in the incubation period is unknown, precise clinical diagnosis cannot be made, and modes of transmission are uncertain, quarantine should be used not only to directly prevent possible asymptomatic infections but also to screen out potentially infective persons and thus prevent secondary or even tertiary infections.", "of the ideas for this work and to the anonymous referees for their many valuable comments. Sincere thanks are also extended to central and local public health personnel and medical staff who devoted all of their efforts to the quarantine and prevention of SARS in Taiwan Dr. Hsieh is a professor of applied mathematics at National Chung Hsing University. His primary research interests are focused on mathematical and statistical modeling of infectious diseases epidemiology." ] },{ "paper_id": "1be0e0b85312fb2bf7e2f6914fb89dec82ff29d8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CHIKV VLPs plasmids (strain 37997) were provided by G. Nabel (Vaccine Research Center, NIH) and expressed in Expi293 cells as previously described 18 . The supernatant was harvested four days after transfection, 0.2 \u03bcm filtered, and stored at 4\u00b0C.", "Statistical significance was assigned when P values were < 0.05 using Prism Version 7 (GraphPad). Cell culture experiments were analyzed by multiple t-tests with a Holm-Sidak correction or ANOVA with a multiple comparison correction. Analysis of levels of joint swelling or viral burden in vivo was determined by a Mann-Whitney, ANOVA, Kruskal Walllis, or unpaired t-test depending on data distribution and the number of comparison groups.", "Our mutagenesis mapping studies suggest that amino acids in the E2 A and B domains contribute to the interaction of CHIKV with Mxra8. Higher resolution structural experiments are needed to define the complete footprint of binding between Mxra8 and CHIKV E2 protein. Such studies could facilitate the development of small molecules or biologicals that disrupt Mxra8 interaction with E2 protein, which could form the basis of therapeutics that ameliorate disease caused by multiple emerging alphaviruses.", "Genomic DNA was extracted from the uninfected cells (5 x 10 7 ) or the mKate2-negative sorted cells (1 x 10 7 ), and sgRNA sequences were amplified 30 , and subjected to next generation sequencing using an Illumina HiSeq 2500 platform (Genome Technology Access Center, Washington University). The sgRNA sequences against specific genes were determined after removal of the tag sequences using the FASTX-Toolkit (http:// hannonlab.cshl.edu/fastx_toolkit/) and cutadapt 1.8.1. sgRNA sequences were analyzed using a published computational tool (MAGeCK) 6 (see Supplementary Tables 1 and 2) ." ] },{ "paper_id": "1c1c1e38bc3c71b4b634b86998ed2e12be6c89de", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1c38d6ab050242d8a1552846481949dc6aa75690", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A nasopharyngeal swab was collected from each patient and then dipped into saline and stored at \u221280\u00b0C until nucleic acid extraction. Nucleic acid was extracted using a kit (High Pure Viral Nucleic Acid Kit; Roche Diagnostics Corp., Mannheim, Germany) according to the manufacturer's recommended procedures. Then PCR/reverse-transcription PCR (RT-PCR) was performed using previously described methods with slight modifications [1, 3, 4, 9, 22, 24] . Briefly, for the RNA viruses, a superscript one-step RT-PCR system (Invitrogen Corp., Carlsbad, CA, USA) was used for reverse-transcription and first-round PCR with virus specific primers under the manufacturer's instructions. For DNA viruses and also nested PCR, Ex Taq DNA polymerase (Takara Bio Inc., Shiga, Japan) was used along with the manufacturer's supplied buffer under the appropriate thermal cycle conditions for each primer. Each sample was examined for RSV, rhinovirus (RV), hMPV, HBoV, adenovirus (AdV), and parainfluenzavirus (PIV). Following amplification, PCR products were separated on the 1.5% agarose gel with Tris-boric acid-EDTA buffer and visualized with SYBR-green (Cambrex Corp., Rockland, ME, USA) under a UV transilluminator. The PCR products were purified; their nucleic acid sequences were determined to confirm PCR results. Nucleotide sequences were processed using software (GENETYX) and compared to nucleotide sequences of the DNA database using a BLAST system [20].", "This study did not survey all respiratory viruses such as coronavirus or influenza virus. Quantification of viral loads might provide useful information, especially information that would be useful to analyze co-infection cases more clearly.", "During the same study period, we prospectively collected swabs from 30 age-matched children with no respiratory symptoms and analyzed them similarly. Except for one patient, who was positive for rhinovirus, no virus was detected in these 30 children.", "We compared clinical data of the 18 patients with the data of hospitalized patients who were positive for RSV and negative for other viruses in the same study period (n=99, Table 2 )." ] },{ "paper_id": "1c55b6759fc6303eedae05d52530ced11c30a6d6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1c5dca0eea0fa4b2ae7f523c8b8b076e56fd623f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Naturally emerging and deliberately released pathogens demand new detection strategies to allow early recognition and containment. We describe a diagnostic system for rapid, sensitive, multiplex discrimination of microbial gene sequences and report its application for detecting 22 respiratory pathogens in clinical samples.", "As a first test of this technology, we focused on respiratory disease because differential diagnosis is a common clinical challenge, with implications for outbreak control and individual case management. Multiplex primer sets were designed to identify up to 22 respiratory pathogens in a single Mass Tag PCR reaction; sensitivity was established by using synthetic DNA and RNA standards as well as titered viral stocks; the utility of Mass Tag PCR was determined in blinded analysis of previously diagnosed clinical specimens." ] },{ "paper_id": "1c5f9e0dfbba108b9d431f99fe2274ad0c47e7bc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In addition, due to limited genomic resources and accurate high-throughput genotyping tools, there is still much to be learned about the contribution of IG genetic polymorphism to variability in expressed repertoires and the implications of this variation for susceptibility to infectious and autoimmune diseases, responses to therapeutic antibodies and vaccines, and other clinical outcomes. These outstanding questions continue to stress the importance of accurately representing standing genetic variation in the human IG loci.", "We analyzed sequences from 17 CH17 BAC clones (IGL, 9; IGK, 8) comprising tiling paths across the two loci (Figures 1 and 2) -one of the clones in IGK, CH17-158B1 (AC233264), had been sequenced previously. Clones unique to either IGK or IGL were then used to construct locus-wide contigs; clones in IGKV proximal and distal regions were aligned separately because the gap separating these two regions was not completely filled by the current sequencing effort.", "A direct comparison of the IGL CH17 and NG_000002.1 revealed the presence of only a single structural variant. This 11.9 kb insertion was located in the region between the pseudogenes IGLV7-35 and IGLV2-34 within the BAC, CH17-242N13; the region between these pseudogenes spans ~120 kb and is devoid of IG genes. Gene prediction analysis did not identify any genes within the insertion, nor did the insertion disrupt the non-IG related genes, ZNF280B, ZNF280A, and PRAME, located in this region; the breakpoints of the event occurred between ZNF280A and PRAME. No structural variants were observed in the IGK CH17 haplotype." ] },{ "paper_id": "1c63b88923b15b7733aac9630ae9e73aa09c8e1d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1d207b14f92ffce3c151c86f9483c159065e0646", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Results are routinely displayed as mean \u00b1 s.e.m, with statistical differences between experimental groups determined using a two-tailed unpaired Student's t-test, where a p value of < 0.05 was deemed significant. Statistical differences in survival were determined by log rank (Mantel-Cox) analysis. Graphs were produced and statistical analyses were performed using GraphPad Prism.", "Refer to Web version on PubMed Central for supplementary material. " ] },{ "paper_id": "1d618133a3ebc9e6e55ba44933616cd0c07771cd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In 17th and 18th century Europe, most of the aristocracy and gentry shaved their hair and wore wigs. Had this custom arisen to protect them from lice as Zinsser [1] suggests? Not according to Samuel Pepys' diary, as he complained more than once about his wig being infested: \"Thence to my barbers, to have my periwig cleared of its nits.\" I wonder if they were head or body lice -is a wig hair or clothing?", "H Hu um ma an ns s a as s a a s so ou ur rc ce e o of f i in nf fe ec ct ti io on ns s", "A Ac ck kn no ow wl le ed dg ge em me en nt ts s I am grateful to Tim Harrison and David Reed for commenting on a draft of this paper. R Re ef fe er re en nc ce es s" ] },{ "paper_id": "1dba435e932ac0171832c22334dff3a382a0ad14", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1dbff143322886fdbdd833b8052ea3e3e0cc2d6d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "M olecular biology has revolutionized the diagnostics of infectious diseases through the introduction of more sensitive and specifi c diagnostic tests. Despite these advances, the etiologic agents of many apparent infections are still unidentifi ed. For example, the etiologic agent is unknown for many cases of apparent pneumonia (1); in a study conducted in California, USA, despite extensive testing and evaluation, an underlying cause of encephalitis was unidentifi ed for 207 (62%) of 334 patients (2) .", "We tested previously submitted CSF samples for SAFV, reviewed the patients' medical records, and sequenced the viruses isolated. ", "During the next 2 months, the ataxia remitted completely without sequelae. The diagnosis at this time was viral encephalitis, possibly caused by parechovirus type 3." ] },{ "paper_id": "1dc18baed79c3ae009d73d109a7aaec9f9195a2f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Although the remaining 470 predictions had tested negative once, their high probability (90.5%) still prioritized them as candidate interactions. Therefore, as dictated by the Prediction strategy these pairs were tested again immediately using a second assay type.", "Detailed descriptions of the interaction probability model, the combined-evidence method for interaction prediction, the computation of thresholds, and the yeast two-hybrid test protocol appear in the Supplementary Methods." ] },{ "paper_id": "1dc89329e8a644d5dc0e2b0b845e65cbe17a782a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1dd2490b867180bd86c105c46fd880f9955f7ff8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1e1286db212100993d03cc22374b624f7caee956", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Background: Rhinovirus, the most common cause of upper respiratory tract infections, has been implicated in asthma exacerbations and possibly asthma deaths. Although the method of transmission of rhinoviruses is disputed, several studies have demonstrated that aerosol transmission is a likely method of transmission among adults. As a first step in studies of possible airborne rhinovirus transmission, we developed methods to detect aerosolized rhinovirus by extending existing technology for detecting infectious agents in nasal specimens.", "Following extraction, we first amplified the picornavirus RNA using primers OL26 (5'-GCA CTT CTG TTT CCC C-3') [33] and OL27 (5'-CGG ACA CCC AAA GTA G-3') [33] using the Invitrogen SuperScript One-Step RT-PCR with PLATINUM Taq ", "Amplified products were detected by electrophoresis analysis on 2% agarose gel containing 8 \u00b5l of ethidium bromide per 200 ml of gel followed by examination under UV light.", "The OL26 and OL27 primer pair generates a 388 base pair amplicon from a region of the 5' noncoding region of the picornavirus genome. The semi-nested primer pair of OL26 and JWA-1b generates an amplicon of ~292 base pairs from within the original amplicon. The 292 bp amplicon does not differentiate between rhinovirus and enterovirus [34] .", "Although rhinoviruses have been thought to be transmitted via large droplets or contact [7] , studies in the 1980's demonstrated that fomites are not an effective means of transmitting rhinovirus infections [8] [9] [10] . While direct inoculation of respiratory secretions has been shown to transmit infection, this is not a likely route of transmission in older children and adults as survival on hands is brief [9] . Airborne transmission of infection was clearly demonstrated in one experimental study on adults [8] . However, in the absence of epidemiological studies designed to conclusively identify modes of transmission, the role of airborne transmission in viral respiratory infection remains controversial.", "We obtained rhinovirus 16 strain 11757 from ATCC (Manassas, Virginia) with a titer of 10 7.25 particles per 0.2 ml. The suspension was diluted with phosphate buffered saline (PBS) to create four different concentrations to be used in the experiment." ] },{ "paper_id": "1e2678ba55265e7afbeee0af9b5dee86342f85f6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We isolated a novel MRV strain (named MRV1HB-A) from a mink with diarrhea in Hebei Province in northern China. To track virus evolution and look for evidence of genetic reassortment, we used PCR sequencing and phylogenetic analysis to compare genetic relatedness of MRV1HB-A and other orthoreoviruses.", "We identified a novel mink orthoreovirus, MRV1HB-A, which seems to be closely related to human strain MRV-2tou05, which was isolated from 2 children with acute necrotizing encephalopathy in 2005. Evolution of this virus should be closely monitored so that prevention and control measures can be taken should it become more virulent.", "Our study provides genomic evidence and molecular confirmation of a novel reovirus in mink. Although there is no direct evidence to prove the origin of MRV1-HB-A, the close genetic relationship of MRV1-HB-A with strains from humans and swine indicated a high probability that MRV1-HB-A resulted from a reassortment of human and swine strains. In view of the lack of sequence data for the reovirus from mink in public databases, addition of the complete genome sequencing information for the mink reovirus will aid in the characterization of mammalian reovirus diversity and evolution. Although MRVs were assumed to cause rather mild respiratory or gastrointestinal diseases, recent findings indicate the occurrence of higher virulent MRV strains in man and other mammals. To be prepared for the potential emergence of more virulent variants, we should carefully monitor virus evolution in real time." ] },{ "paper_id": "1e3e37bcaf9a7cb93acef49776b6c3dead54c430", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Legionella infection in neonates occurs rarely among both healthy and immunocompromised patients (3) (4) (5) (6) (7) (8) .", "Water birth and use of cold-mist humidification have been associated with neonatal legionellosis (9) (10) (11) , but investigations of transmission modes are limited. We report 2 cases of neonatal Legionella infection associated with contaminated water used in infant formula in a hospital setting.", "an American Legion convention in Philadelphia in 1976 (1) . The disease has a variety of clinical manifestations, ranging from mild respiratory tract illness to fatal pneumonia, especially among immunocompromised persons (2) ." ] },{ "paper_id": "1e77d7c7edc8692bbe4056e0ea0bb52ffabafa96", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Spontaneous tumour regression has followed bacterial, fungal, viral, and protozoal infections. Intratumoral infections may reactivate defensive functions, causing tumour regression.", "New technologies including gene-expression profiling has increased the list of candidate tumor antigens. Investigators have focused on targets which are either tumourspecific, including idiotypic antigens of B-cell tumours [11] or tumour-associated antigens [12] that are also expressed by the normal cell of origin [13] and that include the so-called cancer-testis antigens [14] ." ] },{ "paper_id": "1ebb99d6c23999bab025feddb7a13b81b36d1947", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "After further approximating biomolecules using the spheroid approximation, the effective diameter (d) would be", "As a result, the length, diameter, and of course length-todiameter ratio (\u03a6) could be obtained for each simulated conformation.", "The authors declare no competing financial interest.", "Article in which m is the mass of the ion. After solving eq 4, ion displacement with respect to time is" ] },{ "paper_id": "1f9e68c3b98b3ea6a98fbdba8ddbaadd1b2eb018", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sustained human-to-human transmission in community settings has not been observed (6) , but transmission has been documented in healthcare settings (9, 10) and in households (11) (12) (13) (14) . Specific risk factors for secondary transmission remain unknown.", "The Saudi Arabia Ministry of Health and CDC provided funding for the study.", "Because this investigation was part of a public health response, it was not considered by CDC and the Saudi Arabia Ministry of Health to be research that was subject to review by an institutional review board. Participants gave verbal consent." ] },{ "paper_id": "1fc650db3448c38d83fbe7cdd07db4f45dda9223", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Immunoglobulin (Ig) G against SARS-CoV were detected by enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's instructions (Beijing BGI-GBI Biotech Co., Ltd.) (10) . This ELISA has a sensitivity of 89.9% and a specificity of 99.0% (11) .", "For each healthcare worker, 10 mL of peripheral venous blood was collected; the serum was separated and stored at -70\u00b0C. A standardized interview with a structured questionnaire was used to obtain information on sociodemographic characteristics and the history of SARS according to a case definition of SARS by the Ministry of Health, China (9) .", "Means and standard deviations were used to describe continuous variables. Proportions and prevalence rates were used to describe categorical variables. Chi-square tests were performed to test the association between SARS-CoV IgG seropositivity and the sociodemographic characteristics of the healthcare workers." ] },{ "paper_id": "1fd44d22a387ba56fd367ceb0737762e9ee9d5cb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "20029dc39eb2b7cd0a8392445e6596f93933258a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Human diploid fibroblasts, strain MRC5, were used as recommended by Nishimura [7] . For our most consistent results, cells were used between the thirtieth and fortieth passage. Cells in the earlier passages grew very well, but the virusinduced changes were not as readily seen as in the older cells. Beyond the fortieth passage, growth was slow and sparse.", "A viral etiology is supported by the epidemiology of MS. Its onset is usually between the ages of 15 and 50, but chiefly in young adults, with females outnumbering males. The frequency of the disease in those migrating between areas of high and low prevalence is age-dependent. Those who migrate after the age of 15 develop MS with the same frequency as those in the area they come from, whereas those who migrate in childhood develop MS with the frequency of those in the region they migrate to.", "Multiple sclerosis (MS), a progressive disease of the white matter of the central nervous system (CNS), is characterized by ataxia, spasticity, visual impairment, and sensory changes. The disease is the result of a loss of myelin, producing a lesion or plaque which grows by extending its boundary. Small lesions may also merge into confluent plaques. The myelin-producing cells, the oligodendrocytes, are lost from the center of the plaque and astrocytes proliferate at the periphery. MS is an inflammatory disease with lymphocytes, plasma cells, and macrophages present within the lesions." ] },{ "paper_id": "203339b042e51e4489fd7a1ffd7911a5443b9a82", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2038c68ce9ec2990a003c0ac0d5d87d8c072e102", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2111f7e8255fbbc35aa48c3cee385c2c3665a727", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "212caadd66e6c2c7c4af2b8fb0c48cfe1ebeb17d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "13. Heaton PR, Johnstone P, McElhinney LM, Cowley R, O'Sullivan E, Whitby JE. Heminested PCR assay for detection of six genotypes of rabies and rabies-related viruses.", "We report the discovery of a lyssavirus (designated as BBLV) from a Natterer's bat that died with rabies-like clinical signs. Initially, a distinctive pattern in the reaction with a panel of antinucleocapsid monoclonal antibodies indicated the presence of an antigenically atypical isolate. The differentiation from other lyssavirus species was confi rmed by phylogenetic analysis (Figure 2) .", "BBLV is pathogenic because it caused a fatal disease in the Natterer's bat that was similar to the clinical picture of rabies seen in other bats. Viral antigen was present in many locations of the brain (Figure 1 ) but surprisingly not in the salivary glands." ] },{ "paper_id": "2132357512ad6873036487fb997bba2a600fd554", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2140635bd0abbea93a3dbb83af50aff3485b6b8c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2144267cf424681c6f75208bd17198b59e630fe2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Emerging Infectious Diseases \u2022 www.cdc.gov/eid \u2022 Vol. 10, No. 4,", "C yclospora cayetanensis is a protozoan parasite that may cause gastroenteritis with prolonged, intermittent diarrhea in humans. Characterization and magnitudes of risk factors associated with food and water consumption are unclear because the dose-response relationship and other host-parasite factors for infection with Cyclospora are unknown. To characterize infectivity, we performed a study in which inocula of Cyclospora oocysts were administered to human volunteers.", "Inoculum treatment and challenge conditions of this study are described in the Table. Numbers of stools examined per volunteer ranged from 19 to 40; no oocysts were detected in any of the stool samples. Volunteer 1 experienced a brief episode of abdominal cramps on day 7 postdosing. This volunteer attributed the symptom to possible dehydration due to strenuous activity performed in the heat that day. Volunteer 5 produced four loose stools on day 10 postdosing but reported feeling well. This volunteer also had a mildly elevated leukocyte count (15.8 x 10 9 /L; normal range 4.5-11.0 x 10 9 /L) on day 13 postdosing. However, this volunteer had a mildly elevated baseline leukocyte count (13.8 x 10 9 /L) 14 days before dosing. Overall, no conclusive evidence based on clinical or parasitologic diagnostic procedures showed that any volunteers became infected." ] },{ "paper_id": "218e334c991ac7840a535ceddb2ac7e026a4919e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We ", "The proportion absent at any given time is", "In a prophylaxis strategy, j =1 when both conditions, V g >\u03c5\u03b9 and P>0, are satisfied; otherwise, j = 0. " ] },{ "paper_id": "21a745df80bcdc816a59568b99f3f1fbc87955b3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Potential cases of infectious atypical pneumonia, later called SARS, were reported by hospitals to the Beijing Center for Disease Control, which initiated epidemiologic investigations. Data sources included case report forms, epidemiologic investigation forms, and other investigation records at Beijing's Center for Disease Control.", "SARS is not the only respiratory infection characterized by superspreading (8) (9) (10) ; other respiratory pathogens are often transmitted to large numbers of contacts.", "Cases were defined, in accordance with the \"National Case Definition of Infectious Atypical Pneumonia (SARS) in China, 2003,\" which was updated by the China Ministry of Health on April 23, 2003. Criteria for probable and suspected SARS included travel to a SARS-epidemic area in the 2 weeks before onset of symptoms or close contact with a probable SARS patient; fever of >38\u00b0C; chest x-ray abnormalities; normal or decreased leukocyte count; and no response to treatment with antimicrobial drugs." ] },{ "paper_id": "21b6c038511e8897875bae8dad4ee6f574bad5d2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Identification of specific non-influenza organisms associated with outbreaks can assist with outbreak management as the period of patient isolation and when to declare an outbreak over are dependent on the incubation period and period of communicability, which varies by organism. Documentation of HRV as a cause of LTCF outbreaks is important, as recent studies suggest that HRV outbreaks can cause severe and fatal disease in LTCFs, especially among the elderly. 1 A study comparing viral outbreaks in different community \u2044 facility settings with prospective gathering of detailed clinical and epidemiological information, supported by comprehensive microbiological analysis, will help further understand the role of different respiratory viruses as etiologic agents.", "There was an increased likelihood of identifying multiple viruses if 5 or more samples were tested (P < 0AE05; Figure 1 ). Nineteen outbreaks with multiple viruses detected were reported in LTCFs and 12 in CSDs. ENT \u2044 HRV and A(H1N1)pdm09 were the most common co-circulating viruses reported in all outbreaks with multiple viruses detected, found in 7 of the 19 multiple virus outbreaks reported by LTCFs and 10 of the 12 multiple virus outbreaks reported by CSDs (Table 1) . was detected in the majority of respiratory outbreaks in LTCFs, where the vast majority of residents were elderly.", "We investigated all respiratory outbreaks in LTCFs and camps, schools, day cares (CSDs) tested at PHO laboratories from June 11 through November 30, 2009, in Ontario, Canada. A confirmed respiratory infection outbreak in a LTCF, as defined by Ontario's Ministry of Health (MOH), requires two cases of acute respiratory illness within 48 hours of which at least one has to be laboratory-confirmed, or three cases of acute respiratory illness occurring within 48 hours in a geographic area, none of which are laboratory-confirmed. 5 ]. An alternate multiplex NAAT kit (Seeplex RV; Seegene USA, Rockville, MD, USA) was used in conjunction with the Luminex assay during periods of higher demand. An in-house assay specific for A(H1N1)pdm09 was also performed. 6 " ] },{ "paper_id": "220b242a5251299e0effdd406a1fd6a08cf313c9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "SARS-CoV best illustrates the remarkable potential for CoVs to change their tropism. Tropism switching has been implicated in the zoonotic emergence of human coronavirus OC43 from a bovine coronavirus and in turning transmissible gastroenteritis virus, an enteric porcine coronavirus, into porcine respiratory coronavirus, a respiratory pathogen (3, 4) . Such changes can be accompanied, although not necessarily, by crossspecies transmissions; thus, the erratic occurrence and unpredictable new disease manifestations of tropism switching are a matter of public health concern.", "C oronaviruses (subfamily Coronavirinae, order Nidovirales) are enveloped, plus-strand RNA viruses that infect mammals and birds. They are quite common and cause infections in humans and a wide variety of animals; infection typically results in respiratory or enteric disease. Severe acute respiratory syndrome coronavirus (SARS-CoV), which emerged suddenly in 2002 and caused severe acute respiratory disease in humans, is the most notorious coronavirus. SARS-CoV spread rapidly around the globe, infecting thousands and killing \u2248800 persons. The virus presumably originated from bats and was transmitted to humans either directly or by using civets or raccoon dogs as intermediate hosts (1, 2) .", "We suspended fecal specimens to a fi nal concentration of 10% (wt/vol) in phosphate-buffered saline by vigorously vortexing the specimens. The supernatant was cleared (centrifugation for 10 min at 3,000 \u00d7 g) and then used for RNA extraction. Following the manufacturer's protocols, we used the QIAamp Viral RNA Mini Kit (QIAGEN, Valencia, CA, USA) to extract viral RNA from 140 \u03bcL of fecal supernatants or ascites and the QIAamp RNeasy Mini Kit to extract viral RNA from 30 mg of organ tissue homogenate." ] },{ "paper_id": "22212b4c01be73b039da9396b7d20fb4a3429cb5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "SNPs: single nucleotide polymorphisms. ", "*P,0.05." ] },{ "paper_id": "22279bef01140a61dda67aad293824d04f6bcc23", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "282 ARDS = acute respiratory distress syndrome; DHEA(S) = dehydroepiandrosterone (sulphate); NO = nitric oxide.", "So will stress doses of hydrocortisone attenuate severe systemic inflammatory response syndrome after cardiac surgery with cardiopulmonary bypass? Kilger and coworkers [3] would suggest that in high-risk patients this is so. They found that severe systemic inflammatory response syndrome (serum interleukin-6 concentration >1000 pg/ml) was best predicted in their population by a bypass time in excess of 97 min and cardiac ejection fraction below 40%. Thus, by targeting their predefined high-risk patients to receive hydrocortisone, they showed recipients to have significantly lower interleukin-6 levels, reduced duration of ventilation and catecholamine support, and reduced duration of stay in the intensive care unit and the hospital. Nothing yet suggests a mortality benefit though.", "Using inhaled nitric oxide (NO) in patients with ARDS improves oxygenation, but it has not been proven to improve outcome. Why is this so? Gerlach and coworkers [10] looked at dose-response characteristics when long-term NO is used and found that these characteristics changed. Patients could become sensitized to NO, such that the number of responders to low NO doses increased and some became nonresponders at higher NO doses. It would seem that constant dose NO is not right for all patients throughout their treatment, and that there is more inter-patient and intrapatient NO dose-response variability than we had thought. Titrating doses at each step may improve long-term benefits from NO therapy." ] },{ "paper_id": "226afecf9d1d5dabbbf7f6b0e3ae0d114ecff299", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Primary biliary cirrhosis (", "Compatible histological findings confirm the diagnosis and allow staging before therapeutic intervention, but in many cases, histological workup is not necessary to diagnose PBC [29] .", "Autoimmunity is a phenomenon of dysregulated immune response against self-antigens. If persistent, this can result in inflammatory tissue damage. The immune response to antigens is tightly controlled by various pathways whose deregulation may lead to autoimmune responses. Genetic predisposition and environmental factors affect the susceptibility to such deregulation [86] ." ] },{ "paper_id": "22a307b3c964d16821fcf30a809d1cbd408939f8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "S evere acute respiratory syndrome (SARS) was first observed in 2002 when cases of a life-threatening atypical pneumonia occurred in Guangdong Province, China (1) . A novel coronavirus (CoV), designated SARS-CoV, was quickly identified as the etiologic agent (1, 2) . Although the origins of the virus have not been established, evidence suggests that it is an animal virus that was recently transmitted to humans (3) . Several wildlife species consumed as delicacies in southern China, including Himalayan masked palm civets, Chinese ferret badgers, and raccoon dogs, possess antibodies consistent with natural infection with related CoVs (4) .", "An isolate of SARS-CoV, strain HKU 39849, was passaged on 2 occasions in Vero E6 cells to establish a hightiter stock that was used in all infectivity experiments. Because SARS-CoV is classified as a risk group level 4 pathogen in Australia, all procedures performed with the virus, including infecting cell lines and viral lysis before RNA extraction, were carried out in a physical containment level 4 (PC4) laboratory.", "After the SARS epidemic ended, several cases have occurred as a direct or indirect result of breaches in laboratory biosafety (11) (12) (13) . These breaches highlight the need to safely handle virus in the laboratory, which includes knowing which cell lines may be susceptible to infection. In this study we add to the list of cells known to support replication of SARS-CoV." ] },{ "paper_id": "22e1dd30a5cbd30d28a4d121e4876c8e327f027e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cells were treated with RIPA lysis buffer with phenylmethyl sulfonylfluoride (PMSF). Protein concentration was determined with BCA Protein Assay Reagent (Pierce, Rockford, IL, US) and separated on a 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel and subsequently transferred to a polyvinylidene difluoride (PVDF) membranes (Millipore Corp, Atlanta, GA, US). The PVDF membrane was blocked with 5% non-fat dry milk for 2 h at room temperature, and then incubated with primary antibodies overnight at 4 \u2103 and subsequently with HRP-conjugated secondary antibody at room temperature for 1 h. The signal was detected with enhanced chemiluminescence (ECL).", "CDCA7 polyclonal antibody (15249-1-AP) was obtained from ProteinTech Group (ProteinTech Group, Chicago, IL, US). Monoclonal \u03b2-actin (sc-69879) was purchased from SantaCruz Biotechnology (Santa Cruz, Inc., CA, US). Horseradish peroxidase (HRP)-conjugated secondary antibody was purchased from Pierce (Pierce, Rockford, IL, US). PK-15 cells were obtained from American Type Culture Collection (ATCC) (CCL-33) and grown in Dulbecco's Minimal Essential Medium (DMEM) supplemented with 10% fetal bovine serum (Gibco BRL, Gaithersburg, MD, US), 100 IU of penicillin and 100 mg of streptomycin per ml, at 37 \u2103 in a 5% CO 2 atmosphere incubator. The TGEV Shaanxi strain was isolated from TGEV-infected piglets by Ding L et al [20] .", "The miRNAs are small RNA species (containing about 22 nucleotides) which are found in animals, plants, and some viruses. It has been shown that miRNAs play a variety of roles in many cellular processes including development, differentiation, apoptosis, cell cycle (reviewed in reference [1] ). Generally, miRNAs are derived from introns or intergenes of eukaryotic organisms or viruses and serve as regulators of gene expression [2] . The miRNA-mediated RNA interference includes two patterns. One is perfectly base-paring with 3' UTR of target mRNA leading to degradation of mRNA. The other is imperfectly binding to target 3' UTR of mRNA resulting in the inhibition of mRNA translation. In mammalians, miRNAs perform RNAi through translation inhibition mediated through imperfect complementarity [3] . As a result, a miRNA can directly interact with multiple targets and a gene can be targeted by many miRNAs [4] ." ] },{ "paper_id": "230a3e80afacb1c6a06912b5ad06df56fc4535b2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "1. Monitoring practices and performance feedback.", "The statistical analysis was performed by the software GraphPhad Prism 5.0. The tests applied were: Chi-square (X 2 ), Fisher's exact test for n<5, Mann-Whitney test, with 95% confidence interval, and ANOVA." ] },{ "paper_id": "232d7b83c5e1ab61317eea4aa51cb6d264516b91", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "23e73664ec4374d13d3a5243006bec6f30f5cda4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A recurring theme across these studies was assessing the quality of data, including exploring new venues to measure [22] [23] [24] and improve [25] it. Timeliness and completeness were the two dimensions of data quality (DQ) which were often evaluated. Metrics from DQ frameworks published in literature can be used as guidance in identifying additional parameters for assessment." ] },{ "paper_id": "23f71cec67b168779d76b16f771126d98fc6f22e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "244a3bd441bc1a9400a8529ed9933ae8a1f8d00a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "to an undetectable level within months by microneutralization test, immunofluorescent antibody (IFA) assay, and ELISA (10) .", "We used the MERS-CoV S1 ELISA kit (EI 2604-9601G; EUROIMMUN, Luebeck, Germany) for the detection of human IgG against MERS-CoV spike protein.", "Visit our website to listen: http://www2c.cdc.gov/podcasts/player.asp?f=8631627" ] },{ "paper_id": "24a4abb7e742c132b76b859fd53acfc1a126ba05", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "24da9eb1bf5b54581deda2e999cd5058674ceac4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We performed statistical analyses by using Epi Info 6 software (http://www.cdc.gov/epiinfo/index.html); results with p<0.05 were considered statistically significant. The corrected \u03c7 2 test or the Fisher exact test was used where indicated.", "For DNA extraction, we used a BioRobot EZ1 Workstation (QIAGEN, Courtaboeuf, France) according to the manufacturer's instructions. Extraction was performed in Senegal, and specific quantitative real-time PCR (qPCR) was performed in France.", "We performed genotyping of T. whipplei as previously described (32) . We attempted to amplify and sequence each of 4 multispacer sequences (TW133, ProS, SecA, and Pro184) from positive specimens. When sequences were obtained, we compared them with those available in the GenBank database and our internal laboratory database to determine their corresponding genotype." ] },{ "paper_id": "24dcca53dd31df074a77242d2e2e6053825e1761", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data availability. The complete genome sequence of the Avian coronavirus GA/1476/2015 isolate of the GA08 strain has been deposited in GenBank under accession number MN599049. Raw data were deposited under SRA accession number SRR10742650, BioSample number SAMN13088878, and BioProject number PRJNA556282.", "Avian coronavirus, also known as infectious bronchitis virus, is a highly contagious respiratory pathogen of chickens that is responsible for major economic losses to the poultry industry around the globe. Here, we report the complete genome sequence of strain GA08 of the GI-27 lineage, isolated from a fecal sample from a broiler chicken collected in Georgia in 2015.", "A vian coronavirus, commonly known as infectious bronchitis virus (IBV), is a member of the genus Gammacoronavirus, family Coronaviridae, order Nidovirales (1) (2) (3) . Since the first identification of IBV in the 1930s in the United States, more than 20 different serotypes and variants have been identified worldwide (4, 5) . In 2007 and 2008, an outbreak of bronchitis in broilers in North Georgia led to the identification of a new IBV strain designated GA08, which was further classified into the separate lineage GI-27 (6, 7) . The GA08 IBV strain has since been isolated on farms in Alabama, Tennessee, and Kentucky (8; https://quickvet.net/news-and-media/zoetis-receives-usda-conditional -license-for-first-vaccine-to-control-georgia-08-strain-of-infectious-bronchitis -virus-in-poultr.aspx). Over the past years, its incidence and severity have increased dramatically, resulting in significant losses. To date, only partial genomes of the GA08 strain viruses are available in public databases (6, 7) . In this study, we report the complete sequence of the IBV GA08 strain." ] },{ "paper_id": "24de65541e25ca372d5fb686b733b45a1dd5c0b6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "24ff3659d783f4ae055ca1580b01d7f1ca36b9ab", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "25484d47cd99c0a59cfc9a6b8ab2514a3678417c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Animal samples were collected and examined at the Center of Excellence for Emerging and", "N orovirus infection is a major cause of endemic and epidemic acute gastroenteritis. These viruses have been classified into 7 genogroups on the basis of the major capsid protein, VP1. Noroviruses", ". The evolutionary mechanism and typing of noroviruses can be analyzed on the basis of recombination between the genes for RNA-dependent RNA polymerase and VP1 (2) . Newly emerged norovirus strains might lead to increasing incidence of infection worldwide (3) . The predominant genotype of noroviruses in humans is GII.4. Genetic diversity of noroviruses has been reported in a wide range of animals (e.g., pigs, cattle, and dogs)." ] },{ "paper_id": "25781baaa25b85c1d688e32d35730300a39ac3bd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A n outbreak of human infections with a novel reassortant avian-origin influenza A(H7N9) virus occurred in several provinces of China during March 2013 (1), This outbreak caused 137 laboratory-confirmed cases and 45 deaths as of October 2013 (www.who.int/csr/ don/2013_10_24a/en/index.html). An unusually high proportion of severe cases and a high case-fatality rate have been observed for patients infected with this virus (2) .", "This assay had a detection threshold of 10% for a mutant strain in a mixed viral population, which is more sensitive than Sanger sequencing (detection threshold of 25% for a minor component in a mixed viral population) (6). This assay will help clinicians monitor emergence of drugresistant virus strains during treatment of patients with NA inhibitors to prevent persistent viral replication and severe inflammatory reactions. Sign up for Twitter and find the latest information about emerging infectious diseases from the EID journal. @CDC_EIDjournal", "The NA R292K assay has 2 reactions with 1 pair of primers. One reaction contained a FAM-labeled SNP probe specific for the 292K mutant strain and a second reaction contained a VIC-labeled probe specific for the R292 wildtype strain (online Technical Appendix, wwwnc.cdc.gov/ EID/article/20/5/13-1364-Techapp1.pdf)." ] },{ "paper_id": "25850a7f18984f720731456ef16942a48c6f14a8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Epidemiology studies are often overlooked in the current world of evidence-based medicine. The studies do not rank in the hierarchy of clinical trial data, they are not often considered to influence clinical care and they may be considered merely 'descriptive' of a medical problem. Despite the limitations of epidemiology studies, they remain a critical component of biomedical research without which the remaining 'higher order' studies, such as cohort studies and controlled trials, could not be effectively conducted.", "Epidemiology studies are an essential part of clinical research, often forming the foundation for studies ranked more highly in the hierarchy of evidence-based medicine. Studies of sepsis to date have been conducted on local, regional, national and international scales, with the majority conducted in the past 5 years. Longitudinal epidemiology studies convey an important additional aspect of the healthcare burden from disease, and may additionally serve to compare the effectiveness and efficiency of healthcare systems, to examine specific patient care strategies and to perform quality control analyses.", "Division of Pulmonary and Critical Care, Emory University School of Medicine, Atlanta, Georgia, USA, and Medical and Coronary Intensive Care, Grady Memorial Hospital, Atlanta, Georgia, USA" ] },{ "paper_id": "25ad613a571cd6c9f3ea5af6727a7b1af41eb763", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "25b2102f32004f50167c6d6894d5f4fc6a70b99f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "261141d75b67dd38a19c1a4c9af037587c2357ff", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The zygomycosis cases were classified according to their clinical presentation, when available. When several body localizations were reported, we selected the most severe one, either in a single stay or in subsequent admissions. For instance, the association of unspecified localization (B46, B468, or B469) or gastrointestinal (B462) or cutaneous (B463) localizations, together with a pulmonary (B461), a rhinocerebral (B462), or a disseminated (B464) localization, was classified under 1 of the 3 latter categories.", "The CFR estimates were impaired by the unavailability of accurate information about underlying medical conditions for deaths identified in the CepiDc. In addition, the approximation of the year of birth when using the PMSI dataset limited the CFR studies by age groups. We therefore restricted the analysis to the overall CFR by underlying diseases whenever possible and made no further assumptions on missing data.", "Statistical analysis was performed by using Excel (Microsoft Corporation, Redmond,, WA, USA) and STATA-9 (StataCorp LP, College Station, TX, USA) software. The Fisher exact or \u03c7 2 tests were used where appropriate to compare groups. Trends were assessed by using a Poisson regression. Where appropriate, we present results with 95% CIs and p values, considering p<0.05 as significant.", "We defined as unique cases those that had an identifier detected only 1 time in the PMSI during the 10-year period. Cases detected >1 time were classified as new cases at first occurrence in the database; subsequent ones were coded as readmissions. After checking for duplicates, we analyzed unique or new cases for incidence." ] },{ "paper_id": "27274e02683a0348194933d6f5669741346b7113", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2735c2e5b493fd4e7b7c4ec3d44a775f9399aa0d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "However, human resources are limited for interpreting the large volume of available information. Thus, statistical algorithms are needed to fi lter large volumes of data, focus attention on potential public health problems, and provide an objective measure of increases in disease activity.", "The fourth modifi cation tested was increased minimum value for SD. We studied minimum values of 0.2 and 1.0.", "S ince the late 1990s, the threats of bioterrorist attacks, the potential for outbreaks of natural disease such as severe acute respiratory syndrome and pandemic infl uenza, and the availability of computerized data have prompted the use of automated disease surveillance systems (1) . Sources of information include clinical data, such as records of hospital emergency department visits, and nonclinical information, such as sales of over-the-counter remedies (2) .", "This article describes and evaluates modifi cations of C2 that retain its inherent advantages, address its potential limitations, and improve its performance. We used real daily syndrome counts from 2 sources as baseline data and assessed the ability of various algorithms to detect additional counts artifi cially added to the data. Because all analyses were conducted at a constant alert rate of 1%, improvements in sensitivity were not accompanied by an increase in alerts." ] },{ "paper_id": "2747330a4eca3fc78e67be4fbf4eb5d127d33e73", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "276d1d1c20336ca2a6f54c7a95507001917e4c44", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "27c85eb0542256f6599ba43e90986abfdb1ddc5b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "RSV was detected by immunofluorescence tests and virus isolation. Influenza viruses were identified by direct antigen detection with immunofluorescence techniques, serologic tests with complement fixation, and virus isolation. To isolate influenza viruses, respiratory specimens were added to primary cynomolgus monkey kidney tissue cultures, which were rolled at 33\u00b0C and observed daily for cytopathic effects. If no effect was observed, the HeLa tubes were passaged blind at weekly intervals, and monkey kidney tissue cultures were tested for hemadsorption with guinea pig erythrocytes. Specimens were discarded after 4 weeks if negative. Influenza virus isolates were subsequently confirmed by immunofluorescence and typed by hemagglutination-inhibition tests using strain-specific antisera provided by the WHO Collaborating Centre for Influenza at the Centers for Disease Control and Prevention, Atlanta, Georgia, USA.", "National mortality data were obtained from the Registry of Births and Deaths. Under the Registration of Births and Deaths Act, all deaths occurring within Singapore and its territorial waters are required to be registered within 3 days of the occurrence. Each death was categorized according to the International Classification of Diseases, 9th Revision (ICD-9) codes. In this study, death records were aggregated according to month of death from January 1996 through December 2003. Three death outcomes were analyzed: underlying pneumonia and influenza (P&I) deaths (ICD-9: 480\u2212487), underlying circulatory and respiratory (C&R) deaths (ICD-9: 390\u2212519), and allcause deaths (ICD-9: 000\u2212999).", "Dr Chow is a public health physician and currently oversees the Communicable Diseases Surveillance Branch at Singapore's Ministry of Health. Her research interests include infectious disease epidemiology and public health surveillance." ] },{ "paper_id": "27cf8042e0891da58b8c21c382a78efdb76110bc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "285fac85e3bda953636c45b1e600f9e60540938d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. Data were expressed as mean S. D.", "HPLC analysis. The extracts were analyzed by HPLC systems (Agilent model 1200 series, Hewlett Packard, Palo Alto, CA) with a Symmetry C 18 -column (Gemini C 18 , 250 \u00d7 4.6 mm) at 30 o C. Linear solvent gradient of binary mobile phase (solvent A, 0.1% trifluoacetic acid in HPLC grade water; solvent B, 0.1% trifluoacetic acid in HPLC grade acetonitrile) during HPLC analysis was applied as follows (total 40 min): 75% A/25% B at 0 to 5 min, 65% A/35% B at 5 to 8 min, 62% A/38% B at 8 to 16 min, 20% A/80% B at 16 to 30 min and 75% A/25% B at 30 to 35 min. The flow rate of the solvent was kept constantly at 1.0 ml/min. Sample injction volume was 10 \u00b5l and UV absorbance was monitored at 370 nm.", "[standard error of the mean (SEM)]. Statistical analysis was performed using multiple analyses of variance (ANOVA) with repeated measures. When significant main effects or an interaction between the main effects was found, specific comparisons were made with Student's paired t-tests. Statistical significance was represented by p < 0.05, p < 0.01, and p < 0.001. Statistical analysis was performed with SPSS version 12.0 statistical software (SPSS Inc., Chicago, IL, USA)." ] },{ "paper_id": "28c3136f729fa6b60127262e63ee74613597a1e6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In their review recently published in Critical Care, Anantham and coworkers outline the ethical framework that forms the basis of the professional obligations of physicians who respond to health care emergencies, such as an influenza pandemic [1] .", "Because we -physicians in the fields of emergency medicine, pulmonology, intensive care and infectious diseases -will be among the first to confront a pandemic, the article by Anantham and coworkers should remind us of our professional obligations and enhance our willingness to fulfill those despite associated risks. Otherwise, as the authors concluded, 'influenza will run it's course \u2026 leaving entire populations ravaged and the history will judge (us) harshly.'", "After decades of low personal risk for contracting lethal diseases, physicians are suddenly facing the possibility of a substantial increase in occupational risk during an influenza pandemic. If they are not confronted before the onset of an influenza pandemic, feelings of unease and fear or ignorance about physicians' professional obligations could profoundly hinder individual physicians in fulfilling their professional duties. Such feelings could therefore undermine institutional and societal preparations. In their review published in Critical Care, Anantham and coworkers outline the ethical framework that forms the basis of the professional obligations of physicians who respond to health care emergencies, such as an influenza pandemic." ] },{ "paper_id": "28cd0535d235f1323e6da447732751774f207ce1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We conducted a preliminary comparison of the relative sensitivity of a cross-section of published human rhinovirus (HRV)-specifi c PCR primer pairs, varying the oligonucleotides and annealing temperature. None of the pairs could detect all HRVs in 2 panels of genotyped clinical specimens; >1 PCR is required for accurate description of HRV epidemiology.", "We compared primers rather than assay function using clinical material instead of cultured virus, plasmid or synthetic RNA standards, or screening contemporary or archived extracts, which are sometimes of low viral load. When picornavirus epidemiology is the primary research focus, we recommend using >2 primer pairs to maximize the detection of HRVs. Under our conditions, pairs 1-4 returned the highest number of positive results, and the rtP-CRs behaved similarly but with reduced sensitivity. The rtPCR that used pair 5 did not amplify known HEVs.", "Many possible reasons could cause discrepant virus testing results between different sites, including changes to specimen integrity resulting from transport and variable amplifi cation resulting from low viral loads. The effects of viral load can be seen in this study: specimens in population 1 that were positive with multiple (>6 separate pairs) primer pairs had a mean cycle threshold of 33.3 (combining results from both rtPCRs), whereas those with <6 positive results had means of 39.3 cycles. Most (29/33) specimens with <3 positive primer pairs were negative by rtPCR. Amplifi cation variability can also be attributed to the substantial nucleotide sequence diversity between HRVs and the different temporal and clinical characteristics of the 2 specimen populations we used. Population diversity is a feature of HRV studies in the literature." ] },{ "paper_id": "291ac6b6c787766b3628d2b7a3ee304c95e6baa0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "29646e3d897ae1232a6a1577635d75bc9ae94bc6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We attempted virus propagation by inoculating VeroE6 cells with the media used to resuspend nasal and throat swab particulates and checking for the development of MERS-CoV cytopathic effect. Infectious MERS-CoV was not recovered at any time postinoculation from any swab sample.", "We tested the suitability of the domestic pig as a model for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Inoculation did not cause disease, but a low level of virus replication, shedding, and seroconversion were observed. Pigs do not recapitulate human MERS-CoV and are unlikely to constitute a reservoir in nature.", "Serum samples collected on the day of euthanasia were tested for the presence of antibodies against MERS-CoV spike protein 1 (S1) by ELISA. By 11 dpi, antibodies directed against MERS-CoV S1 could be detected in all 4 pigs (Figure 2, panel D) .", "We inoculated 2 groups of four 4-5-week-old farm pigs (Yorkshire cross; S&S Farms, Ramona, CA, USA) intranasally (1 mL/nostril) and intratracheally (5 mL) with a total dose of 10 6 tissue culture infectious dose 50 (TCID 50 ) of the hCoV-EMC/2012 isolate of MERS-CoV. A group of 3 control pigs was mock inoculated with Dulbecco's modified Eagle medium (DMEM); these pigs were housed in a separate room from the MERS-CoV-inoculated pigs to prevent cross-contamination. Animal experiments were approved by the Institutional Animal Care and Use Committee of the Rocky Mountain Laboratories and conducted by certified staff in an Association for Assessment and Accreditation of Laboratory Animal Care International-accredited facility according to the institution's guidelines for animal use; staff followed the guidelines and basic principles in the US Public Health Service Policy on Humane Care and Use of Laboratory Animals and the Guide for the Care and Use of Laboratory Animals." ] },{ "paper_id": "298cf2b429e2d9f800d4605192f37da28bec19a0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2a10dd7be4d35acd837cdec5d058541d13def6c3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2a1ca0c271e014530a0cd2ae77e3cb6457666133", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This work was supported by a Grant-in-Aid for Encouragement of Young Scientists (to TT; No. 12771474) from the Ministry of Education, Science, Sports and Culture of Japan. ", "Serum TG was measured using a commercial radioimmunoassay kit (Ab-Beads Thyroglobulin, Eiken, Tokyo, Japan). Intrassay variability was 8.6% at 5 \u00b5g l -1 . Interassay variabilities across a 1month period were 11.8%, 7.4%, 3.1% at 15, 15, 50 \u00b5g l -1 , respectively. Assay sensitivity as determined from the 20% interassay coefficient of variation (CV) was 0.5 \u00b5g l -1 . The cut off level of this kit was 28.4 \u00b5g l -1 . Serum anti-TG antibody was detected with a semi-quantitative microtitre particle agglutination test for the in vitro diagnostic detection and titration of anti-TG antibodies in human serum, SERODIA-ATG (Fujirebio, Tokyo, Japan).", "1 \u00b5l of total RNA was reverse transcribed in an RT mixture containing 50 mM Tris-HCl (pH 8.3), 75 mM KCl, 10 mM dithiothreitol, 3 mM MgCl 2 , 0.5 mM deoxynucleotide triphosphates (dNTPs), 200 U M-MLV reverse transcriptase (Gibco, Gaithersburg, MD), 2 U \u00b5l -1 RNase inhibitor (Takara, Shiga, Japan), and 2.5 \u00b5M random hexamer (Takara) in a total volume of 20 \u00b5l at 42\u02daC for 60 min." ] },{ "paper_id": "2a2f98e53f7347072c5d8975d76acfa5da084905", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Once draft messages are developed, they should be tested with the target audience. Audience segmentation and message testing will ensure that messages resonate with target populations and can improve uptake of prevention behaviors [66] . In launching a communications campaign, choosing appropriate media channels and determining the best timing for release are also critical. There are numerous ways to disseminate rabies educational messages, and benefits and limitations to each of the channels [67] . After implementing any communications effort, evaluating its impact will help inform and improve future educational outreach, although funding limitations may discourage some localities from undertaking this task. Nonetheless, there are several ways in which rabies programs can be evaluated [68] , and options exist for evaluating communication efforts regardless of funding, such as process evaluation and outcome evaluation [45] .", "The project site in south-east Tanzania includes Dar es Salaam, Lindi, Mtwara, Morogoro, and Pwani Regions, comprising 24 districts, 459 wards, with approximately 6,200,000 people and 400,000 dogs. Infrastructure is being developed, and implementation of prevention and control programs has been initiated in Dar es Salaam and Morogoro regions.", "Operational activities related to public-private partnerships are a challenge because strong partners may be restricted by their own institutions or companies as to their level of involvement and they often do not have the time to dedicate to the administering of required activities to reach agreed upon goals. However, one of the major strengths of a public private partnership is the ability to establish new approaches to overcome administrative barriers. The GARC acts as a secretariat for the PRP and is dedicated to bringing all partners and stakeholders together in a timely manner, without bias, and ensuring that operational activities run smoothly." ] },{ "paper_id": "2a342bddeca93a319539fa01061776543e38a88f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Animal-level prevalences and confidence limits, based on pooled samples, were estimated by using a pooled prev- alence calculator (www.ausvet.com.au/pprev). Generalized linear modeling was used to calculate maximum-likelihood estimates of prevalence and confidence limits (14) .", "Infectious bronchitis virus (IBV) causes a costly respiratory viral disease of chickens. The role of wild birds in the epidemiology of IBV is poorly understood. We detected diverse coronaviruses by PCR in wildfowl and wading birds in England. Sequence analysis showed some viruses to be related to IBV.", "Viral RNA was extracted from pooled fecal samples and pooled oropharyngeal swabs by using a QIAamp Viral RNA Mini Kit (QIAGEN, Crawley, UK) following the manufacturer's instructions. Reverse transcription-PCR was used to detect avian coronaviruses as previously described (9) . The primers UTR41+ (5\u2032-ATGTCTATCGCCAGGGAAATGTC-3\u2032) and UTR11-(5\u2032-GCTCTAACTCTATACTAGCCTA-3\u2032) targeted the 3\u2032 untranslated region (UTR) of the coronavirus genome, which is highly conserved among all known types of IBV (9) . This procedure was followed by use of a heminested PCR with the same forward primer but the reverse primer UTR hemi-(5\u2032-CTTAAACTAAAATTTAGCTCTTCC-3\u2032) under the same reaction conditions as the initial PCR, which had an expected product size of 214 bp. PCR products were purified by using a commercial purification kit (QIAquick PCR Purification Kit; QIAGEN) according to the manufacturer's instructions and were sequenced commercially (Cogenics, Essex, UK) as recommended by the manufacturer (ABI 3730xl DNA Analyser; Applied Biosystems, Warrington, UK). Nucleotide sequences derived from this study have been deposited in the GenBank sequence database under accession nos. FJ490193-FJ490199." ] },{ "paper_id": "2a664c1411e75f9237a896f1a9e120046438586d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "They exhibited normal behaviour and the consistency of their faeces was also normal.", "coronavirus / experimental infection / FECV / persistence / cat", "Monitoring of clinical signs was done on a daily basis by scoring for such signs as depression, general activity, anorexia and faeces consistency. The body temperature and body weight were determined once or twice a week. Body weight was expressed as the percentage of the body weight measured at the day of inoculation." ] },{ "paper_id": "2a95ca7f6df1b967ca2fe08cedede51cda46f1b8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ " Kung Oo, ano ", "Kung sumagot ka ng Oo sa alinman sa # 1 o # 2, mangyaring ipahiwatig kung aling mga sintomas: " ] },{ "paper_id": "2b20afed6f91c23379ef9524c0eeb58cd616b0d5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2b239fe6cdaea749fbfd5c219b70ceb99ba5a844", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "O ver the past few years, global migration has led to emerging infectious diseases that pose substantial risks to public health. To prevent potential outbreaks, early detection of infectious pathogens is necessary. In particular, the recent outbreak of severe acute respiratory syndrome (SARS) provided important lessons on how unknown viruses should be detected rapidly. Thus, a standardized and qualified system is required for rapid nucleic acid sequence determination for newly emerging viruses.", "When the number of viral particles in the sample was high, we omitted the RNase A and DNase I treatments and used the RNeasy Mini Kit (Qiagen) for RNA extraction. We occasionally used a whole transcriptome amplification kit (Rubicon Genomics Inc, Ann Arbor, MI, USA) instead of the WGA kit because both kits yielded similar amplification results.", "Recently, we developed a new method for detecting RNA viruses. This method, based on cDNA representational difference analysis (cDNA RDA), uses 96 hexanucleotides that are not suitable for priming ribosomal RNAs but that normally prime most of the genome of an RNA virus as primers for reverse transcription in cDNA RDA (1) . However, the RDA method with a cloning step requires at least 1 week for the determination of the nucleic acid sequence." ] },{ "paper_id": "2b269d2f3f05bfcd6dd61c1ce2eb19937d338f98", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2b554bfe12a457f1092ae7b12537e48cb3392f67", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Among 176 patients who had had severe acute respiratory syndrome (SARS), SARS-specifi c antibodies were maintained for an average of 2 years, and signifi cant reduction of immunoglobulin G-positive percentage and titers occurred in the third year. Thus, SARS patients might be susceptible to reinfection >3 years after initial exposure.", "Our results provide strong evidence that SARS-CoV antibodies are reduced >3 years after the symptom onset. Because antibodies play an important role in protective immunity against SARS-CoV (15), the fi ndings from this study will have important implications with regard to assessing risk for reinfection among previously exposed populations (e.g., hospital staff) and evaluating the duration of antibody-mediated immunity that any candidate vaccine could provide.", "S evere acute respiratory syndrome (SARS) represents the fi rst pandemic transmissible disease to emerge in this century. It was caused by a previously unknown coronavirus, the SARS-associated coronavirus (SARS-CoV) (1) . SARS-CoV spreads from animals to humans by a rapid adaptation and evolution process (2, 3) . A large number of closely related viruses are present in wildlife reservoir populations (4) (5) (6) . Therefore, due to cross-species transmission of the same or a similar coronavirus, SARS could recur. Immune protection against infection with other human coronaviruses, such as OC43 and 229E, is short-lived (7) . To assess SARS patients' risk for future reinfection, we conducted a longitudinal study of immunity in convalescent patients." ] },{ "paper_id": "2b74ca42f9a1083f01aeb7e7ee221953b2ed57fc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2bee310d03a0fb03e14ba89d07407b7463fab209", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Page 5 of 9", "We collected serum samples from 50 healthy blood donors (Cohort A) as negative controls Sanquin Blood Bank (Rotterdam, the Netherlands) obtained written informed consent for research use. We assessed specificity using cohorts B and C, which consisted of 145 serum specimens from patients confirmed by RT-PCR to be positive for human respiratory infections." ] },{ "paper_id": "2bf8ae683ef919a724c5623efda3a71110d57ddd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "IFITs are among the most potently expressed proteins of a group of interferon-stimulated genes (ISGs) 3 , which are the culmination of virally triggered signalling pathways that lead to the production of interferon \u03b1/\u03b2 and other cytokines. They are evolutionarily conserved from mammals to fish, of which in humans there are four well-characterized paralogues, IFIT1 (p56/ISG56), IFIT2 (p54/ISG54), IFIT3 (p60/ISG60) and IFIT5 (p58/ISG58), ranging in mass from 54 to 56 kDa. IFITs are composed of tetratricopeptide repeats (TPRs), which are a degenerate, 34-amino acid, helix-turn-helix motif usually present in multiple copies as tandem arrays that generate solenoid-type scaffolds well suited for mediating protein-protein interactions 4 ", "Finally, given that bacterial mRNAs also bear a free 5\u2032-PPP and can access the cytosol during infection to potentiate induction of interferon-\u03b2 26 , it is plausible that IFITs could also play a role in anti-bacterial innate immunity. Taken together, it is clear that unravelling the structural details that underlie IFIT biology will improve our understanding of the complex interplay between pathogens and host innate immunity, and hopefully pave the way for the development of new immunotherapeutics.", "The structural basis for IFIT recognition of foreign RNA described here validates the new paradigms put forth for how this family of ISGs carry out their effector functions, and brings to the forefront the versatility of the TPR motif in recognizing diverse ligands, paralleling established receptors of the innate immune system such as those containing leucine-rich repeats 1 ." ] },{ "paper_id": "2bfa631d66f7e59bd7de5316ecc45b9f44352f1b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.", "This publication was made possible by grant #1R01GM100471-01 from the National Institute of General Medical Sciences (NIGMS) at the National Institutes of Health. In addition, Rick Horan acknowledges funding from the USDA National Institute of Food and Agriculture, grant #2011-67023-30872. Marm Kilpatrick acknowledges NSF grant #81140 -443559. Peter Daszak acknowledges the generous support of the American people through the United States Agency for International Development (USAID) Emerging Pandemic Threats PREDICT.", "The contents are the responsibility of the authors and do not necessarily reflect the views of the NSF, NIGMS, USDA, USAID, or the United States Government." ] },{ "paper_id": "2c8f94a4a58f03648ff5d88c1d6bff6c6ba7354b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Using immunofluorescence and neutralization assays, we detected antibodies to human severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and/or animal SARS-CoV-like virus in 17 (1.8%) of 938 adults recruited in 2001. This finding suggests that a small proportion of healthy persons in Hong Kong had been exposed to SARSrelated viruses at least 2 years before the recent SARS outbreak.", "Serum samples collected in May 2001 from 938 healthy Chinese adults in Hong Kong and 48 confirmed SARS patients diagnosed in February and March 2003 in Guangdong were studied. All serum samples were aliquoted and stored at \u221220\u00b0C. The healthy adults were totally asymptomatic persons randomly recruited after a telephone interview concerning hepatitis B virus. The signs and symptoms of the SARS patients met the World Health Organization's definition for surveillance, and SARS-CoV infection had been confirmed virologically.", "Seventeen (1.8%) archived samples from healthy adults showed IF antibodies against the human virus, animal virus, or both (titer range 1:20 to 1:1,280) and were confirmed by serum neutralization assay. An additional six samples were IF-antibody positive at a 1:10 dilution to either animal or human viruses, but they were negative in neutralization assay and were treated as negative. The positive rate was highest in the group ages 51 to 60 years and appeared to be more prevalent in female (13/561, 2.3%) than male patients (4/377, 1.1%) (Table) . Of the 17 seropositive serum samples, 10 were from housewives, retired, or unemployed persons; 6 were from clerks, unskilled workers, or students; and one was from a professional (Table) . Most of the seropositive persons (13/17) had a higher IF or neutralization antibody titer to the animal virus than the human virus ( Figure) . By contrast, the control group, comprising convalescent-phase sera from Figure) ." ] },{ "paper_id": "2cdb7b3be2a0c0e1c276302897afc6d3f4a16ef4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2d102f7db396b4358f23cab728f3af3d8871c39c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2d97940930d80363a94347a1356e4059a0b867d6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2da16887635db893ede660723a373467674a9884", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2ded225df8c6a428c0356f30df7656d574b648e6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Guangdong Province has a population of 85.2 million, including 9.9 million in Guangzhou city (7) . All public health and most hospital services are under the direction of the Health Bureau of Guangdong Provincial People's Government. The public health function is performed by one provincial Center for Disease Control and several municipal centers, together with a network of district and county centers, each responsible for a population of 500,000-1 million. Nearly all hospitals are operated by the public sector, but patients are charged for medical treatment. Primary health care in the province is rudimentary, and most patients report directly to hospital emergency rooms.", "A total of 1,454 SARS cases were reported in Guangdong Province from November 16, 2002, through April 30, 2003, including 55 deaths, a crude case-fatality rate of 3.8% for all ages, and 12.7% in people >65 years. Two children died: a 4-year-old, previously healthy girl with lobar pneumonia of unknown cause and a 10-year-old boy with recent acute hepatitis B.", "O n March 12, 2003 , the World Health Organization (WHO) issued a global alert about cases of atypical pneumonia in Guangdong Province and Hong Kong Special Administrative Region, China, and in Vietnam (1). The disease, now known as severe acute respiratory syndrome (SARS), is caused by coronavirus infection (2, 3) and subsequently spread rapidly worldwide. The earliest identified cases of the disease occurred in Guangdong Province in late 2002 (4) ." ] },{ "paper_id": "2e285596b823368b401a5df5b07b6bbedd9a444a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "*World Health Organization, Geneva, Switzerland", "for fi eld collections; J. Andre for research permits; T. Kreeger for access to his facility; R. Massung for positive-control DNA; and G. Dahlem for identifying Ravinia spp.", "Further elucidation is needed about the factors that infl uence the duration of an outbreak, disease severity, and duration of individual protective immunity after an episode of cholera." ] },{ "paper_id": "2e2bc679c8393230bac2af64115bab7ed1ba62c0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2e6b763befef8fc1df4868231c49171d57793e8a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "332 (13) 100 (9) 19 (4) 208 (51) 659 (14) Karyotype 1 , n (%) Favorable 259 (10) 142 (13) 66 (15) 50 (12) 517 (11) Intermediate 1,447 (55) 682 (60) 242 (55) 197 (48) 2,568 (56) Unfavorable 275 (11) 275 (24) 90 (20) 152 (37) 792 (17) Missing 634 (24) 35 (3) 45 (10) 10 (2) 724 (16) NPM1 Mutation 1", "981 (38) 95 (8) 90 (21) 108 (26) 1,274 (28) Male Gender, n (%) 1,407 (54) 588 (52) 234 (53) 213 (52) 2,442 (53)" ] },{ "paper_id": "2e8fb12daa448c956d8b7b348df5e46d29c5f51a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The probe target was chosen to detect the 2 products ( Figure 1 ) and thereby to maximize analytical sensitivity. A probe spanning the spliced segment between positions 241 and 2236 would have been an alternative approach, ensuring specific detection of mRNA spliced at this exact location ( Figure 1 ). However, because our results indicated high specificity with the chosen probe, we did not develop this approach further.", "Twenty-eight HBoV1 DNA-positive NPA samples were collected from a group of children who were admitted for elective surgery and who had exhibited no signs or symptoms of RTI during the previous 2 weeks. The children were included prospectively during the same period in 2007-2010. Median age was 31 months (range 15 months-6 years), and 70% were boys.", "Amplification efficiency was calculated by using the formula E=10 (\u22121/S) \u22121, where S is the slope of the standard curve. A human DNA PCR (specific for the \u03b3-glutamyltransferase light chain 1 gene on chromosome 20) was used as amplification control (8) . Nucleic acid extract from a clinical sample positive for RSV was used as cDNA control. To make sure that mRNA had not been degraded during storage, we used an RT-PCR to detect human \u03b2 actin mRNA (9)." ] },{ "paper_id": "2ea888daab5051a877778175c2349b630c5728f6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To include all 99 HRV reference strains and new di- Table 2 ).", "Distance matrices were computed from alignments with the distmat program in EMBOSS (http://bioweb2. pasteur.fr/docs/EMBOSS/embossdata.html) by using the Tamura distance correction. This method uses transition and transversion rates and takes into account the deviation of GC content from the expected value of 50%. Gap and ambiguous positions were ignored. Final values were then converted to similarity matrices by subtracting each value from 100. ", "H uman rhinoviruses (HRVs) and enteroviruses (HEVs) are leading causes of infection in humans. These 2 picornaviruses share an identical genomic organization, have similar functional RNA secondary structures, and are classifi ed within the same genus (www.ictvonline.org/virusTax-onomy.asp) because of their high sequence homology (1) . However, despite their common genomic features, these 2 groups of viruses have different phenotypic characteristics. In vivo, rhinoviruses are restricted to the respiratory tract, whereas enteroviruses infect primarily the gastrointestinal tract and can spread to other sites such as the central nervous system. However, some enteroviruses exhibit specifi c respiratory tropism and thus have properties similar to rhinoviruses (2) (3) (4) (5) . In vitro, most HRVs and HEVs differ by their optimal growth temperature, acid tolerance, receptor usage, and cell tropism. The genomic basis for these phenotypic differences between similar viruses is not yet fully understood.", "In summary, we have highlighted the large genomic diversity of the most frequent human respiratory viral infection. Our phylogenetic analysis has characterized circulating strains relative to reference strains and has identifi ed a previously unknown enterovirus genotype. We have shown that recombination also contributes to rhinovirus evolution in its natural environment.", "Picornavirus-positive samples were detected from patients enrolled in cohort studies in different regions of Switzerland during 1999-2008. The main characteristics of these populations, type of respiratory specimens, and screening methods are shown in the Table. The rhinovirus serotypes used for 3CD sequencing were obtained from the American Type Culture Collection (Manassas, VA, USA)." ] },{ "paper_id": "2edf14d68de169e1e3457fb5134cf5cac92b5afc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2f3883fe9db3bd0858a68a14233e076dd59e3e4f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Site-Directed Mutagenesis. The single mutants were constructed using a QuikChange kit (Stratagene) with a plasmid containing an open reading frame that encodes the full-length HCoV-OC43 N protein as the template for mutagenesis. The PCR reaction used Pfu DNA polymerase, and each cycle involved heating the sample at 95\u00b0C for 30 s, 55\u00b0C for 1 min, and 68\u00b0C for 2 min/kb of plasmid length; this sequence was repeated for a total of 16 cycles. The templates were digested with DpnI and transformed into E. coli XL-1 cells. All mutations were confirmed by automated sequencing in both directions.", "\u25a0 EXPERIMENTAL SECTION Chemicals. The drugs and reagents supplied in \u226595.0% purity as determined by HPLC were purchased from Sigma Chemical Co. (St. Louis, MO) and used without further purification.", "Figures S1\u2212S7 and Tables S1\u2212S3. This material is available free of charge via the Internet at http://pubs.acs.org." ] },{ "paper_id": "2f3f3fc88a1b21cfb6c1e38e5cd61b856e6caab8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study formed part of an international collaborative study involving healthcare workers in Singapore, China, Taiwan, Canada (Toronto), and Japan. The questionnaire was developed in English at the National University of Singapore, translated into Japanese, and adapted to accommodate background conditions (i.e., no outbreak). The questionnaire was anonymous, and procedures involving human participants were approved by the institutional review board of the University of Occupational and Environmental Health, Japan.", "The study population comprised 9,978 healthcare workers working at 7 tertiary-level hospitals distributed throughout Japan; 4 of the hospitals are university-affiliated, 2 are municipal, and 1 is private. The study participants held a wide range of jobs in each institution. The questionnaire was administered from July through September 2003. Overall, 7,463 healthcare workers responded to the questionnaire (crude response rate 74.8%). After missing or invalid responses for sex, age, or job category were excluded, 7,282 were finally analyzed (valid response rate 73.0%) ( Table 1) .", "The questionnaire included 24 items regarding knowledge of preventive measures (15 items), concept of (opinion regarding) institutional measures (4 items), and perception of risk (5 items) (online Appendix 1 available from http://www.cdc.gov/ncidod/EID/vol11no03/04-0631_ app1.htm). These 24 items were measured on a 7-point scale for responses (strongly agree, agree, probably agree, probably disagree, disagree, strongly disagree, and not applicable). In the statistical analyses, we dichotomized this scale into positive response (strongly agree, agree, and probably agree) and negative response (strongly disagree, disagree, and probably disagree) after excluding \"not applicable.\"" ] },{ "paper_id": "2f56502b1b23bd52dcf3e700ff370667fac055ee", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Of the 16 predicted nonstructural proteins encoded by ORF 1a and ORF 1b, 11 show no change at the amino acid level (Table 1) , whereas 5 (NSP2, NSP3, NSP4, NSP13, and NSP15) show >0.3% difference ( Table 1) . As more sequences become available from this virus, such comparisons will yield clues about the adaptation to humans.", "Materials and Methods" ] },{ "paper_id": "2fbf85467d8268da83e90d1cd249978262c8f2a5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "After pharyngeal swab samples arrived at a collaborating district laboratory, they were immediately spread onto 5% sheep blood agar plates and incubated overnight at 37\u00b0C in 5% CO 2 . We tested b-hemolytic isolates for susceptibility to bacitracin and used the Streptococcal Grouping Kit (Oxoid Ltd., Basingstoke, UK) to determine the Lancefield group for each isolate.", "The odds of having strawberry tongue was higher for GAS-infected study participants <5 years of age (odds ra- Table 2 , Appendix, wwwnc.cdc.gov/EID/article/19/6/12-1020-T1. htm, for details).", "emm Typing", "Streptococcal pyrogenic exotoxins also play a major role in the pathogenesis of GAS infections by acting as superantigens. When these exotoxins cross-link major histocompatibility complex class II molecules and T cell receptors, they trigger intense activation of a subset of T cells within a specific b-chain variable region. This process induces a tremendous release of a series of cytokines and may lead to cell, tissue, and organ damage (15, 16) ." ] },{ "paper_id": "30175004a6a58f006a53f32c00e0363c126f667b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Rotavirus is an important pathogen that causes diarrhea in human infants and in animals worldwide [1] . Rotavirus infections in pigs seriously impact the pork industry. The mortality rate in piglets is extremely variable, ranging from 0 to 50%, and is usually of the order of 0-10%; however, the loss in growth in recovered piglets is economically the most important effect of the disease.", "Rabbit anti-PRV serum, 1 : 3200 ELISA titer, was prepared as previously described in our laboratory [8] ; MTT [3-(4,5-dimethylthiazol-2-y)-2,5-diphenyltetrazolium bromide], horseradish peroxidase-(HRP-) conjugated goat anti-mouse IgA, and HRP-conjugated goat anti-rabbit IgG were purchased from Sigma (St. Louis, MO). FITCconjugated goat anti-rabbit IgG was purchased from Beijing Zhongshan Goldbridge Biotechnology Co. (Beijing, China).", "Strains. The lactococcal surfaceexpression vector pNZ8112, including the Cm resistance determinant, repA and repC replication elements, usp45 signal sequence, nisA-promoter, and the cell wall anchor motif obtained from Streptococcus pyogenes M6 protein, and the L. lactis strain NZ9000 were kindly provided by NIZO Food Research (Ede, The Netherlands). The pET-VP4 recombinant expression plasmid containing porcine rotavirus VP4 gene was constructed in our laboratory, and VP4 protein was expressed and purified as described previously [8] . JL94 isolates of rotavirus virus were propagated in MA104 cells (ATCC, Rockville, MD) as described [9] .", "Gut mucosal infection occurs primarily by the invasion route via viral replication at the tips of the villi of epithelial cells in the small intestine, leading to structural and functional changes in the epithelium. The diarrhea that results is caused by the multiple activities of the virus. Malabsorption is a generally accepted mechanism of rotavirus-induced diarrhea, which is characterized by viral replication in villus enterocytes in the small intestine, with subsequent cell lysis and attendant villus blunting, depressed level of mucosal disaccharidase, watery diarrhea, and dehydration [5, 6] . The rotavirus nonstructural protein NSP4, which has recently been suggested to have a toxin-like function, may participate in inducing intestinal inflammation [7] ." ] },{ "paper_id": "306e80d6a8f3885d871f6b16cdce1bd19f9a70c2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "B ats are reservoirs for many emerging viral pathogens, including Ebola viruses, Marburg viruses, henipaviruses, and severe acute respiratory syndrome coronaviruses; >80 bat virus species have been characterized (1, 2) . The diversity of these viruses and their high infection rates in bats may be attributed to multiple factors might that facilitate virus transmission and maintenance, including bats' large social group size, high species diversity, long life, long-distance migration, roost sharing by multiple species, and social habits such as mutual grooming and biting (1, 2) .", "Lung and liver tissues from 60 of the bats used for the pooled metagenomic analyses were screened individually for ABVV by using reverse transcription PCR targeting the polymerase gene (online Technical Appendix). Three (5%) bats tested positive for ABVV: 1 adult female, 1 adult male, and 1 juvenile male. Viral RNA was found in liver tissue from the 2 male bats and in lung and liver tissues from the female adult bat.", "The bat virome has not been fully characterized. Most bat virome studies have been conducted by analyzing fecal, anal swab, or pharyngeal swab specimens from healthy bats (10) (11) (12) (13) . These studies have revealed a variety of viruses but no new rhabdoviruses. However, viruses in fecal and pharyngeal samples could include ingested and inhaled viruses that originated from insects and plants (10) (11) (12) (13) . To focus specifically on viruses infecting the bats themselves, we performed unbiased metagenomic sequencing of RNA viruses purified from the lungs and livers of 120 rabiesnegative big brown bats (Eptesicus fuscus) collected in Maryland, USA." ] },{ "paper_id": "308a157fe5e9a630ded41e9d708dd50df3b6149b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The \u00c01 frameshifting stimulator of SARS CoV contains an atypical H-type pseudoknot with an extra stem-loop in loop 2", "Human embryonic kidney HEK-293T cells were cultured in the DMEM supplemented with 10% fetal bovine serum. The transient expression was performed by LIPOFECTIN (Gibco BRL) transfection of 500 ng of reporter plasmids into 12-wells cultured cells. The cells were then assayed for the transient expression of the reporter gene 24 h after transfection using dual-luciferase assay of cell lysates, and normalized by b-galactosidase activity as an internal control. All the in vivo experiments were repeated three times with four to six assays for each reaction. Luciferase activity measurements for both in vitro reticulocyte lysate and in vivo transfected 293T cell lysates were performed by using the dual-luciferase\u00d4 reporter assay (Promega) according to the manufacturer's instructions on an ABI TR 717 luminometer. Calculation of luciferase-based frameshift efficiency was performed with control plasmids to calibrate the ribosome drop-off effect as described previously (21) .", "Efficient induction of eukaryotic \u00c01 ribosomal frameshifting requires two in cis RNA elements (1, 6) . The first one is a hepta-nucleotides' slippery site sequence of X XXY YYZ, where the recoding occurs. Analysis indicated X can be any three identical nucleotides whereas Y represents three A or U, and Z is A, U or C. In addition, a downstream stimulator RNA structure located 6-7 nt away from the slippery site is also needed for efficient frameshifting. This downstream RNA stimulator is usually an H-type RNA pseudoknot in which nucleotides from a hairpin loop form base pairs with singlestranded region outside the hairpin. This leads to a topology featuring two helical stems of base pairing region (stems 1 and 2) connected by two single-stranded loops (loops 1 and 2) with a quasi-continuous RNA double-helical structure. However, not all RNA pseudoknots can stimulate \u00c01 frameshifting and non-pseudoknot RNA element has been characterized to be responsible for inducing \u00c01 frameshifting in HIV-1 (7, 8) .", "The \u00c01 ribosomal frameshifting is a translational regulation mechanism adopted by a variety of viruses to synthesize two or more proteins at a fixed ratio starting with a single translation initiation site from the same open reading frame (ORF) (1) (2) (3) (4) . In response to the programmed frameshifting signals in messenger RNA (mRNA), the ribosome is induced to move one base backward in the 5 0 direction, and then continues translation in the new \u00c01 reading frame. The ratio between the two protein products from frameshifting can be determined by the frameshift efficiency of the stimulation signals and can be a key factor for the propagation of virus within the host. It has been suggested to be a potential antiviral target for the interference of viral propagation (5) .", "RNA transcripts spanning the SARS 13 377-13 475 region of SARS CoV were generated by in vitro transcription using T7 RNA polymerase. The purified RNA of desired length was then dephosphorylated by shrimp alkaline phosphatase and 5 0 end labeled with [g-32 P]ATP using T4 polynucleotide kinase, and separated by a 12% sequencing gel. All the RNase protection experiments were performed in 50 ml reaction volumes containing 50 000-70 000 c.p.m. of 5 0 end labeled RNA in the presence of RNase cleavage buffer (30 mM Tris-HCl, pH 7.5, 3 mM EDTA and 200 mM NaCl), and 10 mM MgCl 2 was included in the same buffer for RNase V1 experiments. Before the addition of probing enzymes, the RNAs were denatured by heating at 70 C for 5 min followed by instant cooling on ice and brought back to 20 C for structural mapping. The following amounts of RNases were added for each reaction: 0.0088 (1000\u00b7)-0.044 (200\u00b7) mg RNase A (USB), 0.05-10 U RNase T1 (USB), 0.5-15 U RNase T2 (USB) and 0.01-01 U RNase V1 (Amersham Pharmacia). The hydrolysis RNA ladders were obtained by the incubation of RNA in the hydrolysis buffer at 85 C for 10 min and parallel RNA sequencing products were obtained by the treatment of unfolded RNA with RNases T1 and A. They were used as markers for the assignment of guanines and pyrimidines, respectively. All the reactions were incubated at 20 C for 10 min with the exception that RNase V1 was incubated for 15 min. The reactions were terminated by phenol-chloroform extraction, and precipitated, washed with 70% ethanol, and dried by vacuum. Finally, the cleavage products were loaded into a 10% denaturing gel with different running time to resolve different parts of RNA, and visualized by using phosphorimagery." ] },{ "paper_id": "30c832e81049d050f9f0c0b4887d0008d86ebc7c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In 2005 we published the first study to show that mortality can be reduced by prone ventilation [1] . This study followed the large trial by the Prone-Supine Study Group of Gattinoni and colleagues published in the NEJM in 2001 [2] and another in 2005 that failed to show benefit [3] . We have speculated that the earlier trials failed to show benefit because the protocols of these studies stipulated that physicians do not change ventilator settings during the period of prone ventilation (in order to standardize the changes in gas exchange induced by this maneuver). As per protocol, both the prone and supine groups were subjected to the same mean airway pressures (MAP) and tidal volumes even after it was noted that the PaO 2 :FiO 2 had improved in the prone group and they could be managed with lower MAP [4] . Gattinoni responded to our criticism of his study and conceded that, in retrospect, our approach of reducing ventilation as oxygenation improved was more appropriate [4] . Now a new study by the PROSEVA group has found that prone ventilation does indeed save lives. The stated rationale for the new study by the PROSEVA Study Group of Guerin and colleagues, in severe acute respiratory syndrome (ARDS) [5] , was the meta-analysis data showing improved survival with prone position in patients with severe hypoxemic ARDS. The authors overcame the drawback of the older studies by targeting the a tidal volume of 6 ml per kilogram and the PEEP level selected from a PEEP-FiO 2 table and they have demonstrated a survival advantage for prone ventilation. However, analysis stratified according to quartile of PaO 2", "In 2005 we published the first study to show that mortality can be reduced by prone ventilation [1] . This study followed the large trial by the Prone-Supine Study Group of Gattinoni and colleagues published in the NEJM in 2001 [2] and another in 2005 that failed to show benefit [3] . We have speculated that the earlier trials failed to show benefit because the protocols of these studies stipulated that physicians do not change ventilator settings during the period of prone ventilation (in order to standardize the changes in gas exchange induced by this maneuver). As per protocol, both the prone and supine groups were subjected to the same mean airway pressures (MAP) and tidal volumes even after it was noted that the PaO 2 :FiO 2 had improved in the prone group and they could be managed with lower MAP [4] . Gattinoni responded to our criticism of his study and conceded that, in retrospect, our approach of reducing ventilation as oxygenation improved was more appropriate [4] . Now a new study by the PROSEVA group has found that prone ventilation does indeed save lives. The stated rationale for the new study by the PROSEVA Study Group of Guerin and colleagues, in severe acute respiratory syndrome (ARDS) [5] , was the meta-analysis data showing improved survival with prone position in patients with severe hypoxemic ARDS. The authors overcame the drawback of the older studies by targeting the a tidal volume of 6 ml per kilogram and the PEEP level selected from a PEEP-FiO 2 table and they have demonstrated a survival advantage for prone ventilation. However, analysis stratified according to quartile of PaO 2 :FiO 2 ratio at enrollment showed no significant differences in outcome in this study. They assumed a priori that benefits will accrue only to those with severe ARDS and so they report that prone ventilation helps this group, although their analysis shows severity of ARDS has little to do with improved survival. The authors do not acknowledge our previous communications in the literature. We point to more than a matter of priority in science, which is important in itself. Our findings suggest that prone ventilation may be beneficial in reducing ventilator-induced lung injury in all ventilated patients and this needs to be investigated in a wider context." ] },{ "paper_id": "30cde71f98e1b4202ba43473e686ec4b5b23d42f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "draft of the manuscript: DA. Contributed to the writing of the manuscript: DA and RW. Agreed with manuscript results and conclusions: DA, CAS, CWR, and RW. Jointly developed the structure and arguments for the paper: DA and RW. Made critical revisions and approved the final version: DA and RW. All the authors reviewed and approved the final manuscript.", "Transductions. SupT1 cells grown in RPMI at 1,000,000 cells/well in a six-well plate were prepared for transduction. Cells were treated with 4 \u03bcg/mL Polybrene (hexadimethrine bromide, Sigma-Aldrich) and transduced with viral stocks by hanging bucket rotors centrifuge (Becton Dickinson) at 1500 G, for 80 minutes at 32\u00b0C. Cells were then analyzed for expression 72 hours postinfection.", "Generation of infectious viral particles. For production of Moloney murine leukemia virus (MLV)-based retrovirus, the Phoenix GP cell line at 60%-70% confluence in a 10 cm 2 plate was transfected with 3 \u03bcg of the transfer vector (pBMN-HIV Env wt-i-Blasticidin) and 3 \u03bcg of a vector expressing the envelope glycoprotein of the vesicular stomatitis virus (pCI-VSVg). Plasmids were mixed in 500 \u03bcL of FCS-free DMEM with 48 \u03bcL of PEI (8 \u03bcL per \u03bcg of DNA). DMEM media was replaced 24 hours posttransfection, and viral supernatant was collected at 48 and 72 hours after transfection. All viral stocks were filtered with 0.45 \u03bcm polyvinylidene fluoride (PVDF) filters (Olympus Manufacturers) and either used upon collection or frozen at -80\u00b0C in 2 mL aliquots." ] },{ "paper_id": "310df0148d6a22a47355143c065a8b6cef8edd41", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dr. Basler is an assistant professor in the Department of Microbiology at Mount Sinai School of Medicine in New York City. Dr. Basler's research interests include understanding how highly pathogenic viruses, such as Ebola virus, Nipah virus, and pandemic influenza viruses, interact with host innate immune responses.", "T he identification of novel viruses, particularly those with the potential to cause human disease, has important public health and scientific implications. Examples of emerged or recently identified viruses affecting humans include HIV (1), hepatitis C virus (2), West Nile virus (3), severe acute respiratory syndrome (SARS)-associated coronavirus (4), human coronavirus from the Netherlands (HCoV-NL) (5) , and Ebola virus (6) . Among the paramyxoviruses, Nipah virus, Hendra virus, and human metapneumovirus were recently described as causing disease in humans (7) (8) (9) .", "Paramyxovirus genes are separated by cis-acting elements in the genome. The signals that lie between genes include a gene-end signal, an intergenic sequence, and a gene-start signal. The Angrem52 sequence, which contains the continuous sequence for the M and F genes, possesses a sequence with similarity to the regulatory sequences in other paramyxoviruses ( Figure 1A )." ] },{ "paper_id": "3148f3c48df3ecc495ce6ec7caaebcaddd1340fc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3184616f8c024012a6d2d460222d2fb5e56fd98a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Antibody heavy and light chains were cloned into human IgG1, Ig\u03ba and Ig\u03bb expression vectors and expressed by transient transfection of Expi293F Cells (ThermoFisher Scientific) using polyethylenimine. Cell lines were routinely tested for mycoplasma contamination. The antibodies were affinity purified by protein A chromatography (GE Healthcare).", "Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZ) has been shown to be protective, but the features of the antibody response induced by this treatment remain unclear. To Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:", "Following informed consent, blood samples used in this study were collected from malaria pre-exposed volunteers during a clinical phase 1 clinical trial of the safety, immunogenicity and protective efficacy of the Sanaria \u00ae PfSPZ Vaccine in Bagamoyo, Tanzania " ] },{ "paper_id": "31fae2807695521804442fedcd3f7b9f17d0f9ea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "PERC was purchased from Sigma Aldrich (St. Louis, MO; Catalog #270,393-100ML; Lot #SHBD9374V). Alkamuls-EL620 was acquired from Solvay (Deptford, NJ; Lot #SP8J26X07). All reagents used were of the highest purity available.", "Both national (U.S. EPA) and international (WHO) agencies have encouraged replacing these fixed \"uncertainty factors\" with values derived from chemical-specific data, so-called \"chemical-specific adjustment factors\" or \"data-derived extrapolation factors\" (IPCS 2005; U.S. EPA 2014) . For example, factors derived from population PBPK modeling protective of 99% population were used to replace the uncertainty factor for toxicokinetic variability in several U.S. EPA assessments, including TCE (U.S. EPA 2011c).", "All raw data have been made publically available by uploading files into the Mouse Phenome Database (http://phenome.jax.org; MPD: Rusyn7).", "likely addresses a portion of the overall variability, but is less sensitive to additional variability at low doses due to interindividual differences in K M among CC mice. The high dose level also limits interpretation of the lack of correlation between metabolism and CYP2E1, because a stronger correlation may exist at lower exposure levels.", "A detailed protocol for qRT-PCR is provided in the Supplemental Material, \"Materials and Methods.\" Briefly, qRT-PCR was performed on 50 ng of cDNA from the liver (left lobe) with Taqman V R probes targeting Acyl-CoA oxidase 1 (Acox1) and Cyp4a10. b-glucuronidase (GusB) was used as the housekeeping gene." ] },{ "paper_id": "31ff32abd2da30cf9a0ed4414fb83e19eb874314", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3208852c9234f3d7d415af376bdb22cdb95f5bba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "321d1c4149caa030f3ad537e3be1ce3a9201571c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "None of the laboratory staff became ill with SARS symptoms, indicating that clinical specimens for serologic testing and RT-PCR can be processed safely in BSL2 level conditions.", "In summary, SARS is closely associated epidemiologically with the novel SARS-CoV. The unusual profile of viral shedding from the respiratory tract may explain some of the observed transmission pattern of this disease, including the predilection for affecting healthcare workers.", "Virus isolation or preparing cell smears for serologic testing was done in a biosafety level (BSL) 3 laboratory. Routine handling of clinical specimens for RNA extraction and serologic testing by immunofluorescence were done in a BSL-2 laboratory. Basic laboratory practice was reinforced by educating staff and closely supervising work practices. Serum specimens for antibody testing were heat inactivated at 56\u00b0C for 30 minutes before testing.", "Specimens resuspended in virus transport medium (200 \u00b5L) were used for infecting fetal rhesus monkey kidney (FRhK-4) cell monolayers in culture tubes. Approximately 1 g of feces samples was resuspended in 10 mL virus transport medium and centrifuged, and the supernatant was spread onto cells. The respiratory samples were already diluted in virus transport medium and spread onto the cell monolayer. After incubation at 37\u00b0C for 1 h, the cells were fed with 1 mL of minimum essential medium with 1% fetal calf serum (GibcoBRL, Grand Island, NY) and incubated at 37\u00b0C. The cultures were examined for cytopathic effect (CPE) each day for 14 days. At the end of the incubation period or when CPE appeared, the cells were spotted on Teflon-coated slides, fixed with ice-cold acetone, and stained for SARS-CoV antigen by using a convalescent-phase human serum. The identification of the isolate was confirmed by RT-PCR." ] },{ "paper_id": "323ece9056ef7a1d81faf3422e98def1efd38f70", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Insects have diverse mechanisms to combat infection by pathogens. Many insects are protected by a layer of antimicrobial secretions on their exterior, and by a gut environment that is hostile to pathogens. When pathogens move beyond these defences, the epithelium is often sufficient to stop further progress. Should pathogens defeat the morphological defences of insects, they are often met by efficient cellular and humoral immune defences. Insect immunity shows many parallels to the innate immune responses of humans and other vertebrates, involving a diverse set of actions including the secretion of antimicrobial peptides, phagocytosis, melanization and the enzymatic degradation of pathogens (Hoffmann, 2003; Hultmark, 2003) . Further, insect immune pathways share both an overall architecture and specific orthologous components with the innate immune system of vertebrates (Beutler, 2004) . This suggests both a shared root for these immune pathways and selection to conserve many components over hundreds of millions of years.", "Future genomic work can help reveal whether other species of highly social insects, including ants, wasps, bees and termites, also appear to have more simplistic innate defence systems. More generally, social and solitary insects with more 'exposed' life histories are predicted to have a greater number and higher functional diversity of immunepathway genes and end products, when compared to sister taxa that are more sheltered. Data on parasite and pathogen abundance across social (e.g. Boomsma et al., 2005) and solitary insects could be used as a surrogate for disease loads in different taxa, although field and epidemiological data are most needed to assess the relative fitness impacts of disease and the efficacies of different lines of defence.", "With respect to the final hypothesis, bees, like many social insects, are relentlessly hygienic, removing alien organisms from their nests, and secreting antimicrobial substances that can reduce the viability and growth of pathogens in the colonies. Bees also raise their young in individual cells using, as a food source, substances with strongly antimicrobial properties (e.g. royal jelly; Albert & Klaudiny, 2004) . A testament to this hygiene is the fact that, even when facing severe colony-level infections by bacterial pathogens such as Paenibacillus larvae (for which < 10 spores are normally fatal to young larvae (Brodsgaard et al., 1998) , the vast majority of larvae show no signs of exposure (Evans & Pettis, 2005) . 'Social' barriers might also reduce exposure to minor, opportunistic, pathogens or saprophytes that have been proposed as generalized targets of insect immune defences (Hultmark, 2003) . While bees do carry an assemblage of microbes, and bacteria in particular (Gilliam, 1997) , exposure to these microbes is arguably lower than in free-living Drosophila (decaying plant material as larvae and adults) or Anopheles (septic aqueous environments as larvae). Further, bacteria found in bee colonies have only rarely been associated with disease pathologies, despite extensive study. In fact, some resident bacteria in colonies appear to add to external defences through their inhibition of bee pathogens (Evans & Armstrong, 2006) .", "Two experiments were carried out to screen for immune-related transcript changes. In the first, adult worker bees from a single local A. mellifera ligustica colony were removed, then injected abdominally with either dilute phosphate-buffered saline or saline solution containing 103 live cells of E. coli or 103 vegetative spores of the honey bee bacterial pathogen Paenibacillus larvae. These bees, along with uninjected controls, were maintained for 24 h at high humidity and 34 \u00b0C and then were immediately frozen at \u221270 \u00b0C prior to RNA extraction. To assess immune responses following natural infection, eight 1st-instar larval bees from the same stock were given per os challenges of P. larvae in their food [(50 spores/\u00b5l as described in Evans (2004) ], then maintained 24 h at 34 \u00b0C and high humidity. Parallel control larvae were given the same food without bacterial spores. All samples were frozen at \u221280 \u00b0C following incubation." ] },{ "paper_id": "327d5fb31ab8eb04ed90082b0ba448675c90208d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "HLA genotype of the patients was determined by reverse sequence-specific oligonucleotides probes ", "Collectively, our results demonstrate how the integration of peptidomics, structural data, in silico predictions and dissection of the specific B and T cell responses represents a powerful approach to define the immunogenic landscape of therapeutic antibodies and to guide the deimmunization strategies of next-generation biological therapeutics for autoimmune and cancer disease. Currently used fully human antibodies, including checkpoint inhibitors, may also benefit from the deimmunization strategy. Reciprocally, this approach could be used to improve the immunogenicity of vaccines through the engineering of dominant T cell epitopes driving neutralizing antibody responses.", "Natalizumab (NZM), a humanized monoclonal IgG4 antibody to \u03b14 integrins, is used to treat patients with relapsing-remitting multiple sclerosis (MS) 1,2 , but in about 6% of the cases persistent neutralizing anti-drug antibodies (ADAs) are induced leading to therapy discontinuation 3,4 . To understand the basis of the ADA response and the mechanism of ADA-mediated neutralization," ] },{ "paper_id": "329cff721b7b30ea14537ac2a85254cd984691db", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "32b34236bf241a4818cf5763dcc46b92be097e16", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Immunohistochemical staining was performed on 5-\u03bcm paraffin sections of formalin-fixed tissue samples. Samples were de-paraffinized and rehydrated. After blocking endogenous peroxidases with 0.3% H 2 O 2 and 0.03% NaN 3 for 30 min, 10% normal goat serum was applied for 30 min at room temperature. Rabbit anti-SARS CoV nucleocapsid antibody was added at room temperature for 1 hr. Sections were then washed and incubated with peroxidase-conjugated goat anti-rabbit IgG antibody (DakoCytomation) for 1 hr at room temperature. The signal was developed with diaminobenzidine chromogen substrate (DakoCytomation). Sections were counterstained with Mayer's hematoxylin (DakoCytomation) and mounted with Crystal/mounting. Electronic images were visualized under a microscope (Eclipse E600; Nikon), were captured and saved to a computer using the software ACT-1 (Nikon).", "Confocal microscopy was performed using a Carl Zeiss LSM 510 META confocal microscope equipped with four lasers. Adobe Photoshop (version 7.0; Adobe, San Jose, CA) was used to assign colors to the four channels collected: Alexa 568 and HNPP/Fast Red, which fluoresce when exposed to a 568-nm wavelength laser, appear red; Alexa 488 (Molecular Probes) appears green; Alexa 633 (Molecular Probes) appears yellow. The four channels were collected simultaneously. In some tissues and to differentiate between individual cells, Hoechst 33258 (nuclear marker, Molecular Probes) was used at 1 \u03bcg/ml, incubated for 5 minutes, and tissues were then rinsed in water. Co-localization of antigens was demonstrated by the addition of colors as indicated in the figure legend.", "Immunofluorescence staining was performed on 5-\u03bcm paraffin sections of formalin-fixed tissue samples. Samples were de-paraffinized and rehydrated. After blocking with normal goat serum for 30 min at room temperature, rabbit anti-SARS CoV nucleocapsid antibody was applied at 4\u00b0C overnight or for 1 hour at room temperature, followed by Alex 488conjugated goat anti-rabbit IgG antibody for 1 hour at room temperature. Additional immunofluorescence staining was then performed by incubating the second set of primary antibodies for 1 hour at room temperature or 4\u00b0C overnight, followed by the detection of signals with appropriate fluorescent secondary antibodies for 1 hour at room temperature." ] },{ "paper_id": "32c8722461407f64b15ce12595cd8eb7cbe3733c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Infectious bronchitis (IB), caused by the infectious bronchitis virus (IBV), is a highly contagious viral disease of chickens with a worldwide distribution [4] . It is characterized by respiratory symptoms, nephritis, poor performance and reduced egg reproduction [4] .", "In the infected birds, gross lesions were mainly confined to the kidney, which was pale, swollen with interstitial nephritis and showed evidence of severe urate deposition. IBV was recovered from the trachea (90%, or 9/10) and kidney (80%, or 8/10) of infected birds by inoculating tissue homogenate into the allantoic cavity of 9 to 11 day-old SPF embryonated chicken eggs (Lohmann, Germany) using standard methods [5] and identified by dot-immunoblotting assay using monoclonal antibodies [17] . Control birds exhibited no pathological lesions in the kidney, and no evidence of viral load. These results demonstrated that strain Kr/Q43/06 is nephropathogenic in chickens.", "End-points were calculated by the Reed and Muench method [15] . A neutralization index (NI) was calculated, representing the difference (in logarithmic units) in viral titer between virus alone and the corresponding virusantiserum mixture. An NI value of \uff1e4.5 indicated homologous strains, a value of 1.5\u223c4.5 indicated heterologous strains, and a value of \uff1c1.5 was considered a different serotype. As shown in Table 1 , strain Kr/Q43/06 was effectively neutralized by antiserum to the homologous strain (NI of 6.2). However, the NI for antisera to strains KM91 and H120 was 1.4 and 1.2, respectively, which indicated that antisera to strains KM91 and H120 were unable to effectively neutralize strain Kr/Q43/06. NI values were converted to antigenic relatedness (R value) using the following formula created by Archetti and Horsfall [1] :" ] },{ "paper_id": "3399d0fe01c7cb8bff0615a506b7beacc813a05e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Currently, tests for the detection of microbial infections are the only clinical tests that rely on measuring antibody responses. ELISA-based detection methods are often used to detect a patient's antibody titer to epitopes of the microorganisms for diagnosis of the infection.", "In addition to early detection, cancer markers may also enable clinicians to offer personalized treatment. Recent advances using the anti-cancer drugs Herceptin and Iressa illustrate this point. These drugs target specific patient populations: Herceptin is effective against those tumors expressing the Her2 receptor and Iressa is effective for patients with specific mutations in the epidermal growth factor receptor [58, 109] . These drugs offer limited benefits to patients with the same cancer types when these markers are not present. Thus, determining the marker profile of an individual's disease can enable the identification of distinct patient populations, allowing tailored and more effective treatment.", "Although protein microarray technology provides a high-throughput method with high sensitivity and specificity for protein marker discovery, there are particular limitations that investigators need to be aware of before applying the technology to their research." ] },{ "paper_id": "33ca94e310160a0d80e15f1d2bbd2379485789d7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "33cbb0a596335d751617e5ce9d8e89c2123680f7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3415b829bc37f09d2e984666450d1a3af3f448d3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "342d06ebd07e4973d9825fb4767d43074949c022", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3454d8f6a1cfd9321ea90568ac0dc0e138859034", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "346f7bb753e53598554deae2f428d0ce66a8320a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A prospective study of a dromedary camel herd during the 2013-14 calving season showed Middle East respiratory syndrome coronavirus infection of calves and adults. Virus was isolated from the nose and feces but more frequently from the nose. Preexisting neutralizing antibody did not appear to protect against infection.", "Hydrolysis probe-based real-time reverse transcription PCR (RT-PCR) targeting MERS-CoV upstream of E (UpE) and open reading frame (ORF) 1a genes and a broad-range RT-PCR reacting across the CoV family to detect other CoVs were used as described (4) . Specimens initially positive for MERS-CoV were re-extracted and retested to confirm the positive results.", "The unusual genetic stability of MERS-CoV in dromedaries, taken together with its high seroprevalence (7, (10) (11) (12) (13) , raises the hypothesis that dromedaries might be the natural host for this virus. Further longitudinal studies of MERS-CoVs in dromedaries are needed to confirm this hypothesis." ] },{ "paper_id": "34bb9a7b2786bcb577b96dcc04e0f5e04434935b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Probable and suspected SARS cases were defined according to the China Ministry of Health's definitions,", "Methods", "Definitions" ] },{ "paper_id": "34bc96d247a78a804e014e09c997bf5f2ac71b6d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "34d0858071fada0568643bf829c7349f56b28515", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "351fca8e4bd7321d75ec0227794deb0db3567540", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "P orcine epidemic diarrhea virus (PEDV) (family Coronaviridae family, genus alphacoronavirus) has an enveloped, single-stranded, positive-sense RNA genome of \u224828 kb (1). The 5\u2032 two thirds of the genome contains 2 large open reading frames (ORFs), 1a and 1b, that encode 2 nonstructural polyproteins, pp1a and pp1b, that direct genome replication and transcription. The remaining PEDV genome contains ORFs specifying structural and nonstructural proteins in the following order: spike (S), ORF 3, envelope (E), membrane (M) and nucleoprotein (N) (2, 3) .", "We aligned PEDV sequences by using the ClustalW (http://www.clustal.org/clustal2/) method. Phylogenetic trees for the complete genome and each gene segment were constructed by using the maximum-likelihood method with the general time reversible nucleotide substitution model and bootstrap tests of 1,000 replicates in MEGA 6.06 software (30) . The RIP (Recombinant Identification Program; http://www.hiv.lanl.gov/content/sequence/RIP/RIP.html) was used to identify recombination points within the PEDV genome. The RIP analysis parameters were window size of 400 and confidence threshold of 90%.", "Porcine epidemic diarrhea (PED) was first documented in the United Kingdom in 1971 as a swine disease resembling transmissible gastroenteritis (4) . In 1978, the etiologic agent of PED was identified in Belgium as a new coronavirus and was designated as PEDV, prototype strain CV777 (1). Within 2 decades, PEDV was reported in several other European countries; Hungary, Italy, Germany, France, Switzerland, and the Czech Republic (5) . Currently, the virus causes only isolated outbreaks in Europe. In Asia, PEDV was first identified in 1982 and is now considered endemic, causing substantial economic losses to pork producers in China, South Korea, Thailand, and Vietnam (5) . However, it was not until 2010 that massive PED outbreaks were reported in China; the outbreaks have been characterized by 80%-100% illness among infected swine herds and a 50%-90% mortality rate among infected suckling piglets (6) (7) (8) ." ] },{ "paper_id": "35280a72bb06b25d4a02e38efd412e97a40883c5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "H epatitis E virus (HEV) is a major cause of acute hepatitis worldwide (1) . Four HEV genotypes belonging to the species Orthohepevirus A are commonly found in humans (HEV-1 through HEV-4). Genotypes 1 and 2 seem to be restricted to humans, whereas genotypes 3 and 4 also occur in domesticated and wild animals. Zoonotic transmission by ingestion of contaminated meat, mainly from pigs, is the most likely zoonotic source of infection (1) .", "We sequenced a 283-nt fragment of the RNA-dependent RNA polymerase gene of all positive samples for phylogenetic analyses. All camel HEV clustered in a monophyletic clade with the human HEV-7 sequence (Figure 2 ), supporting the classification of camel-associated HEV to a separate Orthohepevirus A genotype (11) .", "Author that separates the prototype HEV-4 sequence from HEV-5 and HEV-6 prototype sequences. This finding suggests that HEV-7 is a strongly diversified clade of viruses that might need to be further subclassified. HEV-7 was recently shown to belong to the same serotype as HEV-1-4 (12) . Therefore, we conducted a preliminary serologic analysis with a subset of 210 specimens (35 per country) by adapting a human HEV ELISA (EU-ROIMMUN, L\u00fcbeck, Germany) for application with camel serum. Serum was tested at a 1:100 dilution. The signalto-noise ratio was optimized by normalizing the optical density (OD) of test samples against ODs of a reference serum included in every run (online Technical Appendix Figure, http://wwwnc.cdc.gov/EID/article/22/7/16-0168-Techapp1.pdf)." ] },{ "paper_id": "3544f2f3beb5aec79815ae9ba463173cbe768172", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "356e180c8bed920420d2b6c5ad48ba9a4568da31", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "357d5838127aad0439fe56f9a619d11919e51d01", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "T he possibility of an influenza pandemic presents a major public health challenge. Since 2003, outbreaks of avian influenza (AI) have occurred in Asian, European, and African countries. As of August 21, 2006, the total number of cases was 240 and the number of deaths was 141 (1) . A crossover of current human influenza virus with the avian H5N1 virus could result in a virus capable of human-tohuman transmission and the start of a new pandemic.", "In line with the protection motivation theory (8), a measure of risk perception was constructed by multiplication of seriousness (scale 1-10) and vulnerability (scale 1-5). To make the scores comparable, the seriousness score was first divided by 2. To normalize the skewed distribution of the new variable, a square-root transformation was performed, which resulted in a measure of risk perception on a scale from 1 (low) to 5 (high).", "Despite extensive media attention for avian influenza, knowledge about risk perception of AI is scarce. We therefore explored the conditions for effective nonmedical interventions. If an influenza pandemic occurs, public health authorities will be dependent on the willingness and ability of the public to adhere to recommendations regarding personal hygiene, vaccination and prophylaxis, quarantine, travel restrictions, or closing of public buildings (2, 3) . Adherence, however, cannot be assumed. Evaluation of the outbreak of H7N7 AI in the Netherlands in 2003 showed that adherence to antiviral therapy and behavioral measures, such as wearing face masks and goggles, was low (4)." ] },{ "paper_id": "35b6dc25346a6ccc941728e55628decf40327a0c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "35c420fb4598e8d833173d957564539f37162d0d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Reagents: TRI Reagent, MG132, 3-MA, NH4Cl, Chloroquine, Wortmannin, Rapamycin (Sigma), Lipofectamine 2000, Vybrant Dil Cell labeling solution, Lysotracker (Invitrogen), mouse interferon ELISA kit (PBL interferon source), recombinant mouse interferon \u03b2 (Millipore). Antibodies: mouse anti-Trex1 (mouse; 1:1,000 dilution; 29; 611987; BD Biosciences), anti-HMGB1 (rabbit; 1:2,000 dilution; ab18256; Abcam), anti-LAMP1 (rabbit; 1:500 dilution; ab24170; Abcam), anti-SQSTM1/p62 (mouse; 1:1,000 dilution; ab56416; Abcam), anti-LC3 (rabbit; 1:500 dilution; NB100-2220; Novus Biologicals), anti-NPC1 (rabbit; 1:1,000 dilution; # 3878-1, Epitomics), anti-Tubulin (mouse; 1:2,000 dilution; B-5-1-2; Sigma), \u03b1-VSV (rabbit; 1:4,000 dilution; R4006-F, kind gift from M. Whitt, University of Tennessee Health Science Center, Memphis, TN), anti-TFEB (rabbit; 1:2,000 dilution; generated in house), anti-Influenza A (goat; 1:250 dilution; B65141G, Meridian Life sciences), anti-Sendai (rabbit; 1:2,000 dilution; PD029, MBL), anti-WNV (rabbit; 20ug total; C19367, Lifespan Biosciences), anti-mTOR (7C10) (rabbit; 1:1,000 dilution; #2983; Cell Signaling), anti-S6 ribosomal protein (5G10) (rabbit; 1:1,000 dilution; #2217; Cell Signaling), anti-phospho-S6 ribosomal protein (Ser235/236) (rabbit; 1:1,000 dilution; #2211; Cell Signaling), anti-phospho-p70 S6 kinase (Thr389) (rabbit; 1:1,000 dilution; #9205; Cell Signaling), anti-phospho-4E-BP1 (Thr37/46) (rabbit; 1:1,000 dilution; #2855; Cell Signaling), anti-4E-BP1 (rabbit; 1:1,000 dilution; #9644; Cell Signaling) and secondary antibodies (1:4,000 dilution; GE Healthcare) were used for immunoblot analysis according to standard protocols.", "Wild-type, Trex1 \u2212/\u2212 MEFs were washed with PBS and fixed in 2% glutaraldehyde (in 0.1 M phosphate buffered saline) for a minimum of 4 hours and post-fixed in 1% osmium tetroxide (in 0.1 M phosphate buffered saline) for 1 hour. After rinsing and dehydrating with graded ethanol solutions (50%, 70%, 95%, 100%), the specimens were infiltrated sequentially with propylene oxide, 1:1 mixture of catalyzed Eponate 12:propylene oxide, and 100% catalyzed Eponate 12. The specimens were then embedded in embedding molds and polymerized in a 60 \u00b0C oven overnight. Thick sections (1.0-1.5 micron) were cut on Leica Ultramicrotome with a glass knife, mounted on glass slides, and stained with toluidine blue stain. Thin sections (60-90 nm) were cut using a Leica Ultramicrotome with a diamond knife, mounted on copper grids, and stained with uranyl acetate and lead citrate. Ultrastructural examination was performed on a Hitachi H-7500 Transmission Electron Microscope.", "Data are presented as the mean \u00b1 s.d. Statistical significance was determined by Student's ttest. P values of less than 0.05 were considered statistically significant." ] },{ "paper_id": "35e9db94099acc5ce344cdf3a2189d69616a12e9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Collectively, we demonstrate a unique injectable hydrogel with desirable properties including ease of preparation, unscathed mechanical properties after injection, sustained delivery of small hydrophobic molecular drugs, and injection with encapsulated cells. Furthermore, the dynamic physical cross-links in this hydrogel enable the infiltration and migration of cells from the surrounding environment to speed up the in situ bone regeneration in a SAON animal model. This injectable hydrogel can be easily customized to carry different portfolios of therapeutic drugs and cells for treating a wide array of clinical conditions via minimally invasive procedures in deep and enclosed anatomical locations. Author Contributions \u25c6 Q.F. and J.X. contributed equally.", "Our previous research also showed that an anabolic and potent molecule icaritin can function as a chemoattractant to induce the directed migration of MSCs within a short time frame. 72 The dynamic and weak cross-links based on host\u2212guest complexation of our Ci-I gelatin hydrogel can potentially support cell infiltration and migration. To demonstrate this, we seeded MSCs on the surface of Ci-I hydrogels with or without the loaded icaritin. enzymes might not be significant enough to support such extensive cell infiltration within the short period of 24 h. We speculated that the cell infiltration was likely facilitated by the disruption of the weak host\u2212guest cross-links in Ci-I hydrogels by cellular forces. Therefore, we speculate that, once implanted into the defect sites, the icaritin-laden Ci-I gelatin hydrogels can promote the recruitment and infiltration of endogenous cells into the hydrogel matrix, thereby speeding up the repair and regeneration of bone defects.", "The authors declare no competing financial interest. " ] },{ "paper_id": "36102f647952cc83d82e800c7069bc2467214d2d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Patients with ARDS were supported aggressively with intubation and mechanical, pressure-controlled ventilation with high positive end-expiratory pressures. Despite these and other supportive measures, three patients died of progressive respiratory failure.", "Laboratory investigations at admission are shown (Table 3) . Lymphopenia, as defined by a cell count of <1.5 x 10 9 /L, was present in 18 of 20 patients. Other common laboratory abnormalities included leukopenia, thrombocytopenia, elevated LDH, mild hyponatremia, mild hypokalemia, and raised hepatic transaminases.", "Results of routine microbiologic cultures, serologic tests, and rapid antigen tests were universally negative. However, viral particles characteristic of coronavirus were found on electron microscopy examination of nasopharyngeal aspirates in 4 of 10 patients.", "All patients were initially treated with either levofloxacin or a combination of intravenous ceftriaxone and a macrolide once x-ray abnormalities were observed. Oseltamivir, 75 mg twice a day, and oral ribavirin, 20 mg/kg body weight three times a day, were prescribed to 6 and 14 patients, respectively. These antiviral drugs were started late in the course of illness: Most were prescribed from day 10 to day 14 of symptoms. Five patients in the intensive care unit were given corticosteroids (intravenous hydrocortisone, 100 mg every 6 hours, or intravenous methylprednisolone, 120 mg once a day)." ] },{ "paper_id": "361e12416e0ff49f28521c2dc5fc69934e419910", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The virus attacked persons of both sexes and all ages. Many were previously in good health and the wage earners in their families. Not infrequently, several members of a family were admitted to the hospital. The need for isolation discouraged close social contact. Unfortunately, some of the patients were also stigmatized. The psychosocial effect of SARS is by no means a lesser problem.", "We need to investigate new antiviral agents and test the efficacy of steroids in randomized controlled trials. SARS is an entirely new emerging disease and its clinical course varies widely. By stratifying our patients according to risk, we could individualize our treatment protocol. In addition, we need a more sensitive and rapid diagnostic test for SARS-associated coronavirus infection, both for treatment and for forming cohorts of patients infected with this deadly disease. ", "Patients who sought treatment early tended to receive antiviral therapy at a later time. This is understandable since the symptoms of SARS are nonspecific, and clinicians also rely on laboratory data for diagnosis. The sensitivity of current RT-PCR assays is not satisfactory. A more sensitive and rapid diagnostic test must be developed, particularly if we have an effective treatment regime in the future." ] },{ "paper_id": "361fcf9eb197bf251946ecf59341fcdb7a524a0f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "P athogen spillover mechanisms vary, but one route involves pathogens moving from heavily infected domestic animal hosts to nondomestic hosts (1). These spillover and emergence events create a dynamic landscape for pathogen transmission.", "Porcine epidemic diarrhea virus, a pathogen first detected in US domestic swine in 2013, has rapidly spilled over into feral swine populations. A better understanding of the factors associated with pathogen emergence is needed to better manage, and ultimately prevent, future spillover events from domestic to nondomestic animals.", "The transmission pathway from infected facilities to feral swine is unknown. Previous research has detected PEDV in the environment (3,7) but did not differentiate viral RNA from infectious virus. Swine facilities often move waste to holding ponds, and these ponds could be a source of infectious virus. Infected swine in backyard operations also could facilitate spillover." ] },{ "paper_id": "363d8e5ae1bb4bc246692ca6ef794b559b046b54", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Obtaining the DNA for hybridization could also be problematic for some infections: infected tissues may be inaccessible and could yield little nucleic acid.", "Genome Biology 2005, 6:112 comment reviews reports deposited research interactions information refereed research", "Probe array" ] },{ "paper_id": "36817ab59a9f5a607f7cdc110e6d7930f5a45658", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "36878ef3cdf585376c19d3f19f3a50a1bd466615", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Patients' demographic and clinical profiles are shown in online Technical Appendix Table 1 (http://wwwnc.cdc. gov/EID/article/21/12/15-1421-Techapp1.pdf). Of the 17 patients, 9 had severe disease (4 required mechanical ventilation, 4 required supplemental oxygen; 1 died) and 8 had mild disease. Serial serum samples were collected and analyzed. The study was approved by the SNU Institutional Review Board.", "An understanding of MERS-CoV antibody response kinetics helps in defining the window during which passive antibody therapy may be useful. In our study, this window was the first 21 days of illness for most patients. However, some patients may not develop strong antibody responses even after 4 weeks of illness, so therapy must be individualized.", "Overall, serologic responses were robust and were detected in most patients by week 3 of illness (Figure) . Of the 12 patients who had serum samples tested beyond day 18 of illness, 9 had PRNT 50 titers >1:320 by day 21 and 2 more had titers >1:320 by day 28. Patient L, a 56-year-old woman with no underlying disease, had weakly positive PRNT 50 (1:20) and borderline ELISA responses (optical density ratio 1.0), even at day 32 of illness. A chest radiograph showed she had lung infiltrates, but she was not oxygen-dependent and was not administered antiviral drugs or corticosteroids; her recovery was uneventful." ] },{ "paper_id": "36c97bef26a4934b9f543c3f67f0ab9cfa55e6b5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "36d93efb83871f3d6d3b92605ae47f5a9c182ca2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "372fcfd74ff4f579704d40ec8fe524357534ef22", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Experience from the international outbreak of severe acute respiratory syndrome (SARS) (33) can shed light on how to approach these complicated issues. In Toronto, obstetric services were moved into a newly designed facility that had entrances, elevators, and air-handling systems that were separate from the rest of the hospital. Hospital staff, patients, and visitors were screened at the hospital entrance for SARS symptoms and to ensure that they had not visited a SARS-affected area. Staff members wore N95 respirator masks, face shields or eye protection, gowns, and non-latex gloves, and employed frequent hand washing with ethanol-based gels. Patients were limited to 1 visitor during labor and delivery, and no visitors were allowed on postpartum wards. All patients and visitors wore N95 respiratory masks. The length of postpartum stay was decreased and, after discharge, women were instructed to stay at home under quarantine for 10 days; a nurse visited them on their third day postpartum. Healthcare workers were asked to observe work quarantine; they were encouraged to go directly to work and home minimizing contact with the public (34) . In Hong Kong, obstetric services were transferred to a hospital separate from hospitals in which SARS cases were managed. Women were discharged sooner after delivery, and all obstetric services considered nonessential (e.g., routine ultrasonography and prenatal diagnosis) were temporarily suspended (33) .", "Pandemic infl uenza planning that specifi cally addresses the concerns of pregnant women is critical because special issues need to be considered for this high-risk group.", "A key component of pandemic preparedness (3) involves addressing the specifi c needs of vulnerable populations, including pregnant women. Pregnant women are at high risk for severe complications of infl uenza during interpandemic periods (4) and previous pandemics (5) (6) (7) (8) ." ] },{ "paper_id": "373474bd0d2c88363e7fad85fa0ca0863687a791", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Bayesian analyses have been shown in theory, simulation, and prediction problems to offer better estimates for measures as varied as baseball batting averages (14) and toxoplasmosis prevalence (15) . We believe that the semi-Bayesian adjusted estimates offer improved overall accuracy for our ensemble of reporting completeness estimates. For example, for completeness proportions where the maximum-likelihood estimation methods result in 0%", "More recently, automated alerting and data collection for case-patients with reportable diseases (e.g., a positive blood culture result with gram-negative diplococci triggers an alert with case-patient contact information to infection preventionists, local health department staff, or both) has been shown to increase reporting rates when applied to traditional passive surveillance systems (22, 23) . Although North Carolina, like many states, has developed and implemented an electronic disease surveillance system, the reporting of communicable diseases by local health departments still remains largely passive in that reporting is accomplished by accessing a secure Internet site and entering patient information. Physicians who practice outside local health departments currently use paper-based reporting.", "When health information exchange becomes a reality, public health surveillance can benefi t signifi cantly by automating processes that currently rely on manual data entry. Disease reporting could be automated by standardized queries directly from the electronic health records for key laboratory results (e.g., positive acid-fast bacillus sputum smear) and for simplifi ed or proxy clinical case defi nitions by using ICD-9-CM diagnosis codes or free-text admission diagnoses. Upon recognition of these potential casepatients, automating surveillance data collection directly from electronic health records to populate data fi elds for basic patient demographics and laboratory results could also reduce administrative time for physicians and health department offi cials and expedite communicable disease investigations." ] },{ "paper_id": "3741c1d2fb8893ca57a949704a64a7a570802543", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The increased threat of terrorism necessitates an evaluation of the risk posed by various microorganisms as biological weapons. Especially, Filoviruses is one of such important microorganisms. Ebola virus and Marburg virus are category A bioweapon organisms. Biowarfare agents are considered as potential biological weapons because they pose a threat as lethal pathogens and because their use by terrorists might result in extreme fear and panic [1, 2] .", "The attraction for bioweapons in war and for use in terroristic attacks is attributed to their low production costs, the easy access to a wide range of disease-producing biological agents, their non-detection by routine security systems and their easy transportation from one location to another [3] . Biological weapons pose the most significant terrorism threat. They are relatively easy to produce and could result in deaths comparable to nuclear weapons [4].", "Traditional Chinese medicine (TCM) database contains more than one lakh of compounds and Asinex database contains 202122 structures, assembled from the collection of 1115000 Asinex platinum compounds. Single low energy conformation is stored for each of the 202122 database entries. 3D database entries were created following AsinexDB_Pt_flex, AsinexDB_flex and AsinexDB -Lipinski-filtered were cleaned using LigPrep, with expansion of stereo centers whose chirality was unspecified. This small molecules collection contains a high percentage of drug like compounds [34, 35]." ] },{ "paper_id": "374834808ed55e895c9da2d0687b007b84972897", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Tables S1 and S2, tabulating the antinociceptive potency of morphine and oxycodone, respectively, for the various vaccinated treatments. MALDI-ToF spectra of heroin\u2212BSA conjugates. This material is available free of charge via the Internet at http://pubs.acs.org.", "Antinociceptive data was transformed from time to % maximum possible effect (% MPE), which is calculated as % MPE = (test \u2212 baseline)/(cutoff \u2212 baseline) \u00d7 100. This data was then fit using a log(agonist) vs normalized response nonlinear regression. These produced ED 50 values for each drug under each pain test for the individual treatment groups, allowing calculation of potency ratios. Differences in potency were determined by one-way ANOVA followed by Tukey's post hoc test.", "Based upon competitive ELISA data, the ip group exhibited the poorest overall opioid affinities, although the ip/sc group 6AM affinity was weakest of all the groups (Table 1 ). In contrast, affinities for heroin, 6AM, and morphine were 2\u22124fold better in the sc group. When CpG ODN 1826 was added to our existing formulation, affinities improved 27-fold for heroin, 9-fold for 6AM, and 12-fold for morphine. Statistical comparisons were not performed because affinities were determined from pooled sera." ] },{ "paper_id": "3770ac55babf2fd6c2efdc3e58c8936a99b7a272", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Initiation complexes were specifically attached to microscope flow cells via biotinylated mRNA to PEG-passivated slides, decorated with biotin-PEG and streptavidin. smFRET experiments were performed in TAM 15 buffer (15 mM MgAc 2 , 50 mM Tris-HCl pH 7.5, 30 mM NH 4 Cl, 70 mM KCl, and 1 mM dithiothreitol) with an oxygen scavenging system (3 mg/mL glucose, 100 \u03bcg/mL glucose oxidase (Sigma-Aldrich), 40 \u03bcg/mL catalase (Roche), and 1.5 mM 6-hydroxy-2,5,7,8-tetramethyl-chromane-2-carboxylic acid (Trolox, Sigma-Aldrich -added from a concentrated DMSO stock solution). Ensemble experiments were performed in buffer B containing 50 mM Tris-HCl (pH 7.5), 70 mM NH 4 Cl, 30 mM KCl, 7 mM MgCl 2 and 1 mM dithiothreitol.", "The mRNA biotinylation procedure was modified from a previous procedure 41 , based on selective periodate oxidation of RNA at its 3\u2032 end and reaction of the oxidized product with biotin hydrazide. Typically, the oxidation of mRNA was performed in a solution containing mRNA (10 -50 A 260 /ml), 100 mM sodium acetate (pH 5.0) and 90 mM sodium mperiodate (prepared fresh). After an incubation of 2 hours at room temperature, periodate was precipitated by adding KCl to a final concentration of 200 mM and incubating for 5 minutes on ice. The precipitate was removed by centrifugation for 5 minutes at 10,000g, 2 \u00b0C and passage of the supernatant through a Sephadex G-25 column (Nap-5, Pharmacia). Biotin hydrazide (21339, Pierce) was then added to a final concentration of 2 mM from a 50 mM stock in DMSO (prepared fresh). Biotinylation was carried out for 2 hours at room temperature, after which the mixture was put through a Sephadex G-25 column (PD-10, Pharmacia). Biotinylated mRNA was precipitated by ethanol addition and dissolved in DEPC-treated H 2 O. The concentration of biotinylated mRNA was determined by A 260 .", "Single molecule spectroscopic microscopy was performed on a home-built objective-type TIRF microscope, based on a Nikon Eclipse Ti with an EMCCD camera (Photometrics Cascade 512b), and solid state 532 nm and 640 nm excitation lasers, as described before 18 . For tRNA-tRNA experiments, alternating excitation between 532 nm and 640 nm excitation 42 was achieved with an acousto-optic tunable filter (AOTF, AA Opto-Electronic, Inc.) synchronized with the camera. Fluorescence emission from the probes was collected by the microscope and spectrally separated by interference dichroic (630 nm) and bandpass filters, 585/70 nm (Cy3) and 680/50 nm (Cy5), in a Dual-View spectral splitter (Photometrics, Inc., Tucson, AZ)." ] },{ "paper_id": "377d8d4560cb8cca5ca75e49f9f5be8047c767ea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study received ethics approval from the Tongji University Human Research Ethics Board.", "The novel H1N1 Influenza outbreak in April 2009 was unprecedented in several respects including the new virus, the season of origin (spring, not late fall), and the cohort at risk for infection and death (children and young adults, not infants and the elderly) [1] [2] [3] [4] . The pandemic H1N1 2009 virus is currently the dominant influenza strain in most parts of the world [5] [6] [7] [8] . By March 2010, almost all countries had reported cases of infection and over 17,700 related deaths had been reported to the World Health Organization [9] [10] [11] [12] ." ] },{ "paper_id": "3800c3eb94b585de91c4c52f585719c0fef6b6bb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Camels carry Middle East respiratory syndrome coronavirus, but little is known about infection age or prevalence. We studied >800 dromedaries of all ages and 15 mother-calf pairs. This syndrome constitutes an acute, epidemic, and time-limited infection in camels <4 years of age, particularly calves. Delayed social separation of calves might reduce human infection risk.", "The restricted and highly compartmentalized social structure of livestock camels would provide population niches in which viruses can differentiate in isolation after bottleneck-type transmission events. This situation holds promise for control of the spread of MERS-CoV through flock management practices, and it also suggests a rather simple way of avoiding camel-to-human transmission by avoiding camels <2 years of age. Camel calves are not easily accessible by humans and instinctually avoid humans. They are generally separated from their mothers after 12 months of age (i.e., at an age when they are still likely to be infected with MERS-CoV). Humans normally come into contact with calves only after the animals have been separated from their mothers. A change in this practice (i.e., postponing separation until the calves are older) might reduce the risk for camel-to-human MERS-CoV transmission.", "Although we did not designed our study to cover the duration of virus shedding in young dromedaries, our (8) , which seems longer than the length of virus shedding observed for young camels in our study. However, detection sensitivity in the defined conditions of a laboratory trial might have been higher than in our study. Both studies agreed in their finding of short-lived infectivity of excreted virus: in our study, we did not detect virus in any calf on day 8, and none were detected beyond day 7 in the study by Adney et al. (8) . Nevertheless, virus can be maintained in flocks over several weeks or months, as exemplified by the detection of the same virus clade in March and June on 1 dairy farm.", "We sequenced genomes of 9 virus isolates, representing 3 different phylogenetic lineages, from dromedaries on the 3 farms. Phylogeny of full genomes showed that all viruses clustered according to their place of origin. The phylogenetic position of 1 of these clades suggested recent separation from viruses circulating in the eastern part of Saudi Arabia; some of the animals in the breeding flock from which the viruses were isolated had been moved temporarily to Saudi Arabia for grazing. The other clade separated from these viruses somewhat earlier, but it shared recent common ancestors with other viruses from the eastern part of the Arabian Peninsula. Samples collected in June from animals on the dairy farm yielded viruses from the same clade as that for viruses derived from different animals sampled on the same farm in March (dairy farm samples I and II) (Figure) ." ] },{ "paper_id": "382b6772598f7d07dde36a4377fe8e25302e212a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Early trophic feeding for 7 days in ARDS patients [43] and permissive underfeeding for up to 14 days in mechanically ventilated patients [44] have been shown to be equivalent to target feeding for most outcomes including survival. Underfeeding may be preferred for patients in the prone position.", "The WHO has issued guidance for the definition of MERS-CoV cases, based on clinical criteria, exposure history and diagnostic findings as shown in Table 1 [3] .", "This article is one of ten reviews selected" ] },{ "paper_id": "38323c6d7602627e8979b5a4a6939f8991a68bf1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "384c14fbb8287badd7f0f1823ea34b6cc4ab86cb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Environmental Health Perspectives * Vol 107, Supplement 1 * February 1999 200 exposure risk, as is currendy being attempted for chemicals alone (190) , will eventually be necessary if accurate assessments are to be made.", "Environmental Health Perspectives * Vol 107, Supplement 1 * February 1999 (2), WHO (10), Hazen and Toranzos (11) , and Geldreich (12) .", "Legionella or Mycobacteria spp., or from gh the early 1900s, over", "Far less is known about protozoan and viral survival mechanisms. Many protozoa form cysts or oocysts that are extremely resistant to disinfection and, as already discussed, many of the bacterial pathogens take advantage of these cysts for their own survival strategies. A recent report identified microsporidialike parasites infecting amoebae (Vanella spp.) isolated from a domestic potable warm-water system (15) . If the parasites are confirmed as microsporidia, it will be interesting to see if the intracellular survival state is common for these organisms, including species that infect humans." ] },{ "paper_id": "3858fd802f76401901ec985a5996b77319299098", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "38731c8391dd2178df3d10c3db375d000428407d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The current global outbreak of SARS is associated with a novel coronavirus, SARS-CoV, which is phylogenetically distinct from other known members of the virus family (Coronaviridae) and genus (Coronavirus) (6) (7) (8) . The full clinical spectrum of this novel infection in humans has not yet been defined. Among the 674 HCWs that we examined, none showed evidence of seroconversion to SARS-CoV.", "It is possible that a proportion of our study participants might not have actually been exposed to SARS-CoV. Although these participants were working in our hospital when a large number of patients with SARS were staying there, vigilant infection-control measures had been in place since the outbreak was recognized (9) . All staff working in high-risk areas were required to wear a mask, gloves, eye goggles, and protective clothing. These measures have been shown to reduce the risk for infection (10) .", "Whether severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infection can be asymptomatic is unclear. We examined the seroprevalence of SARS-CoV among 674 healthcare workers from a hospital in which a SARS outbreak had occurred. A total of 353 (52%) experienced mild self-limiting illnesses, and 321 (48%) were asymptomatic throughout the course of these observations. None of these healthcare workers had antibody to SARS CoV, indicating that subclinical or mild infection attributable to SARS-CoV in adults is rare." ] },{ "paper_id": "38961185beb38aa928232a73801aa76944468e07", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "There is growing evidence that dromedary camel is a reservoir for the virus and a source of human infection (3) .", "As a result, the rate of secondary transmission among family contact is higher than other contacts (19) . Thus, Infection in the healthcare setting is an important risk factor for human-to-human transmission and close and prolonged contact with the index case seems to be a necessity for the disease transmission (20) . ", "variable, ranging from asymptomatic to very severe pneumonia with acute respiratory distress syndrome, septic shock and multi-organ failure resulting in death." ] },{ "paper_id": "3899c3b15d80afef1944752dafbebaa99ee43187", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistics. Log-transformed virus titers were compared in a Mann-Whitney U test, and statistical significance was assigned to differences with p-values ,0.05.", "Competing interests. The authors have declared that no competing interests exist.", "This is an open-access article distributed under the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose." ] },{ "paper_id": "38c2570bc1b51e286def9e0dcf27ec6bcf893dd8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "38e37fa66e4acf2931dbc37ac44d66cce82bae55", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The geographical distribution of cases within Bangladesh is shown in Figure 1 . Cases generally occur in areas near inland water, predominantly the Ganges, which provides a suitable habitat for date palm trees. In 2013, there were cases reported from 14 districts, more than in any other year, but generally only a few cases per district; the largest number was five cases reported from Manikganj [41] . The pattern of cases suggests multiple small outbreaks in different regions, rather than large outbreaks caused by one source. [40, 41] .", "The content of the manuscript was researched, written and prepared by Robin Simons, Paul Gale and Verity Horigan, with ideas and contributions by Emma Snary and Andrew Breed. The idea and design for the project was developed by Emma Snary and Andrew Breed.", "This work was funded by the European Union FP7 project ANTIGONE (Anticipating Global Onset of Novel Epidemics 278976) and the UK Department for Environment, Food and Rural Affairs (Defra) project SE4213. The authors would also like to thank Trevor Drew and Tony Fooks (AHVLA) for their valuable contributions to this paper." ] },{ "paper_id": "38f8dd5509748038aea9b4b7a8a2a39d3edee225", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "394a138dbcb0699e087ecd3747fa370c69565909", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To clarify the evolutionary relationships among betavoronaviruses that infect bats, we analyzed samples collected during 2010-2011 from 14 insectivorous bat species in China. We identified complete genomes of 2 novel betacoronaviruses in Rhinolophus pusillus and Chaerephon plicata bats, which showed close genetic relationships with severe acute respiratory syndrome coronaviruses.", "We estimated the approximate locations of those reads on the CoV genome and their relative distances on the basis of alignment results exported with MEGAN 4-MetaGenome Analyzer (http://ab.inf.uni-tuebingen.de/ software/megan/). The located reads were then used for reads-based nested PCR to identify genomic sequences. We established the complete genome sequences of 2 betacoronaviruses (Bat Rp-coronavirus/Shaanxi2011 and Bat Cp-coronavirus/Yunnan2011), which are 29,484 nt and 29,452 nt, respectively. The G+C content of Bat Rp-coronavirus/Shaanxi2011 and Bat Cp-coronavirus/ Yunnan2011 is 41.6% and 40.9%, respectively." ] },{ "paper_id": "39ba47cc9e50b03f0de4eb4e1b0af22e0a5014a3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "39baa82181ff59bba638bda992aafd22b41e4abe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "39c3cd333c7f1556827c2318f07b93cb90e81553", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Based on the complete sequences of ORF025, four pairs of siRNAs, D704, D1017, D1388 and negative siRNA control (scrambled siRNA) were designed and synthesized by Shanghai GenePharma Co., Ltd. The sequences are shown in Table 2 .", "Isolation of genomic DNA DNA was extracted from CPE-positive cell cultures using a Takara MiniBEST Viral DNA Extraction Kit (Takara, Dalian, China) according to the manufacturer's instructions and was used as template in PCR.", "Primary ovine fetal turbinate (OFTu) cells were cultured in minimal essential medium (MEM; (Hyclone) with 10 % fetal bovine serum (FBS; Hyclone), 2 mM L-glutamine, and 100 U of penicillin, 100 lg of streptomycin, and 20 lg of nystatin per ml in a 37\u00b0C, 5 % CO 2 incubator. Orf virus was isolated from scabs collected from lesions of a 6-weekold small-tailed Han sheep showing typical symptoms of orf virus infection in November 2008 in Jilin Province, China [2] . When 90 % of the virus-infected cells showed a cytopathic effect (CPE), the cultures were collected after undergoing three freeze-thaw cycles." ] },{ "paper_id": "39cfbf03d49e10e11570e18ae30e0a4dc1a63d7b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "39ee2164fd26eb50a770a31e1fb67c230b4f2ee4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3a6a9f669d1d3bf1880190cd747efed573dc5dab", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3a6f606e9489f6f9ae05e6f0a5fec50572fd0208", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3aa5c9f53c616efdef4103a7e8c3ebf433437a83", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3aa64273e4b7c80baee8fe40bbbe5339dfc87c3b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "T he emergence and reemergence of zoonotic diseases are becoming increasingly important issues for numerous reasons, including deforestation and habitat fragmentation, increased globalization of travel and trade, urbanization, and bioterrorism concerns. Diseases such as severe acute respiratory syndrome (SARS), avian infl uenza, transmis-sible spongiform encephalopathies, Rift Valley fever, West Nile disease, anthrax, and Escherichia coli O157 infections recently have resulted in major public health and economic concerns, as well as public anxiety. Over 60% of the 1,415 known human pathogens and 75% of the 175 emerging pathogens are zoonotic (1) . Many emerging diseases have spilled over from wildlife directly (e.g., West Nile virus infection, hantavirus infection, and Lyme disease) or indirectly through domestic or peridomestic species (e.g., avian infl uenza, SARS, and Nipah virus infections, plague) (2) . Early detection of new disease outbreaks in domestic and wild animals is an essential prerequisite of disease control and eradication. Development of methods for early detection of diseases in free-ranging wildlife is problematic.", "Coyote samples were processed by following protocols used for histologic examination and mycobacterial culture of white-tailed deer samples (6, 10) . Fresh tissues for bacterial culture were digested and decontaminated with a sodium-hypochlorite-sodium hydroxide method (21) . We then spun tissue suspensions in a refrigerated centrifuge at 6,000 \u00d7 g for 20 minutes (21) . Half of the supernatant was discarded, and the pellet was resuspended and swabbed on the following solid media: Middlebrook 7H10 agar containing sodium pyruvate (National Veterinary Services Laboratory [NVSL], Ames, IA, USA), Middlebrook 7H11 agar containing sodium pyruvate (NVSL), BBL Mycobactosel L-J medium slant (Becton Dickinson, Sparks, NJ, USA) and Middlebrook 7H11 with aspartic acid and pyruvate (Becton Dickinson) (22) . We then injected the suspension (0.5 mL) into BACTEC 12 B liquid culture vials (Becton Dickinson) and BACTEC MGIT liquid culture tubes (Becton Dickinson) (21) . The solid media tubes were incubated at 37 \u00b1 2\u00b0C in a 10% CO 2 incubator and examined weekly until colonies were observed or until an incubation period of 8 weeks was complete, at which time tubes with no growth were discarded (21) . We incubated the BACTEC 12 B vials at 37 \u00b1 2\u00b0C and monitored them in the BACTEC 460 instrument for 6 weeks (21, 22) . We incubated MGIT 960 tubes at 37 \u00b1 2\u00b0C and monitored them in the BACTEC MGIT 960 instrument for 6 weeks (21-23). Colonies from solid media and liquid culture bottles that showed positive signals were confi rmed as M. tuberculosis complex identifi cation by a combination of Ziehl-Neelsen acid-fast staining and the AccuProbe M. tuberculosis complex nucleic acid probes (Gen-Probe, San Diego, CA, USA) (21, 23) . We then used niacin and nitrate biochemical tests to distinguish M. bovis from M. tuberculosis isolates (21, 23) .", "We used a log-linear model (26) to determine whether the count of M. bovis-positive coyotes was independent among age classes and sexes. We used adjusted residuals for describing and making inferences about the true association structure among the response variables. We used a Mann-Whitney test (27) to compare prevalence of M. bovis in coyotes to white-tailed deer sampled by MDNR during the same period." ] },{ "paper_id": "3ac3823b31229b9754a336bf17f5ff76fdcaadf2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cross-reactivity of these anti-SARS Abs against human coronavirus (HCoV) 229E and HCoV OC43 were determined by Western blotting. The Abs produced reacted with recombinant SARS virus nucleocapsid protein, but not with HCoV 229E or HCoV OC43.", "Coronaviruses are a group of large, enveloped, positivesense, single-stranded RNA viruses that are known to associate with respiratory, enteric and neurological diseases in humans and domestic animals [2] . Many researchers have reported cross-reactivity with other HCoV when the diagnostic systems are based on SARS N protein [9, 14] . It is therefore important to explore the possibility of developing a diagnostic test for SARS-CoV that does not show this cross-reactivity with the other HCoVs. Only two coronaviruses, HCoV 229E (Group I) and HCoV OC43 (Group II), have previously been known to cause illness in humans [2] . These coronaviruses are responsible for 10\u223c35% of upper respiratory tract infections [9] . Another human coronaviruses, HCoV NL63 and Co HKU1, were reported in 2004 and 2005 [11, 13] . As such, a SARS diagnostic system that cross-reacts with HCoVs could easily result in false-positive reactions. Previous researchers have tried to develop a monoclonal Ab against SARS N protein based ELISA. Some checked cross-reactivity with chicken CoV [3] , HCoV OC43 [8] and various CoVs [1] . We need more Ab candidates for the diagnosis of SARS. In this study, we checked Abs cross-reactivity against SARS virus with HCoVs 229E and OC43, before developing a diagnostic system. Because the polyclonal and monoclonal Abs produced in this study did not react with HCoV 229E or HCoV OC43 in Western blotting, it could be possible to develop a specific diagnostic system to detect SARS-CoV in infected patients with theses Abs. Crossreactivity with HCoV NL63 and Co HKU1, newly arising HCoVs, should be confirmed to strengthen the specificity of our Abs against SARS-CoV.", "Severe acute respiratory syndrome (SARS) virus nucleocapsid (N) protein is abundantly released in the patients' blood during early infection [6] , which suggested that the N protein is a suitable candidate for diagnostic applications. Detection of specific circulating Abs is potentially a highly sensitive and specific way to diagnose SARS. However, detection of SARS Abs from early-infected patients is difficult, because most patients experience IgG seroconversion on average 20 days after the onset of symptoms [5] . On the other hand, a highly conserved motif (FYYLGTGP: 111-118 a.a.), occurs in the N-terminal half of all coronavirus N proteins, and other conserved residues are reported to occur near this highly conserved motif [6] . The cross reactivity regions between SARS-coronavirus (CoV) and porcine CoVs were located in 120-208 a.a. of N protein [12] . Cross-reactivity between SARS-CoV N protein and anti-human CoV (HCoV) 229E Abs or anti-HCov OC43 Abs has been reported [14] . It is therefore necessary to develop an assay that shows no cross-reactivity with other CoVs, especially HCoVs, to detect SARS proteins. Such a test could be used for early detection and follow-up of patients during treatment. In this study, we raised polyclonal and monoclonal Abs using a recombinant SARS N protein to develop a specific diagnostic test for SARS. The cDNA of SARS-CoV strain Hanoi provided by Dr. Kariwa of Hokkaido University was used as a template for PCR by Accupower premix (Bioneer, Korea). The full length of the SARS-CoV N gene was inserted into vector pET21a (Novagen, German). After transformation, E. coli strain Origami B (DE3) pLysS competent cells were induced using 1 mM IPTG (Invitrogen, USA) at 37 o C for 4 h. The expressed proteins were purified using the His-Bind kits (Novagen, German). Production of polyclonal and monoclonal Abs was performed as described by Shang et al. [7] . Human coronaviruses, HCoV 229E (ATCC, VR-730) and HCoV OC43 (ATCC, VR-1558), were infected to MRC-5 cells (Korean Cell Line Bank). Replication of these viruses was confirmed by RT-PCR of cell lysates infected with HCoV 229E and HCoV OC43. RT-PCR was performed as described in a previous study [10] . To examine whether Abs against recombinant N protein of the SARS virus react with other HCoVs, we performed Western blotting on recombinant SARS N protein or cell lysates infected with HCoV 229E and HCoV OC43. In our previous study, the antigenicity of recombinant of SARS-CoV N protein was checked with a mouse anti-SARS-CoV N protein monoclonal IgG2a (Zymed, USA), and convalescent SARS serum provided by the National Institute of Hygiene and Epidemiology in Vietnam [4] . We selected polyclonal and monoclonal Abs that showed the highest reactivity with the N protein in an ELISA. With these Abs, we determined cross-reactivity against cell lysates infected with HCoV 229E and HCoV OC43 by Western blotting. The viruses in these cells lysates were confirmed by RT-PCR (Fig. 1 ). Abs reacted with recombinant N protein, but did not react with HCoVs in cell lysates (Fig. 2) . To determine the specificity of these Abs, cross reactivity with porcine epidemic diarrhea virus (coronavirus group I) and mouse hepatitis virus (coronavirus group II) were analyzed by Western blotting but showed no reaction (data not shown)." ] },{ "paper_id": "3b265edacf7baf698286ac29b6ca808bf1dd599b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3b3b3bce4bd9b3e44f01dbacad3e39fa9dad7a3c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3b5290a5bd5c9ac633320eed77f1a7929d72b749", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The inclusion criteria were as follows: clinical diagnosis of influenza-like illness (ILI) defined by the presence of fever plus at least one respiratory symptom (cough and/or sore throat) and one constitutional symptom (headache, myalgia, sweat, or chills); clinical diagnosis of ARI, defined by the presence of respiratory symptoms that did not fulfill the definition of ILI; hospitalized patients suspected of 2009 H1N1 influenza A infection presenting fever >38\u00b0C, cough, and dyspnea. Lower respiratory tract illness was defined as having suggestive clinical findings and one of the following: chest radiograph revealing possible or definite infiltrates, mechanical ventilation requirement, or supplemental oxygen requirement." ] },{ "paper_id": "3b5579588b12f1f4bd5e6c1eea4c8ba0258a4f57", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors wish to thank J. Griffith for slides of CAR bacillus. ", "The relative importance of direct mycoplasmal damage, as opposed to immune and nonimmune inflammatory reactions forM. pulmonwn has yet to be completely discerned (19) . It is known that cytolysis follows attachment of M. pulmonis to upper airway epithelial cells. Ciliastasis, loss of cilia, distension of intercellular spaces, cytoplasmic vacuolization, disruption of mitochondria, epithelial hyperplasia and metaplasia, and syncytial cell formation have also resulted following attachment of this organism (19) .", "Lesions typical of mycoplasmal chronic respiratory disease have been noted following natural and experimental infection with the CAR bacillus. These lesions include massive accumulations of predominantly mononuclear inflammatory cells surrounding bronchi and bronchioles (Plate 3), as well as various degrees of suppurative bronchopneumonia, squamous metaplasia, and bronchiectasis. The ciliated epithelium of the airway is usually heavily colonized with filamentous bacteria, which can be readily demonstrated with Warthin-Starry silver impregnation techniques (Plate 4)." ] },{ "paper_id": "3b8be6719d642862ae96fc5614e4f555c38f2af2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "was present in PLP2-TM immunoprecipitates, suggesting a higher affinity of LC3-II for PLP2-TM than that of LC3-I.", "Autophagy is an evolutionarily conserved intracellular process which plays an important role in eliminating damaged organelles and long-live proteins for maintenance of cellular homestasis (Mizushima, 2009) . During autophagy, cytoplasmic constituents are engulfed by double-membrane vesicles termed autophagosomes that are destined for fusion with lysosomes for content degradation. Under stress conditions such as starvation, autophagic acitivity is greatly augmented from its basal levels, providing recyclable resources that help maintain metabolism and ATP levels for cell survival (Rabinowitz and White, 2010) . Recent studies have demonstrated that autophagy is involved in various physiologic and pathologic processes including cancer, cardiovascular disease, metabolism, viral infections and immune response, etc. (Deretic, 2012; Levine and Deretic, 2007; Mihaylova and Shaw, 2011; Shintani and Klionsky, 2004; Yang et al., 2011) .", "In summary, results of this study demonstrate that the coronavirus papain-like proteases along with their transmembrane anchors activate incomplete autophagy by interacting with Beclin1. Autophagosomes induced by CoV PLP2-TM/PLpro-TMs may provide a platform for viral targeting Beclin1 to sequester STING and possibly other critical innate signaling components to impede downstream antiviral responses, thereby promoting viral replication. Further studies will be needed to elucidate the precise mechanisms of autophagosome induction by CoV PLPs and the exact roles that autophagy plays in coronavirus replication, antiviral innate immune responses and disease pathogenesis." ] },{ "paper_id": "3c020dec5b062a2b10f71b7a3030ac306a093cd5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3c3572ba243d61e7631725669c8f88347fdbd5bc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CalcapR (5'-TTGAGAATTGAACACATCAATAGATC-3') amplify a 673-bp conserved region in the capsid protein gene of FCV.", "Three pairs of oligonucleotide primers were used for the amplifying reaction. We used the previous designed primer sequences by Sykes et al. [16] . HerpF (5'-GACGTGGT GAATTATCAGC-3') and HerpR (5'-CAACTAGATTT CCACCAGGA-3') amplify a 292-base pair (bp) region in the thymidine kinase (TK) gene of FHV-1. ChlaF (5'-ATGAAAAAACTCTTGAAATCGG-3') and ChlaR (5'-CAAGATTTTCTAGACTTCATTTTGTT-3') amplify a 1069-bp fragment in the outer membrane protein gene of ", "The prevalence of feline herpesvirus-1 (FHV-1), feline calicivirus (FCV), and Chlamydophila (C.) felis was studied in cats of an animal shelter in Korea. Total 78 cats without ocular and upper respiratory tract disease were examined. Specimens were obtained from ocular conjunctiva and oropharynx. Using multiplex polymerase chain reaction (PCR) and reverse transcription PCR, three pathogens were simultaneously detected. In examined 78 cats, 49 (63%) cats were positive for FHV-1. However, all specimens were negative for C. felis and FCV. In conclusion, many cats recovered from FHV-1 infection remain subclinical carriers in shelter environment." ] },{ "paper_id": "3c6b88ab8a6694c82e04480184ae76dbe302c95d", "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.", "During October 2015, the Saudi Arabia Ministry of Health (MoH) reported a cluster of MERS-CoV infections identified in female janitors working at a university in Riyadh [10, 11] . We summarize below the clinical course and concomitant laboratory investigation of a case identified early in this cluster.", "The variant alleles of the isolate would predict amino acid changes (N>D in spike [S] protein and V>L in ORF4a) that may reflect adaptation in culture. Virus isolation was not attempted for the MERS-CoV RNA-positive stool specimen because of low virus load." ] },{ "paper_id": "3c928eef1ab9e10c33a73c0dec240b088b82c06f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3cdfc63c3790d0bc50c45fe33b2b7ca304641a5d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(D1)", "(D5) r max $ 1000:", "These are the estimates that we provide in the Discussion of the main text." ] },{ "paper_id": "3d0023b0e5f3b5a5d544abfede465a54fcf2f0bb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 What is the current knowledge on the topic?", "Refer to Web version on PubMed Central for supplementary material.", "Parameters Cl (liters/hr) Vc (liters) k cp (hr \u22121 ) k pc (hr \u22121 ) k cELF (hr \u22121 ) k ELFc (hr \u22121 ) V ELF (liters) ", "Three non-directed bronchial lavage (NBL) specimens (two from a single patient) were not collected because of a clinical requirement for a high fraction of inspired oxygen (FiO 2 ) that precluded sampling. A single patient had a drop in oxygen saturation from 95% to 88% that required a temporary increase in FiO 2 . A change in oxygen saturation was not observed in any other patients. No other changes in respiratory or cardiovascular parameters were observed in the four hours following collections of the other NBL samples." ] },{ "paper_id": "3de1a5a224b154bb91728f71697ca7bd3db17ee5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "B ats have been considered natural hosts of a wide diversity of viruses, including human pathogens such as lyssaviruses, severe acute respiratory syndrome coronavirus, henipavirus, and filoviruses (1) . Within the genus Lyssavirus, 12 (2) and Ikoma lyssavirus (IKOV) (3) .", "No human exposure to the new virus has been reported. However, because of the divergence exhibited by LLE-BV and IKOV, and the growing evidence of inadequate protection/cross-neutralization against viruses outside phylogroup I, the effectiveness of current rabies vaccines for these viruses remains a concern (15). ", "Consequently, it is difficult to imagine that WCBV or LLEBV are locally restricted; both could be located far from where they were found. Neutralizing antibodies against WCBV have been found in bats in Africa (14) . The cumulative description of new bat lyssaviruses in recent years shows the convenience of always using generic amplification primers for rabies diagnosis based on RT-PCR to complement antigen detection." ] },{ "paper_id": "3dfce0f1586b904eb6afcda376c0295d3de6c295", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3e184094797d77a9169bb3e572c2567ede84535d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3e2677a96d2f707426791f1802e64483d8ccaabb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3e8f1cce602f86dd1f7227dbfe0c21ac995ff470", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3eb27a4a8fe46f979c80da67e044c3d7042a5ec6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "OC 2 H 5 O H II III 7aj S3 Scheme S1. Catalytic cycle of organo-NHC catalyzed aldol-type condensation product", "Calculated the E-factor and atom Economy (%) as E -Factor = Amount of waste Amount of product Amount of waste = Total amount of reactants -Amount of product (assuming that the same amount of solvents in the beginning and end of the reaction) S4", "In the view of green chemistry, our methodology was compared with reported methodologies constructing isatin derivatives in Table 1 . Our method presented efficient E-factor and 100% atom economy from starting material to product. THF, the major solvent in our methodology showed the low or middle range scores in scoring information of solvent elicited from ACS GCI pharmaceutical roundtable consists of safety, health, air environment, water environment, and waste. In addition, our method (within 15 min at ambient temperature) could show comparative advantage in energy consumption and accident prevention. Our catalysis condition was impressive difference in loading amount and didn't require protecting group (additional protection/deprotection steps). With the mentioned merits, the most outstanding advantage of our methodology in factors of green chemistry was only renewable catalyst between each other batches among thirteen methods. 13" ] },{ "paper_id": "3ecf8a34e3a43ad60b934db992e34171e20659d9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In conclusion, much hope rests on the promise of translational medicine 9 , and its potential to address certain of the shortcomings of empiricism through a more interdisciplinary and pluralistic approach to both the methodological and theory-development processes of medical science. Going forward, however, epistemic caution may be an important watchword in a world in which political forces may increasingly have the power to harnessscientific and medical denialism in pursuit of ideological agendas.", "The McKeown thesis has, however, led to what some have termed medical health nihilism 26 , whereby some (perhaps \"an entire generation of social scientists, historians, and policymakers\") have considered the contributions of economics and nutrition to overshadow the role of public health interventions (p.1014) 27 . While some, for example, have questioned the provision of treatment for multi-drug resistant tuberculosis,in certain contexts, in that it may not be cost effective, Farmer and Nardell 27 stress that it is important to avoid the trap of medical health nihilism, in that even though poverty and inequality persist, it is necessary to, nevertheless, \"move forward with focused interventions and insist on universal access to high-quality TB care (p1015).\"", "An important debatein the literature relates to discussions of medical nihilism. The McKeown Thesis derives from McKeown's argument that in certain contexts the fall in the crude mortality rate over time was largely \"due not to life-saving advancements in the field of medicine or public health, but instead to improvements in overall standards of living (p.725),\" and especially those related to advances in nutrition that resulted from improved economic conditions 25 . Debates about McKeown's thesis have persisted in light of the question, are \"public health ends better served by targeted interventions or by broadbased efforts to redistribute the social, political, and economic resources that determine the health of populations? (p.725)\" 25 ." ] },{ "paper_id": "3ed0c2cb0dd726b902f5470fd984ce7cc7d6c62f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "LETTERS a cause of endocarditis as well as the occurrence of mycoplasma bacteremia in the absence of underlying infection of the endocardium.", "This work was partly fi ", "We thank H\u00e9ctor R. Morbidoni for critical reading of this manuscript and Paola Gallo for English revisions." ] },{ "paper_id": "3ed670f60a7be2e3e2a991ea8af1fdd5fa5e2b2c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The HIV-1 gp160 precursor protein sequence used here is gi|9629363. Gp41 starts at residue 512, after the basic cleavage site. Authors' contributions Y.K. was responsible for the initiation of this project. E.Y.L. & Y.K. carried out the technical work, analyzed the data, drafted the manuscript and approved the final manuscript.", "Results: Sequence analysis reveals that the two viral proteins share the sequence motifs that construct their active conformation. These include (1) an N-terminal leucine/isoleucine zipper-like sequence, and (2) a C-terminal heptad repeat located upstream of (3) an aromatic residue-rich region juxtaposed to the (4) transmembrane segment." ] },{ "paper_id": "3ed8570c9e422b49c3583e04543e636a4154777b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We thank the family in this study for making their clinical data available.", "Dr Jula is a house officer in the pediatric unit of Turku University Hospital, Turku, Finland. Her research interests include infectious diseases and neonatology. " ] },{ "paper_id": "3ee377ece8b8a1fb6a4468d39d410f0f33042051", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As in previous studies, rhinovirus was also the most frequent organism detected, accounting for followed by influenza among those asthma exacerbations with virus isolated in our cohort.", "The study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster. The study was conducted in accordance with the Declaration of Helsinki. Verbal consent was obtained from the participants and written consent was obtained from their parents or legal guardians.", "Patient's demographic data, treatment at enrolment, family history of atopy and asthma, and exposure to environmental tobacco smoke were recorded at the time of recruitment. Measurement of lung function using Vitalograph Model 2120 was obtained according to American Thoracic Society recommendations in children who were able to perform spirometry [1] . Skin prick test was done according to the standardized International Study of Asthma and Allergies in Childhood Phase 2 protocol [12] . Ten aeroallergens including Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat, Alternaria tenuis, mixed tree pollen, mixed grass pollen, dog, cockroach (American and German), and mixed moulds were tested. A wheal diameter of 3 mm greater than the diameter of the negative control was defined as positive response. Children with \u22651 positive responses were defined as atopic." ] },{ "paper_id": "3f01702c71fa172be560638b826441239c956227", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors report no conflicts of interest in this work.", "T10B9 (\u03b1\u03b2-TCR) Figure 1 T and B cell response and peak incidence of opportunistic infections after thymoglobulin, T10B9 and campath \u00ae administration.", "Another important feature of their \"first-line defense\" is well documented in the skin. When skin is injured by any mechanism, a population of \u03b3\u03b4 T lymphocytes called dendritic epidermal T cells (DETC) responds quickly to injury and attach to keratinocytes (the primary cells of the skin). These DETC's secrete pre-growth factors (keratitic growth factors 1 and 2 and insulin growth factor 1) that stimulate regrowth of the epithelium. This phenomenon has been demonstrated in murine lung and is presumed to occur when injury occurs to any epithelial tissue. exposure to mild immune response. This capacity allows \u03b3\u03b4 T lymphocytes to control a variety of infectious agents, such as Nocardia asteroids, Pneumocystis carinii, Mycobacterium bovis, Bordatella pertussis, etc. 21, 22, 30 In tissue culture, \u03b3\u03b4 T cells killed tumor cells" ] },{ "paper_id": "3f05323273dcefec161e84d7e3f814e31feedb50", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3f0df8f8017cbe949add8bb74b4afb0597e54330", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The possibility of a false-positive RT-PCR test result was also considered. To our knowledge, a genuine falsepositive test has not been reported in the literature in any clinical specimen. Nonetheless, the CSF sample could have been contaminated with the patient's own blood, which contained genetic material of SARS-CoV. However, finding only 20 erythrocytes per mm 3 in the CSF makes this unlikely.", "S evere acute respiratory syndrome (SARS) is an acute febrile illness predominantly involving the lungs, and a high proportion of patients die of respiratory failure (1) . However, the novel coronavirus causing SARS appears not to be confined to the lungs, as suggested by observation of diarrhea (2) , impaired liver function tests, lymphopenia, and thrombocytopenia (3) . We report a case of possible involvement of the central nervous system by the SARScoronavirus (SARS-CoV).", "Human coronavirus (HCoV) is responsible for up to one third of upper respiratory tract infections (7) . It can enter susceptible cells through the endocytic pathway (8) . Two strains (229E and OC43) have been implicated in multiple sclerosis (9, 10) , and both can persistently infect human oligodendrocytic and neuroglial cell lines (11) . More recently, a combination of RT-PCR and Southern hybridization on human brain autopsy samples provided more definitive experimental evidence for the neurotropism and neuroinvasion of HCoV and its possible association with multiple sclerosis (12) . Preliminary work in Hong Kong with RT-PCR on SARS autopsy specimens of brain tissue were positive for SARS-CoV, although electron microscopy did not show ultrastructural features of the virus (W.-C. Yu, unpub. data). The findings from our patient are not compatible with multiple sclerosis, and the PCR result suggests that the central nervous system (CNS) is affected by SARS-CoV." ] },{ "paper_id": "3f18a67fe497ea56d25018fe7b88b5b5f0925621", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "According to World Health Organization (WHO) criteria, a person seeking treatment after November 1, 2002, with a history of high fever (>38\u00b0C), coughing, or breathing difficulty, and having resided in or traveled to an area with recent local transmission of SARS during the 10 days before onset of symptoms was classified as a suspected case-patient. A suspected case-patient with radiographic evidence of infiltrates consistent with pneumonia or respiratory distress syndrome on a chest x-ray was considered a", "SARS was quickly identified as a new coronavirus species, now referred to as SARS-associated coronavirus (SARS-CoV) (4) (5) (6) . With epidemiologic evidence, droplet and close contact transmission are the major routes for the spread of SARS (7) . Suspected SARS patients need to be quarantined and treated with intense care to minimize transmission to others. Therefore, sensitive and specific laboratory tests to differentiate SARS from other mild atypical pneumonia must be developed to shorten the quarantine period for contacts with SARS patients and further to contain SARS outbreaks.", "The preparation of recombinant proteins of SARS-CoV and the procedures for Western blot assay have been described recently (14) . Briefly, the amplified gene products of SARS-CoV including N, M (membrane), and S (spike), were gel purified and cloned into the pQE30 expression vector (Qiagen, Valancia, CA). The constructs were then transformed into Escherichia coli JM109 cells (Invitrogen, Carlsbad, CA). After induction by isopropyl\u03b2-D-thiogalactopyranoside, the cells were sonicated, and the recombinant proteins were extracted with 1.5% sarcosine. Finally these recombinant proteins were bound by BD TALON metal affinity resins (BD Biosciences, San Jose, CA) and examined by 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The Western blot assay was carried out to examine the pattern of antibody development against different recombinant proteins of SARS-CoV." ] },{ "paper_id": "3f3401216256123b750a1d70058fea8af14ec311", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(2) Weapons, equipment or means of delivery designed to use such agents or toxins for hostile purposes or in armed conflict.", "\u2022 Demonstrate how to render a vaccine ineffective;", "\u2022 Confer resistance to therapeutically useful antibiotics or antiviral agents; \u2022 Enhance the virulence of a pathogen or render a non-pathogen virulent;" ] },{ "paper_id": "3f4fc78e53396ab0573664ed3ff5d665751861f6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Though simple and clinically useful, this defi nition is narrow in its scope and several important symptoms of exacerbation such as chest congestion, chest tightness, fatigue and sleep disturbance are not included.", "Respiratory viruses implicated in COPD are able to cause acute tracheo-bronchial infections in healthy hosts, clinically referred to as acute bronchitis. In the setting of COPD, with diminished respiratory reserve, this acute bronchitis has more profound manifestations and serious clinical consequences.", "Patients should be re-assessed at 48-72 hrs, in which time frame clinical improvement should be apparent. In patients who fail initial empiric antimicrobial therapy, it would be appropriate to re-examine the patient to confi rm the diagnosis, consider sputum studies to ascertain for resistant or diffi cult to treat pathogens and treat with an alternative agent with better in vitro microbiological effi cacy.", "Other important considerations in antibiotic prescribing are safety and tolerability of the agent, drug interactions and fi nally cost of treatment. Cost of the antibiotic however should not be interpreted in isolation. As shown elegantly by Miravittles and colleagues (2002) exacerbations for which initial empiric treatment fails are ten times as costly as clinical successes (Miravitlles et al 2002) . In fact, the overall cost of care could be reduced by half with only a 33% reduction in clinical failure rates. Clinical failure rates are likely to be reduced when antibiotic choice is appropriate and logical, as discussed above.", "Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States and the 6th leading cause worldwide. It is estimated that by 2020, it would become the 3rd leading cause of death in the US and worldwide. Affecting 24 million people in the US, up to half of them undiagnosed, it accounts for 13.76 million offi ce visits, 1.5 million emergency room visits and 726,000 hospitalizations annually, at an estimated direct cost of $18 billion (NHLBI 2003) ." ] },{ "paper_id": "3f54832532dcb732e268f8a6d022d833cda56687", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical Analysis. Statistical analysis was performed using GraphPad Prism (version 6, GraphPad Software, Inc., CA and USA) and Origin 8.5 (OriginLab Corporation, Northampton, MA). Each experiment was performed in triplicate, and values are expressed as the mean \u00b1 standard deviation (SD). ", "The authors declare no competing financial interest. ", "The manuscript was written through contributions of all the authors. All the authors have given approval to the final version of the manuscript." ] },{ "paper_id": "3f893c8176209b798e129adac6c6ce6b17631a27", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The finding of this isolate provides evidence of the pathogenic role of this rare mating type, emphasizes the critical function of molecular genetic tools in the characterization of C. neoformans populations, and represents an advance in knowledge of this fungal species whose genome is undergoing identification by a worldwide research team.", "finding of the clinical and the environmental isolate (1,2). The existence of MATa in nature is also supported by recent studies designed to established the origin of the serotype AD strains (4, 5) . These studies demonstrated that AD strains were diploid or aneuploid hybrids derived from a fusion of serotype A and D parents and that several of them were harboring a serotype A MATa locus. These hybrid strains have been found fairly often in Europe (9,10).", "The patient attended outpatient clinic on day 35, complaining of exertional dyspnea, low-grade fever, and malaise since her discharge. Her chest radiography showed extensive shadowing. Computer tomographic scan of the thorax indicated widespread ground-glass shadowing in both lung fields, which was especially prominent at left lower and lingular lobes." ] },{ "paper_id": "402b53bd0eb35adc900cc262a1c20d5ef198aeb6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Serum samples were immediately processed, stored at \u221225\u00b0C, and shipped frozen on dry ice to CDC. To measure influenza A H5-specific antibody, microneutralization assay was conducted as previously described (10) ", "The attributable risk percent (AR%) was estimated as follows: ([odds ratio (OR) -1]/OR) \u00d7100. The population attributable risk percent (PAR%) was estimated as follows: PAR% = AR% \u00d7 proportion of case-patients exposed.", "The finding of a significant positive association between level of education and risk for infection was unexpected and is difficult to explain. It may be the consequence of a bias introduced by proxy respondents for deceased case-patients reporting higher levels of education than case-patients had actually achieved." ] },{ "paper_id": "40416d6c18e932e8c5d553c696e9a45c89f4f269", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "404ca779551d8f2defd48fa692a4ae44bb729e15", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "40e41f0c52b39669dee24e37875d7a9fabc38636", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Reporter fusions were expressed in S.cerevisiae INVSc1 (his3D1/his3D1, leu2/leu2 trp1-289/trp1-289 ura3-52/ura3-52) (Invitrogen) overnight. Protein fusions were purified in denaturing conditions using Ni-NTA agarose (Qiagen), and analysed in 6% SDS-PAGE gels. Proteins were visualized either by Coomassie staining, or by using antisera raised against the CfMV polyprotein region 1386-1724 encoding CfMV VPg (28) . Protein antibody complexes were visualized with horseradish peroxidase-conjugated anti-rabbit antibodies (Sigma) and ECL chemiluminescent reagents (Amersham).", "All cloning steps were performed using standard protocols. Plasmids were amplified either in Escherichia coli DH5a or JM110, and purified with Qiagen columns. Inserts were verified by sequencing. Yeast transformations were done using the LiAc method (27) , and transformants were selected on a synthetic minimal defined medium (SC) lacking the corresponding auxotrophic marker(s) encoded by the used plasmid(s). Bacteria (E.coli DH5a) were grown in LB-medium containing ampicillin, whereas yeast cells were grown either in YPD, or in an SC medium. Protein expression from GAL1 promoter was repressed during growth at SC medium containing 2% glucose. Expression was induced by replacing glucose with 2% galactose and 1% raffinose.", "Three regions from the CfMV polyprotein ORFs ( Figure 1A) were cloned into the NheI and BclI sites between the lacZ and the luc ORFs in pAC74 (26) . This dual reporter vector was a generous gift from Dr J. Rousset of the Universite Paris-Sud, France. The inserted sequences 1602-1720 (A region), 1386-2137 (B region) and 1551-1900 (C region), were amplified by PCR using pAB-21 as a template (18) . Primers were used to introduce NheI and BglII sites to the flanking ends of the inserts. Since NheI digestion removed lacZ ORF, it was reintroduced into the plasmids as a final cloning step. The resulting plasmids were named pAC-A, pAC-B and pAC-C.", "The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oupjournals.org antibiotics, certain mutations in the translation apparatus, and in translation elongation factors that change the translation fidelity and kinetics, have been shown to influence \u00c01 PRF efficiency [(10,15) ; reviewed in (16) ]." ] },{ "paper_id": "40f51d700f24dd40b22d574cb92f5eb1edfe288c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Currently, laboratories share databases weekly with WHO and national authorities. WPV, VDPV, and partial genomic nucleotide sequence results, however, are shared within 1-2 days of their availability. Separate databases are maintained by laboratories that sequence viruses, but sequences are shared among laboratories as needed to perform phylogenetic analyses, particularly related to virus importations and VDPV emergence. In the event of new scientific discoveries, all laboratories making significant contributions to testing and analysis are represented among coauthors of scientific publications.", "As foci and intensity of WPV transmission decreased, WHO shortened target laboratory reporting time ( Figure 4 ) to expedite implementation of responsive immunization campaigns. The GPLN achieved a 50% reduction in reporting time by changing the testing algorithm, which shortened the observation time for inoculated cell cultures and replaced serological based testing with faster molecular tests to determine serotype and intratype and screen for VDPVs [2, 6, 7] . Another significant change was building capacity in more laboratories to perform molecular tests, which eliminated the time associated with shipping specimens and isolates between laboratories.", "WHO has standardized procedures used in the GPLN for testing of stool specimens from AFP cases. A consensus on recommended procedures was achieved through periodic informal consultative meetings convened by WHO for discussions among GPLN subjectmatter experts. Briefly, stool specimens from AFP cases are inoculated into cell cultures, and any polioviruses isolated have serotype and intratype determined. Partial genomic nucleotide sequences are generated for wild and programmatically important Sabin-related poliovirus isolates, and phylogenetic relationships among isolates are analyzed to investigate transmission linkages [2, 3] ." ] },{ "paper_id": "410a3623ec545b80542d885b2c66848466c43c7c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "profound respiratory failure secondary to infection in an immunosuppressed patient. 5 Most of the literature reviews have already shown the good application of ECMO in SLE-induced diffuse alveolar hemorrhage. 6 Our case report presents a promising application of rescue ECMO therapy in a lupus-induced immunosuppressed patient with pneumonia, acute respiratory distress syndrome, 7 ", "Background: Extracorporeal membrane oxygenation (ECMO) has evolved as a treatment option for patients having rev ersible severe respiratory failure who are deter iorating on conventional ventilation. 1,2 We describe our experience with a patient who received ECMO for refractory hypoxemic respiratory failure due to community-acquired pneumonia associated with systemic lupus erythematosus (SLE). Methods: This is a retrospective case report for which approval for presentation has been obtained from the administration of the department and can be submitted upon request. Our patient was an 18-yearold female with a long history of SLE with nephritis who was recently started on immunosuppression, admitted with azotemia, fluid overload, and respiratory failure, and initially improved with fluid removal. 3 Her respiratory status later worsened with saturations in the low 80s despite 100% FiO 2 and a positive end-expiratory pressure (PEEP) of 14 cm H 2 O. She had a trial of prone positioning together with PEEP optimization, but her condition continued to deteriorate. 4 The patient was evaluated for rescue ECMO therapy as a life-saving measure. 5 Both femoral veins were cannulated, and when ECMO started, there was immediate improvement in oxygenation. The ventilator was soon switched to the pressure control setting (PEEP 10 cm H 2 O/inspiratory pressure 10 cm H 2 O/rate 10 cycles/min) with 40% FiO 2 . The patient's hospital stay was complicated by lupus-induced thrombocytopenia, resulting in our decision to run heparin-free ECMO. She was decannulated after 25 days of ECMO without receiving any systemic anticoagulation. Results: The patient improved and was decannulated, extubated, and discharged from hospital, with no residual lung comorbidity. Conclusions: ECMO without any systemic anticoagulation is an acceptable therapy when there is" ] },{ "paper_id": "41148756482815041a85c11c6b01cb832bf1de9b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We further identified a set of articles (N=7) we refer to as \"readiness studies,\" or studies that assess training; availability of health care workers, health delivery facilities, or ICT; phone ownership; and data access in LMICs [102, [114] [115] [116] [117] [118] [119] . These studies specifically identify the extent to which an environment within an LMIC is prepared to adopt some form of HIT.", "For GHI, volunteers had graduate degrees in public health, informatics or informatics-related field and experience in applying ICT in global settings. They reviewed the full text of each selected article published before 2014 (N=83). Given the expanded size of the corpus in 2014 (N=199), volunteers were asked to examine the abstract and full text if possible. Reviewers categorized and summarized the articles using the following metadata: article type (e.g., review, research, methods, models); main keywords; main objective; principal findings; possible impact on the practice of GHI; and other notes. Like PHI, these observations from the reviewers were captured in a spreadsheet and reviewed by the GHI team lead (JP) to identify themes and trends.", "\"lesser developed economy\" OR \"lesser developed economies\" OR \"under developed economy\" OR \"under developed economies\" OR \"underdeveloped economy\" OR \"underdeveloped economies\" OR \"middle income economy\" OR \"middle income economies\" OR \"low income economy\" OR \"low income economies\" OR \"lower income economy\" OR \"lower income economies\" OR \"low gdp\" OR \"low gnp\" OR \"lower gdp\" OR \"lower gnp\" OR lmic OR lmics OR \"third world\" OR \"lami country\" OR \"lami countries\" OR \"transitional country\" OR \"transitional countries\" OR Africa " ] },{ "paper_id": "41f28afec098e61c475678ac2c8546f640c8b284", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "41ff8966b05ab778bb135d48143800f2792807fa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(1) Prediction of subcellular localization. Vaxign predicts different subcellular locations using optimized PSORTb 2.0 that has a measured overall precision of 96% [10] .", "Vaxign integrates open source tools and internally developed programs with user-friendly web interfaces. Input data for Vaxign execution are amino acid sequences from one protein or whole genomes. This Vaxign pipeline includes the following components ( Figure 1 ).", "(8) Protein functional analysis: Predicted proteins can be selected and automatically exported to the DAVID bioinformatics resources [41] for functional protein analysis." ] },{ "paper_id": "4230f45cdf439e789aa57cbb1a080823c74d7e8a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Procalcitonin concentrations were determined with the VIDAS BRAHMS PCT automated test (bioM\u00e9rieux, Marcy, France). PCT has a reported sensitivity of 88% and specificity of 81% in distinguishing a bacterial infection from other inflammatory processes [18] . Routine laboratory reporting denotes values of\\0. 25 ", "PCT\\0.25 lg/mL, 601 with a positive viral RP result, and 31 with both. Antibiotics were administered to 307 patients (39%) within the first 72 h. In these, antibiotics were discontinued within 48 h of laboratory results availability." ] },{ "paper_id": "42660ed19540a2bb59a9fb7481cb0c526fd12846", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "*From Western Europe (19) . \u2020Patients whose purpose of travel was the initial immigration travel from their birth country to Europe were excluded.", "a paradigm of an infectious disease that rapidly became global as highly viremic travelers acted as effi cient carriers of the virus (7) . After CHIKV-infected persons in eastern Africa, Indian Ocean islands, India, and Southeast Asia, a new CHIKV variant reached Europe and affected local populations in Italy through 1 infected traveler (the index case-patient) and transmission by indigenous European mosquito vectors (8) . In April 2009, an infl uenza A pandemic (H1N1) 2009 virus emerged in humans in North America and reached Europe soon after through returned travelers (9) .", "Our study also reinforces the view that dermatologic conditions are a leading cause of health problems in travelers (37) . Pretravel advice should support the traveler's use of impregnated bed nets and repellents, promote the practice of effi cient clothes drying and ironing to prevent myasis, and discourage direct contact of skin with wet soil to prevent larva migrans transmission." ] },{ "paper_id": "42822532587ea4f62ac2b8df0502ac1db09a9552", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Risk does not always respond to claims of fairness and is unfortunately encountered by both choice and chance [14] . Professional and institutional solidarity is likely to play a role in distributing these risks. The risk that is refused by any individual physician is left to be absorbed by someone else. In a crisis, this someone else does not become another hypothetical doctor, but a known colleague [14] .", "Expecting a physician to treat without any regard to his or her own safety is both an extreme and unrealistic approach [5] . Reasonable limits to an acceptable level of risk are necessary. Risks become reasonable when they are proportional to the probability of successful rescue and when the overall good that is achievable from undertaking that risk is substantial [4] . Professional obligations can then be weighed against competing personal obligations to health and families.", "The suspected cyclic pattern of antigen shift suggests that the next outbreak is not only predictable, but is in fact imminent [18] . An influenza pandemic is therefore not a hypothetical crisis but a foreseeable one.", "Capability is based on Kant's principle of 'ought implies can'. In rendering aid during an infectious disease crisis, the benefits that can be gained at the expense of the same risks undertaken are much higher for physicians by virtue of the expert knowledge they possess. This professional expertise may also provide doctors with better self-protection in dealing with any infection risks." ] },{ "paper_id": "42f1a4559a7a54113e1d9b341cf6cb6815c0e023", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4305e4ee478f16759146ed5ae853e0ea5b017cdb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Background Few drugs are currently licensed to treat influenza A infection, and new therapies are needed, especially for highly pathogenic strains. Traditional medicinal plants, such as Lycoris radiata, are a potential source of new antiviral agents.", "Oseltamivir carboxylate Ro64-0802 (GS4071) was kindly provided by Hoffmann-La Roche. " ] },{ "paper_id": "431cc0d8bd58bdbe9da45c4402399713d1a882ae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 Evaluate the impact using qualitative approaches based on clinicians' behaviors;", "To perform this function, the AKR should include a natural language processor for categorizing free-text entries of a patient's chief complaint.", "\u2022 Determine if this functionality should be considered as a criterion for electronic health record certification." ] },{ "paper_id": "433adf76ea9adc9f5c540d4c28142d4d020969e2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Differences in survival were compared using the log rank (Mantel-Cox) test. Cell frequencies, enzymatic activity and protein secretion were analyzed with the unpaired Student's t test, and differences in pathogen burden were compared with non-parametric Mann-Whitney test (two groups) or non-parametric Kruskal-Wallis one-way ANOVA (more than two groups). In all cases, P < 0.05 was taken as statistical significance.", "Mice anesthetized with xylazine and ketamine were intra-rectally inoculated with the indicated dosage of ultrapure Escherichia coli LPS (InvivoGen) resuspended in 100 \u03bcL sterile saline as described 12 beginning two days prior to C. albicans infection with repeated dosing every two days thereafter.", "At the indicated time points after C. albicans inoculation, the kidneys, spleen, liver and brain were sterilely dissected, homogenized, and serial dilutions on each organ homogenate spread onto agar plates. After incubation for 24 hours at 37\u00b0C, fungal colony forming units were enumerated. After influenza A infection, the lungs were collected, homogenized, and viral titers enumerated by counting viral plaques formed from serial dilutions of the lung homogenate plated onto confluent Madin-Darby Canine Kidney (MDCK) cell monolayers. 18" ] },{ "paper_id": "43c97885b9857b19786fed791ef44c801ed5c97b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "cause infections in humans. We report a case of Veillonella endocarditis documented by isolating a slow-growing, gram-negative microbe in blood cultures. This microbe was identified as the newly recognized species Veillonella montpellierensis (100% homology) by 16S RNA gene sequence analysis.", "Our isolate has recently been compared with 3 other isolates and classified as a new Veillonella species named V. montpellierensis by Jumas-Bilak et al. (1) . We demonstrate here that V. montpellierensis is pathogenic for humans and may be included as a new agent of endocarditis caused by fastidious pathogens.", "We report here the seventh case of endocarditis due to Veillonella spp. identified by PCR amplification and sequencing of 16S rDNA gene and the first case of endocarditis due to V. montpellierensis. This case reemphasizes the usefulness of molecular methods in identifying fastidious microorganisms and in describing new clinical entities (3) ." ] },{ "paper_id": "43d1ea78fb9a694f81e590f387cbcff0b7d0073f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "43d2d4072d40a3964ea330342b9222376d700531", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "43fa93dd99dc6f9a8204dc22c79fb80ddb44dfba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ms Martin-Granel is a professeur certifi\u00e9e de lettres classiques and teaches French literature, Latin, and Ancient Greek in secondary school in the south of France. She has recently translated a text by Petrarch into French.", "Dr Martin is a bacteriologist and chef de laboratoire at the Pasteur Institute and director of the Pasteur Institute of New Caledonia. His research interests focus on epidemics.", "When works that put forward new ideas are translated, determining the original terminology (in Ancient Greek in this case) is not easy. In 430 BC, when Hippocrates was collecting the clinical observations he would publish in Epidemics, his treatise that forms the foundation of modern medicine, at least 3 terms were used in Ancient Greece to describe situations that resembled those described by Hippocrates: nosos, phtoros, and loimos (2) .", "A t the start of the 21st century, epidemics of infectious diseases continue to be a threat to humanity. Severe acute respiratory syndrome, avian influenza, and HIV/AIDS have, in recent years, supported the reality of this threat. Civil wars and natural catastrophes are sometimes followed by epidemics. Climate change, tourism, the concentration of populations in refugee camps, the emergence of new human pathogens, and ecologic changes, which often accompany economic development, contribute to the emergence of infectious diseases and epidemics (1) . Epidemics, however, have occurred throughout human history and have influenced that history. The term epidemic is \u22482,500 years old, but where does it come from?" ] },{ "paper_id": "44217677cfbc7011d80be49e7087b539fe4fab0b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "442483b51febb0ef0cedea0d4283da1cb8c7ec01", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4438de01e4b0376bfa446b4234e599fb234cb6b1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The sequence of human USP18 (hUSP18) cDNA encoding residues 16-372 was PCR amplified using as primers attB1-3C-hUSP18-for and attB2-hUSP18-rev and as template the vector pCMV5a-hUSP18-Flag containing the full-length hUSP18 cDNA (kindly provided by Prof. Claudio Brancolini, University of Udine). The PCR fragment was cloned into pVL1393-His 6 -GST vector (in house modified) using the Gateway system (Invitrogen). The resulting sequence, coding for His 6 -GST-3C-hUSP18(16-372), was sequence verified by an external service (BMR Genomics, Italy).", "Vector pTriEx2-USP21cd encoding residues 197-565 of human USP21 was generated by amplification of USP21 cDNA from vector Flag-HA-USP21 (Addgene) with primers KpnI-USP21cd-for and XhoI-USP21cd-rev. The PCR product was digested with restriction enzymes KpnI and XhoI and cloned into vector pTriEx2 (Novagen).", "The authors declare no conflict of interest.", "The expression vector for mouse ISG15 pACE-m(ouse)ISG15-C76S was generated as described previously28. Briefly, a synthetic cDNA encoding residues 1-155 with codons optimized for expression in E. coli fused to an N-terminal His 6 -tag and a HRV 3C protease cleavage site was cloned via NdeI and XhoI into vector pACE. The coding sequence contains a serine instead of a cysteine residue at position 76. Expression vectors pACE-mISG15-C76S-W121 and pACE-mISG15-C76S-W121-P128G-H149V were generated likewise using synthetic cDNAs. In the coding sequences tryptophan 121 or tryptophan 121, proline 128 and histidine 149 were replaced by the corresponding residues of ubiquitin, respectively." ] },{ "paper_id": "4461e9c905b651248f56c1d107331240b706eeb4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "449a4b7b716fca8b205ee4ede84769419f15ed32", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "44a3cf460f8ce1edf8df41d96242735398773acd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "44b17c2f802ed2716fdf040dc05633b35d4b6dcb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "44c0a8230ff9d4468cebe29f69a0a985f5b7a4d1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Because this study is based on a cohort of 77 suspected case-patients, of whom only 2 laboratory-confirmed cases were identified during the surveillance period, estimates on the basis of identified symptoms are very imprecise ( Table 2) . However, in the context of an emerging pathogen, reporting such data progressively helps optimize case detection and surveillance systems.", "Enhanced surveillance involved the collection of a minimum dataset for each possible case, including demographic data, clinical symptoms, travel and contact history, and results of testing for respiratory pathogens (6) . Nose and throat swab specimens and, when possible, lower respiratory tract specimens, were tested at 1 of 4 regional laboratories. Although the testing guidelines recommended MERS-CoV testing after exclusion of alternative etiologies, other tests were conducted in parallel with MERS-CoV testing for most suspected cases.", "In addition to testing the 77 persons who met all of the possible case criteria, MERS-CoV testing was conducted on 13 patients who had severe acute respiratory disease but did not meet the travel requirements: 2 had a travel history outside the Middle East, 4 had no travel history in the relevant exposure period, and travel histories of the remaining 7 were unknown. MERS-CoV was not detected in any of these persons." ] },{ "paper_id": "44ca543f5528ca4d7b33b401623cc1bf0afb84c6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "An influenza pandemic is likely to increase demands on healthcare providers, especially in hospitals. Except in Japan, current levels of NI use are low. Any strategy involving NI use would require stockpiles of these drugs.", "The population was stratified as for seasonal influenza; persons were considered to be either at high risk for severe outcome or at low risk (22) . The at-risk group included those with chronic respiratory disease, chronic heart disease, chronic renal failure, diabetes mellitus, and immunosuppression; this group also included all persons living in long-term care facilities, such as nursing homes (23) , and all those >65 years of age (24) .", "A number of intervention strategies can reduce the impact of influenza pandemics. During interpandemic years, influenza vaccination is used to reduce deaths and disease. However, vaccine is unlikely to be available in time or in sufficient quantities for use during a pandemic (8, 9) . Other, nontherapeutic, disease control options may be used, such as those used during the outbreak of severe acute respiratory syndrome (10) ." ] },{ "paper_id": "44f6a983bc7eba1620e1d53ff2721f9a0aea1a6a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "450842232c176d0422a8d77300dec428f7c81d61", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4566e8328c0ee3f5a68f04651dafb852786cb121", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4598e96f24115b1fd9bc0247cdd88e52beb5268f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis of possible differences between mean values was performed with a two-tailed Student's t-test. Po0.05 was considered significant.", "Furthermore, BLM and BRO cells grown as subcutaneous xenografts in nude mice have a very high rate of spontaneous metastasis formation (Lockshin et al, 1985; Van Muijen et al, 1991) .", "\u00f0CD13 firefly luciferase value\u00de=\u00f0pRL \u00c0 CMV Renilla luciferase value\u00de \u00f0pGL2 \u00c0 basic firefly luciferase value\u00de=\u00f0pRL \u00c0 CMV Renilla luciferase value\u00de :", "Cells at 70% confluence were harvested by short trypsinisation, washed and resuspended in phosphate-buffered saline (PBS) containing 0.1% bovine serum albumin (BSA) and 0.05% NaNO 3 . 1 \u00c2 10 5 cells were incubated at room temperature for 30 min with 1 : 20 diluted phycoerythrin (PE)-conjugated anti-human CD13 monoclonal antibody L-138 (BD biosciences, Alphen aanden Rijn, the Netherlands), PE-conjugated mouse IgG1 or PBS. Cells were washed and analysed on a FACS calibur flow cytometer (BD biosciences). Results were expressed as the ratio of the mean fluorescence of L-138 divided by that of IgG1." ] },{ "paper_id": "45b68fb7e99fffb722b9ac61ba8b0cbe00370e16", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "45d5977d22dcb1bc57c9cd4348f63c1cc19eaa84", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data for this study came from a cohort of persons >18 years of age who were living in the New York City metropolitan area on September 11, 2001 . The cohort was recruited through a random digit dial telephone survey from March 25 through June 25, 2002. Contact information was obtained and follow-up interviews were conducted from September 25, 2002, through January 31, 2003, and from September 24, 2003, through February 29, 2004. Data regarding knowledge of, worry about, and attitudes toward AIDS and SARS were collected among a randomly selected subset of participants in the second cohort follow-up. The total sample included in this analysis, for whom data about AIDS, SARS, and social support were incomplete, consisted of 914 persons; response rate for eligible participants was 56%. Each participant received a $10 incentive. Additional details on sampling are provided elsewhere (5) . The Institutional Review Board of the New York Academy of Medicine reviewed and approved this study.", "Of the 914 participants, 45.4% were male, 54.1% white, 7.6% Asian or other race, 18.5% black, and 19.8% Hispanic ( Table 2 ). In multivariable models controlling for sociodemographic variables (online Appendix Table, available from www.cdc.gov/EID/content/14/5/825-appT.htm), persons with low or medium levels of social support were signifi cantly more likely than those with high levels of social support to report being poorly informed about AIDS (p = 0.004 for low support, p = 0.038 for medium support), being very worried about AIDS (p = 0.010 for medium support) and SARS (p = 0.010 for medium support), and to express more stigmatizing attitudes toward SARS (p = 0.020 for low support).", "The ability of public health institutions to effectively manage emerging infectious diseases (EIDs) and mitigate their consequences is partly a function of public reaction to an epidemic. Negative reactions may vary from denial to panic to stigmatization. Denial or minimization of the threat of an EID by the population at risk can impede prevention efforts and increase transmission. Alternatively, an overreaction to the threat of an EID can overwhelm public health systems and resources, divert resources from effective disease control activities, and lead to severe economic losses in areas affected by the disease. Stigmatization can increase problems of persons with the disease and facilitate transmission because persons with or at risk for the disease may avoid seeking healthcare and because governments may attempt to suppress information about EIDs, considering their potentially severe economic consequences. From a public health policy perspective, identifying personal characteristics and resources that predict responses of persons to EIDs is important to improve the ability of the public to learn about, rationally appraise the threat of, and minimize stigmatization of EIDs.", "Determinants of a person's knowledge, worry, and stigma about EIDs are poorly understood. Although the quality of information conveyed to the public by various sources (e.g., healthcare providers, media) and epidemiologic characteristics of the disease (e.g., mode of transmis-sion, case fatality rate) are important, early empirical work suggests that responses to EIDs are infl uenced by characteristics that include a greater stock of personal resources. We recently reported that less education was associated with being poorly informed about severe acute respiratory syndrome (SARS), very worried about AIDS, and having more stigmatizing attitudes toward AIDS and SARS (1, 2) . Social relationships may also be important. Helleringer et al. reported that social interactions among friends, peers, relatives, and community members may infl uence perceptions of HIV/AIDS risk and serve \"as a resource for individuals to learn about and evaluate new behavioral strategies in the face of the epidemic\" (3) ." ] },{ "paper_id": "45d747c81ca2c36c26e66349ff45abc6a43b612c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "45dad2e0a82a6a22df9c573f868655018d5233f5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The GPHIN software application retrieves relevant articles every 15 minutes (24 hours/day, 7 days/week) from news-feed aggregators (Al Bawaba [www.albawaba.com] and Factiva [www. factiva.com]) according to established search queries that are updated regularly. The matching articles are automatically categorized into >1 GPHIN taxonomy categories, which cover the following topics: animal, human, or plant diseases; biologics; natural disasters; chemical incidents; radiologic incidents; and unsafe products.", "As an initial assessment of data collected during July 1998 through August 2001, WHO retrospectively verifi ed 578 outbreaks, of which 56% were initially picked up and disseminated by GPHIN (9) . Outbreaks were reported in 132 countries, demonstrating GPHIN's capacity to monitor events occurring worldwide, despite the limitation of predominantly English (with some French) media sources.", "HealthMap processes an average of 133. 5 Most alerts come from news media (92.8%), followed by ProMED (6.5%) and multinational agencies (0.7%).", "Users can view the latest list of published articles or query the database by using both Boolean and translingual metadata search capabilities. In addition, notifi cations about events that might have serious public health consequences are immediately sent by email to users in the form of an alert.", "EpiSPIDER connects to news sites and uses natural language processing to transform free-text content into structured information that can be stored in a relational database. For ProMED reports, the following fi elds are extracted: date of publication; list of locations (country, province, or city) mentioned in the report; and topic. EpiSPIDER parses location names from these reports and georeferences them using the georeferencing services of Yahoo Maps (http:// maps.yahoo.com), Google Maps (http://maps.google.com), and Geonames (www.geonames.org)." ] },{ "paper_id": "45e91042ac20319b849f63a7dd00dda7d11de638", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "45f32bef75c27869b3553a11684b3212eb4319de", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "46202621202a28e12bb2444d9f4b9763ed8b1881", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To receive feedback on performance of this method and other methods of CHIKV detection, a profi ciency study was organized among ENIVD members. All participants were informed about the option of obtaining the preformulated assay. Laboratories in Europe (22), Asia (6), South America (2), and Africa (1) participated.", "C hikungunya fever, caused by chikungunya virus (CHIKV), is an acute febrile illness that causes severe and long-lasting arthralgia (1) . A recent and ongoing epidemic in the Indian Ocean area extended far beyond this region and caused hundreds of imported cases worldwide (2) (3) (4) . Chikungunya fever is diffi cult to clinically distinguish from co-endemic diseases such as malaria or dengue fever. Laboratory testing is required for appropriate case management and public health response (5) . Pilot studies have shown that reverse transcription-PCR (RT-PCR) reliably detects acute infections in humans (3, 6) , but many laboratories were not ready to conduct such tests when this epidemic occurred.", "Information distributed to laboratories asking for assistance with CHIKV RT-PCR included reaction chemistry setup, cycling profi le, and primer and probe sequences. A quantifi ed CHIKV in vitro RNA transcript containing 9 \u00d7 10 10 subgenomic RNA copies/\u03bcL was used as a noninfectious positive control. Additional measures were taken to provide proper primers and probes because these components are most vulnerable to variation when assays are adapted from protocols, e.g., because of synthesis errors or poor purifi cation. Primers and probes were synthesized in large reference lots and stored centrally at an oligonucleotide factory. Samples of these lots were validated by the reference laboratory and confi rmed to provide full sensitivity as achieved with the original primers used in developing the prototype assay (3). Recipients of protocols were invited to order and use aliquots of primers directly from the validated reference lot.", "Inactivated and stable testing material was generated from cell culture supernatants of 4 CHIKV strains from the epidemic in the Indian Ocean area (1 each from Seychelles, Mauritius, R\u00e9union Island, and India) and 1 East/Central Africa strain (S27). Virus solutions were inactivated by heating at 56\u00b0C for 1 h and gamma irradiation with 30 kGy. Residual infectivity was excluded by 3 blind passages of a sample of each solution on Vero cells. Solutions were diluted in human fresh-frozen plasma, aliquoted (100 \u03bcL), and lyophilized. Test aliquots were reconstituted in 100 \u03bcL of water, and CHIKV RNA was quantifi ed by RT-PCR (3). Lyophilized samples were shipped at ambient temperature to participating laboratories. Each shipment contained a coded panel of 9 CHIKV RNA positive-and 3 CHIKV RNA-negative lyophilized samples with virus concentrations shown in Table 1 . Participants were asked to test the material with any molecular assay routinely used for detecting CHIKV in human plasma or with the preformulated test. We requested test results and assay details (PCR formulations and extraction methods). A total of 36 sets of results were received by the study coordinator, including 3 double sets from 3 laboratories that used 2 methods each. One laboratory provided triple sets of results from 3 tests." ] },{ "paper_id": "4630cc2a962fc78b5f438c4d95f9163f2ee7e189", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "secondary antibody", "In this equation \u03bc represents the arithmetic mean, while \u03c3 indicates standard deviation. However, when using contrast values, the above equation needs to be inserted into the contrast equation to yield the limit of detection for contrast values:", "Bacterial strains and growth media S. Enteritidis strain 125109 (phage-type 4) was used for immunoscreening and the E. coli electrocompetent cell lines Acella\u2122 (www.edgebio.com/, Gaithersburg, MD) and KRX single-step competent cells (www.promega.de/) were used for cloning. S. Enteritidis was grown in Nutrient Broth 2 (www.sigmaaldrich.com/) and E. coli in Lysogeny broth (LB) with addition of ampicillin (100 \u03bcg mL \u22121 )." ] },{ "paper_id": "46365f6b8a2f8ebbfea7feab338c0df7a96842dc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "464575e607e642ade630c3c58620fcfea98cf698", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4667d92ff3cfe1a4ac0c714cf7152e7c7c430a0e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "O n March 5, 2003 , the first patient with severe acute respiratory syndrome (SARS) died in Toronto, Ontario, Canada. This index patient was a 78-year-old woman who, upon returning to Toronto from Hong Kong, transmitted the new variant coronavirus to her family (1). On March 7, her son was admitted to the hospital, and he subsequently died on March 13. His unrecognized disease led to nosocomial transmission of this disease in Toronto (1) . As of August 28, 2003, a total of 375 cases of suspected and probable SARS had been identified in Toronto; most of these cases occurred within healthcare facilities (1) (2) (3) . A minority of cases were related to household and community transmission, most acquired after hospital visits. The last community-acquired case of SARS-associated coronavirus (SARS-CoV) infection was identified on April 13, 2003 (2) .", "Physicians recruited to manage the outbreak included primary-care doctors, infectious diseases consultants, hospital epidemiologists, public health physicians, emergency department physicians, and radiologists.", "During the outbreak, Toronto hospitals developed standardized systems for all implicated procedures, including code blues, patient transfers, and other infection-control procedures.", "The above-mentioned wards were considered SARS units, and the same engineering principles were applied to each. Each patient's room met the minimum requirement of six air changes per hour. Twice daily, the engineering department tested the negative-pressure status in all SARS units and patient rooms and presented the results to the hospital administration. In addition, an external company conducted daily assessments of the air circulation within the rooms. Highly trained engineering staff and clear blueprints and plans of the facility's ventilation system were needed to implement all the required changes.", "Emerging Infectious Diseases \u2022 www.cdc.gov/eid \u2022 Vol. 10, No. 5, May 2004 PERSPECTIVES Figure 1 . Tent assessment clinic built on ambulance loading dock for assessment of the general public for any symptom suggestive of severe acute respiratory syndrome. A, 40-x 20-foot tent constructed on the ambulance bay of the emergency department provided a spacious waiting area adjacent to the clinic area; B, inside the tent, eight cubicles were constructed with metal pipe frames and thick plastic walls, each ventilated with a custom-built ventilation system." ] },{ "paper_id": "466db44b1f77af3237d04ac0313bd03c2b2e94bc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "467694c7a219031c9be1734c7ab3bc42bfa07590", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "More procedure orientated assistance may become available from near-infrared technology, which has been piloted in a computerized bedside visualization device to aid venous cannulation [11] . Applicability to central venous cannulation has not been explored.", "Acquired bloodstream infection (BSI) in the ICU is a serious complication. A study of ICU patients in Calgary [12] demonstrated crude death rates of 45% among patients with ICUacquired BSI, as compared with 21% in those without (P < 0.0001).", "Therefore, this represents another area in which political and technological developments outside the ICU may have a direct impact on clinical practice and patient safety, and intensivists are strongly recommended to consult early and engage with those driving their local and national health economy." ] },{ "paper_id": "4691c2e3a8705236b9eb901abfbca15fc89773da", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "46eed3a4ec7612d74e9295fe57c982755948feae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Regular communication via teleconferences and e-mails became the new means to provide support. These provided a forum to dispel rumours, clarify media reports, synthesize the barrage of government directives, and support those feeling isolated as we sought to work in extremely difficult and demanding conditions, such as seeing our colleagues placed in quarantine after exposure, some of them falling ill, becoming critically ill and even succumbing to SARS.", "The creation of such a system-based disaster management plan is not an easy task. Sharing information and learning from collective experience requires unprecedented collaboration and open communication between all levels of government, health care organizations and front-line workers.", "Front-line workers Any information regarding the transmission of disease to staff, an analysis of how such spread may have occurred and advice regarding future preventative measures should be made available to everyone. In the present era of global travel, it is increasingly unlikely that one centre or one country will be dealing with new emerging diseases in isolation. Disaster planners are challenged to develop a global perspective, including accurate communication of events as they unfold in distant jurisdictions. As a result, links to colleagues locally, nationally and internationally are vital in a disaster situation." ] },{ "paper_id": "46f3939764340a0e8274772f0cda101e7e4cb361", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Please cite this paper as: Vongphrachanh P, Simmerman JM, Phonekeo D, Pansayavong V, Sisouk T, Ongkhamme S, Bryce GT, Corwin A, Bryant JE. (2010) An early report from newly established laboratory-based influenza surveillance in Lao PDR. Influenza and Other Respiratory Viruses 4(2), 47-52.", "Background Prior to 2007, little information was available about the burden of influenza in Laos. We report data from the first laboratory-based influenza surveillance system established in the Lao People's Democratic Republic.", "Respiratory swab specimens were tested for presence of respiratory viral pathogens using the Luminex RVP (ID-Tag\u00d4 RVP) assay (Bioscience Corp, Toronto, ON, Canada) according to manufacturer's instructions and as described elsewhere. 22 RNA extractions were performed on specimens prior to freezing. Subsequently, the RNA underwent a single freeze-thaw cycle during analysis. The RVP primer mix contains 16 primer pairs designed to simultaneously amplify highly conserved regions of viral types and subtypes, specifically influenza A \u2044 H1, A \u2044 H3 and A \u2044 H5, influenza B, RSV A, RSV B, coronavirus (229E, OC43, SARS, NL63, HKU1), parainfluenza virus 1-4, metapneumovirus, adenovirus and enterovirus \u2044 rhinoviruses. The RVP assay uses a single primer pair targeting a conserved region of 5\u00a2-UTR to detect viruses of the closely related enterovirus and rhinovirus genera." ] },{ "paper_id": "47b2413d069283b3278cd69e2777f53758af19b1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "47e5a99b14df794d9c33c1b1e8ff258d3f89a1d2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "PRED BALB/c is a computational system that predicts peptides binding to the major histocompatibility complex-2 (H2 d ) of the BALB/c mouse, an important laboratory model organism. The predictions include the complete set of H2 d class I (H2-K d , H2-L d and H2-D d ) and class II (I-E d and I-A d ) molecules. The prediction system utilizes quantitative matrices, which were rigorously validated using experimentally determined binders and non-binders and also by in vivo studies using viral proteins. The prediction performance of PRED BALB/c is of very high accuracy. To our knowledge, this is the first online server for the prediction of peptides binding to a complete set of major histocompatibility complex molecules in a model organism (H2 d haplotype). PRED BALB/c is available at http://antigen.i2r.a-star.edu.sg/predBalbc/.", "CONCLUSION PRED BALB/c marks a new direction in predictive modeling of MHC-binding peptides and T-cell epitopes. The main advantage is that PRED BALB/c focuses on a complete organism and its predictions represent a complete set of predicted targets of T-cell immune responses. The focus on the complete set of MHC alleles is closer to studies involving laboratory animals. This approach provides a more complete view of the immune responses of an organism. The BALB/c mouse is an important laboratory model and PRED BALB/c is, therefore, useful for the analysis of immunization regimens and deciphering responses to infections. Further development of PRED BALB/c will include addition of matrices for prediction of 8mer and 10mer binders to H2 d class I molecules and further improvement of prediction matrices by cyclical refinement-using newly defined binders and non-binders from experiments.", "Five 9 \u00b7 20 matrices were built, one for each of the five H2 d alleles, and 10-fold cross-validations were performed to test the accuracy of the prediction models. The results show that PRED BALB/c predicts peptides binding to I-E d , I-A d and H2-K d with excellent accuracy [area under the receiver operating characteristic (ROC) curve, A ROC > 0.90], and to H2-D d and H2-L d with good accuracy (A ROC > 0.85). The models were also rigorously tested using experimentally known peptides from viral, prokaryotic and eukaryotic origins (14, (26) (27) (28) (29) and validated by in vivo studies using severe acute respiratory syndrome (SARS) nucleocapsid and HIV GAG proteins. The H2 d models accurately predicted 11 out of 12 ELISPOT positive regions from BALB/c mice splenocytes immunized with SARS nucleocapsid DNA vaccines (data not shown). The web interface of PRED BALB/c uses a set of graphical user interface forms. The interface was built using a combination of Perl, CGI and C programs. PRED BALB/c has been implemented in a SunOS 5.9 UNIX environment." ] },{ "paper_id": "48f7616ac0756fa4bcdb79fef569643b929b108e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Scoring using London DG estimated Gibbs binding energy (DG binding ) from pose of ligand to enzyme was based on the calculation:", "As an outlook of this study, we are aware that some research groups already produced RNA based drugs for interfering with influenza virus [46] [47] [48] . Moreover, a feasible and powerful transcriptomics based tool has been generated for viral bioinformatics research [49] [50] [51] [52] . To this end, it would be interesting to investigate the transcriptomics properties of the H1N1 virus, as supplementary approach to the existing proteomics method.", "Born solvation caused the solvation energy (E sol ) to be calculated in potential energy molecular system function from atom coordinate:" ] },{ "paper_id": "490c64195eec44f9280570aece9732e7a120bd34", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "1\u2192 2 2 \u2192 5 2 \u2192 3 2 \u2192 3 3\u2192 4 4 \u2192 5 4 \u2192 6 5 \u2192 7 5\u2192 6 6 \u2192 7 FRET pairs L11-t t-t L11-t L1-t L1-t L11-t L1-t t-t", "The absolute values of translation rates measured here with different FRET pairs do not exactly match each other, presumably because the specific positions labeled within ribosomes and/or tRNAs may affect the precise magnitudes of some of the rate constants. However, the extents of slowing of translation rates affected by secondary structure are quite similar among different FRET pairs, so differences in labeling positions do not fundamentally affect the trends described in the main text." ] },{ "paper_id": "49130444457c29a469a3d1c054c706c451975391", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "494b65b83c62d007f6ebd38d7ae83516a8fd6971", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All the substrates were made by annealing of a 5' 32 P-labeled oligonucleotide with the complementary unlabelled oligonucleotide(s) (sequence details in Supplementary Table 1 and 2). The oligonucleotides M34 to M46 (lengths from 34 to 46 nt) were derived from the oligonucleotide H3, and were used as radioactive markers in gel analysis to determine the endonuclease incision sites. The annealed DNA substrates were then purified by electrophoresis on a native 8% polyacrylamide gel and recovered by the crushing and soaking method.", "We further calculated simulated-annealing composite-omit difference Fourier maps and the results clearly validated the different DNA conformations observed in the \"substratelatching\" and \"substrate-unwinding\" forms ( Supplementary Fig. 1 ).", "SEC-MALLS data were collected using an Ettan LC system (GE Healthcare) with a Superdex 200 Increase 10/300 column (GE Healthcare) equilibrated in buffer E (20 mM Tris HCL, pH 8.0, 80 mM NaCl, and 0.1 mM TCEP) at a flow rate of 0.5 ml min \u22121 . The system was coupled on-line to an 18-angle MALLS detector and a differential refractometer (DAWN HELEOS II and Optilab rEX, Wyatt Technology). Molar mass determination was calculated with ASTRA 6.2 software." ] },{ "paper_id": "495aabbaf2ffb23eaebe4b3422bfdb4e2cd122da", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "49952f26e28224dcb6345f7bd9abcbc1b1dc32d8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The screening by the RT-PCR assay of astrovirus in rats revealed that six (1.6 %) of 371 faecal samples from R. norvegicus and none of the samples from R. rattus were positive. The positive specimens were collected in 2007 (n54) or 2008 (n52) and were collected from different geographical locations in Hong Kong.", "Interestingly, these RAstVs are shown to be phylogenetically closely related to the human MLB1 and MLB2 astroviruses (hereinafter MLB viruses) with strong statistical support (Fig. 1a, ORF1b and ORF2 ). It should be noted that this sister-clade relationship does not have a strong statistical support in the ORF1a sequence analyses (Fig. 1a) . However, the lack of resolving power in the ORF1a analysis is very probably due to the lack of other viral sequences available for analysis.", "Bats represent the second largest group of mammals (comprises 20 % of all mammals). The remarkably high detection rate of astroviruses in bats prompted us to perform a similar surveillance study on rodents, which is the largest group of mammals accounting for 40 % of known mammalian species. As we were primarily interested in viruses that might be at the animal-human interface, we specifically targeted rodent species that have a long history of living in close proximity to human populations (Sullivan, 2003) . Here, we report the discovery of rat astroviruses (RAstVs) from urban rats. In addition, we also report our recent surveillance of astroviruses in humans." ] },{ "paper_id": "49f7f726a602a3e20d2525a7b696fd4a41d8430c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Microarry-based analyses have been well established and are currently used in a wide range of biological assays (1) (2) (3) (4) (5) . Extrapolation of their use for infectious diagnostics and detection of biodefense related agents provides an attractive alternative to conventional analytical approaches. Hence the critical need for advanced diagnostic systems in microbiology is to detect rapidly genetic information within the known and unanticipated pathogenic microrganisms associated with the human health (i.e. viruses, bacteria and fungi). With the parallelism offered by DNA microarray technology we are able to pursue and develop an approach to large-scale analyses of such abundance of genetic information in these organisms. The main technical challenge in this field arises from the difficulty in labeling sufficient copies of pathogenic biomarkers. However, when integrated in one portable diagnostic device labelfree detection has great potential for addressing this neckbottle and speeds up practical application of microarray technology.", "The fluorescence images were collected with the standard FITC filter by laser scanning confocal microscope (Leica TCS SP) employing a 488 nm Ar ion laser. A low-powerful objective lens (10\u00b7) was used in all the experiments. The system control program is Leica TCS NT software version 1.6.587. The laser moves from point to point to produce the scanned images at medium speed and in unidirectional scan mode. The slide is imaged with a zoom factor of 1 and the image size of the scanning field area is 1 mm \u00b7 1 mm. Adjust the gain and offset of PMT1 until the image is bright enough and shows a good contrast. All relevant parameters of the Leica TCS system were not adjusted again in all the scanning process. Images were analyzed by ImageJ version 1.3 (NIH) (http://rsb.info.nih.gov/nih-image/index.html).", "The PCRs were performed in a total volume of 25 ml containing 1\u00b7 TaqMan Universal PCR Master Mix, which is an optimized real-time PCR buffer supplied by Applied Biosystems for TaqMan reactions, 200 nM of each primer for different fragments, 200 nM amino-modified TaqMan probes and 10 ng different genomic DNAs in a PCR tube. The amplification condition consists of an initial 2 min at 50 C for optimizing the UNG enzyme, and 10 min denaturation at 95 C followed by 40 cycles of 30 s of denaturing at 95 C, 30 s of annealing at 52 C, and 60 s of extension at 65 C. The instrument is the Rotor-Gene 3000 (Corbett Research Ltd, Australia)." ] },{ "paper_id": "4a1e916ed5c14a6c0e5e4587827a4dde53756f52", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4a228865af2c19adf9386a5b04cca3ceb3c8683d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nucleotide variation is distributed along the entire genome. Based on our alignment and the annotation in GenBank, 21 of the 26 open reading frames had the variations, including genes encoding polymerase, spike glycoprotein, envelope, membrane, and nucleocapsid protein.", "The non-synonymous rate was higher in the three genes E, M, and N, suggesting some of those mutations might increase antigenicity, although the number of mutations used to calculate these rates was small." ] },{ "paper_id": "4a25649bbc72d2ef0e57a19221b21c486271bcfd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4a356ebe0d7578b2c9bd8e9bc844d204632019a7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4a3941003ea2673397975ae8bc2536ad59f789e5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Its missions are divided into five scenarios indicating deployment:", "Key recommendations for further development are:", "We have no conflict of interest to the subject matters discussed in the manuscript." ] },{ "paper_id": "4b05e7b9898203b6bf0659c315eb9eb1f66f228c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Customized antibody arrays, consisting of pairs of capture and detection antibodies against 43 proteins, were utilized (SDF-1), IGF1, IFNG, IGFBP3, IGFBP4, IGFBP6, IL-1A, IL-1B, IL-1R1, IL-2, IL-4, IL-5 . Antibody array fabrication, processing, data extraction and analysis were performed as previous described [31] .", "Identification of TIMP1, IL18, RANTES, P-Selectin, MMP9, and L-Selectin as SJIA Plasma Flare Biomarkers" ] },{ "paper_id": "4b371efad68f1f604961744b82c69e625e8faef5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4b452b0428ac7d2aaeaa1b4c313e834e2461e11b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The high mutation rate of the human immunodeficiency virus type 1 (HIV-1) virus is a major problem since it evades the function of antibodies and chemical inhibitors. Here, we demonstrate a viral detection strategy based on synthetic biology principles to detect a specific viral function rather than a particular viral protein. The resistance caused by mutations can be circumvented since the mutations that cause the loss of function also incapacitate the virus. Many pathogens encode proteases that are essential for their replication and that have a defined substrate specificity. A genetically encoded sensor composed of a fused membrane anchor, viral protease target site, and an orthogonal transcriptional activator was engineered into a human cell line. The HIV-1 protease released the transcriptional activator from the membrane, thereby inducing transcription of the selected genes. The device was still strongly activated by clinically relevant protease mutants that are resistant to protease inhibitors. In the future, a similar principle could be applied to detect also other pathogens and functions.", "The principle behind the genetically encoded device for the detection of the viral protease activity is based on the proteolytic cleavage of the peptide linker, which links the orthogonal transcriptional activator Gal4-VP16 to the membrane anchor. The viral presence (specifically the viral protease activity) is sensed by the irreversible proteolytic step, which causes the release of the transcriptional activator Gal4-VP16 from the membrane and activation of the selected transcriptional response. The Gal4-VP16 activator, therefore, exists in two states: an inactive state, where the transcriptional activator is located at the membrane and where it cannot bind to the respective operator site, and an active state, where the Gal4-VP16 is translocated into the nucleus where it can bind to and activate the selected effector gene (e.g., reporter or human IFN-\u03b21).", "We demonstrated the sensing and transcriptional activation of the device using a luciferase reporter assay, with which we measured the expression of the luciferase gene induced by the transcriptional activator, Gal4-VP16. The transcriptional activity of Gal4-VP16 was triggered by the cleavage of the linker to the transmembrane receptor by the HIV-1 protease, which released Gal4-VP16 into the nucleus and activated the transcription of the luciferase under the control of the Gal4responsive operator. The luciferase activity was observed only in cells cotransfected with the HIV-1 genome, and the plasmid for CD4(HA)-hivp-GAL4-VP16 (Supporting Information Figure S2a ) or FAS(HA)-hivp-GAL4-VP16 (Supporting Information Figure S2b ). Synthetic HIV-1 protease inhibitors inhibited the activation of Gal4-VP16, as in the presence of 5 \u03bcM SAQ or 5 \u03bcM ritonavir (RTV), activation of the reporter was reduced by more than 70% for CD4(HA)-hivp-GAL4-VP16 (Supporting Information Figure S2a ) and more than 90% for FAS(HA)-hivp-GAL4-VP16 (Supporting Information Figure S2b) ." ] },{ "paper_id": "4b4a95851bb68a1519d856046d011c084ed8eca6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The Pearson \u03c7 2 and Fisher exact tests, as appropriate, were used to analyze categorical variables. Statistical analyses were performed by using SPSS software package version 17 (SPSS Inc., Chicago, IL, USA). p values \u22640.05 were considered significant.", "Subjective fever was defined as a feverish feeling according to the pilgrims' report. Influenza-like illness (ILI) was defined as the presence of cough, sore throat, and subjective fever (15) . The study protocol was approved by the Aix Marseille Universit\u00e9 institutional review board (July 23, 2013; reference no. 2013-A00961-44) and by the Saudi Ministry of Health Ethical Review Committee. The study was performed in accordance with the good clinical practices recommended by the Declaration of Helsinki and its amendments. All participants gave written informed consent.", "Nasal swab samples were independently tested as described (5) for influenza virus A/H3N2 (16), influenza B virus (16), influenza C virus (17) , and A(H1N1)pdm09 virus (18) ; human adenovirus (19) ; human bocavirus (20) , human cytomegalovirus (21) ; human coronaviruses (HCoVs); human enterovirus (22) ; human metapneumovirus (23); human parainfluenza viruses (HPIVs); human parechovirus (24); human respiratory syncytial virus (25) ; and human rhinovirus (HRV) (26) by using real-time reverse transcription PCRs. HCoVs and human HPIVs were detected by using an HCoV/HPIV R-Gene Kit (Argene/bioM\u00e9rieux, Marcy l'Etoile, France) (27) . HCoV-positive samples were then genotyped by using the FTD Respiratory Pathogens 21 Kit (Fast Track Diagnostics, Luxembourg, Luxembourg).", "Pilgrims who planned to participate in the 2013 Hajj were recruited on September 15, 2013, at a private specialized travel agency in Marseille, France, which organizes travel to Mecca. Potential participants were asked to participate in the study on a voluntary basis if they were \u226518 years of age and were able to provide consent." ] },{ "paper_id": "4b4c47bbc2473d07c8ffd4d940a099e7546b9f25", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The protocol was approved by the ethics (medical research) committee of Beaumont Hospital, Dublin and all patients provided written, informed consent. Colon cancer tissue and matched normal colonic mucosa were obtained from patients at the time of surgery and were immediately placed in RNAlater solution (Qiagen GmbH). Total RNA was extracted from the tissue samples as above.", "Total RNA was isolated from cells and tissue following homogenisation in RNA lysis buffer (Qiagen GmbH, Hilden, Germany) supplemented with 1% b-mercaptoethanol. Extraction was performed using RNeasy Midi kits (Qiagen GmbH). RNA quality was determined by agarose gel analysis and RNA concentration was determined by spectrophotometry (GeneQuant pro; Amersham Biotech, Bucks, UK).", "Analysis of tumour/normal differences were performed using twotailed Student's t-test. Differences in gene expression across time points were analysed by ANOVA with Bonferroni multiple comparisons test. Linear correlation was assessed using Pearson's test. t-Test, ANOVA and correlation statistics were performed using In-Stat, version 3.0 (GraphPad Software, La Jolla, CA, USA)." ] },{ "paper_id": "4b5a80aaf5026238a6c6a440bb5b39ba8497c815", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4b735ca93a77a4443a12ef137288760636db5b41", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "However, thrombocytopenia, elevated transaminases, or raised creatine kinase levels were absent.", "We describe an atypical presentation of severe acute respiratory syndrome (SARS) in a geriatric patient with multiple coexisting conditions. Interpretation of radiographic changes was confounded by cardiac failure, with resolution of fever causing delayed diagnosis and a cluster of cases. SARS should be considered even if a contact history is unavailable, during an ongoing outbreak.", "Our patient had characteristic lymphopenia, which was seen in about 90% of reported cases. In addition, she also had mild hyponatremia and elevated C-reactive protein." ] },{ "paper_id": "4b7bc42834fed4d8fc2ea5446649bec17fddb81a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Photography: All images were taken using an iPhone 8 (Apple) with the default photography application. The background of images was cropped using the masking tool within Adobe Illustrator. ", "PLANT-Dx Reactions: PLANT-Dx consists of two reaction steps. First, Small Transcription Activating RNA (STAR) encoding DNA templates are produced from viral genomic material within an RPA reaction. This reaction product is then added into a cell-free gene expression reaction for signal processing and visual output.", "In vitro transcription was used to produce a representative 4nM stock of CMV's 3 rd RNA. This stock was serially diluted in 1/10 by adding 5\u03bcl to 45\u03bcl of water down to 44fM. One \u03bcl from each dilution was then used in the PLANT-Dx procedure described above, and analyzed on the SynergyH1 microplate reader (Biotek). Significance was determined by computing the Student's t-test between the 4.4pM condition and a (-) template control which did not contain the IVT product." ] },{ "paper_id": "4b7bfd89ad2142ae4d193ed7925dc02889e31c27", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "identification of such strains but still are not so widely available for routinary diagnostic [3, 4].", "Shannon entropy is a measure of the lack of predictability of an element [19] , such as a given base, in a particular position of alignment. Highly variable columns in an alignment will yield maximum values of entropy.", "ISSN 0973-2063 (online) 0973-8894 (print) Bioinformation 9(8): 414-420 (2013) 416" ] },{ "paper_id": "4bb2d045461c493bba023e72c87611ed59cf9f78", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4be1c96386ee9f1750f185e5f790425215cc0075", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "RdRps in the global tree were divided into 5 major branches (supergroups). Up to 15 representatives from each cluster were selected to form supergroup-level alignments. The respective trees were reconstructed from these alignments using the same procedure (PhyML tree with LG evolutionary model with gamma-distributed site rates and empirical amino acid frequencies).", "Branch 4 consists of dsRNA viruses, including cystoviruses, reoviruses, and totiviruses and several additional families.", "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .02329-18. " ] },{ "paper_id": "4c7759f1da349496e9308d9f4f0d4e071a23c19f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4c7f6c52fe043745887db5406196b1d5099c9614", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4c9593ce46963b23b3bdb053ae80a600ed96492a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The NADPH oxidase (Nox) family of enzymes uses NADPH as an electron donor to convert oxygen to superoxide anion (O 2", "Endoplasmic reticulum MHC: Major histocompatibility complex H 2 O 2 : Hydrogen peroxide ERp57: A member of PDI family also know as glucose-regulated protein or 58-kD (GRP58) NF-kB: Factor nuclear kappa B AP-1: Activator protein 1 STAT-3: Signal transducer and activator of transcription 3.", "Some viruses envelop their genetic material within a protein-coated capsid in a further lipid membrane layout, for example, influenza virus, baculovirus, hepatitis-C, HIV, and Herpes virus. These enveloped particles require successive steps to successfully entry and infect host cells. They usually first attach onto host receptors (and attachment factors), and their membranes fuse to interact with endosome vesicles that traffic the virus toward the endoplasmic reticulum, where it is uncoated. The proteins are finally transported to the cytosol and nucleus [64] (Figure 2 ). There is convincing evidence showing that most viral infections are strongly influenced by changes in the redox environment and that host PDI mediates infection of enveloped viruses [65] [66] [67] [68] [69] [70] ." ] },{ "paper_id": "4c9829439f94ee330a01958f332a4d8f6e8b438f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4ca9a831e8193830fab1a4c09a70b2048c174d0c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Background Globally, respiratory infections are the primary cause of illness in developing countries, specifically among children; however, an etiological agent for many of these illnesses is rarely identified.", "Sixty-one percent of the children who tested positive for HBoV were boys, but the gender distribution across sites was not significantly different (P = 0AE110)." ] },{ "paper_id": "4cb9c6ef889605b3149ab8b59c8258074067ba04", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Viral sequences were analyzed and aligned by using ClustalW (http://workbench.sdsc.edu). Phylogenetic trees were constructed by using the neighbor-joining method in the program PAUP* version 4.0 (Sinauer Associates, Inc., Sunderland, MA, USA) rooted with porcine respiratory and reproductive syndrome virus (GenBank accession no. NC_001961). Sequences used for alignment were AF304460 (HCoV-229E), AY567487 (HCoV-NL63), DQ648858 (BtCoV 512), AY594268 (BtCoV HKU2), DQ249224 (BtCoV HKU6), DQ249226 (BtCoV HKU7), and DQ249228 (BtCoV HKU8). The deduced sequences from this study were deposited in GenBank under accession nos. EF544563-EF544568.", "Whenever possible, 3 sample types were taken from each bat (Table) . Sterile calcium alginate swabs were used for oral or anal area samples that were immediately placed into 2 mL of RNAlater (Ambion, Austin, TX, USA). Fecal samples were collected if the bat produced a fresh bolus during handling. Disposable latex gloves were changed between samples, and multiple forceps used to collect fecal boluses were rinsed, wiped in ethanol, and air-dried between samples. Samples were numbered, kept in a cooler in the fi eld, stored at 4\u00b0C, and delivered to the laboratory on August 28.", "E merging diseases are frequently zoonoses caused by RNA viruses (1, 2) . Defense against emerging infectious diseases, identifi cation of reservoirs for such viruses, surveillance for host-jumping events, and elucidation of viral and host factors that may facilitate such events are warranted. The epidemic of severe acute respiratory syndrome (SARS) in 2002-2003 was caused by a newly emerged zoonotic coronavirus (SARS-CoV) (order Nidovirales, family Coronaviridae, genus Coronavirus). Other coronaviruses have also jumped to new host species and caused emerging diseases. For example, porcine epidemic diarrhea virus emerged in European pigs from an unknown host species during the late 1970s and caused severe enteric disease (3) . Human coronavirus OC43 is believed to have been derived from bovine coronavirus (4) . In addition, the genomes of canine and feline coronaviruses can recombine in vivo and have developed into different biotypes that are serially transmissible in their new host species (5) .", "RNA from 140 \u03bcL of each of the 79 samples was extracted by using the QIamp viral RNA mini kit (QIAGEN, Valencia, CA, USA) following the manufacturer's instructions. Extracted RNA was eluted in 50 \u03bcL of RNase-free water and stored at -80\u00b0C. We used Moloney murine leukemia virus reverse transcriptase (Invitrogen, Carlsbad, CA, USA) with random hexamers in a 20-\u03bcL reaction to generate cDNAs by using 10 \u03bcL of RNA as a template according to the manufacturer's instructions. All samples were extracted and analyzed in triplicate. RT products were stored at -20\u00b0C.", "It is possible that another epidemic caused by an emerging coronavirus could occur in the future. As in the SARS epidemic, bats could play a role in future emergence of coronaviruses in humans or other species. Isolation of infectious bat coronaviruses and elucidation of their host ranges, receptor specifi cities, and genetic diversity will greatly aid in our understanding of their potential for emergence." ] },{ "paper_id": "4d073b45fadd07706636593f9c9aee196536eaf3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4d872182302a82a44112df09c3ca01faa11b93d7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "S evere acute respiratory syndrome (SARS) is an emerging infectious disease caused by the SARS-associated coronavirus (SARS-CoV) (1) . Attack rates are >50% in hospitals (2) . A similar trend was seen in Singapore, with SARS spreading to five hospitals and two Specialty Centres within 8 weeks (3) . This rapid rate of transmission caused a national health alert and resulted in large amounts of manpower and resources being deployed.", "Statistical tests (Mann-Whitney, chi-square and Fisher exact test) were used to test for associations when appropriate. The Cox regression model was used to evaluate the influence of demographic and clinical factors on secondary household transmission. All analyses were performed with SPSS version 11.5.", "Factors influencing household transmission were also studied in the Singapore cohort. Univariate analysis (Table 1) showed that household index cases were less likely to transmit SARS to their household contacts if they were younger or were healthcare workers. Contacts were more likely to develop SARS if they were family members or nonhealthcare workers. The Cox regression model (Figure and Table 2 ) verified two of these four factors, index occupation and age." ] },{ "paper_id": "4d96e256e0f1c90ff5456ab1146d85f17bbd3c02", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Co-infections. All samples were screened for detection of influenza A and B and RSV using real-time RT-PCR and hemi nested RT-PCR respec-tively.", "HBoV (later named as HBoV1) was first identified in Sweden from pooled nasopharyngeal aspirate specimens by Allander et al. in 2005 and classified in the genus Bocavirus, Parvovirinae subfamily, Parvoviridae family. Soon after, three other genotypes (HBoV 2-4) were identified in this genus. While HBoV1 was commonly associated with RTIs, HBoV2-4 were isolated from fecal samples (4) (5) (6) (7) .", "Sequencing. PCR products of VP2 genes were cloned by TA-cloning method and sequenced in both directions with the use of Big Dye Terminator v3.1 Cycle Sequencing Kit (Applied Biosystems) according to the manufacturer's instructions. The obtained sequences were assembled by Staden Package-2 and edited using BioEdit Sequence Alignment Editor Version 7.0.5.3.", "During this 6-months study, low positive rate of 4.3% was detected in October 2012 while high positive rate of 15.1% was found in February 2013 in four provinces. The estimated prevalence of each province is given in Table 1 ." ] },{ "paper_id": "4dcc4cda564c914e44c9a3dd9e3d379b1e8cbb91", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4df45b8404d9de0b376a8ae3c282a517df36fe51", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis was expressed as means \u00b1 standard error (SE). A comparison between the individual readings was performed using the student's t-test. p values < 0.05 were regarded as statistically significant.", "The production of a neutralizing antibody is the primary step to combat viral infection. Another important mechanism for virus elimination is the initiation of a cell-mediated immune response involving the induction of effector CD8+ cytotoxic T lymphocytes (CTL). Conserved components within the influenza A viral genome are good targets for inducing CTL responses because they can withstand viral mutations and have the capability to induce cross-reactive immune response among different subtypes and variations [14, 15, 24] .", "The transmission of a pathogenic avian H5N1 virus from poultry to humans in Hong Kong and other Asian countries has caused a number of human deaths [13, 17, 19] . Confirmed cases of H5N1 transmission have also been reported in various African and European countries 1 and all incidences have caused an enormous economic loss in the poultry industries worldwide. The threat of an H5N1 pandemic is becoming a major problem not only in Asian countries but countries worldwide. The urgency of developing a strategy to combat the H5N1 virus is an imperative task for most health authorities, and one possible solution is to develop a human vaccine against the H5N1 virus." ] },{ "paper_id": "4e38e3ba046eee2b6581520ef5e4f33ec8168bb4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4e5eacfc3bdbbfb287913b6ddf6e3ac1ca39c879", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4e97c78baf0d09de4207f0436d01db05826e5b20", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4ea304eab3fcb728a21fb66f902c4c5d2a52ec2e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Serum samples from 317 patients with severe acute respiratory syndrome (SARS) were tested for the nucleocapsid (N) protein of SARS-associated coronavirus, with sensitivities of 94% and 78% for the first 5 days and 6-10 days after onset, respectively. The specificity was 99.9%. N protein can be used as an early diagnostic maker for SARS.", "We thank Rongchang Chen and Yuanda Xu for providing the clinical data for analysis." ] },{ "paper_id": "4f1b29ad62f545bbbce05dcdf1d7a2ce0b72e1d4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Health Protection Agency receives funding for work carried out in M. Z. laboratory from a range of vaccine companies." ] },{ "paper_id": "4f2102dfde801cb0cab691992bbc61cbd98b1ca5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "IRPs would enable characterization of the potency, purity, and identity of complex biological materials, such as antibodies, which would facilitate not only research of immunotherapies but also the standardization of preparations postlicensure.", "Acceptance that human-derived products should not be an object of commercialization or source of profit is enshrined in several key documents (46,47) that would continue to apply to development of IRPs. WHO distributes IRPs either free of charge to National Control Laboratories or with small handling charges and shipping costs to other organizations. Negotiations between relevant parties and preemptive interaction between researchers and donor country authorities could lead to clearly defined, mutually agreed upon processes for acquisition and export of samples. These processes could subsequently be specified in legally binding clinical study agreements, and thus ensure compliance with principles of equitable benefit sharing and provide solutions to complex issues, such as intellectual property, product ownership, and access rights to IRPs.", "*WHO, World Health Organization." ] },{ "paper_id": "4fc3b508543068a9d54f11f0ecf52580df768307", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Conducting AFI surveillance at GDD regional centers is of public health importance because AFI represents a common clinical syndrome for multiple diseases of outbreak potential or emerging zoonotic infections and provides an opportunity to evaluate novel diagnostics. Unlike respiratory illness syndromes such as severe acute respiratory illness and influenza-like illness, no international consensus case definition exists for AFI surveillance, although recommendations for improving methods have been S142", "Research at the GDD regional centers has assisted in the detection and identification of 12 novel strains and pathogens that were new to the world and 62 novel strains or pathogens that were new to the region where they were discovered (9) . GDD laboratorians have helped implement capacity to conduct >380 new diagnostic tests in 59 countries, improving disease detection capability and contributing to faster response times within the region.", "Outbreaks of SARS and avian influenza A(H5N1) highlighted the need to have systems in place for detecting emerging pathogens (3). Thus, establishing populationbased infectious disease surveillance for pneumonia and acute respiratory infections was a primary goal of the GDD Program (3). The resulting surveillance activities also provide a platform for other GDD core activities. Moreover, the GDD respiratory surveillance research projects have helped quantify burden of illness for pneumonia and influenza-associated acute respiratory illness, especially among children, and a high incidence of several respiratory pathogens, including respiratory syncytial virus, parainfluenza, and adenoviruses (6,11,12,17-23)." ] },{ "paper_id": "5010aea39e19c1442f458361abe37771ac76d697", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Na\u00efve CD8 T cell (CD44 low CD62L high ) were purified from TCR-I mice using a negative selection isolation kit (Miltenyi Biotec), and unstained or CFSE-labeled cells were injected i.v. per tail vain in 100 \u03bcl PBS or by i.c. injection in 30 \u03bcl PBS.", "Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:" ] },{ "paper_id": "501a57b3b0e0a5154507b25e23a3f34bf6d2299d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.", "Dichloromethane and methanol, HPLC-grade solvents, were obtained from Merck (Darmstadt, Germany). The phospholipid dimyristoyl phosphatidylcholine (DMPC) was obtained from Avanti Polar Lipids (Birmingham, AL, USA). Spin-labelled phosphatidylcholines (n-PCSL) with the nitroxide group at diVerent positions, n, in the sn-2 acyl chain were synthesized as described by Marsh and Watts (1982; Marsh 1997) . The spin-labels were stored at \u00a120\u00b0C in ethanol solutions at a concentration of 1 mg/ml.", "The Xuorescence intensities of some Wne vibronic structures in the tryptophan Xuorescence spectrum show strong environmental dependence (Konev 1967; Ambrosone et al. 1997) . In particular, the emission maximum shifts from 354 to 329 nm when going from water to an apolar medium. The quantum yield can also undergo large changes, the direction and extent of which depend on the system under consideration (Callis and Liu 2004) . Consequently, Xuorescence experiments allow evaluation of the polarity experienced by the tryptophans of peptide 1 in DMPC liposomes." ] },{ "paper_id": "504684906ab86a5130b59c2557ec73e2226f67e7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "50c1901ebf4db31816c88cc4c2512ca0261730fb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "50dd715b6dfd61f8b87474e37fb0817c14cd465f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5147615c6992d89971127a86047fca6e01a86917", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "516c3a32adbf893d696dec21d087c848b85b3940", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "51792eea98bf36177fc815a79e8bd713c986d393", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The tools for combating malaria (insecticide-impregnated bed nets, indoor residual spraying of insecticide, artemisinin-based combination therapies, and intermittent preventive therapy for pregnant women) need further scaleup, but such tools are susceptible to development of resistance on the part of the vector or parasite, and evidence is accumulating that nets may be less durable than assumed (26, 29) . Despite the challenges, malaria elimination has risen up the global agenda in recent time.", "National public health institutes and strong ministries have the core responsibility for defining policies, goals and targets, and assuring technical guidance, supervision, program implementation, evaluation, and accountability (21) . Although epidemiology remains at the core of such work, the increased complexity of combinations of interventions in public health has highlighted the utility of mathematical modeling for assisting in decision making and policy setting.", "The second decade of this century has been designated as the decade of vaccines (33) . The opportunity exists for a notable effect on the 2.5 million deaths of children annually from vaccine-preventable diseases, including through use of new vaccines for prevention of rotavirus and pneumococcal infection, and by strengthening routine services. Vaccination against type A meningococcal meningitis in the Sahel and against hepatitis B virus and human papillomavirus illustrate the unrivaled possibilities in terms of controlling previously deadly epidemics or virus-induced cancers. A major unfinished priority is polio eradication; this goal is particularly threatened by funding shortfalls and ongoing transmission in Pakistan, Afghanistan, and Nigeria, which have seeded infection in other countries in which polio had been eliminated (34) ." ] },{ "paper_id": "51a2dad6387cc9aa3f9d5d73c83f1df8b4ba021d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "None of these events were detected by the routine surveillance system. However, there was no organised response to any of these outbreaks because the MoH lacked the means to deal with these large events." ] },{ "paper_id": "51ac691426403778f417c61b38f46f85480ca75f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "51fef2a2c2978a6384b1925376b460da142708ad", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5208adba66fd95d02e5358f74ce0c3a45d502c9d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "523a530f03f2cd064a2d2c7cb6b3cb160926a803", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "region, host, isolation source, collection date or country, as well as field-separators such as pipes or slashes. Userselected titles will also be displayed in multi-sequence alignments and trees as described in the following section.", "Finally, there are a variety of enhancements to our tools under development. We are developing improved tree visualizations that support better search and markup functions, similar to those currently used in the influenza virus module. Some limitations of the tree function will be addressed at a later time by giving the user the option of viewing the quick tree which is currently offered, or a more", "Another important aspect of sequence analysis is to place a given sequence within biological, temporal and geospatial contexts. Such associations can provide profound health policy and scientific insights, but unfortunately, descriptors that provide information about the source of nucleotide sequences are notoriously inconsistent. To resolve this issue, the Virus Variation database loading pipeline parses Gen-Bank records, identifies important metadata terms, such as sample isolation host, date, country and source, and maps these to a standardized vocabulary using a hierarchical approach. For example, isolation host terms are first identified in the host field and failing that, then isolate or strain fields, then isolation source, note and finally organism name." ] },{ "paper_id": "529511c62c786dab397b5a3ab3859961a74c8cf8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Huh7.5, U-2 OS, A549, 293T (from C. Rice), 293 (from N. Conrad), and COS-7 (from N. Alto) and all derivatives were maintained in \"complete\" DMEM (Gibco) supplemented with 10% FBS (Gibco) and 1x NEAA (Gibco). Human STAT1 \u2212/\u2212 fibroblasts (from J-L.", "Samples were then dehydrated with increasing concentration of ethanol, infiltrated with Embed-812 resin and polymerized in a 60\u00b0C oven overnight. Blocks were sectioned with a diamond knife (Diatome) on a Leica Ultracut UCT (7) ultramicrotome (Leica Microsystems) and collected onto copper grids. Images were acquired on a Tecnai G 2 spirit transmission electron microscope (FEI) equipped with a LaB 6 source using a voltage of 120 kV.", "Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:", "Viruses in the Flavivirus genus cause significant human disease. Innate immune control of these viruses is mediated by IFNs 3 , which induce transcription of hundreds of ISGs, some of which encode antiviral effector proteins 4 . To identify genes regulating the IFN response to a flavivirus, we used a genome-scale CRISPR approach to screen for single-guide RNAs (sgRNAs) that rendered cells permissive to infection with yellow fever virus expressing Venus (YFV-Venus) despite treatment with a highly suppressive dose of IFN\u03b1 (Fig 1a) ." ] },{ "paper_id": "52ad224b03765bb748a346a5d0586beef490a490", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Environmental Health Perspectives", "The increases in MLN T-cell numbers were abolished by pretreatment with a monoclonal antibody for T-cells (8) .", "Effect of Ozone on Immune Function in the Absence of" ] },{ "paper_id": "52ce19fe79de46d9bb0fa7e75a0631fed2d3efd2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We also used the CLUSTALW program [10] for multialignment as a control process, as well as for phylogenetic investigations." ] },{ "paper_id": "535448073c1721a7928c2814283c5cda6e151902", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "x if pedestrians i and j are touching each other, 0 otherwise.", "For simplicity, the projection of the pedestrian's body on the horizontal plane is represented by a circle of radius r i = m i /320, where m i represents the mass of pedestrian i. The physical interaction with a wall W is represented analogously by another contact force:", "where x i denotes the location of pedestrian i at time t.", "The following paragraphs offer some simple rules that can help one to improve the safety of mass events. These rules should not be considered as replacement of existing regulations, but can nevertheless complement more sophisticated procedures, and are easy to apply for all types of crowding, ranging from large mass events to daily commuting at train stations and airports." ] },{ "paper_id": "539c8819307bd03a90bfd559f47d4c82e7aab58d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Calculation of free energies for forming Stem 1 hairpins and the \"reference\" structures from unfolded RNA, and of free energies for forming pseudoknots from unfolded RNA by models in NUPACK (33) and SPM (42).", "In duplex part, optical melting result (-12.9 kcal/mol) of model duplex (5\u0384GAACAAACGG3\u0384/3\u0384AACUUGUUUGF5\u0384 in Table 1 ) made less favorable by 1.9 kcal/mol for 3\u0384 dangling AA (62) and 2.7 (=0.82+1.9) kcal/mol for 5\u0384FG/3\u0384GGC terminal overhangs, made more favorable by 2.36 kcal/mol for 5\u0384CG/3\u0384GC nearest neighbor parameter (39) and 2.1 (=0.82+1.3+0.0) kcal/mol for 5\u0384FC/3\u0384GGG terminal overhangs. Here 5\u0384FC/3\u0384G is approximated as the 0.82 kcal/mol of 5\u0384FG/3\u0384C (Table 1) Plots of reported vs T m for the BWYV pseudoknot (45) reveal the possibility that the transitions F\u2192PK and PK\u2192HP may have non-zero . Reported errors in values are \u00b115% (45), which does not allow a reliable estimate of . The data, however, indicates the possibility that for transitions F\u2192PK, PK\u2192HP, and HP\u2192U can be on the order of -700, -330, and -20 calK -1 mol -1 , respectively. Points shown as diamonds are excluded from linear fit.", "\u2022 The free energies of Stem 1 hairpins are predicted from INN-HB model (39) combined with hairpin loop (60) and dangling end (61-62) free energy parameters. \u2022 The free energies of \"reference\" structures are from two parts: hairpin and newly formed duplex. The hairpin part is predicted in the same way as Stem 1 hairpin. o In BWYV PSK 1, the duplex part is predicted from INN-HB model (39) with 5\u0384CF/3\u0384GQ free energy increment (Table 1) . o In BWYV PSK 2 and its mutants, the free energies of duplex parts are derived from optical melting result (-12.9 kcal/mol) of model duplex 5\u0384GAACAAACGG3\u0384/3\u0384AACUUGUUUGF5\u0384 (Table 1) , by making it less favorable by 1.9 kcal/mol for 3\u0384 dangling AA (62). Additional assumptions described on the figures are used to estimate stability increments for the fluorescent end of the duplex. The hairpin part and duplex part are coaxially stacked onto each other and stabilize the \"reference\" structure (63)." ] },{ "paper_id": "53abe67758ae950feb6f7ee22501a345f597e98b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Probiotic strains produce various substances that are effective against microbes. Fatty acids, lactic acid, and acetic acid are produced in large quantities. Additional antimicrobial substances that are produced in much smaller amounts by LAB include formic acids, free fatty acids, ammonia, hydrogen peroxide, diacetyl, bacteriolytic enzymes, bacteriocins, antibiotics, and several undefined substances. 59 ", "Overall, few studies are available, and these cannot be compared easily because of differences in study design and formulations used. Consequently, the overall evidence is weak.", "Neonatal foal diarrhea is a common occurrence with >60% of foals developing diarrhea during their first 6 weeks of life. 84 Because etiologies are numerous and prevention measures limited, probiotic administration is an attractive option for the prevention of neonatal foal diarrhea.", "There are 4 main mechanisms of action by which probiotics prevent colonization of the digestive tract by pathogenic strains or prevent disease: (1) modulation of the host innate and acquired immune system, (2) antimicrobial production, (3) competitive exclusion, and (4) inhibition or inactivation of bacterial toxins (Fig 1 A and B) .", "The following sections summarize the various clinical applications for which probiotics have been tested. The exact strains, dosages, and length of treatment used in each of the studies cited in the text are outlined in Table 2 ." ] },{ "paper_id": "53c202275d1fc7697460590ddb247e5675b661fa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "53e010f880f4fc5f6a6832c81cbae2342f98b210", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(1)" ] },{ "paper_id": "5427108068edbf6065fc35c3c96476b41eba56f6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "549932f86b8f9e52e990b8e0b85db63bdd48ac0e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors declare that they have no competing interest." ] },{ "paper_id": "549c70b7e76d19a76e4f6e51aa7fd9755a858a73", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Although there are some reports on other CyP subtypes (Table 1 ), the precise functions and signifi cances of them are largely unknown.", "CyPs are cellular PPIases that catalyze conformational changes in proteins, but the role(s) and substrates for this protein family in cells are not well-characterized. However, discoveries of the signifi cance of CyP in life cycles for several viruses make this protein virologically notable and present novel therapeutic anti-viral targets. Further analyses of the role of CyPs in viral life cycles should reveal novel functions for these proteins as well as provide mechanistic insight into possible therapeutic targets.", "As described above, CyPs play essential roles in diverse cellular processes. Interestingly, several viruses have evolved to use CyPs during their life cycles. In particular, CyPs are demonstrated to be involved in the proliferation of HIV-1 and hepatitis C virus (HCV). Other viruses using CyPs during their life cycle include vaccinia virus (VV), vesicular stomatitis virus (VSV), and SARS-coronavirus." ] },{ "paper_id": "54a31f217ac499b477dd23edb24e41e736d906c0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Illness diaries were started if the subject had either a fever or the acute onset of two or more respiratory symptoms (runny \u2044 stuffy nose, sneezing, sore \u2044 scratchy throat, hoarseness or cough) and were completed daily until illness resolved. Participants were given a thermometer and asked to take their temperature if they felt feverish and were asked to have a nasopharyngeal (NP) swab taken as soon as possible after the onset of respiratory symptoms. Acute respiratory illness was defined as an acute illness lasting >24 hours associated with either fever and one or more respiratory symptoms, or two respiratory symptoms. Oseltamivir adherence was estimated by self-report, by pill counts at each visit and by data from electronic medicine vial caps which recorded the date and time each time the cap was replaced." ] },{ "paper_id": "54c1ec13d3697c96a018ad42935295c9d0aefa55", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Contact network models capture and estimate interpersonal contacts that lead to disease transmission within a community (22). Contacts can take place within households, schools, workplaces, hospitals, and other public venues. Each person in a community is represented as a", "P ublic concern regarding emerging infectious diseases is on the rise. The 21st century began with the emergence or reemergence of zoonotic diseases like severe acute respiratory syndrome (SARS) (1), avian influenza (2) , monkeypox infection (3), West Nile virus disease (4), mad cow disease (5) , anthrax due to bioterrorist attacks (6) , and unusual influenza epidemics (7) . In addition to these new threats, public health officials face a large number of disease outbreaks every year in hospitals, schools, and other small communities. While development of vaccines and diagnostic tools proceeds at an unprecedented pace, development of tools for determining optimal intervention strategies lags behind.", "In response to this problem, we have found that mathematical models of disease transmission can be used to evaluate and optimize control strategies. Such quantitative predictions can be empirically tested through randomized comparative trials, and mathematical models increasingly contribute to public health decisions regarding policy and intervention (8) (9) (10) (11) (12) (13) ." ] },{ "paper_id": "54ce6d742da5a2312aeea36c4d92f5fc0208538c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Emerging ", "We analyzed the dynamics of cumulative severe acute respiratory syndrome (SARS) cases in Singapore, Hong Kong, and Beijing using the Richards model. The predicted total SARS incidence was close to the actual number of cases; the predicted cessation date was close to the lower limit of the 95% confidence interval.", "The transmission mechanism of the coronavirus that causes SARS and the epidemiologic determinants of spread of the virus are poorly understood (2) . Our predictions were based on the trend analysis, assuming effective intervention measures would continue in the three cities. Predicting SARS dynamics on the basis of data from early in the epidemic could have lead to untenable conclusions (11) ; however, we found that the SARS epidemic in Hong Kong and Singapore in May 2003, was not in an early stage. The case data in these two localities clearly indicated S-shaped dynamics. Assuming SARS dynamics in Beijing would follow a similar pattern, we used the Richards model to predict that the SARS epidemic in Beijing would end by late June 2003. This prediction, made on May 21, 2003, was based on the trend analysis and assumed that effective intervention measures would continue." ] },{ "paper_id": "54f05a81f01710c9f2c441e30233bca6163da6a9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5543303ea370910fdff1ef7e9f77ddfe136ff683", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We addressed this conundrum using coxsackievirus B3 (CVB3), an enterovirus belonging to the picornavirus family as a model. Picornaviruses are small icosahedral viruses with a single-stranded 7-8 kb RNA genome of positive (mRNA-like) polarity. This family includes important human and animal pathogens such as poliovirus, hepatitis A virus, foot-and-mouth disease virus and others.", "Although the above hypotheses are speculative, each of them makes specific predictions amenable for experimental testing." ] },{ "paper_id": "5560c5577076d3180d78439586d9ebe75653b20f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A separate study was done to examine the associations between psychosocial factors (stress, social support, fl uctuations in mood) and viral exacerbations of asthma. The study involved naturally occurring illnesses rather than experimentally-induced infections but it maintained several important features of the methodology used by Cohen and colleagues. 21, 24 For example, stress was measured at the start of the study by measuring the immune responses in terms of leukocytes present in peripheral blood in order to determine the extent to which stress could predict subsequent illness. In addition, effects of personality, 25 smoking status, and alcohol consumption 21 were also studied as possible predictors of susceptibility to respiratory viral infections.", "From the preceding discussion it is clear that stress can be defi ned in many different ways depending upon the objectives or perspective of the researcher. All these defi nitions, however, share a common component of adaptive physiological responses following challenges to homeostasis. The adaptive reactions to stressors may involve mobilization of a wide variety of physiological responses including the immune response. Stress responses usually include physical perturbations that can encompass either the entire body or specifi c cellular compartments. Considering the volume of work in various areas of stressors and their effects the main objective of the current review is to focus on one type of stress, which includes psychological stressors.", "While it has been assumed that psychological (psychogenic) and physical (neurogenic) stressors are most closely aligned with depression, the suspicion has arisen that systemic stressors, including immune alterations, may also act in such a provocative capacity. 35 Communication occurs between the immune, endocrine, autonomic and central nervous systems 36 such that psychological events that affect central neurochemical processes may affect immune activity. Conversely, immune activation may affect hormonal processes and the activity of central neurotransmitters. Thus, by virtue of the neurochemical effects imparted, immune activation may affect behavioral outputs and may even be related to behavioral pathology such as depressive illness. 37 The hypothesis that altered immune activation may occur as a result of various stressors emerged over time. The initial theory came from Hans Seyles' GAS, which was derived from observation and experimentation on laboratory animals. Using a variety of stressors (ie, pain, thermal extremes and starvation), Seyle described a common nonspecifi c stress response pathway. 38 After initial perception of a stressor, the animal mounts an emergency alarm or fi ght-or-fl ight response. This catecholamine-driven reaction results in increased cardiovascular function and an overall increase in metabolism. If the stressor persists, the resistance phase or 'conservation withdrawal reaction' is initiated, which is a physiological coping reaction to the increased demands of maintaining homeostasis. Chronic stress leads to the exhaustion phase and may lead to pathology. Seyle's theory unifi ed the stress phenomena because it provided a common response pathway to all the varied stressors encountered.", "Functional genomic techniques of transcriptomics and proteomics and available bioinformatic and statistical analyses promise unparalleled global information during the analyses of complex biological responses. However, if these technologies are used in isolation, the large multivariate data sets produced are often diffi cult to interpret and have the potential to ignore key metabolic events to understand the true biology. High resolution 1 H NMR spectroscopy used in conjunction with pattern recognition provides one such tool for defi ning the dynamic phenotype of a cell, organ, or organism in terms of a metabolic phenotype. In a recent review the benefi ts of this metabonomics/metabolomics approach to problems in toxicology have been discussed. 69 One of the major benefi ts of this approach is its high-throughput nature and cost-effectiveness on a per sample basis. Using such a method, the consortium for metabonomic toxicology (COMET) is currently investigating approximately 150 model liver and kidney toxins. This investigation will allow the generation of expert systems where liver and kidney toxicity can be predicted for model drug compounds, providing a new research tool in the fi eld of drug metabolism. The review also included how metabonomics may be used to investigate co-responses with transcripts and proteins involved in metabolism and stress responses such as during drug-induced fatty liver disease. By using data integration to combine metabolite analysis and gene expression profi ling, key perturbed metabolic pathways can be identifi ed." ] },{ "paper_id": "557c406ad2a9c8dec744c69b3e7ac9621e3d6f66", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "55ddef381063d2056a4f4b1051a0ed3c476bc010", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "55e21f37b34b47c33bdbec518825f78587906ddd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Three multiplex conventional RT-PCR assays were used as described by Bellau-Pujol S et al. All amplified products were visualized after electrophoresis on an ethidium bromide -stained 2% agarose gel (Agarose, Electrophoresis Grade, Ultra pure, Invitrogen). ", "RNA was extracted from 200 \u00b5l of the collected nasopharyngeal secretions and put in VTM. Extraction was performed using the QIAamp Viral RNA Mini kit (QIAGEN \u00ae , Hilden, Germany) with RNA elution into a final volume of 80 \u00b5l., Nuclease free water were included for each extraction run as a negative control. Two aliquots of each extracted RNA were made; one the aliquot is used for PCR and the second stored at -20\u00b0C for future analyses.", "Patients with samples that tested positive were significantly younger than those that tested negative (15.8 months vs. 18.5 months) with p-value p = 0.009. The probability of a child 0-12 months of developing a respiratory infection other than influenza is 1.77 times higher than in a 37-60-month-old child (p <0.05) (Table2). " ] },{ "paper_id": "55ffdd0f4c113e59ddf3ae633d00fb676abff48d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "566b5c62fc77292ebe09295d59e7fbf6fc914260", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "where w i is the weight of observation i,", "The log-likelihood function ll for the censored negative binomial was", "Additional Information. Please access these Web sites via the online version of this summary at doi:10.1371/journal.pmed.0050074.", "Information on social contacts was obtained using crosssectional surveys conducted by different commercial companies or public health institutes in Belgium (BE), Germany (DE), Finland (FI), Great Britain (GB), Italy (IT), Luxembourg (LU), The Netherlands (NL), and Poland (PL). The recruitment and data collection were organised at the country level according to a common agreed quota sampling methodology and diary design. The surveys were conducted between May 2005 and September 2006 with the oral informed consent of participants and approval of national institutional review boards following a small pilot study to test feasibility of the diary design and recruitment [26] .", "The third feature is more apparent in the data for all reported contacts ( Figure 3A ) than for physical contacts only: a wider contact ''plateau'' of adults with other adults primarily due to low-intensity contacts, with many of these contacts occurring at work (see also Figure S4 )." ] },{ "paper_id": "568fec0df53acc098777e861ab6b824bf22ca3e4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Page 5", "We performed genotyping of the HLA locus following the PCR-SSOP (sequence-specific oligonucleotide probing) typing protocol recommended by the 13 th International Histocompatibility Workshop (http://www.ihwg.org/components/ssopr.htm). For KIR3DL1/S1 subtyping, polymorphic exons 3, 4, 5, 7, 8 and 9 were selectively amplified in four PCR reactions using locus-specific primers (a separate PCR for each of exons 3, 4 and 5, and a fourth PCR for exons 7, 8 and 9 combined). The PCR products were blotted on nylon membranes and hybridized with a panel of 56 sequence-specific oligonucleotide (SSO) probes designed to detect unique sequence motifs of known KIR3DL1 alleles. KIR3DL1 alleles were assigned by the reaction patterns of the SSO probes based on the known KIR3DL1 sequences, as previously described 39 . Ambiguous SSO typing results were resolved by sequencing analysis.", "Mucosal Immunol. Author manuscript; available in PMC 2013 August 12.", "Sips et al." ] },{ "paper_id": "56e84cb19a30592280b4f0460ee74f8175eb98b3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "570862c4784b6f780726ec0548fc402a413146b4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "General cell culture supplies were purchased from BD Biosciences (Spain); calf serum was from BioWhittaker (Verviers, Belgium). Cell culture-grade gelatin, trypsin, antibiotics, hematoxylin-eosin, Trichrome Masson staining reagents, Evans blue, and TTC dyes were from Sigma (Spain). HRP-conjugated anti-mouse secondary antibody and liquid DAB substrate were from Dako (Carpinteria, CA). Anti-MMP-2, MMP-9, CD68, and FITC-conjugated secondary antibodies were from Santa Cruz Biotechnology (Santa Cruz, CA). Anti-heavy chain cardiac myosin antibody was from Abcam (Abcam, UK). HRP-conjugated anti-rabbit secondary antibody was from Sigma-Aldrich. Amersham ECL detection kit was from GE (GE Healthcare Life Sciences, Spain). Centrifugation concentrators were from Sartorius (Fischer Scientific, Spain).", "The HL1 cardiomyocyte cell line was kindly donated by Dr. Antonio Bernad.", "Image analysis: For in vivo MR images, the signal-to-noise ratio (SNR) of the region of interest (ROI) is defined by SNR ROI = I ROI /I noise where I ROI is the intensity of either left ventricle of interest (for SNR lv ) or surrounding muscle (for SNR m ); I noise is the standard deviation (S.D.) outside the animal. The normalized enhancement ratio of left ventricle (NER lv ) to muscle is defined as:", "SNR=Signal to noise ratio= Mean signal intensity/SD." ] },{ "paper_id": "57145f9607b426eace5798c4045716ab6e3af5ff", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5722e1b167fe879fc2901ba8ea2fa69fec89a6f7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "infected animals corroborated the observed pattern of antigen staining within the tissues ( Figure 3E ).", "PMOs. PMOs were designed with sequence homology near or overlapping the AUG translational start site of EBOV VP35 (59- were used as controls in these experiments. The PMOs were synthesized by AVI BioPharma, (Corvallis, Oregon, United States), as previously described [35] .", "We have initiated a drug-discovery strategy to identify ''druggable,'' efficacious anti-filovirus PMOs. This proof-ofprinciple study using PMOs demonstrates favorable anti-EBOV activity both in vitro and in vivo; thus, these molecules represent a pool of potential lead compounds for further evaluation and optimization. Future studies will focus on determining the most favorable PMO dose and regimen and also the therapeutic potential of these molecules. Additionally, antisense PMO designed to target other regions within the EBOV genome will be pursued. Genetically designed microbial therapeutics, such as antisense PMOs or other sequence-based approaches, allow quick hit-to-lead optimization and may accelerate time-to-drug development. Together, these strategies could result in a highly efficacious therapeutic treatment regimen for lethal viral infections. Nucleotide-based antivirals, such as PMOs, can be easily produced in large quantities, have already been tested in human clinical trials, and have appropriate safety profiles for use with humans [34] . The results presented here have farreaching implications for the treatment of highly lethal hemorrhagic fever viruses, and for diseases caused by many other acute viral diseases including SARS, influenza, and dengue, or other emerging pathogens.", "Statistical analysis. To compare the survival rates in the rodent experiments, we used a Fisher exact test with stepdown bootstrap adjustment. In the guinea pig experiments, the viral titers were analyzed by ANOVA with post hoc Dunnett's test, and the effect of viral titers on survival were analyzed by logistic regression. A p value of 0.05 was considered significant." ] },{ "paper_id": "573493d746ec76df2e1be09d7a51c100de5267b0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "considering different types of countermeasures or their suitability for use in different resource settings.", "All three components of the prioritization process make use of a common set of criteria and sub-criteria. The criteria represent top level factors which might impact the relevance of a disease to the R&D Blueprint, such as the human transmissibility of the disease, or the societal impact. The sub-criteria then explore different facets of each of these areas, for example", "In advance of the 2015 consultation, WHO reviewed criteria and sub-criteria used in earlier disease prioritization exercises. The results were included in background materials for the consultation (1) . Nine prioritization criteria and numerous sub-criteria were identified through moderated discussions. Following feedback from the R&D Blueprint's Scientific Advisory Group in May 2016, and the subsequent work of the methodology review meeting in November 2016, the original nine criteria were compressed into the current eight criteria below to insure completeness, non-redundancy, nonoverlapping and preference independence (2)." ] },{ "paper_id": "5738aa0be9b2dd358a1a968f90fad4b0723328f0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "It has different minerals such as Ca, Fe, K, Cu and Mg and also contains variety of vitamins (This plant is full of watersoluble organosulfur compounds like Sallyl cysteine (SAC), S-ethyl cysteine (SEC), and S-propyl cysteine (SPC) (Suleria et al., 2015) .", "No embryo in none of dilution showed the death evidence and the growth rate was the same as control group during this study." ] },{ "paper_id": "578def3a338542ea59f0251c8f5fa32acc37a83c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The dataset is available by emailing Kathleen Weldon at kweldon@hsph.harvard.edu.", "The following quotation explains the basic concept of weighting data from a survey.", "Insufficient data for analysis.", "More details about weighting are in the methods section of the article itself." ] },{ "paper_id": "57a67fd5273fb4aac8505d1ae7b32c2582d12df3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "57c6bdd6d7150e2291c899c59152ba816372f265", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Knowledge of MERS-CoV", "Differences in knowledge, impact of monitoring measures, quality of information, and perception between unprotected and protected contacts were compared in contingency tables by using the \uf063 2 test. For assessing knowledge, a summary score was created on the basis of the number of correct answers (range 0-7). Significance was determined at the 5% level (p-\u22640.05). Data analysis was performed with SAS 9.3(SAS Institute, Cary, NC, USA).", "Results" ] },{ "paper_id": "57e6620ed5a7142981da23d408a094c2e01bed35", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "58379e16100bc077171b5ec4af4052a4559c04a3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Step 2: Immune Response", "DNA synthesis. DNA sequences were synthesized on an ABI 3400 DNA synthesizer.", "References (1-5)" ] },{ "paper_id": "584aa286fb6e7f2404ff67c5cfa025b33e110214", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Local CDC staff ascertained a potential imported case according to the field investigation results after diagnosis. A case in a patient who had visited or lived in an endemic or epidemic area outside China within the longest incubation period before the date of onset was classified as an imported case. Conversely, a case would be classified as a domestic case if there was no evidence of an infection acquired abroad.", "Fifth, it is necessary to improve the early warning and response capacity for emerging infectious diseases. We recommend establishing a special system of surveillance, risk assessment, and early warning. Spatiotemporal models linking disease data and different environmental factors are also urgently needed (36) .", "We entered and managed the data using Microsoft Excel 2010 (https://office.microsoft.com/excel). We used SPSS 18.0 (https://www.ibm.com/analytics/spss-statistics-software) to describe characteristics of imported infectious diseases regarding geographic and temporal distribution, gender, age, region, or country of origin. We created distribution maps of imported cases using ArcGIS 10.3 (http:// www.arcgis.com).", "Fourth, multisectoral and regional cooperation mechanisms, especially international cooperation mechanisms in the border areas, should be further enhanced (35) . We suggest that the relevant departments should intensify cooperation by using well-defined responsibilities and should improve communication regarding all aspects of public information sharing, training, monitoring, and control. It is critical that, in the border areas, neighboring countries develop the management of persons entering and leaving, improve the control of mosquitoes, and jointly respond to infectious diseases." ] },{ "paper_id": "5893fce58f11ff4e5510d0c4de7f9097c7a1869a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For euthanized and recently deceased cats, gross necropsy examination and sample collection were performed within 2 hours of death. Samples from liver, spleen, mesenteric lymph node, kidney, jejunum, and colon were taken, fixed in 10% buffered formalin, and routinely embedded in paraffin. Sections (5 \u03bcm) were stained with hematoxylin and eosin (HE). Tissues were also flash frozen in liquid nitrogen (-220\u00b0C) for RNA extraction and stored at either -220\u00b0C or -70C\u00b0.", "FIP pathology is characterized typically by severe systemic inflammatory damage of serosal membranes and widespread pyogranulomatous lesions, which occurs in the lungs, liver, lymph tissue, and brain (8) . Evidence suggests that the host immune system is crucial in this pathogenesis; profound T-cell depletion from the periphery and lymphatic tissues and changes in cytokine expression are observed in end-stage FIP (9, 10) . The clinical finding of hypergammaglobulinemia-associated FIP is indicative of virus-induced immune dysregulation (11) .", "HE-stained slides of spleen, liver, lymph node, intestine, and kidney sections were evaluated for evidence of granulomatous and pyogranulomatous lesions (National Cancer Institute Laboratory Animal Sciences Program, Frederick, MD, USA). Formalin-fixed sections (3 \u03bcm thick) were cut from paraffin blocks and placed on glass slides for immunohistochemical (IHC) testing, as previously described, with CoV p56, a cross-reacting antibody for the demonstration of feline coronavirus (FECV and FIPV biotypes) (9,10) (Washington Animal Disease Diagnostic Laboratory, Pullman, WA, USA) ( Figure 2 )." ] },{ "paper_id": "58a0dfba31e0a2965443ca1edd463fc3daed5138", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "58bb4af3c8facbfe1aa740dc5893a5b4518807f7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "On the basis of newly acquired sequence information, we designed a specifi c real-time TaqMan PCR to detect bat AdV-2 (ABS forward 5\u2032-CACAAgTgg TgTCTTTgAgAgCA-3\u2032, ABS reverse 5\u2032-AgAgggATAC AAACTgATggAAACA-3\u2032, ABS TM 6FAM-CTAACTT-ggCTggTggAgTgCgAAAC-q). Cycler conditions were as follows: predenaturation (95\u00b0C for 10 min), 45 amplifi cation cycles (95\u00b0C for 30 s, 61\u00b0C for 30 s, 72\u00b0C for 30 s), and fi nal extension (72\u00b0C for 10 min).", "For virologic examination, homogenized organ tissue was inoculated onto VeroE6/7 cells and monitored daily for cytopathic effects. Remaining tissue material was used for RNA/DNA extraction and further molecular analysis by generic PCR assays to detect members of several virus families including fl aviviruses, hantaviruses, coronaviruses, orthomyxoviruses, and paramyxoviruses. The species of bat involved was determined by amplifi cation and sequencing of the cytochrome B (cytB) gene, a standard technique for species identifi cation (9) .", "We performed an extensive search for unknown viruses in 55 German vespertilionid bats based on both generic PCR assays and virus isolation techniques, as part of a broader study investigating histopathologic changes in German bats in association with infectious pathogens. Dead or moribund bats of 12 species (Barbastella barbastellus, Eptesicus nilssoni, E. serotinus, Myotis daubentonii, M. mystacinus, Nyctalus leisleri, N. noctula, Pipistrellus kuhli, P. nathusii, P. pipistrellus, Plecotus auritus, and Vespertilio murinus) were collected at certifi ed bat rehabilitation centers in southern Germany and were investigated macroscopically, bacteriologically, and histologically." ] },{ "paper_id": "58c0cc8bc91f5e92814df48b22321af4c7f75d53", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "NoVs (22) . Thus, a cow co-infected with both bovine and human strains of NoV could conceivably produce a recombinant virus with altered virulence properties.", "Fecal samples were suspended in 0.9% NaCl (5% wt/ vol), vortexed briefl y, and clarifi ed through a combination glass fi ber/PVDF 0.22-\u03bcm fi lter (Millipore, Mississauga, Ontario, Canada). RNA was extracted from a 140-\u03bcL sample of the resulting fi ltrate by using the QIAamp viral RNA extraction kit according to the manufacturer's recommendations (QIAGEN, Mississauga, Ontario, Canada). Total RNA was extracted from 25-g meat samples by using Tri reagent (Sigma, Oakville, Ontario, Canada) and Dynabeads coated with oligo-dT (Invitrogen, Burlington, Ontario, Canada) as described (23) .", "Human NoVs have not been shown experimentally to infect cattle; however, the human and bovine NoVs share a cross-reactive epitope in their capsid proteins (35) . The risk for bovine NoV infection in humans is thought to be low (21) . Co-infection of an animal with both human and bovine NoV may result in a recombinant agent with altered virulence, as the bovine NoVs have been shown to undergo " ] },{ "paper_id": "590e55ca7451d6a3aad7b2d84a04b39bc864dbe7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analyses were conducted using the IBM Statistical Package for the Social Sciences for Windows, version 22.0 (SPSS w Inc., Chicago, IL, USA). Sample characteristics of the healthcare professionals are presented with descriptive statistics, n (%) and mean^standard deviation where appropriate (Table 1) . Counts and percentages were used to describe attitude, perception, awareness, and satisfaction of the primary healthcare professionals towards health promotion practices in the MNG-HA (Table 2 ). Counts and percentages were used to summarize the most common/preferred healthcare promotion methods of the primary healthcare professionals (Figure 1 ).", "A descriptive cross-sectional study was conducted between 22 June and 8 July 2014 across five polyclinics in the MNG-HA, which belong to the governmental sector in the Riyadh Province. The selected clinics included Health Care Specialty Center \"Khashm Al Aan\" (n \u00bc 64, 31.1%), Iskan AlYarmouk Clinic (n \u00bc 44, 21.4%), National Guard Comprehensive Specialized Clinic (n \u00bc 46, 22.3%), King Saud Housing Clinic (n \u00bc 40, 19.4%), and King Khalid Military Academic Housing Clinic (n \u00bc 12, 5.8%). The study was approved by King Abdullah International Medical Research Center (KAIMRC). The consent form was attached to the questionnaire, and it contained information related to the study including the purpose of the study and confidentiality of the data. The targeted participants represented a convenience sample of primary healthcare professionals working at MNG-HA hospitals, including general practitioners, family physicians, pediatricians, obstetricians, gynecologists, and nurses working with them in the primary healthcare setting. The minimal required sample size was 196 with^5% margin of error at 95% confidence intervals. Of the 240 questionnaires that were distributed to primary healthcare professionals who agreed to participate in the study, 206 were completed and returned, giving a response rate of 85.8%. We collected the following sociodemographic data of the primary healthcare professionals: age, sex, occupation, nationality (Saudi/non-Saudi), and Arabic native language speaker (yes/no).", "The attitudes and perceptions of primary healthcare professionals towards health promotion and its practice in the MNG-HA hospitals were generally positive, but not to the level of influencing behavioral change. The awareness level of health promotion policies, strategies, and programs conducted in the hospitals was not satisfactory. Therefore, widespread training programs are recommended to improve the health promotion system in the hospitals. These programs include facilitating behavioral change, introducing health promotion policies and strategies in hospitals, mandatory workshops, and systematic reminders." ] },{ "paper_id": "596e1ce4967dd7cbb1fbe4c6b52c3910fee48987", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Understanding the enduring occupational and psychological effects of working during this SARS outbreak is important because it involves the well-being of large numbers of HCWs. Additionally, this information has wider relevance to health systems in planning for emerging infections, including pandemic influenza (http://www. who.int/csr/disease/influenza/inforesources/en) and the potential for bioterrorism (19) . Although healthcare work", "A stepwise regression analysis was performed for each adverse outcome. All potential mediating factors (those identified in the preceding univariate analyses with a significance of p<0.05) were entered. This analysis was performed for survey A and B participants.", "S evere acute respiratory syndrome (SARS) emerged from Guangdong Province, People's Republic of China, in November 2002 and spread rapidly; transmission occurred primarily in hospitals, often to healthcare workers (HCWs). Although initially virtually no literature was available to guide expectations of how an emerging infection would affect the psychological well-being of hospital staff (1) , by the summer of 2003 the acute psychological impact of SARS had been widely studied. Significant emotional distress was present in 18%-57% of HCWs (2) (3) (4) (5) (6) and was associated with quarantine (7), fear of contagion (6, 8, 9) , concern for family (5, 9, 10) , job stress (6, 9) , interpersonal isolation (6, 9) , perceived stigma (6, 7, 11) , conscription of nonspecialists into infectious disease work (12) , and attachment insecurity (10) ." ] },{ "paper_id": "59ffca26c9d1f881e4e37e7c5af626d72d858dc4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "are the mean of V 1 , V 2 .", "XWZ participated in the design of the study.", "All authors read and approved the final manuscript. " ] },{ "paper_id": "5a7af4bc5cc14fbcd0bcc8d26515478c65a24406", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5ad3a3198af0dc26625b9ad9196cb2f1a65aa248", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "be determined; nonetheless, our findings indicate that long-term monitoring may be required to control dissemination of disease.", "S evere acute respiratory syndrome (SARS) is a new infectious disease of humans, first recognized in late February 2003 in Hanoi, Vietnam. The disease spread rapidly, with cases reported from 29 countries on five continents over 4 months (1-7). By July 3, 2003 , this epidemic resulted in 8,439 reported cases globally, of which 812 were fatal (8) . Rapid identification of the causal agent as a novel coronavirus (SARS-CoV) represents an extraordinary achievement in the history of global health and helped to contain the epidemic (7) . Nonetheless, the epidemiology and pathogenesis of SARS remain poorly understood, and definitive diagnostic tests or specific treatments are not established. Since the origin of the virus and its animal reservoirs remain to be defined, the potential for recurrence is unknown. This fact underscores the importance of establishing sensitive and efficient methods for diagnosis and surveillance.", "Primers and probe were selected in the N (nucleocapsid protein) gene region at the 3\u2032 end of the SARS-CoV genome by using Primer Express Software (PE Applied Biosystems, Foster City, CA). The primer set used was: Taq-772F 5\u2032-AAGCCTCGCCAAAAACGTAC (forward) and Taq-1000R 5\u2032-AAGTCAGCCATGTTCCCGAA (reverse), Taq-955T 5\u2032-FAM-TCACGCATTGGCATG-GAAGTCACAC-T-TAMRA (probe), labeled with the reporter FAM (6-carboxyfluorescein) and the quencher TAMRA (6-carboxytetramethylrhodamine) (TIB Molbiol, Berlin, Germany)." ] },{ "paper_id": "5adf6613fe8688c9c324efb8cc68844c3535c81f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Samples were analyzed by conventional reverse transcription PCR assays using panCoV primers targeting a 215-bp replicase fragment as previously described (7) with slight modifications to include more cycles and less extension time in order to obtain more PCR products. Sequencing reactions on a Pancoronavirus-positive anal swab sample (7) were performed at Central Laboratory of High Performance Technologies in Life Sciences (LaCTAD) at UNICAMP (http://www.lactad.unicamp.br) using an automated sequencer (3730xl DNA Analyzer; Applied Biosystems).", "In this study, a total of 20 anal and tracheal swab samples from 10 bats (T. brasiliensis) were collected at the Jequitib\u00e1s Wood, in Campinas, S\u00e3o Paulo State, Brazil (22\u00b054\u203231.34\u2032\u2032S 47\u00b002\u203258.01\u2032\u2032W). We extracted viral genetic material using the RNA Extraction Mini Kit (QIAGEN, Hilden, Germany) and synthesized cDNA using random primers from the High Capacity cDNA Reverse Transcription Kit (Applied Biosystems, Foster City, CA, USA), following the manufacturer's protocol.", "2. Nix WA, Oberste MS, Pallansch MA. Sensitive, seminested PCR amplification of VP1 sequences for direct identification of all enterovirus serotypes from original clinical specimens." ] },{ "paper_id": "5ae641a5bf24b53a895f5f2f04254cc00e909c08", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For the synthesis of a model RNA, the entire molecule of pCIneo plasmid was transcribed in vitro from a T7 promoter.", "MDBK cells were maintained in Eagle's minimum essential medium (Sigma-Aldrich) supplemented with 5% FBS in a humidified atmosphere of 5% CO 2 at 37 C. The cells were infected with BPI3 at an m.o.i of 0.1. The work on infection of BPI3 was performed in accordance with the rules for pathogens that have been notified by Rakuno Gakuen University.", "The synthesized 5.4 kb RNA was treated with RNasefree DNase I (Promega), extracted with phenol/chloroform, precipitated with ethanol and subsequently used as a test RNA. After quantitation, the test and control RNAs were mixed to estimate the sensitivity of cDNA RDA in various conditions." ] },{ "paper_id": "5aea42c8922c84b19c8ae83793d535d53667a772", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The occurrence rate of PTSD features for SARS survivors is in the middle of the range reported in previous samples of other medical diseases (2) . For most SARS survivors, a significant decrease in symptom severity from l month to 3 months after discharge was identified.", "Repeated measures analysis of variance (ANOVA), with time (1 month vs. 3 months after discharge) as the within-subject factor, was used to examine the change of symptom severity. The 1-month scores for IES-R intrusion (mean 1.12, SD 0.73), hyperarousal (mean 1.05, SD 0.79), and HADS anxiety (mean 5.87, SD 3.89) were significantly higher than the 3-month scores for IES-R intrusion (mean 0.91, SD 0.73), F 1, 130 = 18.52, p<0.001), hyperarousal (mean = 0.85, SD = .74), F 1, 130 = 13.96, p<0.001, and HADS anxiety (mean 5.19, SD 4.48), F 1, 130 = 5.23, p<0.05).", "The Chinese HADS (8-10) is a self-report instrument designed to detect symptoms related to anxiety and depression. As in previous studies, the marker for a moderate level of distress (i.e., the subscale score of 11) was used as the cutoff point for HADS subscale scores (8) (9) (10) ." ] },{ "paper_id": "5aefd421655e2155dfc6a2fcb3c12dc14f35e9dc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5b009eb5287c8b9045f32c4e180f1cce5105f52d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5b4118a71d2dc9dae927ebd17ba9dcaa22f57ce2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study received Ethics Committee approval from Beijing Friendship Hospital affiliated to Capital Medical University (Approval ID: 2015-P2-076-01). The committees waived the need for individual consent because of the retrospective nature of the study.", "Descriptive statistics are presented. Continuous data are presented as means \u00b1 standard deviation (SD). Categorical data are presented as frequencies. SPSS 16.0 (IBM, Armonk, NY, USA) was used for statistical analysis. " ] },{ "paper_id": "5b418c0fc9be9eb87329aae74de81b3270e3603d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Serum neutralization tests were conducted as described (10) with camel serum diluted in 25 mL serum-free Dulbecco minimum essential medium. The starting dilution was 1:40. After incubation for 1 h at 37\u00b0C, each well was infected for 1 h at 37\u00b0C with a 50 mL virus-serum mixture. Supernatants were removed and fresh complete Dulbecco minimum essential medium was added. Assays were terminated by fixation with 8% paraformaldehyde for 30 min and stained with crystal violet after 3 days. Neutralization titers were defined as serum dilutions reducing cytopathic effects in 2 parallel wells.", "Viral RNA was extracted from serum and fecal samples by using the MagNA Pure System (Roche, Basel, Switzerland) and an input volume of 100 \u03bcL of serum or fecal material suspended 1:10 in phosphate-buffered saline buffer. The elution volume was 100 \u03bcL for serum and fecal suspensions. To identify CoV-specific nucleic acids, 2 generic CoV PCRs were performed as described (25) (26) (27) , followed by subsequent Sanger sequencing of the amplified DNA.", "Coronaviruses (CoV) are positive-sense RNA viruses. Viruses in the genera Alphacoronavirus and Betacoronavirus are associated with mammals and show a particularly high level of diversification in bats. Viruses in the genera Gammacoronavirus and Deltacoronavirus are mostly avian-associated viruses (6, 7) . MERS-CoV belongs to Betacoronavirus phylogenetic lineage C that, in addition to MERS-CoV, contains 2 distinct bat-associated CoV species (HKU4 and HKU5) (1, 8) .", "Transmission patterns, including the putative zoonotic source of the virus, remain unclear. Hypotheses include frequent zoonotic infections with limited subsequent human-to-human transmission chains and existence of a self-sustained epidemic in humans (4) . A recent study found evidence to support the existence of epidemiologically unlinked cases in a large outbreak in the al-Hasa region, Saudi Arabia (5) . It was speculated that zoonotic introductions of MERS-CoV from an unknown reservoir might occur at high rates, in addition to obvious human-tohuman transmission." ] },{ "paper_id": "5b68a553a7cbbea13472721cd1ad617d42b40c26", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "-S decreases monotonically from its initial value to its final value, while R increases monotonically until it reaches the limiting value R \u221e . Both curves have two distinct periods where the decrease (or increase) is exponentially slow or exponentially fast." ] },{ "paper_id": "5baa1d21e6334a0af38c31d852992e7e6ad2402c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Refolding, protein crystallography, and structure determination", "Detection of HBsAg and HBeAg by ELISA, and HBV DNA by realtime PCR", "Differences between groups were determined using Student's t-test." ] },{ "paper_id": "5bb307428f45e725c931894d2ed7d06d7f8d0991", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5bc64dd87cf5c7502eb06d534d15d718c6c02214", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Funding for this study was provided by the Kansas State Veterinary Diagnostic Laboratory and the Swine Health Information Center.", "Although influenza viruses of other genera can infect cattle, the potential for ICV infection in cattle has not been previously investigated. The objective of this study was to determine if ICV can be found in specimens from cattle with bovine respiratory disease and, if so, determine the prevalence.", "Co-infections with >1 pathogen are common in BRDC cases. ICV-positive samples were also found to be positive for >1 bovine respiratory disease pathogen (n = 12, Table 1 ), the most common being M. bovis (9/12), followed by H. somni (7/12) , and M. haemolytica (6/12). Among the ICVpositive samples, ICV12 was strongly positive (C t 15.81); this sample was also positive for M. haemolytica and P. multocida, both bacterial pathogens commonly associated with secondary infections. Other BRDC pathogens associated", "I nfluenza viruses are contagious zoonotic pathogens that belong to the Orthomyxoviridae family, which consists of 4 genera: Alphainfluenzavirus (influenza A virus), Betainfluenzavirus (influenza B virus), Gammainfluenzavirus (influenza C virus [ICV]), and Deltainfluenzavirus (influenza D virus) (1) (2) (3) (4) . Classification of influenza viruses is based on the antigenic differences in the nucleoprotein and matrix protein and supported by intergenic homologies of 20%-30% and intragenic homologies >85% (3) ." ] },{ "paper_id": "5bfde8cd6b202751b2fd6915fc3ffb256b846ec5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5c59d9e3c66ccee9b1e671f475954e581af7a320", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Journal of Biomedicine and Biotechnology 3 2.6. Statistical Analyses. The Student's t-test was used to evaluate the statistical significance of Nab titers among various groups of animals. The Origin 8 computer software was used for this analysis.", "One limitation of our study is the lack of measurements of T-cell-mediated immunity. Besides Nabs, it is possible that the observed VTT-induced protection was partially contributed by cell-mediated immunity. To this end, the mucosal route of vaccination may also be crucial for the generation of highly protective T-cell-mediated immunity. A recent study demonstrated that protection against lethal respiratory vaccinia challenge requires both respiratory mucosal T EM cells and central memory T cells [42] . A future study is, therefore, necessary to address the protective effects of specific cell-mediated immunity under the similar experimental conditions.", "Line. The background and biological properties of the smallpox vaccine vaccinia Tiantan (VTT) have been described previously [16] . VTT stocks were propagated in Vero cells and then purified by repeated freezing and thawing and centrifugation through a 36% sucrose cushion. The viral pellet was subjected to a sucrose gradient centrifugation. Purified viruses were collected and studied [21] . The plaque forming unit (PFU) of viral stocks was titrated on Vero cells by a plaque-forming assay using crystal violet staining. The construction and characterization of the challenge virus MVTT-S have been described previously [17] ." ] },{ "paper_id": "5c5a6ea2bb2e3865e47d4495eb6ee3e4cddb1134", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Acknowledgments: We are very grateful to the doctors, medics, and clinic staff at the SMRU clinics at Maela, Wang Pha, and Mawker Thai villages for patient enrollment and specimen collection. We thank the laboratory staff in Mae Sot for assistance with specimen processing and Suthatip Jintawon at MORU for technical assistance in performing IFAs.", "All statistical data analyses were perform using STATA/SE 10.1 (StataCorp, College Station, TX). Diagnostic accuracy of the PCRs was calculated by comparing PCR results to the paired sera IFA results in 2 + 2 cross tabulation using the \"diagt\" routine. 10 The McNemar test was used to compare test sensitivities. Binomial exact confidence intervals were calculated throughout." ] },{ "paper_id": "5c8b5beacab1ef316ed826f261d23c87e033a928", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5ca63d7cbf0377f09cb59fd81afbf751f9affef2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5caf51a982d8b7e59cb54b2eb532f1eb43fe8a63", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5caf6fa187000ae494d50b2ed2ab15911b7da3b6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Taking into consideration both the frequency of digestive symptoms in our patients and the former published detection of KIPyV in a stool sample, we looked for KIPyV infection in the available stool samples while the respiratory samples were being assessed for KIPyV (1). Strikingly ", "Six KIPyV-positive patients (37.5%) had co-infections with other respiratory viruses, and 2 of them (12.5%) had a pulmonary bacterial infection (online Appendix Table, available from www.cdc.gov/EID/content/15/1/107-appT. htm). One WUPyV-infected patient who exhibited acute respiratory failure had concomitant pneumonia caused by Pseudomonas aeruginosa infection. None of the 15 patients who were positive for KIPyV or WUPyV and tested for fungi had respiratory or blood samples positive for Aspergillus spp. (Table) . Lung or sinus imaging was assessed by computed tomography scan for 12 KIPyV-positive patients. Lung parenchyma abnormalities were noted in 9 patients, and sinusitis was diagnosed for 2 patients.", "We thank F. Freymuth, P. Lebon, and A. Vabret for advice and technical assistance and for providing positive virus controls.", "Dr Mourez is a virologist in the Laboratory of Microbiology, Saint Louis University Hospital, Paris. His research interests include the development of tests for the diagnosis of emerging respiratory viruses and the study of the circulation and molecular analysis of human respiratory viruses in pediatric and immunocompromised patients. " ] },{ "paper_id": "5ccde00be19e522ea42e8198124df31de00f6afb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "According to China's \"One Belt, One Road\" initiative, the chance that exotic pathogens could be brought into the country has dramatically increased (7) . Our new BSL-4 facility will play an integral role in preventing and controlling highly pathogenic microbes. To safely operate this facility, we designed a training program that ensures all personnel meet the institutional, national, and international standards for working in maximum-containment laboratories.", "The assigned mentor evaluates the trainee's performance, advises on safe and secure operations, and records areas in which the trainee needs further instruction or practice. The mentor then makes recommendations on whether the trainee is prepared for independent access to laboratory facilities.", "On completion of this section, the mentor or trainer observes the trainee performing assigned procedures and evaluates whether they are performed correctly per standard operating procedures. These evaluations are recorded through our online training management software tool." ] },{ "paper_id": "5d9e264d5bedc5753d9feede10389f71b08e0446", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5dc2b500e260938d6db9120669c23b90942bb07c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5deba58c72c66f2c3f47ec82569c9b2527f6f21d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "At 3 and 24 h after each immunization, dermal reactions, including edema and erythema formation, were evaluated using the Draize scale, and any other lesions were noted. Reactions persisting for 48 h after immunization were evaluated daily until disappearance.", "Ophthalmology included assessment of pupillary light reflexes using tropicamide (Mydriaticum, Th\u00e9a, Clermont-Ferrand, France), examination of appendages, optic media and fundus by indirect ophthalmoscopy (Om\u00e9ga 180, Heine, Germany) and of anterior segments and lenses (portable slitlamp biomicroscope, model SL-15; Kowa, Japan).", "Urinalysis (including volume, pH, specific gravity, proteins, glucose, ketones, bilirubin, nitrites, blood (HB) and urobilinogen) was done using a Clinitrek 500 urine chemistry analyzer (Siemens)." ] },{ "paper_id": "5df6a629545e9d444c3ee76b24095606a25e48e1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5e0a713a7436909c940dc70693cf666dd9c8ac62", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The study population was composed of Chinese-speaking residents of Hong Kong (22) who were 18-60 years old. We conducted 2 independent cross-sectional telephone surveys to achieve the 2 aforementioned objectives.", "Ethical approval was obtained from the Chinese University of Hong Kong. The response rate, defined as the number completing the survey divided by the number of valid households contacted, was 65% for survey 1 and 57.7% for survey 2. Relevant sociodemographic characteristics of respondents are shown in Table 1 ." ] },{ "paper_id": "5e1017f2def4ac50f1b63bd52a9a2214c1dfd3b7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In-house X-ray reflectivity (nonisomorphic samples)", "Insertion and lateral lipid response by reciprocal space mapping", "Peptide positioning and orientation from reflectivity using iodine labels", "While the vertical electron density distributions may also be obtained by fitting the diffuse Bragg sheet intensities of the reciprocal space for a single angle of incidence, we have used full scans with background correction (Fig. 1iii ) in reflectivity mode (Fig. 1iv) ." ] },{ "paper_id": "5e25c11546305667e32023f9bdae2c5a3bc7c25c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5eec2a24d87a846e43dacb1f973271ff481eabc4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We modified and expanded a structured questionnaire provided by researchers from the Department of Community ", "We interviewed a representative stratified random sample of 1,202 adults (>21 years of age). To minimize personal contact during the outbreak, participants were interviewed by telephone instead of face-to-face. The residential telephone sampling covered 90% of households in Singapore. The response rate was 62.3%, and the sampling error \u00b13.5% (Table 1) . We used Random Digit Dialing+1, a system commonly used in public health studies, to capture unlisted telephone numbers (3).", "Responses to the survey questions are summarized in Table 2 . Variables were examined by using odds ratios (ORs) at 95% confidence intervals (CI). The statistically significant ORs are reported in Table 3 with their respective level of significance from the Mantel-Haenszel common odds ratio estimates.", "A n outbreak of severe acute respiratory syndrome (SARS) began in Guangdong, China, on November 16, 2002 . The first three SARS cases in Singapore were confirmed on March 6, 2003. By May 5, a total of 204 cases, including 27 deaths, had been confirmed. The last case was isolated on May 11, and by July 30, the end of the outbreak, 205 patients had recovered and 33 had died (1) ." ] },{ "paper_id": "5f04dc1178c4d83e7f673119faa173daf1d19394", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Several virus pathogens utilize \u00c01 ribosomal frameshifting, including the retrovirus HIV-1 (46) , the coronavirus responsible for severe acute respiratory syndrome [SARS-CoV (47)] and numerous plant pathogens [for example, see (48, 49, 50) ].", "5' CCGCCGGGAAACUCCC C G G C C C G U C G C C A G C G U U G G A C C U G G G A G CCAGAA 3' G G A C A", "Pseudoknot model " ] },{ "paper_id": "5f2ac6c6a2cdc245be5786c14f13fa75995be36c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5f2ad6d0fea48889b06eafdc3be79078b9e80504", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5f35a51b9aed0111281ff79055d7566d6ef6c1c7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In the final stage of emergence, increased travel or migration facilitate the global spread of new zoonoses. For example, increased movements between villages or cities and higher between-person contact rates through increased numbers of sexual partners appear to have facilitated the early emergence of HIV/AIDS in Africa (12) . This disease became a global pandemic following the expansion of road networks, changes in workforce demography, and increases in international air travel to central Africa and globally (12, 23) .", "Hunting of wildlife by humans is an ancient practice that carries a substantial risk for cross-species transmission. Despite the discovery of cooking \u22481.9 million years ago (9), the risk of zoonotic diseases emerging from hunting and eating wildlife is still of global importance because of increases in human population density, globalized trade, and consequent increased contact between humans and animals.", "Research in medical anthropology has begun to examine indigenous theories of infectious disease (15) and the cultural contexts within which diseases emerge (16), but little data exist on local perceptions of health or other risks associated with hunting and eating bushmeat. Humans as well as other animals employ behavioral adaptations to avoid exposure to infections, yet the type of protective strategies that hunters might use and the effectiveness of such strategies remain unknown. For this reason, anthropologic studies of bushmeat should include not only the details of hunting, but also the transportation of meat to the village, the market, the kitchen, and onto the table. These practices are often articulated along lines of gender and ethnicity and within cultural contexts.", "Different activities associated with bushmeat trade will involve different levels of risk for microbial emergence. Hunting (tracking, capturing, handling, sometimes basic field butchering, and transporting of the carcass) involves contact with potentially infected vectors, whereas distant consumption may not. Particularly high risks may be associated with hunting nonhuman primates, and even greater risks in hunting species such as chimpanzee, which are phylogenetically closest to humans. Butchering (opening, cutting, dressing, and preparing the carcass) is obviously more high risk for bloodborne pathogens than the transportation, sale, purchase, and eating of the butchered meat." ] },{ "paper_id": "5f4a9c2d6e1f0256ef7c1088f61809fcc6af5734", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5f7a4ea047afec2cad9f019c118233f41057084f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We lysed cells in Triton Lysis Buffer supplemented with HALT protease inhibitor (Roche) and 1 \u00b5M Na 2 VO 4 . We separated equal amounts of protein by 10% SDS-PAGE, transferred it to nitrocellulose, and probed using phospho-ERK1/2 antibody (Thr202/Tyr204) (Cell Signaling Technologies) and STAT3 antibody (Santa Cruz). We used enhanced chemiluminescence (Pierce Biotechnology) and x-ray film (Hyperfilm, GE Healthcare Life Sciences) for detection.", "We carried out quantitative RT-PCR with a BioRad iCycler and used the 2 \u2212(\u0394\u0394C T ) method to calculate relative mRNA expression levels normalized to ACTIN. Primers for AICDA (encoding AID) are described 39.", "Refer to Web version on PubMed Central for supplementary material. ", "While the supernatants of the majority of D25 subclones bound to RSV-infected HEp2 cells similar to recombinant D25, those of some clones bound either less or better than D25 (Fig. 5d ). The differences in binding activities were associated with mutations in the VH regions.", "We analyzed stained cells on an LSRII (BD) and processed flow cytometry data with FlowJo software (Tree Star). The antibodies are described in the online supplementary methods section." ] },{ "paper_id": "5f8af3ed94e16f3560c088fc4ca349fc663f4be3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5f8f57b347928e8586fde5b98a1457146a7b1410", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We identified 268 viruses in 259 (44.0%) of the 589 children. Of the 589 children, 165 (28.0%) were infected with RSV, 50 (8.5%) with HMPV, 18 (3.1%) with influenza A viruses, 18 (3.1%) with rhinoviruses, 9 (1.5%) with parainfluenza type 3 viruses, and 8 (1.3%) with human adenoviruses.", "In 9 (34.6%) instances, HBoV was detected concurrently with another respiratory virus. In the original description of HBoV, 17.6% of coinfections involved human adenovirus or RSV (2) . More recently, a high rate of coinfection (55.6%) was seen in a population of children <3 years of age (3) . Considering these high rates of coinfection, the exact role played by HBoV in respiratory tract diseases needs to be more precisely defined.", "To investigate epidemiologic features of this virus and further specify clinical signs associated with HBoV infections, we retrospectively tested respiratory specimens from children obtained during a 1-year period. We report the incidence and seasonal distribution of HBoV, provide a phylogenetic analysis of HBoV isolates, and describe clinical characteristics of HBoV infection.", "We previously showed that the HBoV NP1 gene displayed limited sequence variation (6) . In the present study, we also observed only minor sequence variations in the VP2 gene, which suggests that the diverse strains of HBoV belong to a unique lineage. This low genetic diversity of HboV was also reported by Sloots et al., who analyzed the NS1 gene (3)." ] },{ "paper_id": "5fb8313680176593b75962be3d056a07c4d31538", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The purified VLPs were concentrated on centrifugal filters (Amicon, Darmstadt, Germany).", "The SOS Dolphin Foundation provided permission to the Department of Viroscience, Erasmus Medical Center (Rotterdam, the Netherlands), for the use of these samples for the present study.", "Since 1967, small cetaceans-mainly harbor porpoises-that strand alive along the coasts of the Netherlands, Belgium, and Germany have been rehabilitated at the Dolfinarium Harderwijk (Harderwijk, the Netherlands) and subsequently released into the wild. Since 2004," ] },{ "paper_id": "601183372b370d59a83b1d68598cb594f9397777", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "607c9e39d3ba883da7c5796c4d102e74f87948b7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "608318d1cbddf1a10ea1d6faca8b4cacf8467c29", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Patients with known tuberculosis (TB), known acquired immunodeficiency such as HIV/AIDS, and cancer were excluded.", "Medical records and chest x-rays were retrospectively reviewed by an expert pulmonologist.", "Proportions were compared using a chi-squared or contingency table randomization test as appropriate. P-values < 0\u00c105 were considered significant. The Mann-Whitney U-test was applied to compare continuous or ordinal measures. Analyses were performed using STATA/SE version 11.1 (StataCorp., College Station, TX, USA) and R statistical software (R 2.8.1, R Foundation for Statistical Computing, Vienna, Austria)." ] },{ "paper_id": "608f11c80d206e1ca59ef5683a1b31d689c79102", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "60a0f190f79987eaf2d5bbe5e2e48b85161caaa9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "During Among the affected areas, Jiangsu reported the highest percentage of PUE positive for A(H7N9) (74%). This was followed by Hunan (33%), Henan (27%), Fujian (18%), Zhejiang (14%), Jiangxi (10%), Shanghai (4%), Beijing (3%), and Anhui and Shandong (0 cases each) ( Table 1) .", "Most confirmed case-patients had severe disease (2) (3) (4) , and an analysis of national influenza-like illness surveillance data has not found evidence of widespread A(H7N9)associated mild illness (5) . After preliminary epidemiologic and virologic information pointed to live-poultry markets (LPMs) as a possible source of infection (2, 4) , retail and wholesale LPMs were closed in several major cities in which A(H7N9) was confirmed, including Shanghai, Nanjing, and Hangzhou. The number of new cases declined in these cities after LPM closures (6) .", "This study identified several major problems with the PUE surveillance system, including low and uneven levels of participation and inconsistency among provinces in how the system is used. Given its potential value in monitoring future A(H7N9) activity, the system's overall objectives and reporting procedures should be further evaluated. The continued threat of additional viral adaptation to human hosts leading to increased transmissibility lends added urgency to the ongoing improvement of the PUE system to better understand the epidemiology of A(H7N9), detect outbreaks, and evaluate control measures. " ] },{ "paper_id": "60b35dbca96ef8c02f90e2aaad56e19bdd150cf6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "615e5a74d3b54ce5e9d1a5dfda4187c1d99a8903", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "615f822ea45e03824b752aabd831e2f594608d4a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6170c6d5c7e660f19226bfd026159c4ba6915fda", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To obtain DNA for genotyping, a 10-\u03bcm section from blocks containing formalin-fi xed, paraffi n-embedded tissues was deparaffi nized with xylene and washed twice with absolute ethanol. After residual ethanol evaporated, tissues were digested overnight at 56\u00b0C in 200 \u03bcL Buffer PKD with 20 \u03bcL proteinase K (QIAGEN, Valencia, CA, USA). Extraction of the supernatant was completed with an EZ1 DNA Tissue Kit or a MagAttract DNA Mini M48 Kit (QIAGEN), with DNA eluted into a fi nal 100-\u03bcL volume. DNA quality was assessed with a human RNase P real-time PCR in 25-\u03bcL volumes by using Agilent Brilliant II QPCR Master Mix as described (4) . Validated TaqMan assays were used to genotype each SNP (protocols, primers, and probes available at http://snp500cancer.nci.nih.gov). Each 25-\u03bcL real-time PCR consisted of 12.5 \u03bcL of TaqMan Universal PCR Master Mix (Applied Biosystems, Foster City, CA, USA), 900 nmol of assay-specifi c primer, 200 nmol of assay-specifi c probe, and 5 \u03bcL of DNA. All controls (extraction blanks, no template controls, and positive controls for each genotype used at 5 ng per PCR; Coriell Institute for Medical Research, Camden, NJ, USA) and unknown samples were assayed in duplicate. Thermal cycling conditions consisted of 1 cycle at 50\u00b0C for 2 min, 1 cycle at 95\u00b0C for 10 min, and 50 cycles of 92\u00b0C for 30 s and 60\u00b0C for 1 min. Data were collected during the annealing plateau.", "This study was exempted from institutional review board review for approval of human subjects research. Data were obtained only from deceased case-patients, and reference sample data were used only in a de-identifi ed and aggregate manner.", "Genotype and minor allele frequencies among casepatients are summarized in Table 2 . Minor allele frequencies comparing case-patients to the NHANES reference sample are shown in Figure 1 .", "To address the paucity of research on host genomics and infl uenza, the Centers for Disease Control and Prevention (CDC) convened a meeting of experts in 2007 to solicit opinions on how to explore the role of host genomics in public health activities for infl uenza conducted by the agency. A study of host genomic factors related to severe infl uenza outcomes in children was recommended as an activity that CDC was well positioned to pursue. This article reports the fi ndings of the study implemented in response to that recommendation." ] },{ "paper_id": "6198c45ade2c9f644ed7556b30e5736439b7e1b2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "61f833b5c4fb1c5d9a82ca699af4457e93d7ab12", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Author(s) disclose no funding sources.", "Author(s) disclose no potential conflicts of interest.", "Wrote the first draft of the manuscript: BSY, VR. Contributed to the writing of the manuscript: BSY, VR, DPV, BS. Jointly developed the structure and arguments for the paper: BSY, VR, DPV, BS. Made critical revisions and approved final version: BS. All authors reviewed and approved the final manuscript." ] },{ "paper_id": "6203b7c7808aac525f83c3cc7d0107cf90344259", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Throat swabs were carried out and a multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) assay was performed to identify possible causative factors.", "The subjects' medical records were obtained by referencing the military medical information system. This study was approved by the Medical Research Institutional Review Board of the Ministry of National Defense (no. AFMC-12-IRB-014)." ] },{ "paper_id": "6204ddfab367830e9fb70d356967ee25b13ab546", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "623c7837507886a9e4cc4e4e58a95aa81cb5406a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All samples were collected in viral transport medium and stored at 4\u00b0C immediately after collection, then transported within 24 hours for storage at -20\u00b0C pending further testing. Nucleic acids were extracted on a MagnaPURE 96 platform (Roche, Mannheim, Germany). Reverse transcription was done using Superscript III (Invitrogen, Carlsbad, CA) and random hexamers (Roche). Multiplex polymerase chain reaction (PCR) was used to identify 14 viral respiratory pathogens: influenza A (Flu A), influenza B (Flu B), adenovirus (AdV), enterovirus (ENT), respiratory syncytial virus A and B (RSV), human metapneumovirus (MPV), rhinovirus (Rhi), parainfluenzavirus 1, 2, 3 and 4 (PIV1-4), coronavirus (Cor, including HKU1, NL63, 229E and OC43), human bocavirus (Boca) and parechovirus (PEV). The PCR was performed as a 4-tube assay on a Roche Lightcycler 480 II using primers and probes as described previously, 15 except for the rhinovirus primers and probes which were: AgSCT-gCgTggCKgCC (forward); ACACggACACCCAAAgTAgT (reverse); CYAN500-TCCTCCggCCCCTgAATgYggCTAAYC-DB (probe). Equine arteritis virus was used as an internal control. Bacterial diagnostics were not performed.", "Associations significant at 0.05 level in adjusted analysis are highlighted in bold. *Only outpatient visits detected by clinical surveillance were included. Outpatient visits associated with hospital admissions were counted as hospitalized cases and not outpatient cases.", "\u2020Cumulative incidence per 1000 infant-years. \u2021Incidence rate ratio (95% confidence interval)." ] },{ "paper_id": "6266766fd9da3175d27c27b38db9054b7dd45c17", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6293160da51ace8a72b0297d94e05ec9ad4276b6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Background Given the enormity of challenges involved in pandemic preparedness, design and implementation of effective and cost-effective public health policies is a major task that requires an integrated approach through engagement of scientific, administrative, and political communities across disciplines. There is ample evidence to suggest that modeling may be a viable approach to accomplish this task.", "In closing the workshop, Dr. Seyed Moghadas (Institute for Biodiagnostics, National Research Council Canada) valued the time and efforts of participants and appreciated their contributions to the success of this event. Key points inferred from presentations and discussions include: 1. In Canada, the pandemic goals are to (i) minimize serious illness and overall deaths; and (ii) minimize social disruption. Pandemic containment has not been a priority to date and may not be feasible." ] },{ "paper_id": "62a0a9024b88c9abef953835a6704042549034ab", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysisconsisted of Pearsons chi-square test for the comparison of categorical values, with a significance level of p < 0.050.Non-conditional logistic regression was used to identify associations between coronaviruses positivity and the studied populations. All reported values were two-tailed.Results were presented as odds ratio (OR) and therespective95% confidence interval (CI) and pvalue. All data were entered into and analyzed by using SPSS version 11.0 (SPSS Inc., Chicago, IL, USA).", "During the nine-year span studied, respiratory samples were collected from patients presenting acute respiratory illnesses. The study period began in June 2001 and was concluded in September 2010. A total of 1,087 samples were collected. Specimens analyzed included 414 from nasopharyngeal swabs (Labor Swab Import, Brazil), 208 from nasal aspirations and 465 from nasal lavages. Subjects were: 50 adults who were attended by generalpractice physicians among community population patients registered by the Medical Department Outpatient ", "Epidemiological and clinical data from outpatients were obtained using a standardized questionnaire while data from hospitalized patients were abstracted from medical charts using a standardized form. Age, gender, occupation, presence of underlying conditions or diseases, clinical findings at first attendance (for outpatients) or during the first 24 hours (for hospitalized patients) were recorded for analysis. Institutional review board approval was received before reviewing any records. This study was approved by the Ethics Committee of Sao Paulo Federal University (CEP 1968/09), and written consent was obtained from all patients or those responsible for the individual patient." ] },{ "paper_id": "62aad0910cdeceb067d2847f0c145c5c785e7085", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Methicillin-resistant Staphylococcus aureus (MRSA) was isolated", "Potentially exposed workers were presumably tested in other laboratories involved, but we are not aware of any publications to this end. The lack of evidence for laboratory-acquired infection with A H2N2 in our study suggests that the risk was low under controlled laboratory conditions. However, only a large-scale serologic study (which might still feasibly be undertaken) could further substantiate this finding.", "To the Editor: A 3-year-old, neutered male, domestic shorthaired cat was referred for treatment to a veterinary specialty clinic in San Francisco, California, with a 1-year history of multifocal patches of crusted and well-demarcated ulcers on the trunk. Initially, small crusts suspected to be associated with flea allergy and pyoderma were present; however, response was poor to multiple treatments, including repeated corticosteroid therapy and antimicrobial therapy with amoxicillin-clavulanic acid and enrofloxacin. The owner reported having skin abscesses and pneumonia 3 months earlier, although no microbiologic testing was performed.", "Cytologic evaluation of exudate from the cat's lesions identified neutrophils and eosinophils with engulfed cocci. Leukocytosis with eosinophilia was found on a complete blood cell count. No notable abnormalities were present on thoracic radiograph, abdominal ultrasonograph, urinalysis, and tests for feline leukemia and immunodeficiency virus. Skin biopsy specimens were collected for histologic examination, and swabs of the exudates were submitted for bacterial culture. Histopathologic findings demonstrated ulcers and dermal granulation tissue with linearly arranged eosinophils, mast cells, neutrophils, and plasma cells between dense, homogeneous collagen bundles (sclerosing dermatitis). This pattern of inflammation is distinct from most staphylococcal infections of the skin, and it has been suggested that this uncommon histologic finding in cats is associated with methicillin-resistant staphylococcal infection (1) ." ] },{ "paper_id": "62b7f419bb3a4af2f439778b85c0b2582461053a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Three main components in the active nucleolus", "Why must viral proteins target to the nucleolus?", "What are the consequences for the cells of the passage of viral proteins via the nucleolus?" ] },{ "paper_id": "62ed08b25033369488b34d3a7aaee0401a3c00a0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We considered the following pathogen groups: viruses (including prions), bacteria (including rickettsia), fungi (including microsporidia), protozoa, and helminths. We did not consider ectoparasites (ticks and lice). Each group was further divided into subgroups (families) to test whether biases existed in numbers of emerging and reemerging species at this level. The viruses were also divided according to genome type (e.g., negative singlestranded RNA viruses).", "We focus mainly on pathogen diversity (as numbers of species) rather than on the effects of disease that they impose, noting that many diseases, e.g., infant diarrhea, can be caused by more than one species of pathogen. However, we comment on the transmissibility of pathogens once they have been introduced into the human population because transmissibility is an important determinant of the potential public health problem.", "Throughout the study, we quantified associations as the relative risk (RR) and tested for statistical significance using a standard \u03c7 2 test (with correction for small expected values). Although these statistical analyses are susceptible to bias introduced by related species (e.g., several species of hantavirus exist, most of which are zoonotic and many of which are regarded as emerging or reemerging), the analysis at the family level is an indication of the extent of any such bias.", "We obtained counts of pathogen species from an updated version of the previously published database (1) . As before, we defined a human pathogen as \"a species infectious to and capable of causing disease in humans under natural transmission conditions.\" We included pathogens that have only been reported as causing a single case of human disease and those that only cause disease in immunocompromised persons. We also included instances of accidental laboratory infection but excluded infections resulting from deliberate exposure in the laboratory. We added recently recognized pathogens listed online by the Centers for Disease Control and Prevention, the World Health Organization (WHO), ProMED, and elsewhere (6) (7) (8) (9) . We obtained taxonomic classifications online from the International Committee on Taxonomy of Viruses, the National Centre for Biotechnology Information, the CAB International Bioscience database of fungal names, and from standard texts (10) (11) (12) (13) (14) (15) ." ] },{ "paper_id": "62fc5c722d09d38217a96f1fb4e6831a0255b25d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Incidence of infection with these agents exhibits a marked cyclic pattern so that it is to be expected that reported rates will vary based on the number of seasons of high viral activity included in a particular study.", "During the 1967 outbreak of 229E infection in Tecumseh, Ml, illness was significantly more common among those with infection than among matched individuals without infection (16) . Similarly, 229E infection among Chicago medical students was statistically associated with illness when those with rises in titer were used as their own controls (21 ) .", "Evidence is steadily mounting that the coronaviruses are of major importance in common respiratory infection of all age groups, especially those occurring in midwinter and early spring. The total impact of coronavirus infections on the general population cannot be calculated at present because not all viral types have been identified. Only 229E and OC43 are amenable to large scale serologic studies; iniection rates for other distinct types such as OC16, cannot be determined. The assumption must be made that the former two types are typical of the other viruses.", "It is premature at present to think in terms of control of coronavirus infection. Not all viral types have been identified and some known agents cannot be easily propagated in the laboratory. Thus, preparation of vaccines of the conventional types is impossible. The frequency of reinfection observed with these agents is so high that control by vaccination may not be practical, but it is possible that further studies may allow identification of truly protective antibodies. There remains environmental control of infection; such efforts have only rarely been useful for other respiratory agents and they are likely not to be more efficacious for the coronaviruses (43)." ] },{ "paper_id": "63188fe828f332759eb902e48628239cb4679964", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 IHR (2005) ", "Spurred by fears of avian influenza (H5N1), the United States embarked on an aggressive policy to put into place a series of plans at the federal, state, and local levels. These pandemic plans address continuity of operations, social distancing strategies, vaccine and antiviral production and distribution, hospital surge capacity, and special considerations for vulnerable populations. In addition to plans, there were accompanying implementation schedules for implementing necessary infrastructure in place to ensure the plans would be useful should a pandemic emerge (11, 12) .", "Response Section 3. ", "WHO and PAHO arranged to have 489,000 treatments (treatment for an adult was 75-mg capsules, twice a day for 15 days) of oseltamivir shipped to Mexico and other countries in the Americas. Approximately 220,000 treatments of oseltamivir were shipped to 21 countries in the Americas from the United Nations Humanitarian Response Depot in Panama (27, 28) ." ] },{ "paper_id": "634ff899aa23d42b3a4941bdf96ad6063edcc206", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "From March 8 to March 28, the hospital admitted five patients in whom SARS-CoV infection was subsequently laboratory-confirmed. The patients were isolated in negative-pressure rooms. Patients 2 and 3 were family members of patient 1. Patients 4 and 5 were believed to have contracted SARS on a March 15 flight from Hong Kong to Beijing. Four of the patients progressed rapidly to respiratory failure and were intubated.", "The Table compares the extent of personal protective equipment use before and after implementing specific infection-control measures. Healthcare workers during the \"after\" period were substantially more likely than the \"before\" period to have used full personal protective equipment (Table) .", "Transmission of SARS was limited initially at our hospital (attack rate 0.4%) when healthcare workers followed standard precautions or specific infection-control measures, including droplet and contact precautions. However, in later stages of the epidemic, SARS was more likely to develop in healthcare workers, despite similar or higher levels of personal protective equipment use. Although one possible explanation for this could have been exposure to unrecognized SARS patients, contamination of the environment leading to indirect contact transmission may have also played a role (11) .", "This study found infrequent transmission of severe acute respiratory syndrome (SARS) coronavirus to healthcare workers involved in the care of the first five casepatients in Taiwan, despite a substantial number of unprotected exposures. Nonetheless, given that SARS has been highly transmissible on some occasions, we still recommend strict precautions." ] },{ "paper_id": "638ce87155f81ea03edcb4e2e16c447550aa8405", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6394756d9759bedd7e0053f7b99a7df74da7a16a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6397e80ffb931ee6f6d03c1fe85ef82aa36e1b9a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "63b48a2db91293fd73f193d76cad74360b561706", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "63f7049d200896290b38b38711113054f7ea1b50", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "641c948cea542b5db2ff6d251a7698e476f6396d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "642f87b9554dc5868a8b876c6f1df729023f5f30", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In conclusion, the data from this study provide valuable information on Aphthoviruses and, more precisely, BRAV to serve as the genetic basis for future studies. Detailed knowledge of the evolution and divergence of Aphthoviruses at the molecular level could aid in the design of BRV-based molecular diagnostic tools and new bio-therapeutics.", "Bovine respiratory disease (BRD) is a leading cause of death of feedlot cattle in the USA. Annual costs associated with BRD total more than one billion dollars. Environmental stress, compromised host immunity, and virus infection predispose the animal to bacterial lung infection (broncho-pneumonia). 1 Primary virus infections damage the respiratory tract and subdue the host immune system. The respiratory tract commensal bacteria cause opportunistic secondary infections and lung pneumonia under immunecompromised conditions (caused by viral infection and other factors). In fact, previous studies have reported bovine viral diarrhea virus, bovine respiratory syncytial virus, bovine herpesvirus 1, parainfluenza 3 virus, adenovirus, and bovine coronavirus from cattle with BRD. [2] [3] [4] [5] [6] Although more than 40 years ago, studies concluded that bovine rhinitis viruses (BRVs) (then known as bovine rhinoviruses) cause mild respiratory disease in cattle, [7] [8] [9] [10] it is a surprise that BRVs are sparsely studied. This is partly due to the fact that the virus grows poorly in cell culture and is known to cause only selflimiting mild respiratory illness.", "The findings of these algorithms (Tables 3 and 4 ) for the assessment of recombination potential are consistent with other published studies regarding the potential of Picornavirus genomes to undergo recombination events. 34 We concluded based on these findings and what was previously described in the existing literature that the likelihood of detecting recombination events between FMDV and BRV could be described as highly remote. We also inferred that given the absence of prior exchanges between the genomes with two different sample pools, the chance of future exchanges would be novel and highly unlikely.", "This study details new and important genomic information regarding Aphthoviruses in general and specifically, we report a new member of the bovine rhinoviruses, which is BRAV. Several bioinformatics tools employed in this study help to elucidate the molecular diversity of Aphthoviruses, and help to distinguish BRAV from other members of the virus lineage. The knowledge gleaned herein and the applications of these bioinformatics tools will assist other researchers to investigate novel viral pathogens." ] },{ "paper_id": "6450de33d673aaaeef75fc898f74ca3e9caec89d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "64778c71390d68e402c5999fcfd3eb8723cdaf49", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Direct sequencing was performed by using the forward or reverse primer.", "The system for rapid determination of viral RNA sequences (RDV) version 3.0 (1) was modified to simplify the procedure. The modified method was designated version 3.1. Adapters and primers for construction of second cDNA library in RDV version 3.1 were newly designed and", "1. RNA extraction. To eliminate contaminating cellular RNA and DNA from the samples, culture supernatant was treated with DNase I and RNase A as described previously (2), following RNA extraction by using a Total RNA isolation mini kit (Agilent Technologies, Santa Clara, CA, USA). Page 2 of 4 4. Direct sequencing. After electrophoresis of PCR products on agarose gels, bands >120 bp were excised, and DNA was extracted from the gel by using MonoFas." ] },{ "paper_id": "649e93103cd970604570c424279a7d6a53a99ef4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "64b175f9110dce9c9995d872ba7f7b3671e52f5b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "healthcare workers performing intubation that involve increased protection (available from: URL: www.sars. medtau.org) (11) , and protective eye wear is currently mandated for patient encounters. In the second case, transmission could have occurred in a number of possible routes. The nurse may have come within sufficient range of the SARS patient to be exposed to large droplets.", "Our results suggest that proximity and duration of contact to a patient with SARS are associated with risk for viral transmission, an observation suggested by others (2) (3) (4) . In addition, certain procedures, such as endotracheal intubation, pose increased risk. These findings may be predictable given that SARS is thought to spread primarily by large droplets (9) .", "including ventilator-associated pneumonia and critical-care delivery models." ] },{ "paper_id": "64f75ab0933b2639497b4d607de656a09a1a3284", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "PCR mixtures were prepared in 50-\u03bcL volumes containing 25 \u03bcL 2\u00d7 EXTaq DNA polymerase (TaKaRa, Kyoto, Japan). Two pairs of primers, Bat_Cytb_1 (5\u2032-TAG AAT ATC AGC TTT GGG TG-3\u2032) (21) with Bat_Cytb_2 (5\u2032-AAA TCA CCG TTG TAC TTC AAC-3\u2032) (21) , and Bat_Cytb_2 with BAT15R (5\u2032-TCA GCT TTG GGT GTT GAT GG-3\u2032) (22) , were used because of amplifi cation specifi city of certain primers in some species. Amplifi cation was conducted at an initial denaturing temperature at 94\u00b0C for 30 s; 34 cycles of denaturation at 94\u00b0C for 30 s, annealing at 55\u00b0C for 30 s, and extension at 72\u00b0C for 90s; and a fi nal extension at 72\u00b0C for 10 min. The PCR samples were then stored at 4\u00b0C. The complete mitochondrial cyt b gene (1,140 bp) was amplifi ed and sequenced. These sequences have been submitted to GenBank and accession numbers are shown in the Table." ] },{ "paper_id": "65084f5b311cb50b0eca19c8f1a97ca89a69f5fb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In order to protect patients, families, doctors, nurses and other health care professionals, public health systems and their component hospitals must have access to up-to-date scientific information [13] , as well as conceptual, ethical and practical frameworks in place to minimize the damage and support all parties when an unforeseen and unexpected enemy such as SARS arises. These modern day plagues are unlikely to go away, and in fact SARS perhaps was a light dress rehearsal for the next anticipated massive outbreak of influenza, for which there is ongoing planning and intense surveillance [14] .", "Another challenge to our previously unconditional trust of our colleagues occurred when staff members found themselves watching others to ensure that infection control measures were strictly adhered to and confronting them when they were not. Although such vigilance is crucial to the success of infection control protocols, it engenders a lack of trust and challenges multidisciplinary professional relationships in an unprecedented manner.", "There are many ethical issues raised by the SARS epidemic, including global cooperation and information sharing [2] , isolation of patients and their families, quarantining of patients and health care workers [3] , lack of patient access to medical care [4] , loss of privacy, stigmatization of individuals or populations [5] , and appropriate priority setting and use of limited resources.", "Much has already been published describing the epidemiology of the illness, its clinical symptoms and its treatment. There has also been some discussion of the nonmedical effects of SARS and potentially future similar outbreaks on the relationships between health care providers and patients and families, their notions of professional integrity, and issues of resource allocation [6] . Such ethical and psychologic issues -the 'collateral damage' of the outbreak -cannot be ignored because they challenge some deeply held convictions and ethical conceptions in ways that they have never been questioned previously and, as a result, may be altered for ever." ] },{ "paper_id": "652c4ca6d601033177d0dd2d9e0831950963b6f8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Not only viral infections but also sterile inflammation, which can be induced through different stimuli (chemical, physical, or metabolic noxious), 70 can increase the USP18 expression through certain inflammatory cytokines (TNF-\u03b1 and LPS), which impairs IFN-I responses and viral control. For example, ischemic reperfusion injury upregulates USP18 expression in the liver and induces an IFN-\u03b1 refractory state. 22 That may raise the risk of an opportunistic viral infection.", "In general, owing to the multiple functions of USP18 and its expression in various cell types, it would be complicated to generate one drug that can be used to treat all the diseases in which USP18 is involved. We believe that this difficulty can be resolved by using targeted drug delivery. Such technology would be the best strategy to overcome the protein's wide expression and will allow recovery from various types of immunological dysfunctions.", "In humans, two isoforms of USP18 have been described. 12 They differ in their N-terminal region because of translation from a non-canonical rare start codon CUG; this translation produces a full-length protein or a canonical start codon, AUG, and results in the N-terminal truncated isoform USP18-sf. Although USP18 is mainly located in the cytoplasm, USP18-sf is evenly distributed in the cytoplasm and the nucleus. Both proteins maintain their functional activity in term of enzymatic and IFNAR2 binding ability, but the USP18-sf isoform is the main delSGylation enzyme for nuclear proteins and therefore may serve cell-specific functions. In addition, because USP18-sf is controlled by two independent mechanisms, its regulation is more flexible. Additional studies are needed to characterize the role of each isoform and to determine whether the regulation pathway can influence the outcome of USP18 function. 12", "Ubiquitin-specific peptidase 18 (USP18) is known as an ISG15 isopeptidase and a negative regulator of type I and type III interferon signaling. 1, 2 The Usp18 gene was originally called Ubp43 because it encodes a 43-kDa protein homologous with ubiquitin-specific proteases (UBPs). It was first cloned by Liu et al. 3, 4 from mice expressing the leukemia fusion protein AML1-ETO and later by other groups from virus-infected porcine alveolar macrophages 5 and human melanoma cell lines. 6 The gene and protein were renamed Usp18 and USP18, respectively, according to the systematic nomenclature suggested by Baker et al. 7 for UBPs and ubiquitin-like (Ubl) proteins. On the basis of its amino-acid sequence, USP18 is a member of the USP family, which is responsible for removing ubiquitin or Ubl proteins from their conjugated substrates." ] },{ "paper_id": "6581fa08f3fffd579f9a627ea9ba7596a5dcaee6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "659dbc689ddfded5d655534f1e03041279f3942d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "66311ae91af1d27827b42b3ad96bca60cb58db03", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ ": stool. : urine. Blocked symbols denote SARS-CoV-positive specimens by RT-PCR.", "S evere acute respiratory syndrome (SARS) was recently described as the clinical manifestation of infection by a novel coronavirus (CoV), the SARS-associated CoV (SARS-CoV) (1) (2) (3) (4) (5) . This syndrome was first recognized in February 2003 in Vietnam, but it was later realized that the first cases occurred in southern China in November 2002 (6, 7) . Subsequently, the infection rapidly spread throughout the world, and by July 2003, when the World Health Organization declared that the outbreak was contained, 8,437 cases and 813 deaths in 32 countries had been reported (8) .", "As the outbreak developed, epidemiologic evidence suggested that SARS-CoV was transmitted by respiratory droplets or direct contact with infected patients and possibly by fomites (9) (10) (11) (12) . In certain circumstances, transmission of SARS-CoV was particularly efficient and resulted in individual patients infecting large numbers of people (referred to as \"super-spreading events\"), whereas in other situations, no secondary transmission was observed (13) ." ] },{ "paper_id": "66435f60ea3030e572cc8306d4e7be3354737583", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "On May 15, we collected 119 environment samples, including 100 surface samples and 19 air samples ( Table 2) ", "On May 15, surfaces of environment and equipment were sampled with moistened sterile cotton swabs. The swabs were spread immediately onto 3 mL of viral transport medium. Samples were collected from various objects in different areas of ER.", "This study has several limitations. Comprehensive serologic surveys were not conducted among all of the healthcare workers and patients during the outbreak. We may have missed persons with subclinical or mild infections who might have transmitted SARS by person-to-person contact. Viral cultures were not performed on samples taken from inanimate objects. SARS virus detected by RT-PCR may not have been viable.", "Air samples were taken with both high-volume and low-volume samplers in 10 locations in the ER. We used a high-volume air sampler (XMX Virtual Impactor, Dycor Technologies Ltd., Alberta, Canada) to draw air at calibrated sampling rates of 400 L per min for 5 min into a collector with 5 mL of phosphate-buffered saline (PBS). We also used a low-volume pump (Sidekick, SKC Inc., Eighty Four, PA) to draw air at a calibrated sampling rate of 2.0 L per min for 10 h onto a 37-mm diameter, 0.3-\u00b5m pore size polytetrafluoroethylene membrane filters. The collected samples were then frozen at -70\u00b0C before RNA extraction. Once environmental contamination was identified, cleaning was performed. Follow-up surveillance for contaminated objects was conducted on May 25." ] },{ "paper_id": "664563d8f7858aa1fe412414d4728b9243930e5a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6658283efba628db14a76984b7d3f39d79712f4c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The assembled full-length sequence of EBV strain derived from C666-1 was submitted to the GenBank database and assigned accession number AB828190. The sequence of Raji EBV strain was also submitted and assigned accession number AB828191.", "The MAFFT [37] software was used to align the EBV genomes of C666-1 (AB828190) and Raji (AB828191) with other 18 strains reported previously: EBV-WT (NC007605) [34] , B95-8 (V01555) [34] , AG876 (DQ279927) [38] , Akata (KC207813) [39] , Mutu (KC207814) [39] , K4123-Mi (KC440851) [40] , K4413-Mi (KC440852) [40] , GD1 (AY961628) [41] , GD2 (HQ020558) [42] , HKNPC1(JQ009376) [43] , and HKNPC2 ~ HKNPC9 (KF992564 ~ KF992571) [44] . Molecular Evolutionary Genetics Analysis (MEGA) [45] software, version 5.2 was used to perform the Phylogenetic analyses by Neighbor-joining (NJ) algorithm, based on multiple sequence alignments of the eight viral genomes and encoded genes. Protein sequences were aligned with Megalign (DNAStar, Lasergene, version 7.1).", "The C666-1 and Raji reads were aligned to the reference (EBV-WT) by BWA software [35] . Single nucleotide variations (SNVs) were detect by the SAMtools [30] software and applying the following criteria to filtering the raw variations result: (1) the minimal depth cover the variation site is not less than 4; (2) the minimal variation quality score is not less than 20; (3) the distance between two nearby variations is not less than 5; (4) the reads support the mutated allele is not less than 4." ] },{ "paper_id": "667d842d13def9658375872a415e504f0945dcfe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "668d738d46daa0b1a2a32486746d117add1750f5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6699fa6eb0b4fb603f3baf51add71f7ec29ed2a5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "On October 4, 2016, Hurricane Matthew, a category 4 storm, made landfall in southwestern Haiti, causing major damage and flooding, killing at least 540 persons, and displacing \u2248175,000 persons (29,30). Torrential rains washed away roads, bridges, and crops, threatening food security, water safety, telecommunication capabilities, and medical services (29). The hurricane devastated healthcare facilities, including 46 cholera treatment centers (29), and disrupted key public health programs.", "To illustrate the breadth of GRRT's response work and its influence on agency response capacity, we describe selected responses to the Zika virus epidemic, urban outbreaks of yellow fever, and Hurricane Matthew in Haiti. Case studies demonstrate GRRT ability to support large complex outbreak responses, fill response needs when CDC expert capacity is strained, and manage smaller responses without EOC activation.", "The yellow fever response highlighted the benefits of agency surge capacity, particularly when specialized technical expertise is needed for multiple responses in multiple locations. The response also underscored the benefits of accurately identifying responders with highlevel foreign language fluency but demonstrated the need to strengthen language capacity. Fluent speakers of Portuguese and French were identified for mobilization to Angola and DRC, respectively. However, because insufficient numbers of Portuguese speakers were available, fluent Spanish speakers partially filled the language gap.", "From September 1, 2015, through December 31, 2016, GRRT responders were mobilized 291 times for 10,148 person-days to work in 35 countries, territories, and the CDC EOC (Figure) . Most of the mobilization time was spent responding to outbreaks of Zika virus infection (65.0%), yellow fever (9.4%), Ebola (4.3%), cholera (3.9%), polio (0.5%), and measles (0.5%). The remaining time went to natural disasters (Hurricane Matthew [12.8%] and wildfires in Indonesia [3.2%]). Responders aligned themselves with existing response activities, working directly with ministries of health, the World Health Organization (WHO), CDC country offices, and other partners." ] },{ "paper_id": "66d2443a9cacf7efd16112043485ce2692af1c2b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In 2006, a 79-year-old woman sought care at a public assistance hospital in Paris; she reported having had asthenia, breathlessness, and decreased appetite for 2 weeks. She had had node-negative, localized gastric adenocarcinoma 2 years earlier, which had been treated by partial gastrectomy, and pulmonary tuberculosis in 1948, which had been treated by partial pneumonectomy. As a result of a pleuropulmonary tuberculosis relapse diagnosed 6 weeks earlier, she was receiving antituberculous treatment with rifampin (400 mg/day), isoniazid (150 mg/day), ethambutol (800 mg/day), and pyrazinamide (1,000 mg/day). She received no other concomitant medications.", "Her initial physical examination showed nothing abnormal. Laboratory analysis showed hemoglobin 6.3 g/ dL, leukocyte and thrombocyte counts within normal limits, 1% reticulocytes, and zero schizocytes. Other test results (liver and renal function, serum folate and vitamin B12 levels, lactic dehydrogenase levels, C-reactive protein, serum protein electrophoresis, direct and indirect Coombs tests, and antinu-clear antibody tests) were within normal limits, as were viral serologic test results (HIV, hepatitis B virus, hepatitis C virus, parvovirus B19). Upper and lower digestive tract endoscopic examination and carcinoembryonic antigen showed no abnormalities, which lessened the likelihood of a tumor relapse. Bone marrow aspiration from the sternum showed a hypocellular marrow with complete absence of the erythroid series, a normal myeloid series, and megakaryocytes. The marrow fi ndings were consistent with PRCA.", "The favorable outcome after isoniazid withdrawal increased the likelihood that isoniazid was the cause. Although rechallenge with isoniazid could have confi rmed isoniazid as the cause, it is not an ethical option because of the hazardous adverse effects." ] },{ "paper_id": "670ef52bc9d875ae6086b6b76d739fe85652ab6c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors report no confl icts of interest in this work.", "A possible association of VN autoimmunity with retinopathy in humans seems plausible and suggests the need for further research. Specifi c therapeutic interventions may already be available or could be developed for the prevention and treatment of VN autoimmune retinopathy. Recent evidence suggests that VIP may be useful in the treatment of experimental autoimmune uveoretinitis (EAU). The possibility of vasoactive neuropeptides acting in a therapeutic context may support the hypothesis of VN impairment as an etiology in retinal pathology. 37", "As PACAP has a role in the relaxation of pericytes, this may form the basis for a diagnostic procedure for diabetic retinopathy. 14 In view of the vasodilatory roles of these VNs along with hypoxia protection, they may have a place in the prevention of ischemic retinal degeneration. 15 VIP and PACAP are likely to have an important role in retinal development. 16 PACAP and VIP autoimmunity has been hypothesized previously as a causal agent in retinopathy. 17 VN function and postulated autoimmunity is an emerging fi eld and may be relevant to clinical ophthalmologists because of the opportunity to develop novel treatments." ] },{ "paper_id": "678afd3fc1f3aba4346f2513ce3a4550794d5cad", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The estimated values were the means of samples\u00b1standard deviation of the mean. Significant differences were determined by one-way ANOVA test using SPSS v. 13. Differences were considered significant at p<0.05.", "Determination of JA Extraction, purification, and determination of endogenous levels of JA by an indirect enzyme-linked immunosorbent assay technique were performed as described by Yang et al. [15] .", "Quantitative analysis of baicalin in S. baicalensis seedlings was performed according to the reported procedure [16] . Briefly, the air-dried roots of individual S. baicalensis plants (500 mg) were ground into power (20 mesh), soaked in 75 % ethanol (100 mL), and sonicated (300 W, 25 kHz) for 30 min. The extract was filtered through a 0.45 \u03bcm membrane filter, and 10 \u03bcL was injected for each HPLC analysis. HPLC analysis was performed on a Kinetex C 18 (4.6\u00d7100 mm, 2.6 \u03bcm) column. The detection wavelength was set at 275 nm and the column component was main- " ] },{ "paper_id": "67946abf87640b5b9106aaaf732c11e4b7b07a28", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "67a8fef0eb4922c0e41e028b400f11fa88942e04", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "685eba5fefce2d8dff007fa996ecf065e56da933", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "TMT10-labeled samples were fractionated using high-pH reversed phase chromatography performed with an Onyx monolithic 100 \u00d7 4.6 mm C18 column (Phenomenex, Torrance, CA). The flow rate was 800 \u03bcL/min, and a gradient of 5\u221240% acetonitrile (10 mM ammonium formate, pH 8) was applied over 60 min using an Agilent 1100 pump (Agilent) from which 12 fractions were collected. Fractions were desalted using homemade Stage Tips, 29 lyophilized, and analyzed with an Orbitrap Fusion mass spectrometer (Thermo-Fisher Scientific, Rochford, IL) using the SPS-MS3 method as described previously. 28, 29 Protein identification was performed using a database search against a mouse proteome database (downloaded from UniProtKB in September 2014) concatenated to a mammalian orthoreovirus 3 (Dearing strain) database (downloaded from UniProtKB in September 2014). All false discovery rate (FDR) filtering and protein quantitation was performed as previously described. 28 A protein was required to have a minimum total signal-to-noise of 100 in all TMT reporter channels, and the maximum number of missing channels was equal to 8. Data for heat maps and individual protein profiles are represented by relative intensity, which is based on the summed signal-to-noise.", "The following reagents used were purchased from Biolegend (San Diego, CA): FITC-antimouse Ly6G (1A8), Alexa Fluor 647-antimouse Ly6G (1A8), PE-antimouse Ly6C (Hk1.1), APC-antimouse Ly6C (Hk1.1), Alexa Fluor 647-antimouse CD206 (C068C2), PerCP/Cy5.5-antimouse CD11b (M1/70), Alexa Fluor 647-antimouse MHC-11 (I-A/I-E) (M5/114.15.2), and PE-antimouse H.2kb bound to SIINFEKL (25-D1.16). Antimouse CD16/32 (93) and APC-antimouse CCR2 (cat# FAB5538a) were purchased from BioXCell (West Lebanon, NH) and R&D Systems (Minneapolis, MN), respectively. Metabolic stains, DAF-FM diacetate (4-amino-5-methylamino-2\u2032,7\u2032-difluorofluorescein diacetate) (D23844), and CM-H2DCFDA (C6827) were purchased from Molecular Probes (Thermo-Fisher Scientific, Rochford, IL, USA).", "RNA extractions, cDNA synthesis, and qPCR were conducted as previously described 26 on independently collected samples. The indicated gene-specific primers were purchased from Invitrogen. Data were analyzed using Livak and Schmittgen's 2 \u2212\u0394\u0394CT method 40 and normalized to Gapdh." ] },{ "paper_id": "6861186b7e7dd18bce1b605b8fe879bf4c341207", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "personnel quickly confi rmed the diagnosis by reverse transcription-PCR and DNA sequence analysis of the samples from cerebrospinal fl uid, saliva, and trachea while the patient was still alive (13) . The patient had been bitten by a domesticated dog in mainland China 2 months earlier.", "During the SARS outbreak in 2003, the surveillance system received reports of 6 cases; autopsies were performed on 3 patients. As a result, the correlation between clinical course and pulmonary pathology at different stages of the disease was possible, and corroborative evidence for control measures was provided (14) .", "Throughout this project, we have increased the autopsy rate and established a population-based bank of specimens for future research. This collection could provide a better opportunity for corroboration or refutation of any previous diagnosis of infectious disease. This improved decision making in regard to control of infections was demonstrated in November 2003, when infl uenza virus (H5N1) was diagnosed in a patient who had a previous misdiagnosis of SARS (15) .", "Emerging Infectious Diseases \u2022 www.cdc.gov/eid \u2022 Vol. 14, No. 10, October 2008 (11) and approximately the midpoint of this study period, included all people in the age groups under surveillance at the various sites and were used to calculate the incidence rate." ] },{ "paper_id": "6861259e73b53c482dea9ed97abad64f5c1c479a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "68680c43a6baf085d18dbc567d93647d2d01ce72", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The transitions through the different stages in time is described by the system of difference equations.", "The model was implemented and run in Mathematica 4.2.", "The outbreak can be controlled if R \u03c5 < 1. In the Table, the model parameters and their baseline values are listed. In the Appendix, the formal model definition is given. " ] },{ "paper_id": "687d11c75e96fdb573a27b6ac0ec3802de6de48a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Several countries have already begun active stockpiling efforts (12) , sufficient in some cases to allow antiviral treatment of up to 25% of the population (13) . We believe that antiviral stockpiling should be considered a prudent investment that may help mitigate this impending global threat.", "T he widespread epidemic of highly pathogenic avian influenza that emerged in east Asia continues today. As the epidemic grows, so does the probability that this virulent virus will acquire genetic traits for increased personto-person transmissibility, potentially setting the stage for the next global influenza pandemic (1) .", "When one considers a ring prophylaxis strategy, the risk of \"strategy failure\" due to early antiviral stockpile depletion must be considered. If postexposure prophylaxis does not confer sufficient immunity upon exposed contacts who underwent prophylaxis, and if vaccines or additional antiviral agents do not become available, rapid consumption of available stocks may leave the population vulnerable to additional outbreak waves, potentially caused by influx of new cases. The probabilities of similar \"failure\" scenarios are difficult to assess and were not included in our analysis. Application of this strategy for the entire population without surplus antiviral reserves should therefore be considered cautiously and monitored closely." ] },{ "paper_id": "68816a089550c8de2cf3e05e3ae31238554cfa99", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Two-tailed, unpaired student's t-tests were performed, assuming equal sample variance, using GraphPad Prism. Differences were considered to be statistically significant when P < 0.05. For graphs, data are shown as mean +/\u2212 SD, unless otherwise indicated. Sample size was not specifically predetermined, but the number of mice used was consistent with prior experience with similar experiments.", "The following antibodies were used: \u03b1CD45 (30-F11), \u03b1CD31 (390), \u03b1PDPN (8.1.1 ", "Isolated tissues were fixed in 4% paraformaldhehyde (PFA) for 2-4 h, and placed in 30% sucrose until saturation. Tissue was embedded in OCT medium (Optimal Cutting Temperature), frozen, and cut into 10-20 \u03bcm sections. Sections were immunostained, and imaged using a Leica SP5X laser-scanning confocal microscope. All of the images with EYFP signal were counterstained with a chicken GFP-specific antibody (Life Technologies), followed by FITC-conjugated anti-chicken antibody." ] },{ "paper_id": "68a2a48d4c67318b019928c9e1d1e896153a6cd2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "68c75abe54d5b162839f0e67a9dceb28f5caeb05", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "693101049b23404d0ea907223cdcd0777fcc604c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6939348451319caef5c642925739778b12a41d52", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As sinh x > x whenever x > 0, and lim x\u21920", ": otherwise ", "The approximation" ] },{ "paper_id": "6993451f527d3f206e315e404687a38c97a495ff", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Rhinovirus was found the most frequently (n=67), followed by RSV (n=39) and coronavirus (n=14) ( Table 2 ).", "Nasal swab NPA Nasopharyngeal aspirate PCR Polymerase chain reaction hMPV Human metapneumovirus RSV Respiratory syncytial virus", "A total of 163 respiratory pathogens were identified in 94 children. The majority of children (73.5%) were ill for less than 4 days at the time of sampling. The median age at primary infection was 104 days (range 33-269) and the median score of symptoms was 3, indicating a mild illness (Table 1 ). In all children with an illness of 5 days or longer, one or more pathogens were detected." ] },{ "paper_id": "6999b89c08c8a72fc0e86e78e4fd67666516a63a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Provides a set of measures to avoid infection that should be followed by anyone giving or receiving care at home or at a health centre http://www.cdc.gov/ncidod/dhqp/index.html Guidelines for keeping patients and health care workers in health care settings protected from infectious diseases http://www.nhsplus.nhs.uk/nhsstaff/infection.asp Limited information", "Our search was conducted to identify websites reporting on methods and techniques that are needed to prevent crosscontamination and to control potential sources of pathogens that could be transmitted from patient to patient or from health care professional to patient. Specifically, the listed websites include updated information on isolation, standard precautions (hand hygiene, wearing of gloves, mask and gowns, manipulation of sharp objects, and proper use of patient care equipment) and transmission-based precautions." ] },{ "paper_id": "69ad5dfa7eb8ada52f203b2130a89ecf2ec5c6fa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A BAL specimen was obtained from a 47-year-old man within the first week of the onset of symptoms. A portion of the specimen was centrifuged at 2,000 rpm for 10 min, and the pellet was processed for standard EM.", "We present here the ultrastructural features of SARS-CoV in cell culture and in a bronchial alveolar lavage (BAL) specimen. Viral immunogold labeling and ultrastructural in situ hybridization (ISH) were used to further analyze the morphogenesis of this newly emergent virus.", "A large outbreak of severe pneumonia associated with human deaths occurred in late 2002 in Guangdong Province, China. Beginning in late February 2003, a similar illness was reported concurrently in Vietnam, Hong Kong, Canada, Singapore, and other countries (1, 2) . The disease, now known as severe acute respiratory syndrome (SARS), causes an influenzalike illness with fever, cough, dyspnea, and headache. Person-to-person transmission, combined with international travel of infected persons, accelerated the worldwide spread of the illness. By the time the outbreak was contained, 8,098 probable cases, resulting in 774 deaths, were identified in 29 countries (3) ." ] },{ "paper_id": "6a07f0ba055d2d843908ad7683bc36c3f46e1550", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Table S1 Searches performed on electronic sources of information.", "(DOC) " ] },{ "paper_id": "6a45024a424c3a6f8c31fd16d57756a34992b495", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6a4a0de0df03bfd7860d0732ea9d42daeac06b10", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Echovirus 30,", "DNA sequencing was performed by using an automated DNA sequencer (ABI 3730, Applied Biosytems, Foster City, CA, USA). Each RT-PCR product was sequenced in both directions to resolve possible ambiguous nucleotides.", "For more information on participating in the peerreview process of Emerging Infectious Diseases, email eideditor@ cdc.gov or call the journal office at 404-371-5329." ] },{ "paper_id": "6a53c9947edc4772e593300a652b20875114befe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To the Editor: Malaria continues to cause disease and death in millions of persons living in areas of the world where it is endemic, despite 4 decades of research on vaccines, new drugs, and alternative methods of control. Still, by far the most effective method for reducing and controlling the impact of this disease is indoor residual spraying (IRS) of insecticides. The most cost-effective and safe insecticide has been, and in many instances still is, dichlorodiphenyltrichloroethane (DDT). This intervention is continually under scrutiny, and we address these issues in this letter.", "Our study was limited by sample size and its retrospective status. Nonetheless, we demonstrated the accuracy of diagnostic criteria in an outbreak and the importance of epidemiologic criteria. Further studies are needed to evaluate the diagnostic accuracy of these criteria in a nonoutbreak situation when the case prevalence is low. ", "The National Institute of Environmental Health Sciences study (4) reported a causal association between DDT and preterm and small-for-gestational-age births but this has not been replicated for African births. The study was not based on a random population of births, and no explanation is offered for including diverse categories of births in the study population." ] },{ "paper_id": "6a558dabdd9c594f052ef2cc70f1b5202bad5203", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Methods: 3273 participants community members enrolled in a cluster randomized trial of influenza vaccine were studied.", "Conclusions: A decline in the incidence of infections with age was observed for influenza as well as for most other respiratory viruses.", "The weekly occurrence of influenza and non-influenza viruses was plotted in bar graphs ( Figure 2 " ] },{ "paper_id": "6a68dadda9052b8be43679f6aca30887677ffabb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The jamboree was held on a large site, \u2248600 m \u00d7 1,000 m. Jamboree participants were divided into 7 camps according to age: 3 camps each for participants 11-14 and 15-17 years of age and 1 camp for staff >18 years of age. The 7 camps were situated around a central fi eld for joint activities; most activities were organized within the camps. The camps were labeled A-G, according to the day the fi rst participants became sick. For 296 (91%) of 326 casepatients, the camp label was known ( Figure 1 , Table) .", "Norovirus was epidemiologically implicated as the causative agent (21) of the outbreak and was confi rmed in stool samples through a standard reverse transcription-PCR protocol (23). Typing of 7 samples from case-patients in whom symptoms fi rst developed 7-9 days after the outbreak began resulted in 3 norovirus genotypes: 2 samples typed as norovirus genotype GI.4, 1 sample typed as genotype GI.5, and 4 samples typed as genotype GII.4-2004. We did not detect any multiple infections.", "The time course of the reproduction number during an outbreak can be inferred from the epidemic curve (19, 20) ." ] },{ "paper_id": "6a98c9b230674dbe10a4e42f93436b229966ae46", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Diverse coronaviruses have been identifi ed in bats from several continents but not from Africa. We identifi ed group 1 and 2 coronaviruses in bats in Kenya, including SARS-related coronaviruses. The sequence diversity suggests that bats are well-established reservoirs for and likely sources of coronaviruses for many species, including humans.", "These data demonstrate that the CoV diversity in bats previously detected in Asia, Europe, and North America is also present, possibly to a greater extent, in Africa. The extent of this diversity among CoVs may be shown more clearly through additional studies in bats, and increased demonstration of CoV diversity in bats may require a reconsideration of how they should be grouped. The frequency and diversity of CoV detections in bats, now in multiple continents, demonstrate that bats are likely an important source for introduction into other species globally. Understanding the extent and diversity of CoV infection in bats provides a foundation for detecting new disease introductions that may, like SARS, present a public health threat.", "Of 221 bat fecal swabs examined, 41 (19%) were positive by at least 1 of the 2 seminested RT-PCR assays (Table) . One specimen had 2 distinct CoV sequences, each amplifi ed by 1 of the 2 PCR assays, giving a total of 42 distinct CoV sequences. To characterize the overall diversity of CoV sequences, in this study a phylogenetic tree (Figure 2 ) of the 121-bp fragment of RdRp was generated from 39 coronaviruses from bats in Kenya and 47 selected human and animal coronaviruses from the National Center for Biotechnology Information database based on the Bayesian Monte Carlo Markov Chain method (14) . Three of the 42 sequences were not of suffi ciently high quality to include in this tree. Some nodes had low Bayesian posterior probabilities ( Figure 2 ). Longer sequences from these viruses are needed to refi ne their phylogenetic relationships." ] },{ "paper_id": "6aadca94314fe7e81e278fbbef178f2a5bf4f538", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6c0943194d78de26d9019179760b3ee9ea77fab3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6c0dee643345c93436cfa8d58270aa887ad92e3d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6c72317009dd3ab6117004c7121c1cca52cbdbf6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Online Journal of Public Health Informatics * ISSN 1947-2579 * http://ojphi.org * Vol. 5 " ] },{ "paper_id": "6c781ec28811214ca0cb25d34a6569f975139a58", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "293-F cells were grown in suspension using FreeStyle\u2122 293 Expression Medium (Life technologies) at 37 \u00b0C in a humidified 5% CO 2 incubator on a Celltron shaker platform (Infors HT) rotating at 130 rpm (for 1 L culture flasks). Twenty-four hours before transfection, cell density was adjusted at 1.5 \u00d7 10 6 cells/ml, and culture grown overnight in the same conditions as mentioned above to reach ~ 2.5 \u00d7 10 6 cells/ml the day of transfection. Cells were harvested by centrifugation at 1250 rpm for 5 min, and resuspended in fresh FreeStyle\u2122 293 Expression Medium (Life technologies) without antibiotics at a density of 2.5 \u00d7 10 6 cells/ml.", "For size exclusion chromatography coupled with multi-angle light scattering (SEC-MALS) analysis, samples (0.2 mL at 1mg/mL) were loaded onto a Superdex 200 10/300 GL column (GE Life Sciences, 0.4 mL/min in gel filtration buffer) and passed through a Wyatt DAWN Heleos II EOS 18-angle laser photometer coupled to a Wyatt Optilab TrEX differential refractive index detector. Data were analyzed using Astra 6 software (Wyatt Technology Corp., CA, USA)." ] },{ "paper_id": "6d3a152b0d6066f6575684cce29eab1a7ed84b5a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Keywords Communicable disease control, disease outbreaks, disease transmission, influenza A virus, H5N1 subtype, historical cohort studies, mathematical model. Please cite this paper as: J. McVernon, CT McCaw, JD Mathews. Model answers or trivial pursuits? The role of mathematical models in influenza pandemic preparedness planning. Influenza 2007; 1: 43-54.", "reducing the apparent attack rate. The proportion immune (x) within a particular population determines the effective reproductive number (R) by the relationship:", "R 0 \u00bc b c" ] },{ "paper_id": "6d4c75d6c089ec27a4e019c0ea659ab27662d163", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "One limitation of the present study is its retrospective nature. Only specimens provided at approximately day 10 could be tested and analyzed. Changes of lymphocyte subsets were also not analyzed. Nonetheless, lymphocyte changes in SARS patients were well reported by two other groups who showed a consistent decrease in the peripheral blood level of dendritic cell subsets, natural killer cells, CD4+ and CD8+ T lymphocytes, and B lymphocytes (26, 27) .", "mechanical ventilation; laboratory evidence of lymphopenia, renal impairment, liver dysfunction, or abnormal urinalysis during the first 15 days; and death. Diarrhea was defined as bowel movements >3 times per day for 2 consecutive days. Oxygen desaturation was defined as <90% oxygen saturation measured by pulse oximetry while breathing room air. Some of these patients later required mechanical ventilation. Hepatic dysfunction was defined as a mean level of alanine aminotransferase (ALT), alkaline phosphatase (ALP), or both, greater than the upper limit of normal from day 10 to day 15 after onset of symptoms. Impaired renal function was defined as a serum creatinine level higher than the reference range on 2 consecutive days. Lymphopenia was defined as an absolute lymphocyte count <1,000/\u00b5L on 2 consecutive days. Abnormal urinalysis results were defined as proteinuria (>30 mg/dL), microscopic hematuria (>10 erythrocytes/\u00b5L), pyuria (>50 leukocytes/\u00b5L) on a dipstick test, or casts in urine (Combur Test, Roche Diagnostics GmbH, Mannheim, Germany) examined with inverted microscope by an experienced technician.", "SARS is predominantly a respiratory infection, which possibly spreads through the mucosal lumen or the bloodstream to extrapulmonary sites where viral replication leads to nonrespiratory manifestations. Concomitant immune dysregulation and associated inflammatory damage could accentuate disease progression and death. High viral load in NPA, with or without high viral load in serum, is a useful prognostic indicator of respiratory failure or death. The presence of viral RNA in multiple body sites also indicates poor prognosis. Early treatment with an effective antiviral agent before day 10 may decrease the peak viral load, ameliorate symptoms, and improve outcome; early treatment may also reduce viral shedding and thus the risk for transmission." ] },{ "paper_id": "6d7851259dcf3f3a78c8f34b7784b07d2cd65296", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6da81d5a45c958bbd505b7775741c9e7a94ca04b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Acute respiratory distress syndrome (ARDS) was defined in compliance with the Berlin conference on ARDS. 69 Adjunctive therapies of ARDS including prone positioning, inhaled nitric oxide (NO), and extracorporeal circulation membrane oxygenation (ECMO) were recorded.", "France has recently witnessed a nationwide outbreak of", "Data are reported as median (25thY75th interquartile range [IQR]) or proportions as appropriate. Statistical analysis was performed using GraphPad Prism (GraphPad Software, v. 5.0).", "We collected data related to antiviral therapies directed against measles. This category comprises therapies aimed directly at measles, ribavirin and polyvalent immunoglobulin (IVIG), therapies directed against measles-induced inflammation and cross-immunization, steroids and plasma exchange, and vitamin A. Variables of interest were time between measles onset and initiation of the first measles-directed treatment, duration, and dose of treatment." ] },{ "paper_id": "6dc8c0724577e0dc219ddb91ef0fc54569e56d37", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Postmortem examination of 4 STSS patients (2 confirmed and 2 probable infections) showed features of disseminated intravascular coagulation. Evidence of multiple organ damage was observed, primarily involving kidneys, adrenal glands, lungs, liver, pancreas, and heart. Histologic findings included microthrombosis (hyaline thrombus) in organ capillaries; necrosis of parenchymal cells; and congestion, exudate, and hemorrhage of interstitial vessels of kidneys, lungs, and other organs.", "We collected 348 specimens of blood (271), CSF (53), and tissue (24) from postmortem examination of 172 casepatients. We isolated S. suis from blood (36), CSF (27), and postmortem liver, spleen, and heart tissues (3). Fiftyfive (83%) of the confirmed patients were diagnosed after July 23, 2005, representing 42% (55/130) (data not shown) of all tested samples, compared to that of 26% (11/42) (data not shown) before enhancement of surveillance.", "To assess the extent of underreporting, notification statistics on meningococcal meningitis were reviewed. Meningococcal meningitis is a statutorily notifiable disease in China. Because laboratory diagnosis was not routinely performed for all meningitis patients, the figures on suspected meningococcal cases could reflect nonmeningococcal meningitis caused by other bacteria, including S. suis. In this investigation, statistics in the 12 affected prefectures of Sichuan Province from January 2003 to August 2005 were reviewed.", "Laboratory examination confirmed virulence factors in the S. suis isolates from this outbreak. They include mrp, sly, and ef, although their precise clinical role has not yet been shown. These isolates (mrp+, ef+, sly+) are related to European strains that are considered to be more virulent than North American strains (1) . Genome analysis could determine if novel virulence genes were involved." ] },{ "paper_id": "6e4cf144e298b4825f3717f6e8f03ab2bb7851e9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6e6b122886cf7d009604cdd36ef743ddb632a9c1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Reaction Assay for SARS-associated Coronavirus", "Vero E6 cells were inoculated with clinical specimens and observed for cytopathic effect, consisting of cell rounding with a refractive appearance followed by detachment from the flask surface (5) . Plaque titrations were conducted by standard methods (14) .", "A total of 340 clinical specimens collected from 246 persons with confirmed or suspected SARS-CoV infection (13) were used in this study. Specimens included oroand nasopharyngeal swabs (dry and in viral transport media), sputa, nasal aspirates and washes, bronchoalveolar lavage, and lung tissue specimens collected at autopsy. Specimen processing was performed in a class II biological safety cabinet using biosafety level three (BSL3) work practices. Three 100-\u00b5L aliquots of each specimen were distributed to vials each containing 900 \u00b5L of NucliSens lysis buffer (bioM\u00e9rieux, Durham, NC) and stored at -70\u00b0C until testing." ] },{ "paper_id": "6e771d40d5f81b24dbf7ca95bd6f86538790f9ae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6e8f150cd587ddd87cd4220351db7f0b6cd1e006", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ac-LRKLRKRLLRX-Bpg-G TET-1", "Ac-HLNILSTLWKYRX-Bpg-G THR Ac-THRPPMWSPVWPX-Bpg-G gH625", "Ac-HGLASTLTRWAHYNALIRAFGGGX-Bpg-G PFV Ac-PFVYLIX-Bpg-G SynB3" ] },{ "paper_id": "6ea2532aacbdcea4609067523e9e72fa8cd73200", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The final outcome of this depends on the balance between the effects exerted by residue substitutions and receptor density. Both can affect functional affinity of bacteria-host interactions. ", "Overall, the three strains tested exhibited similar binding to all receptor constructs that had substitutions at residue", "CHO-CC1(Q89N)" ] },{ "paper_id": "6ea2f62005558ec8368cecfec61be9635aab6410", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dr. Payne is the principal investigator and project officer for the Centers for Disease Control and Prevention study Enhanced Active Surveillance of Pediatric Infectious Diseases and Vaccines, and he conducts phase IV vaccine effectiveness evaluations. Additionally, he has led several MERS investigations and worked to establish post-Hajj acute respiratory illness surveillance in the Middle East.", "For the 7 probable case-patients, ELISA titers at 34 months ranged from <400 to 1,600, representing reduced antibody titers compared with the 13-month estimates Persistence of Antibodies against MERS-CoV (400-6,400) for all but 1 person (Table) . A nurse who worked in an intensive care unit (participant 06) and cared for confirmed case-patients during the outbreak was the only participant for whom ELISA indicated a consistent titer of 1,600 at both times.", "All surviving members of the 2012 outbreak in Jordan, their exposed contacts, and their household members who were identified serologically as either MERS-CoV positive or indeterminate were asked to consent to further participation. Participants were asked to provide a follow-up serologic specimen so we could compare 34-month results with 13-month results." ] },{ "paper_id": "6edb6aecb92419c8aa964cecabc115e732f85344", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6eeaffdb22b4e310867262d1891a1442769c7803", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The following primers were used for the construction of pMatNH-pMatH-, pMatNH-HVR-, pMatH-HVR-, pMatNH-X-, pMatH-X-RNA3: ", "To address both issues, we decided to construct a so-called mixed system, homo-and heteromolecular at the same time.", "Restriction enzymes (EcoRI, SpeI and XbaI) T7 RNA polymerase, RNasine, RQ DNase RNase free, MMLV-reverse transcriptase, Taq polymerase and pUC19 cloning vector were from Promega." ] },{ "paper_id": "6f22bd9b49b8d4e320160285611adac4cdbe9e1a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Virus particles in bunyavirus-infected cells bud upon smooth cytoplasmic membranes and are found in vesicles and also extracellularly ( Figure 2, panels C, D) . The spherical, enveloped virions have surface projections visible on the surface of some particles. Virions have a granular interior with varying densities.", "Of the variety of tissue culture cells available, many are maintained in minimal essential medium at 37\u00b0C. Once cells have become confluent, they can be inoculated with suspensions of ground tissues (e.g., lung, liver), incubated for 1 hour, and grown until there is an \u22483+ cytopathic effect. Cells are then removed from the growth vessel by scraping or with glass beads, rinsed with 0.1 mol/L phosphate buffer, centrifuged, and fixed in buffered 2.5% glutaraldehyde for 1 hour.", "Specimens are postfixed in 1% osmium tetroxide, en bloc stained with 4% uranyl acetate, dehydrated through a graded series of alcohol and propylene oxide, and embedded in a mixture of Epon substitute and Araldite. Thin sections are stained with 4% uranyl acetate and Reynolds's lead citrate." ] },{ "paper_id": "6f323c90b04d5ff3fbcfdd8ff38c805d7c13fb7f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "During 2017-2018, we obtained blood samples from 100 participants from nomadic, seminomadic, and sedentary populations. The age range was 8-76 years (average", "30.1 years). We obtained demographic and clinical information at sampling by written questionnaire, including participant age, lifestyle (nomadic, seminomadic, sedentary), role in family (husband, wife, child, etc.), underlying medical conditions, numbers of camels owned, history of tobacco use (smoking or chewing), and consumption of camel products (milk) ( We transported samples to the microbiology department at the University of Veterinary and Animal Sciences (Lahore, Punjab, Pakistan). We prepared serum samples, stored them at -80\u00b0C, and shipped them to the University of Iowa (Iowa City, Iowa, USA) for analysis.", "All but 2 of the study participants were exposed to camels. There was no significant correlation (p>0.5) between MERS-CoV seropositivity and lifestyle, presence of concurrent conditions, drinking unpasteurized camel milk, or tobacco use, with the caveat that the sample size was small.", "M iddle East respiratory syndrome (MERS) coronavirus (MERS-CoV), identified in 2012, causes a highly lethal pneumonia with a 34.5% mortality rate (https://www. who.int/emergencies/mers-cov). As of July 31, 2019, a total of 2,458 cases and 848 deaths have been reported to the World Health Organization, with all cases in the Middle East or in travelers from this region or their contacts (1) . MERS cases fall into 2 categories, primary and secondary. Secondary cases, which result most commonly from human-to-human transmission in hospitals, were most prominent during the early years of the outbreak. However, as stringent infection control measures have been followed more closely, a greater proportion of cases are classified as primary. Camels are believed to be the zoonotic source for primary infections, but a large proportion of patients describe no camel contact, raising the question of how they acquired the disease (2) ." ] },{ "paper_id": "6fb5908423137fe666c68038150e783398bd50f8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6fea38758661f89b35ac1bba4b6f78d58994d5bd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Adenovirus encodes small noncoding RNAs, known as virus-associated RNA or VAI and VAII RNA, which are generated by RNA polymerase III. This noncoding RNA plays an important role for viral replication and neutralizes the antiviral action of interferon by blocking the dsRNAinduced protein kinase (PKR), which phosphorylates and thereby inactivates the eukaryotic translational initiation factor 2 [60] . A recent study showed that a minor fraction of VAI RNA is processed by Dicer into functional RISC-associated ssRNA which can act as miRNA ( Table 1) . Blocking of VAI-derived small RNA by 2'-O -methyl AMO complementary to VAI decreased virion production [61] [62] [63] .", "Journal of Biomedicine and Biotechnology", "In an attempt to identify potential targets for VAI-derived miRNA, computational analysis was used. Putative targets include genes encoding apoptosis-related protein NAPOR and PKR-activating protein PACT. Therefore VAI RNAderived miRNA may help adenovirus to escape the actions of the host defense mechanisms [64] ." ] },{ "paper_id": "7000185289991946d912ac5f4b9451cce4d228a2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "70192ccdd02a91b15853fd3556114d83f88cc4d5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "702962623f2e16d33d405327b3de64f6751035b6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In 2006, the paediatric intensive care (PIC) cardiovascularrelated subjects that were discussed in Critical Care included sepsis, viral infection, extracorporeal circulatory support, and outcome after cardiopulmonary arrest.", "Van der Vorst and colleagues [20] reported a cohort study that retrospectively analysed continuous intravenous use of furosemide in extracorporeal membrane oxygenation (ECMO) patients. The goal was to perform an analysis comparing patients who received continuous furosemide with those who were prescribed only bolus doses of loop diuretic. Urine output and haemodynamic stability were similar in the two groups. The authors are now undertaking a prospective comparative study.", "In children, death and morbidity from sepsis and septic shock are particular problems [1] . Hypotensive, catecholamineresistant shock is increasingly recognized as a cause of death in the post-resuscitation period. Arginine-vasopressin (AVP) and terlipressin (TP) are capable of improving blood pressure but not without adverse effects such as limb gangrene [2] [3] [4] [5] [6] . The action of AVP is mediated via two receptors, vascular V1, leading to arterial vasoconstriction, and renal tubular V2.", "Eisenhut [10] undertook a review of the systemic effects of respiratory syncytial virus (RSV) infection in children. The findings indicate that this infection induces systemic disease, and it is therefore important to consider effects on cardiac rhythm, blood pressure, and serum sodium. Whether these effects are due to the presence of the virus in the tissue or whether they represent the severity of the lung disease, however, is still not clear." ] },{ "paper_id": "704f0c7ab057483ee618adfe0926eacab4227187", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7051169cee12dbca19764986a24af534e60c3ab4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Five-week-old female SJL/JHanHsd-mice (Harlan Winkelmann, Borchen, Germany) were inoculated into the right cerebral hemisphere with 1.63 \u03eb 10 6 PFU/mouse of the BeAn-strain of TMEV [10, 17] . Unless otherwise stated, all experiments were performed with groups of six TMEV-and mock-infected mice killed at 14, 42, 98 and 196 ", "Abstract" ] },{ "paper_id": "7052dc3cb4e9de110fbec8baddc369d6d53b3fba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Oro-pharyngeal swabs collected between 2004 and 2006 were preserved in 1 ml of lysis buffer (4 M GuSCN (Sigma), OS% N-lauroyl Sarcosine (Sigma), 1 mM dithiothreitol (DTT, Sigma), 25 mM Sodium Citrate and 20 pg/tube Glycogen (Boehringer Mannheim). Oro-pharyngeal swabs and faeces collected in 2007 were preserved in both 1 ml of lysis buffer and 1 ml of viral transport medium (VTM) (Eagle's minimal essential medium (EMEM) supplemented with 10 UI/ml of penicillin, 10 lg/ml of streptomycin, 160 lg/ml of gentamicin, 50 UI/ml of mycostatin and 1% of bovine serum albumin). All samples were frozen at -80\u00b0C before sending them to the Rabies Reference Laboratory at the Centro Nacional de Microbiolog\u00eda, ISCIII in Madrid. Faecal samples were clarified by centrifugation. Total nucleic acid was extracted from a 200 ll aliquot of each specimen for PCR assays and the rest were stored to -80\u00b0C in two different aliquots. Final pellets were always resuspended to 55 ll of water.", "The emergence of infectious diseases is a major threat to global public health in this century (WHO, World Health Report http://www.who.int/whr/previous/en/index.html) and many of these new infectious human diseases are caused by viruses emerging from wildlife. In the last 50 years, more than 30 new infectious human diseases have been identified (WHO, World Health Report http://www.who.int/whr/previous/en/index.html) including the Severe Acute Respiratory Syndrome (SARS). The aetiological agent of this disease was identified as a previously unknown coronavirus (SARS-CoV) [1] and BatCoV are putative precursors of SARS-CoV [2] . The outbreak of SARS-CoV and subsequent identification of two additional human coronaviruses (HCoV-NL63 [3] and HCoV-HKU1 [4] ) has drawn human and animal health attention to Coronavirinae subfamily, that includes three genera, Alphacoronavirus (a CoV), Betacoronavirus (b CoV) and Gammacoronavirus (c CoV), replacing the classical groups 1, 2 and 3 [5] (http://talk.ictvonline.org/ media/g/vertebrate-2008/default.aspx).", "To determine the presence and distribution of putative zoonotic CoV in Iberian bats, 576 individuals from 26 bat species were captured and sampled in 13 different locations throughout Spain during 2004-2007 (Fig. 1) . These samples were collected in the context of bat rhabdoviruses and lyssaviruses Surveillance Program in Spain. Most of the sampled bat species are also distributed across Europe, but Eptesicus isabellinus is a meridional serotine bat restricted to North Africa and the Iberian Peninsula [23] , and Myotis escalerai is endemic in the Iberian Peninsula. Bats were caught with mist nets mainly as they left diurnal roost and by hand with polyethylene butterfly nets within roosts. Oro-pharyngeal swabs (n=390) between 2004 and 2007 as well as faecal samples from individual bats (n=216) in 2007 were taken before bats were released (Table 1) .", "In conclusion, previous studies showed the presence of BatCoV in Europe. However, to our knowledge, this is the first report describing the presence of CoV RNA in Iberian bat species. Phylogenetic data indicate high diversity, wide distribution and complex ecology of CoV in bats captured in diverse Spanish locations. The sequences reported herein provide new insights into the diversity of coronaviruses and describe new phylogenetic linages that appear to diverge from all genotypes previously detected in other European locations. Future studies should clarify whether such apparently high diversity reflects the bio-geographical peculiarities of the Iberian Peninsula or not. This study contributes with a new dataset to the global surveillance of emerging BatCoV with pathogenic potential in humans. Our data reinforce the notion that the ecology and transmission of CoV in bat reservoirs is far from being completely understood and that more studies will be necessary to evaluate the magnitude of the potential threat that these viruses pose to human health." ] },{ "paper_id": "7084dcfb81d40460f7ea05abe01a04285a45b095", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "70cb54e32fbc19f5a34a37e75cc9e9d6afc6c2f2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dr. Goldmann, who is professor of pediatrics at Harvard Medical School, has a research focus on the epidemiology and control of hospitalacquired infections, especially antimicrobial drug-resistant infections in intensive care units. In addition, he studies the epidemiology and prevention of medical errors and adverse events in pediatrics. Dr. Goldmann collaborates with colleagues at the Channing Laboratory in Boston regarding the pathogenesis of staphylococcal foreign body infections and is working to develop imunologic approaches for their prevention.", "The common cold is a profound nuisance in everyday life, although seldom a cause of serious illness. The average child can expect to have four to eight episodes per year, and adults three to five infections. Many viruses, such as parainfluenza, RSV, and coronavirus, can produce similar symptoms, but rhinovirus is by far the most frequent etiologic agent. Repeated colds are virtually guaranteed because there are >100 distinct rhinovirus serotypes, and infection with one serotype does not confer substantial immunity against the others.", "Influenza is a substantial threat to hospitalized patients despite the availability of a relatively effective vaccine and two classes of drugs (M2 ion channel inhibitors and neuraminidase inhibitors) shown to prevent infection in clinical trials (24) . Although influenza is widely viewed as affecting primarily elderly patients and adults with coexisting illnesses or conditions, such as chronic pulmonary and cardiac disease, nosocomial transmission has been well documented in young children (25, 26) . Perhaps nosocomial disease is less frequently diagnosed in hospitalized children because infants are unable to articulate many of influenza's characteristic symptoms, and influenza often presents simply as an episode of fever in this population." ] },{ "paper_id": "713670f3bba541ae77e6ac7bb32c9ea27c01e19d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Abu Dhabi is the largest of the 7 emirates of UAE. It has \u22482.3 million residents, including 1.9 million expatriates, and 35 hospitals (14).", "Descriptive analysis of healthcare-associated cases and clusters was conducted by using SAS version 9.3 (SAS Institute, Inc., Cary, NC, USA). Fisher exact test and independent t-test were used to compare clinical and demographic characteristics of source-cases and healthcareassociated cases; a 2-sided \u03b1 level of 0.05 was used to determine significance.", "All case isolates were laboratory confirmed as positive by rRT-PCR for the upstream E gene and open reading frame 1. Average time between sample collection and laboratory results was 1 day (range 0-3 days). All 23 PCR-confirmed case isolates included in the validation sample were verified by using the N2 assay at CDC." ] },{ "paper_id": "71762af6792d1aae86e6632954a6ca0085ee86bb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "721ae2395d3848eebb9fea8ec837109d4cee111e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "724be3f77bbbdcc7e73de43f4cfe22335ffb9ef9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "72a5640aa0c307fbe171ca7ad55d3fda48b53988", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "72af637abdc92f045426ef76b39818510cd5053a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "AS has received consulting income from BOC, GSK, Hamilton Medical, KCI, Maquet and Ventana. AS has also been paid for being a member of the following Data Safety and Monitoring Boards: Asthmatx, Broncus and Leo Pharma.", "This article summarizes the original research in the field of respirology that was published in 2005 in Critical Care. We grouped the articles into subcategories to help the reader get a rapid overview of the key articles and thus focus on topics of interest.", "In sepsis and ARDS a cascade of inflammatory responses leads to production of proinflammatory cytokines. This cascade might be inhibited by eliminating the pathogenic toxins using haemoperfusion with a polymyxin B immobilized fibre column. In a prospective uncontrolled observational study, Kushi and coworkers [19] used this technique in 36 patients with ARDS caused by sepsis. Haemoperfusion reduced levels of plasminogen activator inhibitor-1, neutrophil elastase and interleukin-8 in blood at 48 hours, and improved arterial oxygen tension/fractional inspired oxygen ratio at 96 hours after the start of treatment.", "Abrahamson and coworkers [27] described the effective implementation of a simulation protocol during SARS to train health care workers in managing cardiac arrest while wearing unfamiliar equipment and following a modified advanced cardiac life support protocol. Simulation provided insights that had not been considered in earlier phases of development of the protocol. It was used to detect and correct flaws and omissions in a protocol specific to treatment of SARS patients. The insights gained from this experience will be valuable for future infectious disease challenges in the ICU." ] },{ "paper_id": "72eea61339d1f964cc302b20af2842e8ca77d3bb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For microbiologic studies, selected organs and swabs were collected by using sterile plastic tubes. Serum was separated from the blood clots by centrifugation. All samples were transported on dry ice and stored at -80\u00b0C until testing.", "A heavy suspension of the microorganisms was heated for 10 min at 95\u00b0C followed by 1-min centrifugation at 8,000 rpm to precipitate the lysed cells. The supernant containing the genomic DNA was then moved to a clean centrifuge tube to be examined. PCR amplifi cations were performed in a 25-\u03bcL reaction mixture containing 5 \u03bcL 5\u00d7 Green GoTaq PCR buffer (Promega, Madison, WI, USA), 0.4 \u03bcmol of each primer, 200 \u03bcM each dNTP, 1 U Taq DNA polymerase (Promega), and \u224820 ng of template DNA. Two oligonucleotides, BhCS781.p (5\u2032-GGGGACCAGCTCATGGTGG-3\u2032) and BhCS1137.n (5\u2032-AATGCAAAAAGAACAGTAAACA-3\u2032) were used as PCR primers to generate a 379-bp amplicon of the Bartonella gltA gene. Positive and negative controls were included with each PCR to evaluate the presence of appropriately sized amplicons and contamination, respectively. Each PCR was performed in a PTC 200 Peltier thermal cycler (MJ Research, Inc., Waltham, MA, USA) or in an Eppendorf Mastercycler Gradient (Eppendorf, Westbury, NY, USA). PCR products were separated by 1.5% agarose gel electrophoresis and visualized by ethidium bromide staining.", "The level of gltA sequence identity between 16 Bartonella genotypes identifi ed in E. helvum bats varied greatly, ranging from 78.6%-100%. Eight genotypes (sequence variants) were clustered around 4 clades (genogroups), which are marked as E1, E2, E3, and EW in Figure 2 . Intergroup identity values ranged from 78.6%-87.2%, much higher values than the suffi cient criteria proposed for species demarcation within the Bartonella genus (28) .", "Species were identifi ed phenotypically by using available fi eld keys. Additionally, representative tissues of each collected species were submitted for confi rmation to Guelph University (Guelph, Ontario, Canada), where partial sequences of the cytochrome oxidase gene were generated and compared with those available from the database of the Barcode of Life Data Systems (BOLD; www.barcodinglife.org). Because the taxonomy of African bats is under development and reference sequences for several species were unavailable in the BOLD database, the examined sequences were identifi ed to the genus level only." ] },{ "paper_id": "7317e3c5fd2c9bd0c1581a9e05b11d5e4203c622", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A formal definition of sepsis has long been tried by several researchers and must lack specificity given the broad spectrum of reactions to pathogens.", "High-dose corticosteroid treatment (>300 mg hydrocortisone per day)", "Low-dose corticosteroid treatment (\u2264300 mg hydrocortisone per day)", "Bicarbonate therapy is not recommended for the purpose of improving haemodynamics or reducing vasopressor requirements in the presence of lactic acidosis and pH >7.15 (DII) [38, 108]." ] },{ "paper_id": "731829483bf1acb462e1be27f8873725169e2e88", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "736b7d64512deea08729df55af4d2aa0d1423cce", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sequence editing and multiple alignments were performed with Bioedit software package version 2.1 (24) . Phylogenetic analysis (neighbor-joining and unweighted pair group method) with arithmetic mean with bootstrap analysis (1,000 replicates) and no-distance correction was conducted by using MEGA4 software (25) .", "The conservation of such a sequence motif across multiple viral families suggests that it may play a broad role in the biology of positive-stranded RNA viruses (28) , although the exact function of this conserved region is still unknown.", "Upon EM observation, none of the AstV-positive samples contained SRV-like particles. Rotaviruses, coronaviruses, and phages were detected in 8 samples in various combinations, and 2 samples did not contain viral particles (Table 1) ." ] },{ "paper_id": "73c2273b28118421239c1275af22d309f1a44e4b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "DNA must be purified from cellular material in such a manner to prevent degradation. The absorbance ratios (A260/A280) of DNA samples were found to be in range of 1.68-1.73, indicating the purity of DNA ( Figure 1B ).", "Methods for sex determination using PCR for amplification of SRY gene have also been reported (11, 12) . These methods can indicate a male genotype by the presence of the amplified product of", "By means of the Primer Explorer V.4 software (specific for LAMP), specific primers were designed based on SRY genes (GenBank accession JQ811934.1) (Table 1). Figure 1A shows the schematic position of LAMP primers within SRY gene. A basic set of four primers was needed, including FIP (Forward Inner Primer), BIP (Backward Inner Primer), F3 (Forward Outer Primer), and B3 (Backward Outer Primer) to identify six distinct regions on the target DNA. To accelerate the LAMP reaction, two additional primers, i.e., LF (Loop Forward Primer) and LB (Loop Backward Primer) were also used. FIP consisted of the complementary sequence of F1, a T-T-T-T linker, and F2. BIP consisted of B1c, a T-T-T-T linker, and the complementary sequence of B2c. Primers F3 and B3 were located outside F2 and B2 regions, while loop primers LF and LB were located between F2 and F1 and between B1 and B2, respectively (13) (14) (15) (16) . Finally, " ] },{ "paper_id": "7415b0e3fd0142110b218a154658e0171feb4a91", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "N orovirus is a major cause of viral gastroenteritis worldwide, accounting for at least 28% of all foodborne outbreaks (1) . However, its pathogenesis is poorly understood (2) . Although the disease is usually perceived as mild and self-limiting (symptoms generally subside within 2-3 days in otherwise healthy persons) (1, 2) , protracted diarrhea and serious complications may develop in elderly or immunocompromised patients (2) (3) (4) .", "Stool samples were collected from all patients when initially observed and processed immediately for RNA extraction. Diagnosis of norovirus infection and its quantitation were based on real-time reverse transcription-PCR assay of stool samples as described (5) . The lower detection limit of the assay was 2 \u00d7 10 4 copies of cDNA/g stool. Phylogenetic studies were also performed as described (5) .", "Stool samples from 40 patients were analyzed. Mean \u00b1 SD age of patients was 60.4 \u00b1 24.3 years and 15 (37.5%) were males. Seventeen patients (42.5%) had pre-existing medical conditions, and 21 (52.5%) were hospitalized. Diarrhea was observed in 100%, whereas vomiting and fever were observed in 64.9% and 36.8%, respectively. Median duration of diarrhea was 3 days (range 2-6 days). Median fecal cDNA concentration was 8.93 log 10 copies/g stool (interquartile range 8.22-10.24 log 10 copies/g stool)." ] },{ "paper_id": "746397a8fa84468dcf0a9e8465d7cc090441f058", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Urinary antigen test for Legionella pneumophila and Streptococcus pneumoniae were negative as were IgM antibodies for Mycoplasma pneumoniae.", "PCR for the identification of Adenovirus, Human Coronavirus, Metapneumovirus, Chlamydia pneumoniae, Haemphilus influenzae, Legionella pneumophila, Mycoplasma pneumoniae and Streptococcus pneumoniae. antigens of Aspergillus and Ziehl-Neelsen stain for acid-fast bacilli and nucleoid acid amplification tests to identify Mycobacterium tuberculosis in blood and bronchoalveolar lavage were also negative.", "Admission chest X-ray showed diffuse bilateral interstitial and alveolar infiltrates ( Figure 1A ); computed tomography (CT) scan of the thorax showed diffuse asymmetric alveolar infiltrates, ground-glass opacities associated with reticulo-nodular pattern ( Figure 1B) . Arterial blood gas performed by administering oxygen FIO 2 60% by Venturi mask showed a severe acidosis (PaO 2 44 mmHg, PaCO 2 121 pH 6.96)." ] },{ "paper_id": "7478fba4c601f5330f85e76a8be0182effdb9ae5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dr. Aldana Reyes is a senior lecturer in English literature and film at Manchester Metropolitan University and a founding member of the Manchester Centre for Gothic Studies.", "Adults have been identified as 1 of 3 key underserved audiences in terms of engagement with science (6) . The reading group format addresses this need and contrasts with unidirectional science communication activities from scientists (experts) to members of the public (nonexperts) (7) in that reading groups provide an opportunity for adults to contribute their knowledge, experience, and perceptions about the reading subject matter on a level platform.", "Dr. Verran is a professor of microbiology at Manchester Metropolitan University, Manchester, UK. Her laboratorybased research focuses on the interactions occurring between microorganisms and inert surfaces, but she also investigates how art and literature can facilitate discussion and enhance understanding of infectious disease epidemiology among students and public audiences." ] },{ "paper_id": "748ef951c31564eb3eb37a7bc947ce5ff4cb5fdd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "From eqs 1 and 2", "Solving for [RS] gives", "Substituting [P] in eq 5 by eq 11 gives" ] },{ "paper_id": "74a6430d5021dafa50400460adc13f0e8ee4d457", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "74ae352ed6606527cca17ab3b773687251f38590", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "74f8669398e63312feb0b386234ce36ee8d873f6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Article parts per million (ppm) and coupling constants (J) are referenced in hertz (Hz) . Fourier transform infrared (FT-IR) spectra were reported in reciprocal centimeters (cm \u22121 ) recorded on a BRUKER Tensor 27 (KBr beam splitter) FT-IR spectrometer. Organic solvents were concentrated on EYELA SB-1200 Rotavapor and vacuum pump EYELA CCA-1111. Silica gel (60\u2212120 mesh) was used for purification of crude products by column chromatography. Thin-layer chromatography (TLC) presented on precoated silica gel 60 F254 MERCK and were visualized by exposing UV light or by iodine vapors.", "General. All reactions were carried out with dry solvents under a nitrogen atmosphere at room temperature. Oven-dried rubber septum-containing round-bottomed flask and glass syringes for the addition of reactants and solvents were utilized for these reactions. THF and other solvents were dried based on a standard literature procedure. All purchased reactants and reagents were used without further purification. Imidazolium salts were synthesized in our lab. BRUKER NMR instruments used for 1 H NMR (600, 500, and 400 MHz) and 13 C NMR (150, 125 , and 100 MHz) spectra were recorded in CDCl 3 and acetone-d 6 with regard to tetramethylsilane as the reference for chemical shift values. Chemical shifts (\u03b4) were described in ", "Article DABCO compared with DBU. 63 At this time, the nucleophilic attack of the NHC acrylate zwitterionic species I to the electrophilic C 3 -keto carbonyl site of NS-isatin forms the second zwitterionic species V followed by proton transfer toward the elimination of free-NHC to form the aza-Michael\u2212 Baylis-oxindole derivative VI." ] },{ "paper_id": "758e9c4e4ff49b4e2a9a3a14014edfc567e521fa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The views expressed in this paper are not necessarily shared by the Australian Government Department of Health.", "Dr. Selvey is Director of Epidemiology and Biostatistics at the Curtin University School of Public Health. Her research interests include the epidemiology and control of communicable diseases.", "The use of T-HANs and other communication methods is a potentially worthwhile border measure that could assist with the early identification and appropriate management of incoming passengers with a disease of interest. Such measures need to be accompanied by the provision of appropriate health care for travelers who are deemed ill, and must be easily understandable. As with any health communication endeavor, effective communication requires multiple modes of communication and tailored messages (38) ." ] },{ "paper_id": "75ebad1e8641e5fe2a51214f4d97742ab59a8dae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Background: Severe acute respiratory syndrome (SARS) has claimed 349 lives with 5,327 probable cases reported in mainland China since November 2002. SARS case fatality has varied across geographical areas, which might be partially explained by air pollution level.", "Our studies demonstrated a positive association between air pollution and SARS case fatality in Chinese population by utilizing publicly accessible data on SARS statistics and air pollution indices. Although ecologic fallacy and uncontrolled confounding effect might have biased the results, the possibility of a detrimental effect of air pollution on the prognosis of SARS patients deserves further investigation.", "Publicly accessible data on SARS morbidity and mortality were utilized in the data analysis. Air pollution was evaluated by air pollution index (API) derived from the concentrations of particulate matter, sulfur dioxide, nitrogen dioxide, carbon monoxide and ground-level ozone. Ecologic analysis was conducted to explore the association and correlation between air pollution and SARS case fatality via model fitting. Partially ecologic studies were performed to assess the effects of long-term and short-term exposures on the risk of dying from SARS." ] },{ "paper_id": "75f820d5baa32148f309c3661128a6c10a2eee24", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "762d9040c711ef9f7ad28c28b7d4b65f9e51296d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "766398b576402973f5fe2e2e5b0c5a9d6017b0c0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Looking back at my time in county service and my previous experience as a state Public Health Commissioner, a number of important lessons stand out. Some have already been mentioned but merit repetition.", "Copyright \u00a9 2015 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.", "We must continue to initiate these discussions in the public sphere until these interconnections are universally understood and are the basis for political actions." ] },{ "paper_id": "7685358860b9b2a9d1dd54d63813a4f115814b85", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "768fb5bff1898a4076849b7d5318402a62cb0bfe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "76afb423879efd78bcd26ac2be9086727030f990", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "These cases illustrate the diagnostic difficulties that can occur in evaluating patients for SARS. The ability to confidently confirm or negate a diagnosis allows control efforts to focus on the most important cases and minimizes unnecessary social and economic disruption. The cost of missing a case can be high if further spread occurs, and the cost of false-positive diagnosis to the patient, family members, healthcare facility, and community can also be substantial.", "Sequences from the 3\u2032 third of the SARS-CoV genome were obtained from overlapping RT-PCR products that covered the envelope (E), membrane (M), and nucleocapsid (N) structural protein genes, plus several other gaps of unknown function, such as S-E gap between S ORF and E ORF and M-N gap between S ORF and E ORF, by using a previously described method (16) .", "Dr. Liang is a professor and virologist specializing in arboviruses with a focus on Japanese encephalitis and alphavirus research." ] },{ "paper_id": "76bd7e45c1c026b89423857cad797033b30aca39", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "76d2a690120b972075f49370c5b27aaa61763df2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "BAC laws are hypothesized to exert their effect primarily through powerful psychological deterrence of alcohol consumption (28) . Most drivers are never stopped and tested for suspected alcohol-impaired driving (28) . By virtue of their threatened penalties (e.g., loss of driver's license, jail time, fines, public humiliation), these laws deter drivers from consuming alcohol or cause them to limit their consumption before driving.", "Competency of public health professionals to apply those laws Information on public health law best practices ", "Essential legal authorities", "In 1999, the World Health Organization (WHO) initiated the Framework Convention on Tobacco Control (FCTC) as an international treaty focusing on a health issue (34) . In May 2003, the treaty text of the FCTC was unanimously adopted by the World Health Assembly (35) . This landmark health treaty will be put into force when 40 member states have signed and ratified it. The FCTC is both an international legal framework for tobacco control (e.g., addressing international cigarette smuggling issues) and a framework for a broad range of legal, regulatory, and policy approaches (e.g., excise taxes, clean indoor air policies, restrictions or bans on advertising and promotion, package warnings and labeling, product regulations, and ingredient disclosures) that all WHO member states are encouraged to implement.", "In 2000, alcohol-related motor-vehicle crashes resulted in 17,380 deaths and more than 300,000 injuries in the United States (27) . The BAC at which the majority of drivers are impaired can be established as the legal per se limit for motor vehicle operation (illegal per se means that a BAC above the set limit is a violation in and of itself and that actual impairment need not be demonstrated). Until recently, most states set this level at 0.1%. As early as 1983, however, some states lowered the BAC limit to 0.08%." ] },{ "paper_id": "76f130b68624f44fc610de3deae25f2ba703b304", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "76fa539727b0df902f541bf999c6b3912207fd8c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7716cb3ff9dd83dbbd2b5c85eb25b31436a1bd9c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7718cbb91f57cc5e715277c2c6fda2f404573c1f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Macrolides have increasingly been used for their immunomodulatory properties in a wide range of chronic disorders.", "These will not be discussed in detail but results in chronic, inflammatory pulmonary disorders will be highlighted with a goal of presenting the rationale for their potential use in COPD.", "Bronchiectasis is a disorder of the bronchi and bronchioles manifesting cough, chronic sputum production, dyspnea, and wheezing (Barker 2003) . The cornerstones of therapy include early identifi cation and treatment of acute exacerbations, suppression of the microbial load, treatment of underlying conditions, promotion of bronchial hygiene, control of bronchial hemorrhage, surgical resection of extremely damaged/focal disease and reduction of excessive pulmonary infl ammation (Barker 2003) ." ] },{ "paper_id": "7740cafff20a808697d26091851c30416eadfe53", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "777328a5bc26d551df06e62b64682c03c25dde03", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We thank Simone Miller, Cornelia Lombardi, and Rita de Giuli for expert technical assistance." ] },{ "paper_id": "77992c5e2e8442d8786bd1c80ec5b336680ed03b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "77fd0472e928d4de06d38d23f069467e0bc6b4c0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7871f62facbecd9f3a12f4278c7aefaaec8899d6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As discussed above, the majority of high-throughput data to emerge from the biodefense field has been microarray mRNA expression data, rather than from high-throughput protein interaction data that directly lend itself to network analysis. However, genomics-and proteomics-level analyses have produced interaction networks that are beginning to yield some consistent and overlapping signaling pathways across different model systems, and novel computational approaches are providing alternative strategies for virus comparison and attenuation.", "As new viruses continue to emerge and the risks from emerging and remerging pathogens remain, the need for vaccines against these pathogens remains significant. The introduction and spread of West Nile virus to North America illustrates how quickly viruses can become established in a new area and present novel threats to public health [75] . The continuing investment in biodefense and emerging pathogens will result in even greater amounts of basic data to input into novel bioinformatics tools. As our understanding of the molecular determinants of protection and pathogenesis continues to grow, the development of safe, effective vaccines to these important pathogens will continue to accelerate.", "The use of global approaches, particularly microarray gene expression technology, has provided a wealth of information detailing the host responses to infection. While these data are often limited to transcription rather than expression at the protein level, they have provided significant insight into which classes of host genes are up-and downregulated in response to virus infections. A novel application of this technology is to use the differentially expressed genes as a marker of upstream transcription factor activation using bioinformatics tools such as CARRIE [24, 25] . In this way, host signaling pathways activated or repressed by virus infection can be inferred and studied further, in particular those inhibited by virus-induced proteins that are critical in the pathogenesis of the virus (see below)." ] },{ "paper_id": "78cd9e16e1faec0b2b68a13b58d5be78408269b0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "78e7570c26bdf3477fad36eed435207dffe21305", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "791bb7fd75fdeed7781334dfb35f216bcea492df", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors declare no competing financial interest. ", "In order to obtain urethane in good yields, dense-phase CO 2 under high pressure was necessary to lower the major side reactions, namely imine formation from acetone and alkylation of amines by alcohols.", "AD, Alzheimer's disease; Cat-D, cathespsin D; FAAH, fatty acid amide hydrolase; PPAR, peroxisome proliferator-activated receptor; GABA, \u03b3-amino butyric acid; HAART, highly active antiretroviral therapy; bis-THF, bis-tetrahydrofuran; BACE1, beta-site amyloid precursor protein cleaving enzyme 1; MDR, multidrug resistant; NNRTI, non-nucleoside reverse transcriptase inhibitors; ADEPT, antibody-directed enzyme prodrug therapy; GDEPT, gene-directed enzyme prodrug therapy; MCT1, monocarboxylate transporter type 1; SMVT, sodiumdependent multivitamin transporter; CES1, carboxylesterases 1; MAGL, monoacylglycerol lipase \u25a0 REFERENCES " ] },{ "paper_id": "791e42babcf7e8b6edf94918b034f15ce32ec402", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "79b3b568e3410a49377a23263dc326927d54e187", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Phylogeography, an emerging discipline in public health, allows researchers to model the evolution and migration patterns of viruses, and can be an especially useful tool for studying rapidly evolving viruses like RNA viruses [1] . Given that RNA viruses such as influenza, Ebola, and hepatitis C account for approximately a third of emerging and re-emerging infections, phylogeography is growing increasingly popular among public health researchers. It allows researchers to estimate the origin and drivers of infectious diseases, and has recently been applied to study outbreaks of Ebola [2] , avian influenza [3] , and Zika virus [4] , among others.", "Lexical features encapsulate various lexical properties of the token to be classified. These include, the token itself and n surrounding tokens (we experimented with several values of n and chose n=4 for our final experiments). In addition, we derived a number of simple additional lexical features such as lowercased tokens, capitalization, presence of digits, tokens with any punctuations removed and Part-of-Speech (POS) tags for the token and surrounding tokens.", "Phylogeographers need precise locations of hosts infected by a virus of interest to build models of its origin and spread. Such locations are often not available in existing databases and phylogeographers are forced to read original research articles to search for the information. Depending on the size of the dataset, this can be a very arduous manual process and motivate its automation using NLP systems.", "Recent studies on NER apply deep learning techniques to automatically learn features used during the classification of the Named Entities (NEs). Although the mechanism is still not fully understood, in [18] the authors show how different layers of a deep convolutional neural network capture morphological features from character-level vectors, as well as syntactical/semantical features from word-level vectors. Without any handcrafted features, the authors' classifier achieved better performances than state-of-the-art systems on two well-known corpora. These results were confirmed in [19] , among other publications." ] },{ "paper_id": "79b9de8046987ccda00f034d86d599edb77bc32b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "79e0f0277142b321ccd75630f2405565e2ee64f3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7a054783434b19b3fb546990d25b735659fc851a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Analysis. 1 H NMR spectra were recorded at 25\u00b0C on either a Bruker Avance 400 (400 MHz) or Bruker Avance 500 (500 MHz) instrument and processed using MestReNova NMR processing software. Chemical shifts (\u03b4) are reported in parts per million (ppm) downfield from tetramethylsilane and referenced to the residual protium signal in the NMR solvents. Data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, and q = quartet), coupling constant (J) in Hertz (Hz), and integration. 13 C spectra were recorded at 25\u00b0C on a Bruker Avance 500 instrument operating at 126 MHz. Chemical shifts (\u03b4) are reported in ppm downfield from tetramethylsilane and referenced (except in D 2 O) to the primary carbon resonance in the NMR solvent. FT-IR spectra were recorded on a Shimadzu FT-IR spectrophotometer. High-resolution mass spectra (HRMS) were acquired at the University of Buffalo Chemistry Department Mass Spectrometry Facility, Buffalo, NY.", "The infections were performed using TZM-bl reporter cells that contain stably integrated firefly luciferase that is driven by the HIV-LTR promoter. Therefore, luciferase is expressed upon successful HIV infection. 53 Triplicate infections in 96-well plates at 10,000 cells/well with 500 pg p24/well proceeded for 48 h before the addition of SteadyGlo Reagent (Promega) to each well for 30 min. Luminescence was measured as a quantitative metric for changes in viral infectivity in the presence of compound. " ] },{ "paper_id": "7a5bc9a848fbf197657c7ccb6f8d7ae361a4b9d2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7a776da1c0d3e0368750bd6ef1984d371b97b102", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7a8f5602e6965231fd63c55c95b2d1523c3f8091", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Specimens from symptomatic children who tested positive for KIV or WUV were also screened for human bocavirus (HBoV); human metapneumovirus (hMPV); human coronaviruses (HCoV) 229E, NL63, and HKU1; and human picornaviruses (including rhinoviruses [HRV]) by using previously described methods (6) (7) (8) (9) (10) (11) (12) . To screen for human parainfl uenzavirus type 4 and HCoV OC43, RNA extraction and reverse transcription were performed as previously described (7) . The primers used to amplify hPIV4 were 5\u2032-GCGAGAGGATCCAGCTGGTGGC-3\u2032 and 5\u2032-GCGCCCTAATCTTTCCTGTTGATGG-3\u2032. The primers for HCoV-OC43 were 5\u2032-GCATAAGCCCC GCCAGAAGAGGAG-3\u2032 and 5\u2032-GCGCTGACGCTGTG GTTTTGGACT-3\u2032.", "Detection of WUV in 3 patients hospitalized since birth suggests the potential for nosocomial, congenital, or perinatal infection. One of these children had 2 respiratory Emerging Infectious Diseases \u2022 www.cdc.gov/eid \u2022 Vol. 14, No. 11, November 2008 1767 (13). This fi nding may represent persistent or latent infection.", "Of 25 WUV-positive children whose records were available for review, 11 (44%) had underlying illnesses. Of the 6 asymptomatic children whose specimens tested positive for WUV, 1 had a history of prematurity and the other 5 had no underlying illnesses." ] },{ "paper_id": "7aa5c87d322c83d77e3a4d1a3ae55b0bace68625", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7abd3b3fc21fc2ff41ef6a23f988236f2065a045", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7af37cc39c5f2eeb88b98ea439da7fc687eddb60", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The natural transmission routes of the three feline haemotropic mycoplasmas -", "Statistical analyses were performed using the Excel add-in Analyse-it (Analyse-it Software, Leeds, UK) and Graph-Pad Prism (GraphPad Software, San Diego, CA, USA). For the correlation analyses, the Spearman rank correlation test was used (p S ). Continuous variables were analysed for significant differences among the three groups using the Kruskal-Wallis test ( p KW ) and Dunn multiple comparisons post-test. The comparisons between two groups were made using the Mann-Whitney U-Test (p MWU ). A p-value less than 0.05 was considered significant.", "The recombinant HspA1 protein of Mhf (FJ463263) was used as an antigen. The 899 bp fragment was ligated into the pQE-30 Xa Vector (Qiagen, Hombrechtikon, Switzerland), which was then transformed into Top10 Escherichia coli cells (Invitrogen, Basel, Switzerland). Protein production, SDS-PAGE, and immunoblotting were performed as described previously [15] , with the following modifications: protein expression was induced using 1 mM IPTG, and E. coli cultures were grown in LB medium containing 100 lg/mL of ampicillin. The 6xHis-tagged protein was purified by nickel affinity chromatography (Qiagen) or chelating sepharose (GE Health care biosciences, Uppsala, Sweden). A total of 10 lg of antigen was used per stripe, and the feline samples were incubated at a dilution of 1:100. Immunoreactive proteins were visualised using horseradish peroxidase-conjugated goat anti-cat IgG (Sigma-Aldrich) and 4-chloro-1-naphthol as substrate.", "Three haemotropic mycoplasmas, the causative agents of feline infectious anaemia, have been described in cats: Mycoplasma haemofelis (Mhf), 'Candidatus Mycoplasma haemominutum' (CMhm) and 'Candidatus Mycoplasma turicensis' (CMt) [6, 23, 25, 27, 36] . Recently, a fourth species similar to 'Candidatus M. haematoparvum' has been suggested to infect cats [29] . The pathogenic potential of the feline haemotropic mycoplasma isolates studied to date varies, and immunosuppression or pre-existing retroviral infections may potentiate the severity of the anaemia [9, 36] ." ] },{ "paper_id": "7affb8951346d72458b9aa05be31531d43695add", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7b329eb91fdc5ea7e947a48e414a7a1f10ed40c9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analyses were carried out using R software version 2.9.0. (The R Foundation for Statistical Computing, Vienna, Austria). Longitudinal effects (time) on antibody titres of the different groups were compared to each other by multivariate analysis of variance (MANOVA). A p value < 0.05 was considered to be statistically significant.", "Week 0" ] },{ "paper_id": "7b5f035fa37b84d80757e91805bdb1dc470f3f7c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We generated recombinant retroviruses pseudotyped with arenaviral GPs by transfecting HEK293T cells in a 1:1:1 ratio of plasmids encoding the respective arenaviral GP, the MLV gag and pol genes, and the pQCXIX retroviral vector (BD Biosciences) expressing GFP, as previously described 17 . We harvested cell supernatants 24 h post-transfection and filtered them through a 0.45 \u03bcm filter. We transfected CHO cells with plasmids expressing wt-hTfR1 or hTfR1-R208G, and replated the cells at 24 h for flow cytometry and pseudovirus infection. At 48 h post-transfection, we assessed TfR1 expression levels by flow cytometry using an anti-flag M2 antibody. In parallel, the cells were infected with the pseudoviruses for 1 h. Forty-eight hours after transfection, we detached the cells with trypsin and measured the GFP expression levels by flow cytometry. We normalized GFP expression levels to that of mock-transfected cells.", "We used ClustalW 35 to align the NW arenaviral GP1 and TfR1 sequences and adjusted the positions of gaps in the sequence alignments by referring to the three-dimensional structures. We selected the following GP sequences: AMAV (strain BeAn 70563, GenBank accession no. AF512834), Chapare virus (810419, NC_010562), GTOV (INH-95551, NC_005077); JUNV (MC2, D10072); MACV (Carvallo, NC_005078); SABV (SPH114202, NC_006317). The sequence of TCRV GP (a gift from Stefan Kunz, University of Lausanne, Switzerland) is that of a laboratory adapted strain, which has a deletion spanning residues 121-132, and substitutions at three residues (I134A, G418S and E458R) compared to GenBank NC_004293. We used the following TfR1 sequences: human TfR1 (NM_003234), C. callosus TfR1 (EU164540), C. musculinus TfR1 (EU164541), Z. brevicauda TfR1 (EU340259), A. jamaicensis TfR1 (FJ154605), N. spinosus TfR1 (FJ154604). We made figures and did pairwise sequence identity calculations using Jalview 36 , 37 .", "We maintained HEK293T cells (human embryonic kidney, ATCC, CRL-11268) in Dulbecco's modified Eagle's medium, and CHO cells (Chinese hamster ovary epithelial, ATCC, CCL-61) in F12 medium, in the presence of 10% fetal bovine serum. Plasmids encoding hTfR1 and hTfR1 with the R208G mutation, with the addition of a C-terminal flag tag, have been described previously 23 ", "The arenavirus envelope glycoprotein (GP) is the sole protein on the virion surface. During its maturation, GP is processed into three non-covalently associated subunits; the stable signal peptide (SSP), GP1, and GP2 (ref. 9 ). Unlike most signal peptides, SSP remains on the surface of virions and participates in maturation and pH-dependent membrane-fusion activity of the GP complex 10 -13 . The GP1 subunit interacts with cellular receptor(s), and GP2 mediates membrane fusion after virus particles are internalized into acidified endosomes 14 -16 ." ] },{ "paper_id": "7b9fb5e842666cdb5418bacb81aefb0226088c06", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The predicted confidence interval for Y (new) is the following: ", "As an epidemic declines, the doubling time increases. Variation in doubling time among countries probably arises from variation in both transmission rates and control efforts ( Figure 3 ). Transmission rate (with units of time -1 ) is determined by the expected number of susceptible persons with whom each infectious person comes into contact during a time unit in their infectious periods and by the probability of disease transmission per contact. High-density population centers, crowded public transportation systems, and hospital waiting rooms increase the number of contacts, while personal hygiene affects the probability that transmission will occur with each contact. In all countries, seasonal effects may also play a substantial role with the virus spreading faster in winter.", "Estimates of CFR may change as polymerase chain reaction (PCR) assays become more widely used in diagnosis (5) . Diagnostic tests could identify mild cases that currently are not reported. Our estimate of the size of the epidemic would then increase in terms of number of cases, but the estimates of CFR would decrease. Conversely, PCR tests might eliminate the diagnosis of SARS in some suspected cases. Ultimately, accurate estimates of population distributions of parameters reflecting the clinical course of disease will be best provided by follow-up of clearly defined cohorts of infected persons identified by appropriate diagnostic procedures." ] },{ "paper_id": "7bf0ed5268fb6a4f25291a4a0841b50791be018b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7c6305da78645e761c09e007105cfc47262773ec", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7c754c95f6614150c41ea4c07cfe7e781f3a165d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7c7c02af9951523fe4147d5e43f322b139cc966c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "One microgram of each plasmid DNA was transcribed and translated in a total of 50 ml reaction mixture in a TnT coupled in vitro translation system (Promega) in rabbit reticulocyte lysates (RRL), labeled with 50 mCi/ml of [ 35 S]methionine (Amersham Biosciences). The translation products were analyzed on 12% SDS-PAGE and visualized by autoradiography.", "Cells transfected with plasmid DNA were lysed in 500 ml Trizol solution. After transferred to fresh tubes, 100 ml of chloroform were added and mixed well by vortex before centrifugation. The upper aqueous phase was precipitated with 2 vol of ethanol at \u00c020 C for 30 min. After centrifugation, the pellets were washed with 70% ethanol and air-dried. The total RNA was resuspended in 20 ml of RNase-free distilled water.", "One microgram of total RNA was used as template for reverse transcription in the presence of reverse transcriptase at 42 C for 1 h. One microliter from the reaction was taken out for PCR using the appropriate primers." ] },{ "paper_id": "7d102f0d9bd25cf5ac225ae0312a2f6c66f4b9a5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7d301234c3251abee951f0877e8d3a3b1fca6221", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ethical approvals for GRAPHS were obtained from the Ghana Health Service Ethical Review Committee, the Kintampo Health Research Centre Institutional Ethics Committee, and the Institutional Review Board of Columbia University Medical Center.", "MassTag PCR analysis yielded positives for 13 of the 22 microbes listed in " ] },{ "paper_id": "7d53d33c7dc9188bb757f20b10714041aa84f59e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We first focused on the simple issue of what percentage of all sequences are unique within a series of model genomes. This uniqueness measure is directly linked to the effect of read length on re-sequencing, where sequence information is assembled on a known template. In its simplest form, resequencing requires that a probe is uniquely identifiable with a single location on the template sequence.", "As more complete genome sequences become available the quality of map information will increase. However it is not currently clear how reliable much of this information is, nor how best to apply it to the problem of reassembly from very short reads. We have therefore restricted our analysis to reassemble with no additional mapping information. In this analysis we use a suffix array to examine all possible fragments of a given size and use this information to predict which contigs could be assembled.", "Such a length is beyond the reach of sequencing by hybridization as selectivity for single mismatches will not be possible (12) . Single molecule (23) and sequencing by synthesis approaches currently claim read lengths of 25 to 115 nt 10 and therefore the application of the techniques to whole human genome re-sequencing shows promise.", "Re-sequencing applications require that there is a known template sequence of sufficient quality to provide a map on which reads can be placed. In the case of de novo sequencing, such as the sequencing of a new organism, this map is not available. In the extreme case where no map information is available it is necessary to assemble these reads into contigs without the aid of any external information." ] },{ "paper_id": "7d60e86e17b289ff581de119742058c51540d58b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All cell lines were cultured in Dulbecco's Modified Eagle Medium (DMEM) with Glutamax and high glucose (Gibco, Paisley, Scotland, UK), supplemented with 10% fetal calf serum and penicillin/streptomycin. To make the quail QT6/ACE2 cell line, the gene encoding the receptor for SARS-CoV, human angiotensin-converting enzyme 2 (ACE2) (35) , was cloned from a human primary kidney cDNA library (Invitrogen, Paisley, Scotland, UK) using 21-mer primers designed to the start and stop of ACE2, and subcloned into pcdna3.1+. QT6 cells were transfected by using lipofectamine 2000 and selected with G418, and a bulk ACE2-positive, G418-resistant population was grown.", "Construction of the plasmid pCAGGS-S harboring fulllength SARS-CoV S from the Urbani strain has been described previously (23) . The MLV gag/pol construct, pCMVi, and the green fluorescent protein (GFP) reporter construct, pCNCG, have been described (32) . Vesicular stomatitis virus envelope protein (VSV-G) expression vector pMDG has been described previously (33) . HIV constructs were used as described (34) .", "Confluent plates of 293T cells were split 1:4 the day before transfection. Each plate of 293T cells was transfected with 1 \u00b5g gag/pol construct, 1.5 \u00b5g of enhanced GFP reporter construct, and 1.5 \u00b5g envelope-expressing construct by using the Fugene-6 transfection reagent (36) . Supernatant was harvested 48 h and 72 h posttransfection, filtered through 0.45-\u00b5m filters, and stored at -80\u00b0C. MLV and HIV vector titer were measured on 293T, TE671, and QT6/ACE2 cells and are presented as infectious units (IU) per milliliter. Briefly, cells were infected with vector, and eGFP titers were determined 72 h later by fluorescenceactivated cell sorter (FACS)." ] },{ "paper_id": "7d7255ec9a213b7fe04cb8c08b326e0aacd2fd9b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We excluded records for persons <18 years of age and records that omitted any of our variables of interest: age, sex, payer, race, admission month and year, and hospital location. We also required the hospital to have >1 weather station within 100 km (62 miles).", "exposures for patients also should help inform the design and interpretation of CAP-treatment trials. Future work examining more granular environmental data may ultimately enable clinicians to safely limit initial empiric antimicrobial drug selection for CAP to monotherapy with a \u03b2-lactam in specific seasons and regions.", "We extracted individual-level inpatient-event data from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) for 1998-2011. The University of Iowa Institutional Review Board deems such studies as non-human subjects research. The NIS, a stratified 20% sample of discharges from nonfederal US hospitals, contains data from 47 states; after excluding the 21 NIS states that do not report the American Hospital Association identifier (AHA ID), patient race, or admission month, we used data from 26 states: Arizona, Arkansas, California, Colorado, Connecticut, Illinois, Iowa, Kentucky, Maryland, Massachusetts, Mississippi, Missouri, Montana, Nevada, New Hampshire, New Jersey, New York, North Carolina, Oregon, Pennsylvania, Rhode Island, Utah, Vermont, Virginia, Washington, and Wisconsin. Next, we mapped the hospitals in these 26 states to the AHAreported addresses using the AHA ID; we then converted the addresses to geographic coordinates by using the US Census Bureau Geocoder (https://www.census.gov/ geo/maps-data/data/geocoder.html) and Google Maps' Geocoding API (Google; Mountain View, CA, USA). We located 2,079 unique hospitals ( Figure 1) .", "We compared several demographic and severity measures between the portion of the data dropped because of missing values and the proportion retained (Table 2) . Among the cases, the only substantial difference was in the percentage of patients not insured; for 10.8% of dropped records, no insurance was reported, compared with 7.4% of those used in the model. Many statistically significant differences existed between the controls retained and those lost; however, the large sample size (retained sample n = 189,412) meant many non-clinically relevant differences would be statistically significant." ] },{ "paper_id": "7dec79b2d676d371ae0a82d32862aa59e5040870", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7e136fdfc76cd52435cf224414e8a59fa3eaf227", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Onset associated with change in stool frequency", "Onset associated with change in stool form Functional diarrhea [24] Defined by Rome III criteria as C75 % of stools that are loose (mushy) and without pain for C3 months with symptom onset C6 months before diagnosis", "When exposed to protease inhibitors, the cells were found to have decreased alkaline phosphatase activity and thereby an increase in unfolded proteins. The accumulation of defective proteins in the cytosol may persistently activate the cell's unfolded protein response, a specific signaling pathway that aims to return the cell's protein folding function back to normal. If the levels of unfolded proteins do not decrease, the cell may induce apoptosis.", "Antimotility agents include loperamide, diphenoxylate/ atropine, and tincture of opium [65] . These agents act upon opioid receptors in the gut to slow motility by decreasing peristalsis and increasing tone in the large intestine. This allows for greater fecal transit time and therefore longer time for water absorption." ] },{ "paper_id": "7e1c6ccf9c329afc2fbb53e028c9412a61c25926", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7e3344bab4007d0b919ca28f879e1b6452178041", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The contact with family members at home suffering from an upper respiratory tract infection was collected.", "We obtained information on each patient's upper respiratory tract (nasal congestion, rhinorrhea, and sneezing), lower respiratory tract (cough and expectoration), and constitutional symptoms (dysthermia, fever, chills, asthenia, anorexia, headache, arthromyalgia, and impaired consciousness)." ] },{ "paper_id": "7e4571a77ec135db692d41693918b9663e6e08c3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7e4f3fdf70d647d0530a94f12f90f0927fbc1ff5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "1 \u03bcM N-methyl isatin \u03b2-thiosemicarbazone (Me-IBT) inhibited Rous sarcoma virus RNA-dependent DNA polymerase by 50%, whereas in combination with 1 \u03bcM CuSO 4 , which caused minor (10%-15%) inhibition, it caused nearly total inhibition of the enzyme activity (Levinson et al 1973) .", "We have recently demonstrated that ubiquitin binds to an isatin analogue immobilized at the Biacore cell (Buneeva et al in preparation) . Although the K d value of 0.27 mM is rather high, this phenomenon may have implications for ubiquitin interaction with isatin analogues (see below).", "N-substituted isatin derivatives (but not isatin itself ) inhibited parasitic cysteine proteases identified in trypanosomes (cruzain and rhodesain) and malaria parasites (falcipain-2) . Webber et al (1996) synthesized isatin-based inhibitors of human rhinovirus 3C protease, a viral enzyme that is absolutely required for the proteolytic cleavage of viral precursor polyproteins to functional proteins (Wanga and Chen 2007) ." ] },{ "paper_id": "7e5895cf23d87d2246903fc27c53130ab5b4d9e4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "reporting timely age-specifi c community surveillance in sentinel and laboratory networks.", "We reviewed prospective surveillance data on infl uenza and infl uenza-like illness activity during the 2008 winter infl uenza season. We then considered the effects of the school closures on community transmission.", "In winter 2008, kindergartens and primary schools in Hong Kong were closed for 2 weeks after media coverage indicated that 3 children had died, apparently from infl uenza. We examined prospective infl uenza surveillance data before, during, and after the closure. We did not fi nd a substantial effect on community transmission." ] },{ "paper_id": "7e71b0b68479d59fe662f53a7ba3e6037b7e09a2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7e78314c36ae7c4c1c8caa99dd9d562d0c08f40f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7e951ff88008de16ecc2aeaecea54ed5b5c84abf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Keywords Antiviral drugs, belief, influenza, perception, travellers. ", "A 12-item, anonymous, self-administered questionnaire was completed by travellers while waiting for pre-travel advice. The questionnaire took approximately 7 minutes to complete. Travellers were approached sequentially for participation and provided with a study information sheet and an informed consent form. The Information Sheet described the voluntary nature of participating, the benefits and risks of participation, and a statement on data privacy and protection; the study information sheet did not provide information on antiviral drugs or influenza.", "S.T. is a former employee of, and is a paid consultant to F. Hoffmann-La Roche and different influenza vaccine and antimalarial manufacturers; J.N.Z. has been a consultant to several manufacturers of vaccines and antimalarial chemoprophylaxis and has received unrestricted educational grants from GlaxoSmithKline, Novartis, Sanofi Pasteur, SBL Vaccines and Pfizer, for attending conferences, running educational programmes and undertaking clinical trials. No other potential conflicts of interest have been reported. ", "In addition to answering questions on influenza, subjects also provided socio-demographic data (sex, age), travel information (travel history, planned itinerary including travel duration, season, purpose of travel, whether travelling alone or accompanied) and health information (underlying conditions, perceived health, allergies, drugs consumption, pregnancy). Included in the analysis were those individuals who travelled for trekking (as backpacking), volunteering or missionary work (as cooperation), tourism (as holidays), labour (as business) or to visit their friends and \u2044 or family (as VFR). The health of each traveller was recorded at the time of their attendance at the travel clinic and this was used to determine their self-perception of their health at that time. Administered travel-related vaccines and the prescription of antimalarial chemoprophylaxis were also recorded." ] },{ "paper_id": "7ea8a6e74e46f70f70c151746ef2df2bada07216", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7ee6196d0be6f703dd2e2a96b94cbe899f7400d2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7f02b0d7567aa90c77c7fe13dc67f1bac185f88e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Both authors contributed to the writing of the manuscript and have approved the final version.", "A Ac ck kn no ow wl le ed dg gm me en nt ts s " ] },{ "paper_id": "7f0b1ae991e40333c7bd010c6a621322f09ac888", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Pathogen reduction technologies allow inactivation of viruses and bacteria in contaminated platelet concentrates. Two main different approaches have been described.", "Sensitivity* Sensitivity* Good specificity** Detection of aerobic and anaerobic bacteria, yeasts, and fungal microorganisms Closed system", "The bottles are continuously analyzed and tested, for up to 5-7 days Easy and quick handling Easy and quick handling Disadvantages" ] },{ "paper_id": "7f5099683746562c52ba0577d95b02864b1d2661", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7f90265c6f254f3c10e47394f1a573a36507a7e5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8004486cd94fe30d59168de8109ebfe241223a13", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We thank Kartik Chandran and Jayne F. Koellhoffer for assistance with figure preparation and helpful discussions. ", "Perspective pubs.acs.org/journal/aidcbc" ] },{ "paper_id": "803f7053c2a6c053e0ebcd748c6a0f2462a5c067", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Protease inhibitors have been purified from an array of leguminous and nonleguminous species encompassing Torresea cearensis [1] , Erythrina caffra [2] , Dolichos lablab [3] , Crotalaria paulina [4] , Medicago scutellata [5, 6] , Canavalia gladiata [7] , Pisum sativum [8] , Dimorphandra mollis [9] , Swartzia pickellii [10] , Psophocarpus tetragonolobus [11] , Delonix regina [12] , Poecilanthe parviflora [13] , Adenanthera pavonina [14] , Cajanus cajan [15] , Dolichos biflorus [16] , Phaseolus acutifolius [17] , Arachis hypogaea [18] , Leucaena leucocephala [19] , Bauhinia bauhinioides [20] , Bauhinia variegata [21] , Bauhinia ungulata [22] , Vigna unguiculata [23] , Lens culinaris [24] , Glycine max [25] , Peltophorum dubium [26] , Pithecellobium dulce [27] , Glycine soja [28] , and barley [29] .", "The N-terminal sequence of the protein was analyzed by using a Hewlett-Packard HP G1000A Edman degradation unit and an HP 1000 HPLC System [47] .", "Inhibitor. DTT treatment curtailed the trypsin inhibiting activity in a doseand time-dependent manner ( Table 3 ). The two trypsin inhibitors did not inhibit HIV-1 reverse transcriptase when tested at various concentrations up to 100 \u03bcM (Table 4) ." ] },{ "paper_id": "80d9d5734676b9a27d165dbb2826d4ba1da23da5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Since an interim analysis on 60 specimens indicated no positive yields 14 days after discharge, a decision was made to stop all subsequent collections until after day 28 of discharge. Specimens already collected were processed.", "The relationship of potential virus secretion to seroconversion is also undefined, as is the optimal time to test for seroconversion. Seroconversion has been suggested to occur at a mean of 20 days of illness (4) . Recently available laboratory tests for detecting antibodies against SARS-CoV provide a means to answer these clinical questions.", "By performing weekly tests, the optimal time of seroconversion in recovering patients could be determined. This information will assist clinicians in planning a reasonable time for serologic testing in patients with suspected cases of SARS." ] },{ "paper_id": "81496ab8f06bbb9f90b5e7773b8e6c6db6e02b2a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In the examples that follow, readers should bear in mind that there are still relatively few peptide vectors currently being considered for therapeutic use and few if any publications have addressed toxicology, potential immune recognition, or demonstrated cost/ benefit analysis. Most of the vectors describing enhanced cell delivery represent therefore research in progress.", "Therapeutic approaches for neuromuscular disorders currently lead the way in clinical development of peptidemediated delivery. Repeat systemic dose-escalation studies of naked PMO and 2\u2032-OMe/PS oligonucleotides having been completed recently in DMD patients and further doseescalations studies planned 37, 167 (current trials reviews in ref. 168) , while recruitment for a clinical trial to treat spinal muscular atrophy is underway (clinicaltrials.gov identifier: NCT01494701), which is another neuromuscular disease where peptide-conjugated PMO is likely to be applied.", "An interesting new application is the use of triplex-forming PNA conjugated with the classic CPP Penetratin to direct gene modification in the hematopoietic stem cells of mice, retaining unmodified differentiation capabilities. 16 Sequencespecific gene modification was also observed in multiple somatic tissues following systemic administration, and also preserved in bone marrow and spleen of recipient mice following transplantation of bone marrow from Penetratin-PNA-treated mice. This suggests that peptide-PNA conjugates might have good potential application for treatment of monogenic hematological diseases such as thalassemia and sickle cell anemia.", "Most of the anti-miR oligonucleotide types utilize 2\u2032-OMe, LNA or 2\u2032-fluoro analogues usually as mixmers of more than one analogue type or with DNA ( Table 3 ). In vivo applications all utilize PS linkages. Currently, there are no papers describing peptide delivery of such anti-miRs. As discussed above, it seems that some naked oligonucleotide analogues may have the ability not only to enter cells through endocystosis but also can efficiently block miRNA activity without need for any enhancement of transfection by peptide or other vectors. 19, 20, 35, 82, 83 Thus it seems unlikely that peptidemediated delivery will be of value for such oligonucleotide types." ] },{ "paper_id": "817b21573c7e32c6012a2bc7d34c013ebfdc46f9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All analyses were carried out with Stata 10.1 (Stata Corp., Cary, NC, USA). The data used are all publicly available aggregate surveillance results, and no ethical review was required.", "Week Streptococcus pneumoniae Streptococcus pyogenes Haemophilus influenzae Neisseria meningitidis " ] },{ "paper_id": "819902e2222b531ae0a6016763e43618b2988516", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "PubMed Also-Viewed is a link on some PubMed abstract pages that shows PubMed records that other users have viewed with the current record. When present, the link is labeled Articles frequently viewed together and appears on the right side of the abstract page. At the time of this writing the link was available for about 5% of PubMed records.", "Protein database records now have a prominent link to the Identical Protein Report at the top of the record page. This report displays the accessions of all other protein records whose sequences are identical to that of a given protein.", "PubMed Commons enables the community to share information and opinions on scientific publications. ", "ClinVar supports users who want to determine what has been reported about the medical relevance of human sequence variation (8) . " ] },{ "paper_id": "81bc3b72979ca17bc4385765f5e4452315d4b138", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Th 17 cells are required for host defense against intracellular pathogens [12] . Th 17 promotes infl ammation by inducing various pro-infl ammatory cytokines and chemo kines, recruiting neutrophils, enhancing antibody production, and activating T cells [12] . Th 17 cells secrete", "Further studies would help to understand the harmful or benefi cial roles that these cytokines play in the evolution of mild and severe nvH1N1 infection. But this report confi rms that Th 1 and Th 17 responses are distinctive hallmarks of severe respiratory compromise following nvH1N1 infection. ", "IL-17, IL-17F, and IL-22, thereby inducing a massive tissue reaction. Also, these cells secrete IL-21 to communicate with the cells of the immune system [13] . However, uncontrolled production of these cytokines induces tissue damage in infected tissues [12] . In addition, Th 17 cells have a well-known role in clearing pathogens during infections and inducing tissue infl ammation in autoimmune disease [13] . Interestingly, the key role of IL-17 and its receptor in the immunopathology of infl uenza infection in a mouse model has just recently been reported [14] ." ] },{ "paper_id": "81f9bd0e0377dbd8e67c579b6614003e6d825ab3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Plant B dried potatoes. Samples tested included raw well water; whole raw potatoes; stool samples from four workers who handled raw potatoes; dried potato granules, flakes, and slices; wastewater sludge from primary and secondary treatment; mud washed from the potatoes; floor sweepings; and stool samples from three workers who handled final product. No virus was detected.", "Plant E slaughtered cattle and swine. Samples taken there-contents of cattle and swine large intestines, swine blood, bologna, raw beef scraps, raw pork scraps, cooked mixed scraps, dried mixed scraps, and samples from the combined process wastewater and sanitary sewage treatment system (raw, digested, and dried sludge and aerated effluent)-failed to reveal virus. This plant was more than 1000 miles (*1600 km) from plant C, and climatic conditions were very different.", "Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.", "Increasingly, in recent times, cultures of tissues other than kidney have given rise to lines that have special applications. And, as will be described later, explant cultures may serve special purposes, where the in vivo organization of the tissue is significant to the investigation.", "Plant A manufactured groceries. Samples tested included isomerose, gelatin, well water, wastewater, cheesecake mix, breakfast drink mix, freezer ''pops,'' and strawberry preserves; no virus was detected.", "The article is divided into arbitrary topic areas because putting the entire record together in chronological order would have been hopelessly confusing. I hope the reader finds some coherence in the scheme that I have chosen.", "Plant D shelled eggs and froze liquid egg products. Negative test results were obtained from all the samples: eggs in the shell, washings from the shells, liquid whole eggs, liquid egg whites, ''leakers,'' spent shells, and process wastewater." ] },{ "paper_id": "82722b89a6c49087f09c56d5d6b58e2bfe33bc7e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Treatment-emergent ocular AEs (including perioperative events) were reported in 99.6%", "The rate of C2-grade changes in lens opacities from baseline for subcapsular, nuclear, and ", "Visual field sensitivity was quantified as the mean deficit (MD), measured in decibels (dB). " ] },{ "paper_id": "82ca3ab5d05e7d31f2dcea84251a1eba8aa3f546", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "82d57f25521d98a987a697acda75c05db018436a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "82fb52d462dc847ed33ec87be35bd5c5065844aa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Monoclonal antibodies coupled with phycoerythrin (PE), peridinin-chlorophyll protein (PerCP), allophycocyanin (APC), and phycoerythrin-Cy-7 (PE-Cy7) were combined for simultaneous staining. In this study the following were used: anti-CD4 PerCP (IgG1, clone SK3), anti-CD3 PE-cy7 (IgG2a, clone SK7), anti-IFN-\u03b3 APC (IgG1, clone B27), and anti-IL-2 PE (IgG1, clone 5344.111) (Becton Dickinson). Cells were stained as previously described (19) .", "Multiparametric fl ow cytometry was performed by using a FACSCanto fl ow cytometer (Becton Dickinson). A total of 300,000 live events were acquired, gated on small viable lymphocytes, and analyzed with FACSDiva software (Becton Dickinson). The instrument was routinely calibrated according to the manufacturer's instructions.", "The antibody titer was also established by HI test, using for challenge either the seasonal vaccine or the egg-derived infl uenza (H5N1) preparation. HI assays were performed in V-bottom 96-well plates with 0.5% chicken erythrocytes, as described (16) ." ] },{ "paper_id": "831eced9e695618368c334b5b42159f2172fbe55", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dr. Brug is professor of determinants of public health in the Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands. His research is focused on determinants of health-related behaviors and effectiveness of prevention interventions. ", "SARS diagnostic behavior was rare, with \"paying close attention to coughing\" (3.5%) reported most often. Only 2.7% had visited a doctor because of SARS-related worries, and 1.1% had called a SARS information telephone service. The mean score for diagnostic action was 0.1 (SD = 0.6).", "Respondents were asked whether they felt able to avoid contracting SARS and which actions they had taken to avoid getting it ( Table 2 ). The total number of actions taken was regarded as an overall SARS precautionary behavior score (range 0-19, \u03b1 = 0.72). Diagnostic actions that could be indicated included taking one's temperature; going to a physician; paying attention to coughing, sneezing, feelings of fatigue, and headaches; and calling a SARS hotline. The total number of actions was regarded as a diagnostic behavior score (range 0-8, \u03b1 = 0.77)." ] },{ "paper_id": "833f392ae03b75260838505b490da16d13088cba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The levels of expression of 30S were not significantly different between the liver tumour, control liver and 'normal' tumouradjacent samples (Table II) .", "Animal and tissue samples Male Fischer 344 rats (Harlen Sprague Dawley, Inc, Indianapolis, IN), weighing 140-150 g at the beginning of the experiments, were used. The basal diet was obtained from Dyets, Inc., Bethlehem, PA. BR931 (LPB Instituto Farmaceutica S.P.A., Milan, Italy) and BR931 was incorporated in the basal diet at a concentration of 0.16%. Water was supplied ad libitum. On days 3, 7, 14, 28 and 56 after feeding of the designated diets was started, rats were sacrificed by cervical dislocation, and their livers were removed, quickly frozen in liquid nitrogen, and stored at -70'C. After long term feeding of BR931, approximately 8-9 months, hepatic tumours and normal-adjacent livers were quickly removed, frozen in liquid nitrogen, and stored at -70\u00b0C. RNA isolation and Northern blot analysis Frozen liver tissues were homogenised in guanidine monothiocyanate, using a Polytron homogeniser (Brinkmann Instruments, Westbury, NY), and total RNA was isolated by the method of Chirgwin et al. (1979) . The polyadenylated RNA fraction was then isolated by passage of this RNA through oligodeozy-thymidylate cellullose columns (Collaborative Research, Waltham, MA) (Aviv & Leder, 1972) .", "The levels of expression of c-H-ras were not significantly different between liver tumours, the normal liver samples -8.4 kb from age-matched controls and the 'normal' tumour-adjacent samples ( Figure 2 and Table II) .", "Messenger RNA transcripts homologous to 30S were also detected in all of the liver tumour and the parallel control liver and 'normal' tumour-adjacent liver samples (Figure 2 )." ] },{ "paper_id": "837b4d88c47776128f9adede779624245f3e0494", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "843f0cacbbf8ea36f7638c26564c118035284f40", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The purified proteins, GST-CD-Nef (0.16 mg) and MBP-\u03bc1(158-423) (0.25 mg), or their mutants were mixed in a final volume of 100 ul and incubated at 4\u00b0C for 1.5 hrs. The protein solution was then loaded onto a small gravity flow column containing 0.2 ml GST resin. Flow through was collected and the resin was extensively washed with 5 \u00d7 0.9 ml GST binding buffer (50 mM Tris, pH 8, 100 mM NaCl, 0.1 mM TCEP). The bound proteins were eluted with 5 \u00d7 0.1 ml GST elution buffer containing 10 mM reduced glutathione. The eluted proteins were analyzed by SDS PAGE stained with Coomassie blue." ] },{ "paper_id": "844952cd4f3326959a4bf2e50bc64ab436b8ded8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "environmental changes, new and recurring diseases are likely to continue to emerge.", "Climate change also effects evolution of pathogens, and where relevant, their vectors. Continual mutation and recombination events give rise to variants with altered levels of fi tness to persist and spread. Changing ecologic circumstances and pathogen diversity can give rise to variants with altered pathogenic potential. However, the host must not be ignored. Increased longevity and therapies for persons with diseases can modulate host susceptibility and concomitant infections and upset the evolving and dynamic infection balance.", "Zoonotic pathogens from wildlife may infect humans with little or no human-to-human transmission (e.g., avian infl uenza virus and Hendra virus). Alternatively, increased travel or migration and increased between-person contacts have facilitated emergence of simian immunodefi ciency virus/HIV/AIDS in Africa. Increased exposure to wildcaught animals and high mutation rates of many RNA viruses have increased their predominance among emerging zoonoses transmitted from human to human; RNA viruses from bush meat may therefore play a possible role in future disease emergence." ] },{ "paper_id": "84ba11845e71831d66c57966eb03e3190057fee7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Conformationally restricted analogue 7 was prepared as outlined in Scheme 6. Reductive amination of ketone 29 with ammonium acetate and sodium cyanoborohydride provided amine 30 in quantitative yield. Conversion to piperidine ester 33 was effected with a three-step sequence analogous to that Scheme 5. Synthesis of Quinolinyl-and Isoquinolinylamides a employed in Scheme 3. Saponifiction with LiOH in a mixture (3:1:1) of THF/MeOH/H 2 O furnished the free acid. Finally amide coupling with 3-fluorobenzylamine, EDCI, HOBt, and DIEA led to the production of the target analogue 7. It is worth noting that the shorter ethyl isonipecotate displacement route used in Schemes 1, 2, and 5 was not successful with the mesylate derived from reduction/mesylation of 29, presumably because of excessive steric hindrance.", "Preparation of (R)-amide analogues is summarized in Scheme 4. The starting (R)-1-(1-(naphthalen-1-yl)ethyl)-piperidine-4-carboxylic acid 25 was prepared according to the method of Ghosh et al. 15 Coupling of the acid to various arylmethylamines and arylethylamines was effected either by EDCI in the presence of DIEA or by the uronium-based coupling reagent HATU.", "Liver Metabolism Studies. Compounds (1 \u03bcM) were incubated with mouse liver microsomes (0.5 mg/mL) and NADPH in 0.1 M phosphate buffer at 37\u00b0C as previously described. 29 Mutagenesis of Gln 270 . The mutagenesis of Gln 270 to Ala, Glu, or Asp was performed by QuickChange site-directed mutagenesis as described by Zhen et al. 30 Mutant enzymes were purified as described above for the wild-type SARS-PLpro enzyme.", "The racemic quinolinyl and isoquinolinyl analogues (4a\u2212c) were generated from the corresponding aldehydes 26a\u2212c by treatment with methylmagnesium chloride to give the methylcarbinols 27a\u2212c (Scheme 5). Alternatively, carbinol 27d was prepared from 1-cyanoisoquinoline by addition of methylmagnesium chloride followed by sodium borohydride reduction of the resulting ketone, as described in the Experimental Section. Displacement of the corresponding mesylates with ethyl isonipecotate afforded esters 28a\u2212d (Scheme 5). Saponification followed by EDCI-mediated coupling with 4-fluorobenzylamine provided the final amides 4a\u2212d." ] },{ "paper_id": "84e2013635e4484e5837fb190fad90a871e0f714", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Administrative controls are methods such as standard operating procedures that change the way work is performed. Their effectiveness depends on the availability of the control, employer commitment, and worker acceptance. Regular monitoring and reinforcement are necessary to ensure that workers follow policies and procedures consistently. The CDC publication Biosafety in Microbiological and Biomedical Laboratories addresses recommended practices for working safely from a biosafety perspective (41) .", "Visit our website to listen: https://wwwnc.cdc.gov/eid/ article/24/6/ac-2406_article", "Here are examples of control recommendations made for identified occupational hazards using the hierarchy.", "Pathogens in the environment can also serve as a source of worker infections through the respiratory route." ] },{ "paper_id": "84f1f12eb12aa3a677a3c0efb7417a17d0ac3adc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "850dc8add6efb76a6dc341cb7a5a236c1dd3da7c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8551fc3e19170f1f99d325d6a3283d9a91493d61", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "sources of infection have not been reported. Such an initiative would help assess the infectivity and modes of transmission of the virus in the community setting.", "For the case-control study, odds ratios (OR) were first examined by using univariate logistic regression models. The significant univariate variables were then entered as input for the multivariate forward conditional logistic regression analysis; p values <0.05 were statistically significant. SPSS for Windows Release 11.0.1 (SPSS Inc., Chicago, IL) was used to analyze the data.", "The percentage of patients related to Amoy Gardens (someone who lived there or visited there) is 18.8% (224/1,192) . The percentage of patients with a hospital connection (hospital workers, inpatients, and visitors) is 44% (525/1,192) . The proportion of unknown communityacquired SARS infection among all SARS cases in this study was considerably lower than the proportion of nosocomial infection, which suggests that preventing hospital outbreaks is essential.", "Of the 330 undefined transmissions, 44.2% of the transmissions occurred through hospital visitors. Another study on household transmission also indicated that hospital visits were a significant risk factor for predicting household secondary infection (9) . Therefore, the severity of future outbreaks, if any, would depend on the ability of the hos- " ] },{ "paper_id": "8568798df5346bdd1ae349b11ae1d0160eaed6ba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "85c624c0a20d8ed83f850072ce1e4bfdc197dedc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We thank Charles van Reenen, Philippe Barrault, Roger Farrow, Pascal Rey Herme, and International SOS for developing the PIU and their full support during the transport of SARS patients in Taiwan.", "The use of PIU during the SARS crisis had a number of positive effects in Taiwan. It enabled the safe transport of SARS patients between hospitals by air and road and decreased the risk of cross-infecting transport personnel. The anxiety of transport personnel was decreased, as was the fear felt by the population of the outer islands. In addition, the credibility of the local health authorities was improved among the general population in Taiwan.", "Modern stock raising that involves breeding a large number of domestic animals and fowl in high density has become a risk factor for large-scale outbreaks. The globalization of the marketplace and easy mobility of people and goods have facilitated the spread of many pathogens. Avirulent pathogens that mutate easily may acquire stronger infectious and toxic properties as confirmed in the influenza pandemic of 1918 (1)." ] },{ "paper_id": "85ea36d6f12f1998c292532c97cc228ee305271f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "SPSS statistical software (SPSS, Inc, Chicago, IL) was used for analysis. P , 0.05 was considered statistically significant.", "International Journal of Nanomedicine 2012:7", "Future work concerns packing RIPs with nanomaterials for targeting drugs and low release." ] },{ "paper_id": "85f5df7c9d677a28ffd8dbbc544d268b79bca556", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "85fadc26663d1add5c2e6effd39b37d8720528fc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sequence alignments (nucleic acid and amino acid) were constructed using ClustalW 1.74 (16) and refi ned by visual inspection with SEAVIEW; distance matrix and phylogenetic trees were computed with PHYLO_ WIN (17) . Distances between sequences were computed by observed divergence. Trees were built by using the neighbor-joining method, and tree topologies were tested with 1,000 bootstrap sampling replicates.", "Urine and throat swab specimens from each patient were added to MRC5, MDCK, and Vero cells. Early viral stocks were made from urine and throat specimens added to MRC5 cells as soon as cytopathic effects (CPEs) were observed. Late viral stocks were obtained after inoculation of BGM cells. Cells were harvested as soon as CPEs were observed and fi xed by incubation for 48 h in 4% paraformaldehyde and 1% glutaraldehyde in 0.1 mol/L phosphate buffer, pH 7.2, as described (14) . Cell pellets were embedded in Epon resin (Sigma-Aldrich, Saint-Quentin Fallavier, France), which was allowed to polymerize for 48 h at 60\u00b0C. Ultrathin sections were cut, stained with 5% uranyl acetate and 5% lead citrate, and deposited on electron microscopy grids that were coated with collodion membrane for examination under a Jeol 1010 transmission electron microscope.", "Specifi c primers of each reovirus segment were constructed in the highly conserved regions ( Table 1 ). The PCR products corresponding to large (L), medium (M), and small (S) segments were cloned and sequenced in both directions. Sequence analysis was conducted by using Vector NTI (Invitrogen, Carlsbad, CA, USA)." ] },{ "paper_id": "8604d285ad83e111704365b6dc4cc60e03d71b49", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "86137493357f000507e97acf40e74d2fdf8039a4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "2 0 -O-methyl RNA (5 0 !3 0 ) RNA (5 0 !3 0 ) Average of curve fits T M \u00c01 versus log(C T /4) plots \u00c0DH (kcal/mol) \u00c0DS (eu) \u00c0DG 37 (kcal/mol) T M b ( C) \u00c0DH (kcal/mol) \u00c0DS (eu) \u00c0DG 37 (kcal/mol) T M b ( C) CAUGGG", "The average error limits for the 2 0 -O-methyl RNA/RNA nearest neighbor parameters for DG 37 and DH are 0.17 and 3.7 kcal/mol, respectively (Table 3) . These are roughly 2-and 5-fold larger than the average error limits for RNA/ RNA (18) and DNA/DNA (16) parameters, respectively, where only 12 parameters can be fit and the number of duplexes is larger. Direct comparison with 17 and 18 parameter fits to data for DNA/RNA duplexes is not possible because error limits for individual parameters were not reported (19, 22) .", "Results from optical melting studies of Watson-Crick complementary heteroduplexes formed between 2 0 -O-methyl RNA and RNA oligonucleotides are used to determine nearest neighbor thermodynamic parameters for predicting the stabilities of such duplexes. The results are consistent with the physical model assumed by the individual nearest neighbor-hydrogen bonding model, which contains terms for helix initiation, base pair stacking and base pair composition. The sequence dependence is similar to that for Watson-Crick complementary RNA/RNA duplexes, which suggests that the sequence dependence may also be similar to that for other backbones that favor A-form RNA conformations." ] },{ "paper_id": "863f0c3fde068d1ef7b13ac852e98dea477559b0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Impala ", "Bat Rhinolophidae X X X X X X X 7 7 ", "Nipah virus 2,77,80,230 Cercopithecine herpesvirus-1 (herpes B) 2,75,80,192,193 Lymphocytic choriomeningitis virus 2,29,30,80,222,226 Total Risk Zoonoses in genus Total potential Risk Zoonoses (i.e., Risk Zoonosis found within family) Acinonyx Cheetah Felidae o o X o o X o o o o o o o X o 3 15 Canis Canine Canidae X X X X X o X X X o X X X X X X 14 16 Capromys Rodent Capromyidae --Caracal Caracal Felidae o o o o o X o o o o o o o X o 2 15 Castor Beaver Castoridae X X X 3 3 Cavia Guinea pig Caviidae X X X 3 3 Cebus Monkey Cebidae X o o X o X o 3 7 Cephalophus Duiker antelope Bovidae o o o o o o o o o o X o o o o 1 15 Cephalorhynchus Dolphin Delphinidae o o o o X o o o o 1 9 Ceratotherium White rhinoceros Rhinocerotidae X X o X X 4 5 Cercopithecus Guenon Cercopithecidae X X X X o X X o X o o o 7 12 Cerdocyon Fox Canidae X o o o o o o o o o o o o o X o 2 16 Cervus Deer Cervidae X o X o X X X X X 7 9 Chaeropus Bandicoot Peramelidae --Chaetophractus Armadillo Dasypodidae o -1 Cheirogaleus Dwarf lemur Cheirogaleidae --Chinchilla Chincilla Chinchillidae X X 2 2 Chlorocebus Monkey Cercopithecidae o o o o o o o o X o o X 2 12 Choloepus Sloth Megalonychidae X 1 1 Civettictis African civet Viverridae o X o o o o X 2 7 Coendou Porcupine Erethizontidae X 1 1 Colobus Monkey Cercopithecidae o o X o o o X o o o X X 4 12 Connochaetes Wildebeest Bovidae X o X o o X o o X X o o o o o 5 15 Cricetomys Pouched rat Nesomyidae X 1 1 Cricetus Hamster Cricetidae o X o X o o o o o o o o o o o o o o X o 3 20 Crocuta Hyena Hyaenidae X X X X X X 6 6" ] },{ "paper_id": "863fec2f2894a48b0dbf00f4b934f75a002a9941", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In vitro cytotoxicity assay", "All data subjected to statistic analysis were obtained from at least three parallel experiments, and the results were expressed as means \u00b1 standard deviation. Student's t-test was used for significance analysis, and P , 0.05 was the lowest level of significance to value the difference between two groups.", "In order to prepare VCR-OA-SME, Solutol HS15 was chosen as a nonionic surfactant, which was developed by BASF ( Ludwigshafen, Germany) and is listed in European Pharmacopoeia. As a pharmaceutical excipient, it has been approved for clinical parenteral use due to its low toxicity in vivo, such as low hemolytic ability, low histamine release, and high physical tolerance." ] },{ "paper_id": "866a7c1104e852ef5c06108cf6b9aa3334edc327", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "867e1b0f6ca8757f2a32a625d99b23888ab40d49", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Finally, it is often critical to precisely determine the nature of a sequence change within a given sample in order to properly assess its functional significance. Thus, it is important to consider error rates when assigning the identity of a mutation based on mismatch probe data. When dealing with clinical samples, it will be especially important to confirm the identity ", "As previously described (30) , individual ATM coding exons were amplified from genomic DNA using primers containing T3 and T7 RNA polymerase tails, pooled, and then in vitro transcribed using T3 or T7 RNA polymerase to create biotinlabeled sense and antisense strand targets, respectively. Fluorescein-labeled reference target was made using genomic DNA from an unaffected individual. Reference and test sample targets were fragmented, diluted in hybridization buffer [3 M TMA-Cl (tetramethylammonium chloride), 1\u00b7 TE, pH 7.4, 0.001% Triton X-100] and hybridized to the ATM microarrays as described previously (30) . Afterwards, the microarray was stained with a phycoerythrinstreptavidin conjugate and digitized hybridization images from both reference and test targets were acquired using the Gene Array Scanner (Hewlett Packard, Palo Alto, CA) equipped with the appropriate emission filters.", "Custom software was used to quantify hybridization signals for each probe and subtract background hybridization signals. We exclusively focused on raw data from the biotin-labeled test targets since they provide approximately seven times the hybridization signal of the fluorescein-labeled wild-type reference target in this system (28) . This enhanced signal provides greater sensitivity toward detecting weak hybridization." ] },{ "paper_id": "868afcaa176cdfdc50900313a5657583d5a74e9e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8695a2f335ffb2ccdaa84863bf31002555d0828f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "869d3d4d00795e9ca42618b9207f6dd315b19cd3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "HIV lineages show clear evidence of adaptation to humans (16) , but as discussed earlier, it is not clear whether the SIV lineages that gave rise to HIV-1 or HIV-2 were capable of transmission between human hosts. We speculate that extended infection times make tailor-made emergence more likely for retroviruses.", "We currently have few clues to help us predict which mammalian or avian viruses might pose a threat to humans and, especially, which might be transmissible between humans. One argument in favor of experimental studies of these traits, including controversial gain of function experiments (30) , is that they could help guide molecular surveillance for high-risk virus lineages in nonhuman reservoirs.", "The first line of defense against emerging viruses is effective surveillance (40) . A better understanding of which kinds of viruses in which circumstances pose the greatest risk to human health would enable evidence-based targeting of surveillance efforts, which would reduce costs and increase probable effectiveness of this endeavor.", "Demonstrating that an infected human has the potential to transmit the infection to another human is not always straightforward. High virus titers in body secretions and excretions, blood, or skin are considered indicative. Case clusters are suggestive, but if persons occupy the same environment (e.g., household), then it might be difficult to rule out common exposure. Case clusters must be epidemiologically plausible (i.e., delimited in space and time in a manner consistent with the known or assumed epidemiology of the virus). Genotyping techniques are useful tools for confirming a cluster but do not resolve the source of infection.", "Shifts in pyramid level equate to shifts in the public health threat posed by a virus. We consider possible shifts in the following sections." ] },{ "paper_id": "86d0072187f1f6d092ce296b13d3cb6fae55e70c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8711aed56f3656289b66b987d669c3228977a60f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CATCH's framework for designing probes offers considerable flexibility. This note describes extensions to probe design and methods behind them.", "Since the distinction between A and B is arbitrary, at each t CATCH chooses whether to assign A or B votes to the probes in T no depending on which assignment yields a higher sum. This process yields the maximum sum, and CATCH then assigns adapter A or B to each probe based on which has more votes.", "There are many problems related to probe design that map well to generalizations of the set cover problem. Relevant generalizations are the weighted and partial cover problems 1-3 ." ] },{ "paper_id": "87390d2ae28407b3e03e60a6b24a7fd99ed7229a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Available online http://ccforum.com/content/8/2/105", "Marcus J Kargel and Stephan E Lapinsky" ] },{ "paper_id": "874c67489633255b8ea0b0412f5a9261f5de31cf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The genetic diversity of bat-borne CoVs is currently unclear. Preliminary data suggest that CoVs may be adapted in a stricter sense to a specific host species rather than to specific regions (5, 6, (8) (9) (10) (11) (12) . A variety of pathogenic CoVs occur in other mammals or poultry. However, the genetic range within these animals is considerably less than that observed in even single bat species or subfamilies (7, 8) .", "Samples (1-4 fecal pellets or swabs suspended in RNA stabilization solution [RNAlater Tissue Collection; Applied Biosystems, Foster City, CA, USA]) were tested at the Kumasi Centre for Collaborative Research in Tropical Medicine as described (11, 18) . After initial sequencing, specific primers were designed for each group of CoV found. Nested reverse transcription-PCR (RT-PCR) primer sets used for sequencing of longer fragments of representative viruses are available upon request. ", "To estimate the quantity of CoV genomes in bat feces, we did end-point dilution experiments with the nested pan-CoV RT-PCR (18). The previously determined sensitivity limit of the PCR assay was 5-45 copies/PCR (18) . In the assay, the equivalent of 1 mg feces was tested per PCR tube (100 mg feces collected, 1:10 dilution extracted, 1:10 dilution tested). The highest dilution factor that still yielded an amplification signal in any of the samples was 1:10, which suggested a maximal concentration of 50 to 450 CoV RNA copies/mg of feces." ] },{ "paper_id": "8762e3de42e45d93aebb675328dd466f8be23cf2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "High-quality, timely data are necessary for decisionmakers to direct response activities. Well-designed and effective surveillance systems are critical for identifying the emergence of biological events, but most systems are not designed to facilitate information-and data-sharing between government agencies or between different countries. Without these connections, it might be difficult to identify an emerging outbreak, particularly if cases are spread across several countries.", "This biosecurity dialogue is conducted at the Track II level, rather than as a formal Track I (i.e., ministerial level) exchange. Track II diplomacy involves informal discussions that take place outside official government channels, enabling a more open and frank exchange of ideas and exploration of possible solutions to problems (1) . These types of dialogues provide a forum for participants to establish lasting relationships and partnerships with their counterparts in other countries in advance of a crisis and to discuss common challenges and best practices. Track II formats enable participants to freely share perceptions, vulnerabilities, and new ideas without the constraints experienced when persons are operating in their respective official capacities.", "In addition to the cost of human lives, infectious disease outbreaks can seriously damage or even devastate economies because of impacts on international trade and local tourism, both of which might slow or grind to a halt. Again, when we used the SARS epidemic during 2003 as an example, Malaysia lost \u2248US $1.7 billion and Thailand lost \u2248US $33.5 billion in tourism, and Singapore lost \u2248US $4.9 billion in gross domestic product during 2003 (5) . A dialogue participant also discussed the tremendous economic impact of the outbreak of Nipah virus infection in Malaysia during 1998-1999, which resulted in the culling of >1 million pigs, essentially shuttering the pork industry of this nation and exerting a tremendous economic toll (6) ." ] },{ "paper_id": "87d1712d269ca273a4496d43b91c472df46bbd38", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Following Grabowski's method [43, 45] , the \"pure\" energy of H-bonding, E HB , can be obtained as:", "(2) Analysis of SESE for homodesmotic reactions for substituted salicylaldehyde and appropriate disubstituted benzene derivatives: 4-substituted benzaldehyde and 4-substituted phenols (substituent: OH and NO 2 ).", "Salicylaldehyde is also an interesting subject for various physico-chemical investigations; because it has four isomers, and due to internal reorganization, it can have more than one different hydrogen-bonded conformer [11] . The possible conformations of salicylaldehyde and hydrogenbonded conformers are presented in Scheme 1.", "(1) Analysis of composition of the total energy of interaction, E tot , for H-bonded systems perturbed by substituents." ] },{ "paper_id": "87e5c2fa3f9febab3992aa84f38ebdc324bd9738", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In addition, the Al-Ahsa cluster in Saudi Arabia provides substantial information; we deliberately do not use those data in estimating the incubation period distribution here in order to generate a second independent estimate to be compared with existing estimates derived from analysis of that cluster 21 .", "We fit simple non-homogeneous Poisson processes to these data to investigate how the risk ", "In aligning these sequences, UTRs were ignored as they could be problematic to assemble, and inter-genic spacers as they were conserved. Coding regions were aligned using Muscle to produce an in-frame alignment.", "There are currently nine publicly available full-length MERC-CoV sequences. We also include in our analysis a sequence generated from a viral isolate of a patient diagnosed in France, who had previously travelled and presumably been infected in Dubai. France-UAE/1627/2013 2013-05-07 13 *The first English isolate was sequenced twice, by Public Health England (formerly HPA) with accession number KC16505 and once at the Wellcome Trust Sanger institute (KC667074), which is the sequence included here 30 . **http://www.hpa.org.uk/ webc/HPAwebFile/HPAwebC/1317138176202 ***The sequence of the isolate Hu/France-UAE/1627/2013 (Dubai/France 1) patient was generated at the Pasteur Institute in Paris using Sanger sequencing, essentially as described 31 and will be posted on Genbank as this paper is published.", "The distribution with the best Akaike Information Criterion is presented in the manuscript. " ] },{ "paper_id": "881bb13e961f96f6d3ba6e0cd749126d56245bb8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "88534ac83f589e5b7cfcb52ac0062db7b6b101ac", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The nucleotide sequence of purified PCR products was determined by PCR-based cycle sequencing performed with the inner primers. Sequencing reactions were performed according to the manufacturer's protocol (BigDye Terminator Cycle Sequencing Kit version 3.1, Applied Biosystems, Foster City, CA) and run on the ABI Prism 3100 Genetic Analyzer. All sequences were confirmed by repeated PCRs and sequencing from both directions.", "H uman metapneumovirus (HMPV) was first identified in 2001 in samples from children with respiratory tract diseases (1) . Subsequent studies showed that the virus is responsible worldwide for a proportion of communityacquired acute respiratory tract infections in children (2) (3) (4) , as well as other age groups (5) (6) (7) (8) (9) . Co-infection of HMPV with respiratory syncytial virus (RSV) in infants has been suggested to be a factor that influences the severity of bronchiolitis (10) .", "Selected cell cultures that showed cytopathic effect were examined by electron microscopy. Cell culture supernatants were coated on formvar-carbon grids and stained with 2% phosphotungstic acid." ] },{ "paper_id": "885ca5f85c120048c30b3f74bd2a6ddf9b79736f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "RSV, respiratory syncytial virus; hMPV, human metapneumovirus. *P < 0AE05 versus age group 4-14 years." ] },{ "paper_id": "8890802024d971865d693869aa338494806233b4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "88e67b379a452f7aad18f4ed1746fceb0e301466", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8903fdfd69ea2f76dfde69fad78d73027fc59993", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8970ef10049816050cb1bc5fbf600865a5996ad4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Any restrictions to use by non-academics: Contact authors" ] },{ "paper_id": "89860bed01edcabbb95ae9ea724e7f60feac25da", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Measures, Singapore and Japan", "Infections of healthcare workers at the onset of an outbreak may be due to perceptions that recommended policies and measures are unnecessary or excessive. Thus, efforts to educate and communicate the rationale and importance of protective measures may be especially important when outbreaks seem distant and perceived danger is low.", "To the Editor: Healthcare workers accounted for 21% of all cases of severe acute respiratory syndrome (SARS) during the 2002-2003 outbreak (1) . We studied perceptions of risk for SARS infection and preventive measures among healthcare workers in Singapore, who handled cases of SARS and where >41% of the cases occurred among healthcare workers, and in Japan, a SARS-free country." ] },{ "paper_id": "8a244626a996d30b62a52bb8705b889e74f3a5cf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Rayon-tipped, plastic-shafted swabs were inserted separately into each participant's nostrils and pharynx, placed into viral transport media, and transported immediately to the laboratory or stored at 4 o C if transport was delayed.", "Upon completion of this activity, participants will be able to:" ] },{ "paper_id": "8a6a728d46caa15618a80746cdac1b0a697f188c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8a7d5de5ea680e784ab2bd877240bf09e4c1c02d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8ae137c8da1607b3a8e4c946c07ca8bda67f88ac", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The electronic version of this article is the complete one and can be found online at", "comment reviews reports deposited research interactions information refereed research Abstract Recent analyses of human pathogens have revealed that their evolutionary histories are congruent with the hypothesized pattern of ancient and modern human population migrations.", "Each cluster found by Falush and colleagues [5] could be divided into subgroups; for instance, the 'Africa 1' cluster could be subdivided further into West and South African subclusters, and the East Asia cluster could be split into East Asian, Amerind, and Maori subclusters. The geographic partitioning within the 200 European strains was particularly complicated, presumably because numerous groups have swept back and forth across Europe over the past several millennia. European strains also occasionally appeared in the Americas, Australia, and among South Africans, presumably reflecting colonial conquest.", "Phylogenetic trees of strains of the bacterium Helicobacter pylori and the polyoma JC virus taken from geographically diverse groups of human beings correlate closely with relationships of the populations in which they are found." ] },{ "paper_id": "8af7d1a7c7744f3ead4f7989ef2529f75d37c16d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8b2141d00757fe30e235fc16fecc7106c96b3088", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8b622c10da164694e7148158875599c31f460b82", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Simulation methods group molecular dynamics and minimization methods. These approaches are often unable to cross highenergy barriers within feasible simulation time periods, and therefore might only accommodate ligands in local minima of the energy surface [5] . As a consequence, they are rarely employed as stand-alone search techniques. However, they can efficiently complement other search methods, by refining locally the poses that are suggested by one MC or EA-based step, like in AutoDock, DOCK or EADock.", "Several studies have estimated this number to be around 10 60 -10 100 [45, [61] [62] [63] [64] , far beyond what can be tested by vHTS.", "FBD has several theoretical advantages over vHTS. First, FBD samples a higher chemical diversity than HTS. Indeed, HTS chemical libraries typically contain 10 5 -10 6 " ] },{ "paper_id": "8b922efc32e8afde38542d35e9941e86c07ca6a0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8baaa5e94c6ee9d9adbd29414dd001d31aefc269", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "William B. Karesh,* Robert A. Cook,* Elizabeth L. Bennett,* and James Newcomb \u2020 transmission of the infectious agents that every animal naturally hosts.", "Many diseases are transmitted through the same species of parasites carried by imported animals. For example, from November 1994 to January 1995, US Department of Agriculture personnel inspected 349 reptile shipments from 22 countries containing 117,690 animals. Ticks were removed from animals in 97 shipments, and infested shipments included 54,376 animals (22). Ticks carry many diseases that threaten livestock and human health, including heartwater disease, Lyme disease, and babesiosis.", "Since 1980, >35 new infectious diseases have emerged in humans (13), \u22481 every 8 months. The origin of HIV is likely linked to human consumption of nonhuman primates (14) . Recent Ebola hemorrhagic fever outbreaks in humans have been traced to index patient contact with infected great apes that are hunted for food (15) . SARSassociated coronavirus has been associated with the international trade in small carnivores (16) , and a study comparing antibody evidence of exposure to this coronavirus demonstrated a dramatic rise from low or zero prevalence of civets at farms to an approximately 80% prevalence in civets tested in markets (17) ." ] },{ "paper_id": "8baba2afe8dd478ae1d7ed13b666098aa3bfb623", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "On the basis of previous reports from Hong Kong, SARS-CoV infection can be associated with critical maternal illness, spontaneous abortion, or maternal death (9, 12) . ", "We report a laboratory-confirmed case of severe acute respiratory syndrome (SARS) in a pregnant woman. Although the patient had respiratory failure, a healthy infant was subsequently delivered, and the mother is now well. There was no evidence of viral shedding at delivery. Antibodies to SARS virus were detected in cord blood and breast milk.", "After informed consent was obtained, the following specimens (collected approximately 130 days after illness onset) were submitted to CDC for coronavirus testing: serum, whole blood, nasopharyngeal and rectal swab specimens from the mother, postdelivery placenta, cord blood, amniotic fluid, and breast milk. No viral RNA was detected in specimens tested by reverse transcriptase-polymerase chain reaction. Antibodies to SARS-CoV were detected in maternal serum, cord blood, and breast milk by enzyme immunoassay and indirect immunofluorescence assay (Table) ." ] },{ "paper_id": "8bcf19aa1484447b3f16aa39f5f6efdaedfa5a5d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8c0585738b7b2c5fd40e0fa0b18687b600ca5aef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study was supported by USDA CRIS project 6040-32000-072.", "The mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture.", "Data availability. The coding-complete genome sequence of the GA9977/ 2019 isolate of the DMV/1639 strain has been deposited in GenBank under the accession number MK878536. Raw data were deposited in the SRA under accession number SRR9763527, BioSample number SAMN12347422, and BioProject number PRJNA556282." ] },{ "paper_id": "8c593d726094e8a047376050bd28806e371a2797", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Post translational modifications 2DE:", "Electrospray ionization FTIC:", "Immobilized pH gradient LC:" ] },{ "paper_id": "8c74c670f9001e13f725a59a04e19b7c07005d39", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The TRBJ exons were translated in the frame that yielded the characteristic FGXG or LGXG motif. 1 The alignments were performed over the total length of the TRBD or TRBJ exon.", "RESULTS" ] },{ "paper_id": "8c8ebf34d7a88d9717419e6bb9a3c3c2e4e02ff9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 Convening a suitable expert group (Prioritization Committee, Table) covering: 1) microbiology of severe pathogens, including virology, bacteriology and mycology, 2) clinical management of severe infections, 3) Epidemiology, in particular during health emergencies, 4) Public health policy, including emergency response, 5) Animal health, including veterinarians and experts in zoonoses from both livestock and wildlife, 6) experts from the defense or security sectors familiar with biological weapons and 7) other experts, including anthropologists, bioethicists, and other relevant social sciences.", "\u2022 Conducting that analysis through the Analytic Hierarchy Process (AHP)/Multi-criteria Decision Analysis (MCDA) method and Delphi process." ] },{ "paper_id": "8cbc79e63c08258edef9ed362498b779a592977a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 Targeted gene may not be truly universal", "\u2022 Determination of taxonomic relationships", "\u2022 Primer bias may alter population structure" ] },{ "paper_id": "8ccaf50414e8f530aaa405630c4e477d377d09ce", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "H epatitis E virus (HEV) is a single-stranded positivesense RNA virus that belongs to the family Hepeviridae, genus Hepevirus, and is the causative agent of hepatitis E (1, 2) . Because the transmission of HEV from deer, swine, and wild boars to humans is well known, hepatitis E is recognized as a zoonosis. Zoonotic hepatitis E is associated mainly with genotype 3 (G3) and G4 HEV infection (3, 4) . In addition to deer, swine, and wild boars, other animals, including monkeys, rats, ferrets, chickens, and bats, harbor HEV or HEV-like viruses (5) (6) (7) (8) (9) . The genus Hepevirus might include 3 additional species (avian HEV, bat HEV, and rat/ferret HEV) (10) . However, whether HEV from these animals is transmitted to humans is not clear.", "Sixty-three fecal samples were collected from laboratory ferrets (Mustela putorius furo) at the National Institute of Infectious Diseases, Tokyo, Japan, on May 24, 2013. These ferrets had been imported from a farm in the United States for influenza research 7 days before sample collection. Fecal specimens were diluted with 10 mmol/L phosphate-buffered saline to prepare a 10% suspension, shaken at 4\u00b0C for 1 h, and clarified by centrifugation at 10,000 \u00d7 g for 30 min. The supernatant was passed through a 0.45\u00b5m membrane filter (Millipore, Bedford, MA, USA), and stored at -80\u00b0C until use.", "Ferret HEV was also recently detected in the United States in serum (11) , suggesting that ferret HEV infection is not restricted to the Netherlands and might be distributed in ferrets worldwide. Because ferrets are susceptible to several respiratory viruses, including human and avian influenza viruses, and severe acute respiratory syndrome coronavirus (12, 13) , ferrets have been used as a small-animal model for these viruses. Ferrets are also kept as pets in many countries. Thus, information about ferret HEV epidemiology, distribution, transmission, and pathogenesis is urgently needed." ] },{ "paper_id": "8ceb037798bd3fa6941261d1b888fe0cb79f2850", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We purified GST-fused proteins expressed in E. coli BL21-CodonPlus DE3 cells (Stratagene) using glutathione Sepharose 4B affinity beads (GE Healthcare) followed by cleavage of GST from the GST-fused protein using PreScission protease (GE Healthcare).", "At 8 h post transfection of 293 cells with RNAs, we prepared the cell lysates in a buffer containing 50 mM Tris-HCl (pH 7.5), 5 mM MgCl 2 , 100 mM KCl, 1% (v/v) Triton-X-100, 2 mM DTT, 100 \u03bcg ml \u22121 CHX, and 0.5 mg ml \u22121 heparin, applied them onto a 10% to 50% sucrose gradient containing the same buffer and centrifuged at 39,000 rpm in a Beckman SW41 rotor at 4\u00b0C for 2 h. After fractionating the gradient fractions using a gradient fractionator, we monitored the absorbance at 254 nm using an ISCO UA-6 spectrophotometer. We precipitated the proteins from each fraction using trichloroacetic acid and detected them by Western blot analysis. We extracted rRNAs from the fractions and visualized them on a gel by staining with ethidium bromide.", "We cloned pST-fLuc by inserting the cDNA encoding the entire fLuc ORF region from the pGL3 control vector (Promega) into pSPT18 (Roche). We cloned the PCR-amplified fulllength nsp1 and nsp1-mt genes into the pGEX vector (GE Healthcare), yielding pGEX-wt and pGEX-mt, respectively. We constructed pRL-EMCV-FL by replacing the fragment containing HCV IRES, fLuc gene and the 3'-noncoding region of pRC22F38 with that containing EMCV IRES, fLuc gene and the 3'-noncoding region of pT7-IRES-fLuc39." ] },{ "paper_id": "8d3800d0ab71b59ea6a298927762a3fd09655107", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8d6b0c0ee9ce6efb0bffee4babfc4b5dba652ff4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8d7876047a1709d32140730550bf5c1fa7808378", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We analyzed changes in immunologic values over time for 28 hospitalized patients with pandemic (H1N1) 2009. Levels of interleukin-6, interferon-\u03b3, and interleukin-10 increased 1 day after illness onset and then decreased to baseline levels. Levels of virus-specifi c antibody were undetectable 1 day after illness onset and peaked 36 days later.", "Flow cytometric results showing development of peripheral blood lymphocyte subsets during the disease course were divided into 3 groups on the basis of time of illness onset until date of blood sample collection: 1-3, 4-6, or 7-10 days. These groups were used because the longest time from onset of illness to hospitalization was 3 days for all patients, and the peak temperature for patients was observed 3 days after illness onset.", "Only 1 patient had an HAI antibody titer \u226510 (titer 20) 1 day after illness onset. The HAI geometric mean titer increased 5 days after symptom onset compared with that 1 day after symptom onset and continued to increase until it reached a peak level of 137.9 at 37 days after symptom onset (25.5-fold increase). Peak HAI antibody titers \u226540 and \u22654-fold increases were observed in 27 (96.4%) patients." ] },{ "paper_id": "8d7c4111c00e7c93455b3a010faf4edf568c4010", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8d7d39313cd9791fca858c229b4af66a8e0927ad", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "At last, we must point out that the controlled experiment is still the gold standard to distinguish TUPs from the specific mimotopes. The report of SAROTUP should be verified with experiment.", "The SAROTUP was implemented as a free online service, powered by Apache and Perl. Three pages are designed and integrated into a tabbed web interface with cascading style sheets codes. The core program of SAROTUP was sar.pl, a CGI script coded with Perl. In this script, the 23 TUP motifs were converted to regular expressions, which were then used to match each input peptide sequence.", "Although the target of all tests described previously were monoclonal antibodies, SAROTUP can be customized and used in scanning the results from phage display technology using other targets such as enzymes and receptors. This is because their screening systems are similar. For the same reason, we can also expect that SAROTUP will extend its use to other similar in vitro evolution techniques, such as ribosome display [29] [30] [31] , yeast display [32] , and bacterial display [33] [34] [35] ." ] },{ "paper_id": "8db11431c2928d45f9c7587b2fb1a9dabbd2916f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8e152f8144e2d2ea5b829aa4b7089a49fa903453", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Here we report that certain interferon subtypes exhibit in vitro inhibitory activity against SARS-CoV and are candidates for follow-up studies in animal models and patients to determine their efficacy in vivo.", "Tenfold dilutions of the drug were tested to cover a broad range of concentrations above and below inhibitory dosages as reported by the manufacturer for other viralhost combinations. Compounds already present in aqueous injections were made up to volume by using Hank's buffered saline solution. For tablet and capsule formulations with soluble active ingredients, the outer coat was removed wherever applicable, and the preparation was ground in a mortar and pestle. The contents were dissolved in water, vortexed, and centrifuged thereafter at 3,000 g. The required volume was pipetted from the supernatant and diluted accordingly. When the active ingredients were insoluble in water (nelfinavir and saquinavir), the contents were dissolved in dimethylsulphoxide (DMSO); care was taken to ensure that the final concentration of DMSO in the dilutions would not exceed 1%. For plaque assays, fivefold drug dilutions were prepared by using growth media as specified below.", "The recent epidemic has shown that knowledge is lacking regarding the clinical management and treatment of infected patients. Ribavirin (6) (7) (8) (9) (10) (11) (12) , oseltamivir (8) (9) (10) , foscarnet (8) , intravenous immunoglobulin (8) , and other agents have been used to treat patients. Preliminary results from in vitro testing indicate that ribavirin concentrations that inhibit other viruses sensitive to ribavirin do not inhibit replication or cell-to-cell spread of the SARS-CoV (5) . However, the U.S. Centers for Disease Control and Prevention concluded that further in vitro testing of antiviral drugs on other coronavirus isolates and more information on the clinical outcome of patients treated with ribavirin or other antiviral drugs in controlled trials is needed (5) ." ] },{ "paper_id": "8e1eaa3b676ca8163c72106b913606f6aeccfc48", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dr. Han is an associate professor at Nanjing University of Science and Technology, Nanjing, China, specializing in film-society interactions. Dr. Curtis is an associate professor at Erasmus University Rotterdam, Rotterdam, the Netherlands, specializing in social responses to historical diseases.", "In The Painted Veil (2006, John Curran), a 1920s rural village in China is unable to deal with a cholera outbreak until a British bacteriologist comes along to investigate and in the end selflessly gives his own life.", "In this article, we bring together a sample of films that we manually selected from a consolidated database of epidemic-related films built from assorted scholarly literature and catalogs (2, 4, 5, (7) (8) (9) . This database was supplemented by accessing \"Films about viral outbreaks\" on Wikipedia (https://en.wikipedia. org/wiki/Category:Films_about_viral_outbreaks) and a list of \"Apocalyptic, epidemic, pandemic and disaster movies\" on the Internet Movie Database (https://www.imdb.com/list/ls058975821)." ] },{ "paper_id": "8e34a3230f0fc157b5d5ed998fa8792f0ecf3d0e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8edd711f742484517e3e3e206b4cb7b3441722f9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8ee9f67cb46223274974fce223eb6c5d4834d809", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The Influenza Virus Vaccine FluMist \u00d2 2005-2006 formula was purchased from MedImmune Vaccine, Inc. (Gaithersburg, MD, USA). FluMist \u00d2 is a live, trivalent vaccine, composed of the A \u2044 New Caledonia \u2044 20 \u2044 99 (H1N1), A \u2044 California \u2044 7 \u2044 2004 (H3N2), and B \u2044 Jiangsu \u2044 10 \u2044 2003 (B \u2044 Shanghai \u2044 361 \u2044 2002-like) strains. These strains are genetically altered to attenuated, cold-adapted, and temperature-sensitive phenotypes, which limits viral replication to the nasal pharynx. Each 0.5 ml dose has been formulated to contain approximately 10 7 TCID 50 (10 6.5 -10 7.5 median tissue culture infectious dose) per viral strain." ] },{ "paper_id": "8ef3d0709843acf3358abcb4144c23478e817097", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Blood cells were subjected to DNA extraction by treating them first with 0.5% SDS lysis buffer and then protease K (1 mg/mL) for digestion of nuclear protein for 4 h at 60 \u2022 C. Total DNA was harvested by using a Gentra extraction kit followed by 70% alcohol precipitation as described in our previous report [23] . ", "All study cases were children enrolled from Chang Gung Memorial Hospital, Kaohsiung Medical Center, between 2001 and 2009, who fulfilled the diagnostic criteria for KD. All patients were treated with IVIG (2 g/kg) and aspirin as per our previous studies [7, 8, 18] . This study was approved by the Institutional Review Board of Chang Gung Memorial Hospital. Blood samples were collected after informed consent was obtained from parents or guardians. CAL formation was defined as the internal diameter of the coronary artery measuring at least 3 mm (4 mm if the subject was over the age of 5 years) or the internal diameter of a segment at least 1.5 times that of an adjacent segment, as observed in echocardiography [8, 22] . IVIG responsiveness was defined as defervescence within 48 h after the completion of IVIG treatment and no recurrence of fever (temperature > 38 \u2022 C) for at least 7 days after IVIG with marked improvement or normalization of inflammatory signs [7, 8] .", "In this study, 37 patients (9.9%) had CAL formation and 49 patients (13.1%) had resistance to the initial IVIG treatment (Table 1) . However, no tSNPs were significantly associated with genotype or allele frequency in the KD patients with or without CAL formation (Table 3) ." ] },{ "paper_id": "8f0e06be9f6ded0251683770d5f9fa0efd15510b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In contrast, the \"industry\" classification classifies all healthcare workers into \"health services\" without additional job-specific information. The annual death totals derived from \"occupation\" and from \"industry\" classifications differ by \u224815%-20%.", "In addition, the tuberculin skin test is notoriously difficult to interpret, with suboptimal sensitivity and specificity, and so may distort the actual trend in tuberculosis infection rates. Finally, as many as 50%, and possibly more, of all percutaneous injuries are not reported, which complicates tracking by the current passive surveillance system (15) .", "The National Institute for Occupational Safety and Health (NIOSH), a branch of CDC, is charged with providing leadership and conducting research to prevent workplace illness and injury. They regularly publish the Worker Health Chartbook, which reports fatal occupational illnesses (14) . Infectious diseases, however, are not included in the illness report. Instead, data are focused on occupational pneumoconiosis, mesothelioma, and hypersensitivity pneumonitis.", "Most of all, a national registry would provide an ongoing reminder of the risk of caring for others, by raising awareness among laypersons and professionals alike. The 9 million persons employed in the healthcare industry and their families merit better protection for their health and greater recognition for their contributions. " ] },{ "paper_id": "8f4ec7b6c58e8cafcc1f8eb3380370621110202b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Urbanization. On a global basis, the proportion of people living in urban centers will increase to an unprecedented 65% by the year 2030 (Population Reference Bureau 1998). The 2000 census shows that 80% of the U.S. population now lives in metropolitan areas, with 30% living in cities of 5 million or more. The environmental issues posed by such large population centers have profound impacts on public health beyond the city limits (Knowlton 2001) .", "Infectious diseases can also pass from people to wildlife. Nonhuman primates have acquired measles from ecotourists (Wallis and Lee 1999) . Also, drug resistance in gramnegative enteric bacteria of wild baboons living with limited human contact is significantly less common than in baboons living with human contact near urban or semiurban human settlements (Rolland et al. 1985) ." ] },{ "paper_id": "8f8eb4f004c2002face0723f2f58cc411954d36e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We thank the Yale University Center for Genome Analysis for their assistance in producing the PacBio sequence data.", "Funding for this research was provided by the USDA Agricultural Research Service. Funding sources did not impact study design, data collection, data analysis, decisions on publication, or preparation of the manuscript.", "Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture." ] },{ "paper_id": "8f92e63e66110b0e8c72eb9385ddfa957c404aea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This work was supported by Grants-in-Aid for Young Scientists (B) from the Ministry of Education, Culture, Sports, Science and Technology in Japan to YF (23790144).", "Authors' contributions YF drafted the manuscript. HT helped to draft the manuscript. All authors read and approved the final manuscript.", "The authors declare that they have no competing interests. " ] },{ "paper_id": "8fac3cde7ec21f88cdaf5a5f6526f12e0353bfdb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8fe8deec61edda35cbb08de93a02c9930c32a1eb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "907f894adb65a78f0d4ee2b936c4637c0bbddcf3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Since the establishment of the ", "Editing. The compact organization of viral genomes is often a challenge for genetic manipulation of virus BACs. Overlapping coding sequences and regulatory elements require a strategy that allows the introduction of minimal sequence modifications that do not interfere with the expression and function of neighboring genes or sequences. In this section, we describe the available techniques that can be used for specific, minimal editing of sequences. The methods allow the manipulation of BACs on the nucleotide level; they include start codon mutation or insertion of a stop codon to abrogate gene expression as well as modification of functional domains of proteins or regulatory elements.", "Chromosomes (BACs)" ] },{ "paper_id": "90a0b231586bf8d6f53f07088f37a73ffe2ffe48", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A case-control study of 72 hospital workers with SARS and 144 matched controls found that inconsistent use of goggles, gowns, gloves, and caps (unadjusted odds ratio [OR] = 2.42-20.54, p < 0.05), as well as perceived inadequate training and perceived inadequate supply of protective equipment were significantly associated with higher risk for nosocomial infection (10) . Another study in China showed that good ventilation, isolation of SARS patients, and use of personal protection equipment were key means of preventing healthcare workers from becoming infected (11) .", "Nonmedical support staff, in general, were not contacting SARS patients as frequently as nurses did. This finding suggests that the fomite theory and the aerosol theory of transmission could not be dismissed. Another study investigating nosocomial infection in Hong Kong (10) reported that breakthrough transmission was likely responsible for nosocomial infection of hospital workers. Inconsistent use of personal protection equipment, perceived inadequate supply of such equipment, inadequate training, and perceived lack of knowledge about infection control were all statistically significant predictors of such breakthrough transmissions.", "A total of 1,755 SARS patients were reported in Hong Kong; they were hospitalized in 16 of the 27 hospitals governed by the Hospital Authority. Fourteen of these 16 hospitals had at least one hospital staff member who contracted SARS. In other words, 2 of the 16 hospitals (hospital 2 and hospital 4, which admitted 7 and 17 SARS patients, respectively) had a zero attack rate ( Table 1) ." ] },{ "paper_id": "90dc562112c5255333e45785fbf77a39fb1ef4cb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data availability. The complete genome sequence of BtKY72 is available in Gen-Bank under the accession number KY352407.", "We and Prevention (CDC), Atlanta, GA, and Bernard Agwanda from the National Museum, Kenya Wildlife Service, Nairobi, Kenya, for excellent technical and logistical assistance and field study.", "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." ] },{ "paper_id": "916602c93360fa550e272dcc72f00bd36be64817", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "917f664cddf8f82b6981fca23210ce68f7aad01d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Mr Terada is a PhD student in the Joint Faculty of Veterinary Medicine at Yamaguchi University, Yamaguchi, Japan. His research interest is evolution of coronaviruses. ", "Fecal samples were collected during August 2012-July 2013 from 79 ferrets from 10 animal hospitals scattered across 5 prefectures in Japan. Most of the ferrets were brought to veterinarians for clinical signs such as diarrhea, abdominal masses, and hypergammaglobulinemia; some had signs unrelated to coronavirus infection or were asymptomatic ( Table 1 ). The diarrhea tended to be mild, unlike with ECE, and was found in coronavirus-negative and -positive animals.", "To further investigate virus transmission routes, oral swab specimens were collected from 14 of the 79 ferrets and examined by RT-PCR using primers FRCoV RdRp-F1 and FRCoV RdRp-R1. Five (35.7%) specimens were positive (data not shown), providing a route leading to infection of susceptible animals. Coronaviruses are known to cause both respiratory and intestinal diseases in various animal species; therefore, ferret coronaviruses should be investigated in respiratory disease." ] },{ "paper_id": "91af6f5f54820a907d235b3d89cc5e94d3587aea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "S evere acute respiratory syndrome (SARS) was contained globally by widespread quarantine measures, measures that had not been invoked to contain an infectious disease in North America for >50 years (1) (2) (3) (4) (5) (6) . Although quarantine has periodically been used for centuries to contain and control the spread of infectious diseases such as cholera and the plague with some success (1) (2) (3) (4) (6) (7) (8) , the history of invoking quarantine measures is tarnished by threats, generalized fear, lack of understanding, discrimination, economic hardships, and rebellion (1, 3, 4, (6) (7) (8) .", "A Web-based format was chosen over random-digit dialing for both cost considerations and time constraints. The project was initiated and completed without a funding source soon after the outbreak period at a time when concerns about SARS were still a part of daily life in Toronto.", "Emerging Infectious Diseases \u2022 www.cdc.gov/eid \u2022 Vol. 10 ", "Qualitative data were coded and analyzed to show emerging themes. The development and confirmation of the thematic coding structure is an iterative process involving two researchers in individual, recursive reading of the textual data and group meetings to discuss and test the emerging themes. Discrepancies were resolved by consulting specific instances in the data, discussing their relationship to established themes, and reaching consensus as a group (14) ." ] },{ "paper_id": "91d05ee767e5582b61781844a76f08951ce43501", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9233087a44732e7cb754add5dd568b11f3dd8850", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Respondents indicating they never heard about SARS (1.3%) were excluded from the analyses. Furthermore, \"don't know\" answers on the questions about risk percep-tion were treated as missing values and, therefore, also excluded from the analysis. On average, 4.4% of respondents did not know how to rate SARS severity and 4.3% could not rate their vulnerability to SARS.", "The questionnaire continued with two questions focusing on knowledge of SARS (name symptoms, whether SARS is a communicable disease)." ] },{ "paper_id": "9241e0b97dce927be4592622e554fe81af5bfb2f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9250bb5a4c335bb86319f5e922698816625c40d8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Both swab and lung specimens were transported on ice to the laboratory within 1-2 hours of collection and stored at \u221280\u00b0C until testing. Collection dates and numbers of samples are listed in Table 1 .", "During the study, a total of 91 lung tissue samples and 96 nasal swabs were obtained from the 2 groups of camels (Table 1) (Table 1) .", "Swab specimens in transport media were mixed and then clarified by centrifugation at 350 \u00d7 g for 10 minutes; the supernatants were recovered for extraction. Lung samples were thawed and homogenized by using a TissueRuptor homogenizer (QIAGEN, Hilden, Germany), and 20% suspensions were prepared in 5 mL of transport medium. The resulting homogenates were subjected to centrifugation as above, and the supernatants were recovered for extraction. Total RNA was extracted from 140 \u03bcL of each nasal swab or lung sample by using the QIAamp Viral RNA Mini Kit (QIAGEN) according to the manufacturer's instructions." ] },{ "paper_id": "925366122df469b96d212da10c5be3e8cdcd385a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "925b804acc0847b8811aecbda567350372b3254f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Our results also suggest that studies dealing with application and efficacy of MERS-CoV vaccines should be modified. A first study involving immunologically naive animals showed a sharp decline in virus secretion after vaccination (14) . However, future vaccination trials should also investigate the effect of preexisting maternal antibodies on vaccine efficacy (15) .", "Knowledge about immunity to Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels is essential for infection control and vaccination. A longitudinal study of 11 dam-calf pairs showed that calves lose maternal MERS-CoV antibodies 5-6 months postparturition and are left susceptible to infection, indicating a short window of opportunity for vaccination.", "Author (Table) . Infectious virus was isolated only from calves but not dams. At 6 months postparturition, when calves showed the lowest antibody titers, MERS-CoV RNA was detected in 2 of 11 calves (Table) , indicating active MERS-CoV infection. All calves seroconverted during the following weeks ( Figure, panel A) ; 1 calf had meanwhile been euthanized because of a congenital forelimb deformity. All calves showed high reciprocal neutralizing titers of >640 at 11-12 months postparturition." ] },{ "paper_id": "927d61c8c5d2d7c892a9f11a454ec80e43b0f46a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "92a874a4d2371061665a018eee85abf9e857ebc2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Quantitation of barcode intensities were then carried out and the statistic mean value for each protein was computed (see Supplementary Fig. S11 ,S12).", "The stored serum samples from 11 breast cancer patients(all female) and 11 prostate cancer patients(all male) were acquired from Asterand. Nineteen out of 22 patients were Caucasian and the remaining three were Asian, Hispanic and African-American. The medical history is summarized in the supplementary materials.", "Page 15" ] },{ "paper_id": "92c3491310afbd2b13368d1e64b5e46ac71934bf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "92d3b21a383e7937cc7e70bc0c1fbb4bf7c09b87", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9305dbadf39b7da72a61b551eb55bda43567b7da", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A complete blood profile on admission showed a leukocyte count 3.1 x 10 9 /L, absolute neutrophil count 2.0 x 10 9 /L, lymphocyte count 0.7 x 10 9 /L, platelet count 112 x 10 9 /L, and hemoglobin 14.7 g/dL. The patient had mild renal impairment, with a creatinine of 119 \u00b5mol/L, urea and electrolytes within normal limits, and alanine transaminase mildly elevated at 90 IU/L (normal <58 IU/L). Bilirubin, alkaline phosphatase, and albumin levels were normal. C-reactive protein was 6.5 mg/L (normal <9.9 mg/L). A diagnosis of atypical or viral pneumonia was suspected because of the low leukocyte count and normal C-reactive protein.", "Other laboratory tests were performed, including blood, sputum, and urine cultures, nasopharyngeal aspirate for influenza and parainfluenza, indirect immunofluorescence for respiratory syncytial viral antigen detection, and atypical pneumonia titer (for adenovirus, Chlamydia psittaci, Q fever, influenza A and B, and Mycoplasma). The patient received treatment with intravenous amoxicillin-clavulanate and oral clarithromycin.", "The patient was isolated in a private room until day 27 of his hospital stay, when his nasopharyngeal aspirate and urine samples were confirmed to be negative for SARS-CoV. Repeat chest radiograph at follow-up 2 weeks later showed no residual parenchymal opacity, and the patient remained asymptomatic." ] },{ "paper_id": "938700b6861f687bac83e4cc9fc056e7d38371de", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Other recent events may offer insight into the desirability of using medical students as volunteers. Anecdotes from the terrorist attacks in New York City on September 11, 2001 , relate how medical students helped in various capacities immediately following the tragedy (10). However, no offi cial school or government mandate was issued forcing these persons to volunteer. In contrast, after the devastation of Hurricane Rita, college leaders at Texas A&M University College of Medicine made a decision to cancel classes and provided orientation sessions for students so that they could begin volunteering as soon as possible (11) . Volunteer tasks in this situation were limited, and many voiced frustration that their relatively limited medical skills greatly restricted their ability to contribute. In a more positive vein, students also claimed that \"the experience made them even more driven to become the best doctors they can\" (11) .", "S cientists believe we may be on the verge of the next great pandemic. Health Canada predicts that 4.5-10.6 million Canadians will become clinically ill and 11,000-58,000 will die in such an event (1) . The current strain of infl uenza A (H5N1), which has been circulating in Southeast Asia among birds, with limited spread to humans, has fueled this concern (2,3). An infl uenza pandemic would cause a shortage of healthcare professionals due to illness and an increased demand for their services (1) . Consequently, Canada and other countries have begun developing plans to deal with the anticipated health crisis (1) , and medical students could play an important role.", "All 510 medical students at the University of Alberta were invited by email to complete the questionnaire; 354 (69%) responded. Most (62%) respondents were women, and all but 1 were reported to be in good health. A variety of past volunteer activities were reported. Although medical students obtained health information from varying sources, they had the highest degree of confi dence in the information provided by physicians." ] },{ "paper_id": "93adcbf3142015ef32b767777b0f4bfaba19a4bc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "93c6eef32a1a511ee989a259eab0e12174dc6859", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Chemicals were from Sigma. Restriction enzymes were from Promega and New England Biolabs. KOD Hot Start DNA Polymerase was from Novagen. Amylose resin was from NEB (catalog no. E8021S). Ni-NTA resin was from Novagen (catalog no. 70666). Ultrafiltration device from Millipore (catalog no. UFC900524). Slide-A-Lyzer dialysis membrane was from Pierce (catalog no. 66415).", "Full-length Taq MutS was amplified from template pETMutS (22) with primers 5 0 -AAA AAA CAT ATG GAA GGC ATG CTG AAG G-3 0 and 5 0 -AAA AAT AAG CTT CCC CTT CAT GGT ATC CAA GG-3 0 and cloned into the Nde1/HindIII sites of vector pIADL14 (23) to give plasmid pMBP-MutS-H6.", "Note: While this manuscript was under review, Carr et al. (30) independently reported the application of Taq MutS in protocols for error reduction on synthetic DNA." ] },{ "paper_id": "93dffbe2dbaf6a930a6ba69004962a4ccc4a4ddb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "These authors argue against the use of these drugs in routine seasonal infl uenza control.", "In general N-inhibitors have low effectiveness, high effi cacy, and appear well-tolerated. The possibility of emerging resistance has been put forward. With oseltamivir, resistance has been reported to be around 0.4% (Zambon and Hayden 2001; Monto et al 2006) .", "They also concluded that there was no evidence of an increase in early exacerbations (Poole et al 2006) . Yet, in the experience of many clinicians, transient increases in symptoms may occur in the weeks after vaccination." ] },{ "paper_id": "940a99850a2fe93223a5ff0d9bb95869094a4a8f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "940fe55ad5d57c4e58076fb38e4aae64694a5baf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "PBMCs incubated with or without CpG ODN (3 \u03bcg/mL) for 12 h and cells from abdominal lavage fluid were washed twice with FACS staining buffer (PBS supplemented with 0.5% BSA, 0.01% NaN 3 and 100 mM EDTA) and then analyzed for the expression of various cell surface molecules by staining with FITC-labeled anti-CD80 mAbs and CD4, CD8a, NK1.1 mAb (used at 1:100 dilution) respectively followed by analysis of FACSCalibur 34, 35 .", "All in vivo and in vitro experiments were performed at least three times. We used a one-way analysis of variance (ANOVA) to analyze the data shown as mean\u00b1SD. Non-parametric analysis was used to analyze the data shown as median. Survival was estimated by the Kaplan-Meier method and evaluated with a log-rank test. A p value of<0.05 was considered statistically significant. All statistical analyses were performed with the SPSS 16.0 software.", "Human PBMCs were isolated from buffy coats (Blood Center of Jilin Province, China) by Fi-coll_Hypaque density gradient centrifugation (Pharmacia) and washed three times with Iscove's modified Dulbecco's medium (GIBCO). The viability of the PBMCs was 95-99% as determined by trypan blue exclusion. Murine B16 melanoma cells of C57BL/6 origin and Vero E6 cells (African green monkey kidney cell line, American Type Culture Collection) were grown in Iscove's modified Dulbecco's medium (GIBCO) supplemented with 10% heat-inactivated FBS (GIBCO), 0.15% NaHCO3, 100 IUmL -1 penicillin, 100 IUmL -1 streptomycin, and 2 mM L -1 glutamine at 37 \u00b0C in humidified air containing 5% CO 2 31 ." ] },{ "paper_id": "941a9a3f0138f7c01ff930023a4aa428a18170e1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "943576d41ee9cd2a8be3379fa2ff1bc8963a3202", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A standard protocol was used for EAE induction using synthetic peptides described above 70, 71 . Mice were injected subcutaneously with 200 \u03bcg of each peptide and 100 \u03bcl of Complete Freund's adjuvant (CFA) in a total volume of 200 \u03bcl. Four hours before peptide injection, each mouse received 200 ng of purified Bordetella pertussis toxin (CalBiochem, San Diego, CA) in 100 \u03bcl of sterilized water intraperitoneally (i.p.) and this was repeated 48 h post-myelin peptide injection.", "All mice were examined daily for 29 days for neurologic clinical signs according to the following criteria: 0, normal/no overt sign of disease; 0.5, tail hypotonia; 1, tail atonia or hind limb weakness; 2, limb tail and hind limb weakness; 3, partial hind limb paralysis; 4, complete hind limb paralysis; and 5, moribund state; death.", "Refer to Web version on PubMed Central for supplementary material." ] },{ "paper_id": "943f2beb4d32bce84617c72677a277224b73fd8f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Environmental conditions at the two hospitals differed, but the impact of these differences on SARS transmission is unclear. Neither hospital had negative pressure rooms. Hospital A was a more modern facility; however, hospital B had designated SARS isolation wards and large spacious rooms with high ceilings and ceiling fans and large windows kept open for cross-ventilation. In contrast, hospital A's rooms were smaller, and individual air-conditioning units were in use early during the outbreak. In addition, hospital A had diverse patients (maternity, postoperative, pediatric, etc.) housed on the same hospital floor when the SARS outbreak began.", "Reported symptoms and personal health behaviors of healthcare workers are also presented in the Table. One SARS ward respondent reported a fever, and less than 23% reported either a cough or sore throat. Extreme fatigue was reported by 50% of the SARS ward workers. Antibodies to SARS-CoV among our study participants were undetectable by both laboratories. ", "This study has several limitations. First, our survey is subject to recall and reporting bias, because not only was it difficult for respondents to recall behaviors during specific periods within the previous 2 months, but respondents may have been concerned that results could be used to evaluate their performance. Estimates of SARS exposures and the frequency of personal protective equipment use among SARS ward workers are therefore probably inflated. Second, we collected serum specimens approximately 10 to 12 days after the last SARS patients were discharged; although these patients were discharged after their 5th to 6th week of illness, the minimal chance that a patient shed virus beyond the usual 2-to 3-week period (2) would theoretically mean that a few participants may have been tested before seroconversion. A third limitation is our lack of data on hand-washing or sanitizing practices, important means of preventing respiratory virus droplet spread." ] },{ "paper_id": "9456caa4e69d2efb19a1dccca6a307bee16548ea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "C oronaviruses (CoVs) are enveloped viruses with a positive-sense, single-stranded RNA genome (1) .", "Emerging Infectious Diseases \u2022 www." ] },{ "paper_id": "94b5bb85c872c0c1db0148b572b78e82f284cf59", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "S evere acute respiratory syndrome (SARS) is a newly emerged disease that spread globally in early 2003; more than 2,523 cases and 181 deaths occurred in Beijing, China (1) (2) (3) . In the initial outbreak period, the diagnosis of infection was mostly dependent on clinical manifestations and epidemiologic findings, until the associated coronavirus (SARS-CoV) was identified as the causal agent (4) (5) (6) , and its immediate full genome was sequenced (7, 8) .", "Viral isolation was performed on RT-PCR-positive stool samples from convalescent patients only. The sample was pretreated by centrifugation, and the supernatant was injected after filtration into the VeroE6 cell culture at 37\u00b0C. All procedures were handled under biosafety level 3 conditions. We looked for the characteristic cytopathic effect for 5 to 11 days after injection. Examination with electron microscope and RT-PCR assays were used for identification of SARS-CoV.", "Our study has demonstrated long-term duration of SARS-CoV excretion in stools. Careful hand and toilet disinfection is required to avoid transmission of the virus to close contacts of patients." ] },{ "paper_id": "951bc7b3cf514d9077b2cd520cad9e6089f0e558", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9595fe80c8e79a20286b0bfad42c930623e13805", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "95aec306660c1b7519e9f019d92cc3a8206481e4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "High-performance liquid chromatography (HPLC) was performed on a Hewlett Packard series 1100 HPLC with a reverse-phase Supelco RP-18 column (4.6 \u00b7 250 mm). Mass spectra were obtained on an LC MS Hewlett Packard series 1100 MSD with API-ES detector or on an AMD 604/402. Thin-layer chromatography (TLC) was carried out on Merck 60 F 254 TLC plates with the mixture 1-propanol/ aqueous ammonia/water \u00bc 55:35:10 (v/v/v).", "Complete LNA substitution is no more stabilizing than substitution at every other nucleotide starting at the second nucleotide from the 5 0 end", "Hybridization of oligonucleotides to RNA is important for applications, such as antisense therapeutics (4, 8, 21, 46, (52) (53) (54) , diagnostics (32, 33, 42, 55) , profiling gene expression with microarrays (18) (19) (20) 56) , identifying bands by Northern blots of gels (57, 58) and probing RNA structure (1, 3, 15, (59) (60) (61) . Oligonucleotides with 2 0 -O-alkyl modifications can be particularly useful for these applications because they are easily synthesized (39, 43) , chemically stable and bind relatively tightly to RNA (39) (40) (41) (42) . However, for many applications, it is desirable to modulate the binding affinity. For example, sequence independent duplex stabilities would benefit applications that involve multiplex detection, such as microarrays." ] },{ "paper_id": "96059507ee9c4acbd419bd96775c652eb4104332", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The surveillance of influenza based on laboratory-confirmed cases is implemented in primary healthcare and in hospitalized patients (9, 11) . Our results open the possibility and show the potential interest of adding a sentinel virological surveillance based on persons who die during the influenza season.", "Of the 57 participants in the study, 29 (51%) were women, 23 (40%) were <85 years of age, 50 (88%) had major chronic conditions, 5 (9%) had been resident in nursing homes, and only 12 (21%) had been hospitalized before death. Nonparticipants did not differ in these characteristics (online Technical Appendix Table) .", "During the study period, 460 deceased persons >65 years of age were registered, 106 were attended in the participating morgues, and 57 (54%) were enrolled in the study. Nonparticipation resulted mainly from logistic problems and lack of signed consent." ] },{ "paper_id": "963dfcc10563ef66cf366f73640ab9b3e84a9a55", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "96650e6fa280653c83e6f9b1ba1e5217f45e4799", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9695a8fb288be9ef014dbaf030498d3c7ce0fc81", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The application of serum proteomics and gene expression analysis to early diagnosis and treatment decisions is a daunting challenge. It will require parties practising in previously disparate disciplines to work together and understand the data, which may be in the form of clinical information, mathematical algorithms and mass spectrometry. The challenge of 'clinical proteomics' and DNA microarrays is no longer just the development of new technologies, but rather the best use and integration of these technologies for the diagnosis and treatment of disease. The process of this integration represents a new, evolving field of 'translational medicine'. ", "The integration of 'global gene profiling' into clinical medicine is exemplified in 2003 by the fact that in the early weeks of the severe acute respiratory syndrome (SARS) pandemic in 2003, the Centers for Disease Control sent tissue samples and viral cultures from SARS patients to Dr Joseph DeRisi's research team at the University of California, San Francisco. They explored the origin of the novel coronavirus using their custom oligonucleotide DNA microarray which represents 1,000 viruses. 52, 53 Of the 12,000 oligonucleotides spotted on the array, the patient samples hybridised only to a group of eight oligonucleotides representing two virus families: Coronaviridae and Astroviridae. 54 Although the identification of the novel coronavirus associated with SARS was made using a broad range of laboratory testing, this example demonstrates the power of microarray technology as a molecular diagnostic tool to test the spectrum of viruses in a single assay and to narrow, to a finite number, the potential pathogens in an unknown disease with a nonspecific clinical presentation. Admittedly, the current review is focused on genomic applications to cancer, but this example deserves special mention, given the worldwide attention on SARS. Moreover, as illustrated in this example, the integration of genomic analysis with traditional clinical and histological assessments is finding its way into clinical management.", "Global gene expression analysis is beginning to move from the laboratories of basic investigators to large-scale clinical trials. The potential of this technology to improve diagnosis and tailored treatment of human disease may soon be realised, now that several comprehensive studies have demonstrated the utility of gene expression profiles for the classification of tumours into distinct, clinically relevant subtypes and the prediction of clinical outcomes. In addition, new data from the emerging proteomics platforms add another layer of molecular information to the study of human disease, as scientists attempt to catalogue a complete inventory of the proteins encoded by the genome and to establish a 'biosignature' profile of human health and disease. As a result, it is anticipated that, together, these technologies will facilitate the comprehensive study of genes, gene products and signalling pathways so that the objective of personalised molecular medicine can be achieved. This paper will review the studies that best demonstrate how genomics and proteomics technologies can be used to improve cancer diagnosis and treatment it will specifically highlight the important work being incorporated into clinical trials." ] },{ "paper_id": "96b1d037fb00eb3ecb7321ca5102d36553ff56ce", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dr Kramer is associate professor of veterinary parasitology at the University of Parma. Her research interests include filarial infections and bacterial endosymbionts.", "Medical awareness of infection risk is essential for a correct diagnosis, and the use of serologic analysis for D. repens somatic antigen merits further study as a diagnostic aid. Further monitoring of the HSD situation in this area is needed to establish guidelines for preventive measures, including effective chemoprophylaxis in animals.", "Information is also lacking on which mosquito vectors are involved in transmission of D. repens in the study area. In other geographic areas where human dirofilariasis is endemic, changes in climatic conditions (temperature, relative humidity, rainfall, rate of evaporation) favor the development of vector mosquitoes (12) and of the larval phase of the nematode in the vector.", "H uman subcutaneous dirofilariasis (HSD) is a zoonotic filariasis caused by infection with several species of worms belonging to the genus Dirofilaria; most documented cases are attributed to Dirofilaria repens (1) . Dirofilarias are natural parasites of a great variety of animals and, with the exception of D. immitis, live in the subcutaneous tissue of their hosts, produce circulating microfilariae, and are transmitted by mosquitoes (2) . The principal reservoir of D. repens is the dog. Humans are accidental hosts with patent infections being extremely rare. Differential diagnoses of HSD include neoplasia and other granulomatous diseases, and a definitive diagnosis usually requires surgical removal and examination of a granuloma." ] },{ "paper_id": "96cd30cbd4f3cecd2d0add83df270e1ae68670b1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Background There is a requirement to detect and differentiate pandemic (H1N1) 2009 (H1N1v) and established swine influenza A viruses (SIVs) by real time reverse transcription (RRT) PCR methods.", "UK pigs positive for avian-like swine H1N1" ] },{ "paper_id": "9741eab85f5510655de379d9e3c11f5bf0d2d560", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "versus 13AE6%), but this difference was not statistically significant." ] },{ "paper_id": "978fcb9694711bd974f21203205a86d359868b3d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9795fe49f827ff0654ce919cd8b7450e8a2b40d8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All these data allow us to make the following conclusions about the role of IL-4 in OME:", "Thus, IL-4 was presented in both groups of patients with OME, allergic and non-allergic. However, local overproduction of IL-4 was associated predominantly with an allergic background of patients.", "IgA (IgA \u00c1/ICs) in both acute and chronic otitis media. 126, 127 The highest level of IgG \u00c1/ICs was found in subacute cases, whereas IgA \u00c1/ICs were predominant in chronic OME. The immunoglobulin immune complexes provided the prolongation of inflammatory process in the middle ear.", "However, it is necessary to note that additional experimental work needs to be done in order: (1) to elucidate the molecular mechanisms of cytokine regulation of the middle ear inflammation; and (2) to analyse the possibility of anti-cytokine therapy in clinical treatment of OME." ] },{ "paper_id": "97a3bb18c51244482cb68d5565389266a0cb7098", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Xiaojuan Chen et al.", "Cell culture, transfection reagent, and antibodies HEK 293T cells were cultured in Dulbecco's Modified Eagle's Medium (GIBCO) supplemented with 10% heat-inactivated fetal bovine serum (FBS) and maintained at 37\u00b0C in a humidified 5% CO 2 incubator. Transient transfection reagent Lipofectamine 2000 was purchased from Invitrogen. Anti-HA (MBL), anti-Flag (MBL), anti-V5 (MBL), anti-Myc (MBL), anti-\u03b2-Actin (Beyotime), anti-IRF3 (Abcam), and anti-pIRF3 (Abcam) antibodies were used in the study.", "STING-TRAF3-TBK1 complex. These results revealed a novel mechanism used by SARS coronavirus to negatively regulate activation of innate immunity (Fig. 6) ." ] },{ "paper_id": "97a632fdbc3ebd9ace9c84c90229bfa08e166ecd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "983154b0c824acdd8a9acf1e6ab1c9fe03c392f3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "983e4e747ad0691e47cb54ed407a014f66f96380", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "987177dd5896befd3e45e5d1fae03839b41b320b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9881cbf87faaee63ada0713e3a8953d3732e0f12", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Lysed cells, mixed with 30 l 2\u03eb SDS loading buffer, were heated at 100\u040aC for 5 min., and centrifuged at 13,000 rpm for 10 min. Protein samples were separated by electrophoresis gel and transferred to nitrocellulose membranes. The membranes were blocked for 1 hr with 10% non-fat dry milk in TBST (135 mM NaCl, 2.7 mM KCl, 24.8 mM TRIS . HCl, 0.05% Tween 20, pH 7.4) and then probed with an antibody in TBST for 1 hr at 25 \u040aC. A monoclonal antibody against HPV16 E7 protein (Zymed) was used to probe the expression of E7. Blots were rinsed with TBST, incubated with rabbit antimouse IgG-HRP second antibody (Sigma) for 1 hr, then rinsed with TBST again, and developed with Super Signal West Pico stable peroxide solution (Pierce).", "The endoplasmic reticulum (ER) is where the major histocompatibility complex (MHC) class I molecules are loaded with epitopes to cause an immune cellular response. Most of the protein antigens are degraded in the cytoplasm to amino acids and few epitopes reach the ER. Antigen targeting of this organelle by Calreticulin (CRT) fusion avoids this degradation and enhances the immune response. We constructed a recombinant adenovirus to express the E7 antigen with an ER-targeting signal peptide (SP) plus an ER retention signal (KDEL sequence). In cell-culture experiments we demonstrated that this new E7 antigen, SP-E7-KDEL, targeted the ER. Infection of mice with this recombinant adenovirus that expresses SP-E7-KDEL showed interferon induction and tumour-protection response, similar to that provided by an adenovirus expressing the E7 antigen fused to CRT. This work demonstrated that just by adding a SP and the KDEL sequence, antigens can be targeted and retained in the ER with a consequent enhancement of immune response and tumour protection. These results will have significant clinical applications. Mice. Female C57BL6 mice (6-8 weeks old) were purchased from Harlan (M\u00e9xico City, M\u00e9xico), housed in the animal facilities of the Histology Department of the School of Medicine, UANL, and cared for in conformity with good laboratory practice guidelines. Cell lines. HEK293 cells were maintained in advanced DMEM supplemented with 4% heat-inactivated foetal bovine serum (FBS). TC-1 cells derived from primary epithelial cells of C57BL/6 mice co-transformed with HPV-16 E6 and E7 and the c-Ha-ras oncogenes, were maintained in RPMI 1640 medium supplemented with 10% heat-inactivated FBS. All of the cell lines were purchased from American Type Culture Collection (Manassas, VA, USA).", "Adenovirus Purification kit (Cell Biolabs, Inc., San Diego, CA, USA)." ] },{ "paper_id": "98e85066186167e53509cadef5d5389f2087da2e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "High-field NMR spectra were acquired on Varian INOVA 500, 600, and 900 MHz spectrometers equipped with triple resonance probes and z-axis gradients, as well as a Bruker AVANCE-800 spectrometer equipped with a cryoprobe. R 1 , R 2 , and NOE data were collected using standard 15 N relaxation experiments (Farrow et al. 1994) , in an interleaved manner.", "Models including an R EX term were not selected by information criteria for any residues. This is in agreement with R 2 relaxation-dispersion experiments performed on SARSN, which also do not identify any significant ls-ms fluctuations (data not shown). The pronounced decrease in R 2 values in the loop and b-hairpin regions (Fig. 5) is consistent with significant ps-ns motions, but not slower motions.", "The SARSN construct was a gift from Dr. Hualiang Jiang (Luo et al. 2004 ). E. Coli BL21 (DE3) cells were grown in 15 N M9 medium to an OD of 0.6 and induced with 1 mM IPTG. Cells were harvested by centrifugation and resuspended in lysis buffer (0.1 M Tris, 0.5 M NaCl, pH 7.0) with a protease inhibitor cocktail (Calbiochem). Following lysis by sonication, cellular debris was removed by centrifugation. The lysate was then dialyzed against 50 mM Na 4 H 2 PO 4 , 50 mM NaCl pH 7.0 and purified over SP-sepharose equilibrated in the same buffer, eluting with 2 M NaCl. Following a repeat dialysis step, the protein was purified over Q-sepharose using the same buffer system. Following dialysis into the NMR buffer (50 mM HEPES, 150 mM NaCl, 0.02% NaN 3 pH 7.0), the protein was purified over S-100 sepharose and concentrated to 1 mM. NMR samples contained 10% D 2 O. All separation media were purchased from GE Healthcare." ] },{ "paper_id": "98fd9db3d54a142771aa760cdfcbd53b7cfbd0ed", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Similar results were obtained in a study conducted by Alexis et al. 25 In subjects receiving fluticasone 0.5 mg and 2 mg, sputum neutrophilia was significantly reduced by 18% and 35%, respectively. The following inflammatory markers were also significantly reduced in a dose-dependent manner in subjects receiving fluticasone: CD11b, mCD14, CD64, CD16, HLA-DR, and CD86 on sputum monocytes. Serum Clara cell protein 16 levels (a marker of pulmonary damage) were significantly increased post-O 3 challenge.", "Rhinovirus is responsible for the common cold and is spread through infected respiratory secretions from one person to another. Human rhinovirus (HRV) replicates at 33\u00b0C-35\u00b0C and thus has been linked to upper airway infections, where mucosal surfaces are cooler. Evidence exists that HRV is not limited to the upper airways. Gern et al 36 HRV binds to intracellular adhesion molecule (ICAM)-1, the major HRV receptor. 37 The low-density-lipoprotein receptor 38 binds to a minor group of HRV (HRV2). The gene for ICAM-1 maps to human chromosome 19, as do the genes for a number of other picornavirus receptors.", "Several studies have shown induction of proinflammatory genes implicated in neutrophil activation following rhinovirus induction of bronchial epithelial cells (eg, IL-8 regulated by NF-\u03ba\u03b2 signaling pathways and Gro\u03b1). [39] [40] [41] Rhinovirus infection of epithelial cells leads to the release of proinflammatory cytokines and chemokines including IL-6 and IL-8. Chemokines attract inflammatory cells (eg, neutrophils, eosinophils). These cells release toxic products, stimulating mucus production and leading to tissue damage, with possible long-term loss of lung function. Some mediators, such as endothelin-1, have a direct effect in causing bronchoconstriction and vasoconstriction, resulting in airflow obstruction and impaired gas exchange." ] },{ "paper_id": "992c7e3cd0a143b2506bcbe51d1cda024fb5b526", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "PMR is traditionally used to treat various inflammatory diseases in Korea and China. In Korean Medicine, the herbal composition of PMR, Lycium chinense Fructus, Psoraleae Corylifoliae Fructus, and Cuscuta chinensis Semen can be used to treat premature graying of the hair and premature aging.", "The mRNA expression of STAT1 (GenBank: NM_009283) was evaluated with the bead-based QuantiGene Plex assay according to the manufacturer's protocol. The relative mRNA level of each sample for STAT1 was normalized to that of GAPDH (GenBank: NM_001001303).", "Materials DMEM, FBS, penicillin, streptomycin, PBS, and other tissue culture reagents were purchased from Gibco BRL (Grand Island, NY, USA). Emodin, poly I:C, indomethacin, Griess reagent, and all other chemicals were purchased from Sigma-Aldrich (St. Louis, MO, USA). The multiplex bead-based cytokine assay kits used for the determination of cytokine concentration were purchased from Millipore (Billerica, MA, USA). The Fluo-4 calcium assay kit was purchased from Molecular Probes (Eugene, OR, USA). QuantiGene Plex 2.0 Reagent System for direct quantification of multiple RNA targets was purchased from Panomics (Redwood City, CA, USA).", "To date, pandemic viral diseases such as Ebola hemorrhagic fever and Zika virus infection is still being undissolved. Both Ebola virus and Zika virus belong to the single-stranded RNA virus. In 2015, people of South Korea suffered from Middle East respiratory syndrome caused by the Middle East respiratory syndrome coronavirus (a novel positive-sense, single-stranded RNA virus of the genus Betacoronavirus). Recently, Zika virus disease in South America was reported to be dangerous for public health. Thus, it deserves to contemplate how to effectively deal with new pandemic infectious diseases such as Ebola hemorrhagic fever, Middle East respiratory syndrome, severe acute respiratory syndrome, Zika virus infection, and avian influenza.", "Cytokine is one of important elements in immunity and inflammation; cytokines are known to be small proteins; as a cell signalling molecule, cytokine plays a role in autocrine, paracrine, and endocrine mechanism of immunomodulation; cytokine are produced not only immune cells but also endothelial cells and fibroblasts; cytokines are classified as interleukins, lymphokines, interferons, tumor necrosis factors, colony stimulating factors, and chemokines; cytokines bind cell-surface receptors, which triggers intracellular signalling and host responses to infection, trauma, cancer, immune reaction, and other inflammatory phenomena; the concentration of circulating cytokine can increase up to 1,000-fold in the case of infection or trauma; the dysregulation of cytokines might become pathological in inflammation and be linked to various diseases ranging from neuroinflammatory diseases to cancer." ] },{ "paper_id": "993145adae199c9f03caa8989e6b82a6e69d2813", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We implemented this survey by using a longitudinal online panel, which was created in March 2014 to address human hygiene and preventive behavior regarding infectious diseases (13, 14) . The panel consists of 1,376 persons 15-69 years of age, who complete short, online questionnaires once a month. Panel members come from 4 districts in Lower Saxony, Germany (Braunschweig, Salzgitter, Vechta, and Wolfenb\u00fcttel). The districts were chosen by convenience: Braunschweig is the location of our research institute (the Helmholtz Centre for Infection Research), Vechta is its rural counterpart, and Salzgitter and Wolfenb\u00fcttel are 2 neighboring districts of Braunschweig. In each district, potential participants were invited to the panel by means of proportional stratified random sampling from the population registry. Of 26,895 invited, 9% were successfully recruited.", "We used an open-source online survey application (Limesurvey; 15) to develop a knowledge-attitude-practice survey", "Because we do not have information about participants' professions, we cannot assess whether risk groups for exposure to EVD (e.g., medical staff) are overrepresented in the study sample." ] },{ "paper_id": "99366c7b20c1a456b14ba2c03cfa67ea0aefcf14", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "99ad07c4a0fdcc24df76b723ff978c84076c56ac", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.", "Total RNA was extracted from 250 ll of supernatant from 5 pooled swabs (2 pools/flock) using an RNeasy Mini Kit (QIAGEN, Germany) according to the manufacturer's instructions. Each RNA was eluted in 50 ll RNase-free water.", "The astrovirus strains used were as follows: Sequences determined in this study have been submitted to GenBank with accession numbers from HQ317705 to HQ317733." ] },{ "paper_id": "99c0958f9fa04d32dcdd13fcc01ffcb531f48950", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "When using the word \"politics,\" we refer not simply to partisan politics but to the broader set of policies and sys-tems. Although ideology is used in many different ways, in this case, it refers to individual systems of belief that may color a person's attitudes and actions and that are not necessarily based on scientific evidence (2).", "The Post's statement may be correct, but academic infectious disease specialists have every right and responsibility to question decision-making that affects their patients and colleagues, especially when the scientificpolitical interface regarding that decision is unclear. Careful review of the literature and expert experience predicted substantial risks from adverse vaccination reactions.", "lord mayor and aldermen of the city of London put into place a set of orders \"concerning the infection of the plague,\" which was then sweeping through the population. He intended that these actions would be \"very expedient for preventing and avoiding of infection of sickness\" (1).", "Debate about vaccines offers an example of the effect of ideology on public health progress in the form of persons who oppose vaccination. These persons put communities at risk by refusing vaccination for themselves and their children and enlist political support to undermine our greatest medical advance.", "Dr. McPheeters is a healthcare epidemiologist whose work focuses on translation and use of research in policy and practice, particularly in the areas of women's health and pregnancy care." ] },{ "paper_id": "99f11f6e7dcf626abe3290b0cdc98d91e291517a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9a473a8b0c6f5a6d34a3201ab9635c5973149fd5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9a5a8345c449ca529d68c57e0b52b8f90b1297bd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "divide the f 12 -f 22 parameter space into regions of different disease outcomes.", "Only through various anthropogenic changes, including urbanization (increasing S 2 ) and increased global travel (increasing \u03b2 22 ) did the HIV pandemic take off in the 20th century.", "An example of an apparent multihost pathogen is rabies in side-striped jackals (H 2 ) in Africa. Until a recent analysis (22) , rabies was considered sustainable in the jackal population (H 2 ), but detailed monitoring showed that rabies is not self-sustaining because of the density of the low susceptible jackal population (S 2 ), and epidemics are frequently seeded from the domestic dog reservoir (high \u03b2 12 )." ] },{ "paper_id": "9a68a4619502c6039c7b67be77cf1e73507ede65", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9afb35f53239d7fc6c241632cef92d1ed9742ef6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9b5ccd6bdaec71cd24d8c9122c6a6b868bdd22a0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9b75fe020ec7b8a5ee0399a61135cbdfe18a50f8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9be839381833cc5da620a0c6c25da09c3a0ea961", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9c4703d955eb0a06809ef3c48ddb829fe0ef3987", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Other articles in this series can be found online at http://ccforum.com/articles/ theme-series.asp?series=CC_Disaster", "Supportive care with intravenous rehydration, mechanical ventilation, vasopressor therapy, and renal replacement therapy are required if multiorgan failure and ARDS are a feature of disease [69, 90] . Due to the progression of pneumonia to ARDS, non-invasive ventilation is not recommended, and early intubation may be beneficial before overt respiratory failure ensues. Corticosteroids have been used in some patients with HPAI H5N1, but no definitive role for steroids has been determined. Other immunomodulatory therapy has not been reported [91] .", "Non-invasive mechanical ventilation Bronchoscopy Humidified oxygen delivery Non-rebreather mask without expiratory filter This article is part of a thematic series on Disaster management edited by J Christopher Farmer.", "The HA glycoprotein mediates attachment and entry of the virus by binding to sialic acid receptors on the cell surface. The binding affinity of the HA to the host sialic acid allows for the host specificity of influenza A [6, 7] . Avian influenza subtypes prefer to bind to sialic acid linked to galactose by \u03b1-2,3 linkages, which are found in avian intestinal and respiratory epithelium ( Table 2 ) [8] . Human virus subtypes bind to \u03b1-2,6 linkages found in human respiratory epithelium [8, 9] . Swine contain both \u03b1-2,3 and \u03b1-2,6 linkages in their respiratory epithelium, allowing for easy co-infection with both human and avian subtypes (thus acting as a 'mixing vessel' for new strains) [10] . Humans have been found to contain both \u03b1-2,3 and \u03b1-2,6 linkages in their lower respiratory tract and conjunctivae, which allows for human infections by avian subtypes [9, 11, 12] . The HA glycoprotein is the main target for immunity by neutralizing antibodies." ] },{ "paper_id": "9cb04b84b292eff39712e9af5a9f4db2c61a6dcd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Another observation was that a great number of admissions for SCZ occurred in countries like Ireland with higher availability of wheat and rye than in England and Wales [24] .", "Human and animal rights This article does not contain any studies with human participants or animals performed by any of the authors.", "Informed consent For this type of study formal consent is not required." ] },{ "paper_id": "9cd3e3b494131726a57bf2d8e5aeb5bc56239dd0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9d02db669e8701c83186d7d3aae69da2f2cb3d34", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9d26cdd19afaaa9f93ff6b4a6741f4fb3eb33e4e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As no prophylaxis vaccination or specific proven treatment is yet available against SARS, prevention is the only measure that one can take to prevent epidemics. Communicating the risks and preventive measures in an effective and acceptable manner is important.", "An epidemic like SARS has an impact on many sectors of the society. Leadership is essential to coordinate activities and information dissemination in order to minimize confused messages and public panic. Coordination should be maintained with all relevant sectors including the health professionals, policymakers, community leaders, media, and the public.", "As with the outbreak of avian influenza, in which humans became infected through the purchase of live poultry, a process that still continues, the SARS virus appears to have been contracted from an animal source (possibly civet cats [23] ) used for human consumption. Close contact between humans and animal vectors in the southern China region has been responsible for a number of epidemics, including influenza A. A reduction in exposure to animal viral reservoirs should reduce the occurrence of such events. To that end, the Chinese government has increased implementation of laws that prevent the consumption of wild animals." ] },{ "paper_id": "9d3a3e66c47a288c1ae7048c853a583c4eabf721", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9d77f5c67963a68f5ede5bf53e95fdb03270fd2b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In conclusion, short-term secondary response following fdOVA 257-264 immunization is independent from T cell help but long-term secondary response is T helper dependent and was not observed following fdOVA 257-264 immunization in mice depleted of CD4+ T lymphocytes.", "The responder cells were prepared as above from either control or immunized mice. Cells were incubated in anti-IFN-\u03b3 mAb precoated multiscreen plates with IL-2 at 20 U/mL and 5 \u00d7 10 5 irradiated syngenic spleen cells, prepulsed with either OVA 257-264 at 10 \u03bcg/mL or medium alone. Responder cells (5 \u00d7 10 5 /well) from each mouse were incubated with either medium alone or ConA at 10 ng/mL. After 40 hours of incubation at 37 \u2022 C, cells were washed and the plates were sequentially incubated with anti-IFN-\u03b3 biotinylated mAb, poly-HRP-streptavidin (Endogen, Woburn, MA, USA), and AEC substrate (Sigma, Milan, Italy). IFN-\u03b3 transfected TSA cells and the parental Journal of Biomedicine and Biotechnology 3 untransfected line were used as controls in each ELISPOT plate, after gamma irradiation. The spots were counted using the ELISPOT reader (A.EL.VIS, Hannover, Germany).", "Cellular immunity, particularly cytotoxic T lymphocyte activity, plays a role in the clearance of viral infections and in the control of tumor development. Therefore induction of CTL activity is a major goal of vaccine development and its achievement may be determined by the ability of a carrier to deliver antigens into the MHC class I pathway. Here we report a study on the use of fd filamentous bacteriophage as an efficient carrier for delivering CTL epitopes. The bacteriophage fd is a nonpathogenic virus that is not able to infect and replicate in eukaryotic cells. All available evidence indicates that bacteriophage administration is completely harmless to humans [10] [11] [12] . In the past few years we have shown that fd bacteriophage particles represent a good antigen delivery system both for T helper and CTL epitopes since these particles intersect both class I and class II pathways [3] [4] [5] ." ] },{ "paper_id": "9d867a0457787225540f0aae55979bea536fb74f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "D iarrhea, characterized by frequent liquid or loose stools, commonly results from gastroenteritis caused by infection with bacteria, parasites, or viruses. Patients with mild diarrhea do not require medical attention; the illness is typically self-limited, and disease symptoms usually resolve quickly. However, diarrheal diseases can result in severe illness and death worldwide and are the second leading cause of death around the world in children <5 years of age, particularly in low-and middle-income countries (1) . For many cases of diarrhea in humans, no causative agent is identifi ed.", "Although no species demarcation criteria have been defi ned for the family Caliciviridae by the International Committee on the Taxonomy (15) . Larger epidemiologic studies using genetic and serologic screening will be necessary to provide more insight into the distribution and pathogenic potential of recoviruses in humans. Dr Smits works at the Virology Department, Erasmus Medical Center, and Viroclinics Biosciences BV, Rotterdam, the Netherlands. Her research interests are hepatitis C virus and severe acute respiratory syndrome coronavirus.", "One sample, no. 289, yielded a novel mammalian virus from the family Caliciviridae that we further characterized by near full-length genome sequencing using random amplifi cation with next-generation sequencing, specifi c reverse transcription PCRs, and 3\u2032 rapid amplifi cation of cDNA ends PCR (Figure 1 , panel A) as described (6,7). We named the virus isolate calicivirus Bangladesh/289/2007 (GenBank accession no. JQ745645).", "For a large proportion of human diarrhea cases, no etiologic agent can be identifi ed, despite multiple metagenomic studies of viruses in human stool aimed at identifying new etiologic agents (3) (4) (5) . In addition, it cannot be known when and where emerging and reemerging viruses will appear in the human population. To identify potential etiologic agents of diarrhea in humans, we performed a metagenomic viral inventory in diarrhea samples from Bangladesh, which led to the identifi cation of a novel calicivirus." ] },{ "paper_id": "9d91b77a524dbfd635e4db011f1e9bfe84c55861", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "T he outbreak of severe acute respiratory syndrome (SARS) that emerged in China in November 2002 was caused by a novel coronavirus (SARS-CoV) that was detected in lungs, nasopharyngeal aspirates, and feces of infected patients (1) (2) (3) (4) . This outbreak in humans is striking because of the high rate of illness and death associated with it. The SARS-CoV outbreak likely resulted from zoonotic transmission, and natural animal reservoirs of viruses nearly identical to SARS-CoV increase the likelihood of its reemergence in humans (5) .", "Murine models of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) will greatly advance research on this emerging virus. When BALB/c mice were simultaneously inoculated intranasally and orally, replication of SARS-CoV was found in both lung and intestinal tissue.", "Coronaviruses are enveloped, plus-stranded RNA viruses that cause important respiratory and enteric diseases of humans and many animal species. Large peplomers or spike glycoproteins (S) are the viral attachment proteins that protrude from the virion and give it the appearance of a corona. Coronaviruses are members of the Nidovirales, which produce 3\u2032 co-terminal nested subgenomic mRNAs upon entry into susceptible host cells. The genome is the largest of all RNA viruses (27.6-31.2 kb), and the genomic RNA is infectious when transfected into cells from a wide variety of species and tissue types. Yet most strains of coronavirus have very restricted species and tissue tropism, illustrating the major role S-receptor interactions play in the species specificity and pathogenesis of coronaviruses. SARS-CoV sequence analysis shows that it has many of the unique characteristics of coronaviruses and that it shares the most predicted amino acid similarity and other molecular signatures with serogroup 2 coronaviruses (6) ." ] },{ "paper_id": "9d97b122ebffbbf28052287cae39cd6c6d3d7cb6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A great number of peptides isolated from different sources have been studied for antiviral activities (Andreu and Rivas, 1998 ; Antimicrobial Peptide Database/ APD: http://aps.unmc.edu/AP/main.html). Several AMPs have been tested, but just a few of them have reached the clinical routine (Oevermann et al., 2003 , Wachsman et al., 2003 .", "All assays were performed in triplicate. Statistical analysis were performed using a two-tailed Student's t-test and values were considered significant when p < 0.05.", "Other peaks corresponding to Na + and K + adducts of fengycin were also observed.", "The mass spectrum of the purified peptide P34 revealed typical m/z peaks of the lipopeptide fengycin (Figure 1). The m/z peaks at 1449.8, 1463.8 and 1477.8 differed by 14 Da, equivalent to a CH 2 group. These peaks were assigned to C15, C16 and C17 forms of Ala-6-fengycin." ] },{ "paper_id": "9d9ad4fc953115d139ae6bad7522c4e685022065", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9da34b54546112d418aa2b0e1ea55758b456a54c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Herein, we highlight biological compositions which maintain membrane protein and scFv stability by retaining native or native-like environments, which are designed for easy production while maintaining specificity and stability when in use with simple detection platforms ( Figure 1 ).", "4.2.2. Modifying Net Antibody Charge. Another method to increase antibody solubility without mutating their CDRs is by increasing the net charge of an antibody. 17, 95, 96 In one study, scFvs were \"supercharged\" by mutating solvent-exposed residues to charged residues of the same polarity. 17 Using a computational program, researchers selected charge mutations in the V H and V L domains of a scFv that were predicted to avoid destabilizing the antibody fold. Interestingly, it was found that positively charged scFvs remained much more stable and retained high binding affinities when heated, compared to negatively charged scFvs or wild-type scFvs This observation does not apply to single-domain antibodies (dAbs), as aggregation-resistant dAbs typically have net negative charges due to their acidic isoelectric points. 16,95\u221298 These studies underscore the need to better understand how charged residues impact aggregation and solubility of antibodies and antibody fragments.", "Together these mammalian membrane fragment technologies demonstrate how mimicking native environments can be beneficial for drug delivery, cellular studies, and proteomic work. Mammalian membranes have many benefits including low toxicity for drug delivery and correct orientation of the fragment to the nanoparticle -which is important to maintain their biological performance. Other molecules (e.g., recombinant antibodies) which are native to other parts of a cell (e.g., yeast cell wall) can also benefit by encapsulation in a native or native-like environment during protein studies." ] },{ "paper_id": "9dfa774c9dee1273ae85f5c7199e83bbb45eb18b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data were compiled by using Microsoft Excel 2000 (Microsoft Corp., Redmond, WA, USA) and transferred into SPSS Version 11.1 (SPSS Inc., Chicago, IL, USA). Statistical analyses included frequencies, proportions, and t tests/analyses of variance to evaluate differences among stratified media groups and results from the SARS knowledge section.", "Assessment of access and usage of 5 forms of mass media communication showed that 89% used the Internet, 88% television, 77% radio, 56% newspapers, and 28%, magazines. The daily use of television, radio, and Internet was categorized as previously reported (4), and participants were grouped into light (<2 h/day), medium (2-4 h/day) or heavy users (>4 h/day). Most students were light users of all 3 media types; however, Internet users were more likely to be heavy users than the other 2 groups combined (odds ratio = 3.55, 95% confidence interval 1.8-7.0, p = 0.0000357).", "In total, 314 students enrolled in the study (186 in phase 1 and 128 in phase 2), but 14 incomplete questionnaires were excluded, resulting in a final sample of 300 students. Of the 300 participants, 219 (73%) were women, and 213 (71%) were majoring in nonhealth-related areas. The average age was 21.1 years (SD = 4.7), with 93% between 18 and 23 years of age." ] },{ "paper_id": "9e04e344099e9f7ae40628aba46e4a2cf65aa876", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In summary, an inactivated SARS-CoV vaccine, produced with a technology that has a safety record established by immunizing hundreds of millions of persons, protects mice from challenge with SARS-CoV. The vaccine adjuvanted with MF59 elicits neutralizing antibodies (titer 1:91) after only 2 doses. We conclude that the vaccine described here has desirable properties, and our data support further development and plans for clinical trials.", "To the Editor: Less than a year after the identification of the severe acute respiratory syndrome coronavirus (SARS-CoV) (1), 3 independent laboratories reported protection from SARS-CoV challenge in animal models using a DNA vaccine or recombinant forms of the modified vaccinia Ankara or a parainfluenza virus, encoding the spike gene (2) (3) (4) . Their protective efficacies are encouraging because they provide proof that a SARS-CoV vaccine is feasible. However, vaccines based on those technologies are not licensed for human use, and recommendation and licensing will likely take many years. We have developed an inactivated virus vaccine that induces neutralizing antibodies and protects against SARS-CoV challenge.", "The vaccine was produced as described elsewhere (5) . Briefly, the SARS-CoV (strain FRA, GenBank accession no. AY310120) was grown in Vero cells, inactivated with \u03b2-propiolactone (BPL), and complete inactivation was confirmed by 2 consecutive passages on Vero cells. Inactivated virus was purified by column chromatography followed by sucrose gradient centrifugation. The fraction containing virus was dialyzed against phosphate-buffered saline pH 7.2, and total protein content was determined by using the Micro BCA Protein Assay Kit (Pierce Biotechnology, Rockford, IL, USA). Immunogenicity of the vaccine was tested by immunizing BALB/c mice at 0, 2, and 4 weeks with 5 \u00b5g of inactivated virus combined with the adjuvant MF59, an oil squalene-in-water emulsion (6) approved for human use in Europe for an influenza vaccine. Ten days after the third immunization, serum samples were tested for the presence of SARS-CoV spike protein-specific antibodies by using enzyme-linked immunosorbent assay, and high titers (1-3 \u00d7 10 4 ) of anti-SARS-CoV spike immunoglobulin (Ig) G antibodies were detected. IgG subclass determination indicated a predominant Th2-type immune response similar to that observed in BALB/c mice vaccinated with a UVinactivated SARS-CoV plus alum (7) ." ] },{ "paper_id": "9e27ba9881ed5c007ce21a415db956db0755e1f4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Further studies in this field brought a new generation of nucleotide/nucleoside analogues in which natural nucleobases were modified as exemplified by the 2,4diaminopyrimidine framework present in antiviral HPMPO-DAPy and PMPO-DAPy [9] [10] [11] and the 1,2,4triazole ring in ribavirin (Fig. 2) [12] .", "Finally, heating dihydrazides 10a-10g with 10 % hydrochloric acid for 2.5 h gave [1, 2, 3] triazolo [4,5-d] pyridazine-4,7-diones 11a-11g (Scheme 1) in 30-66 % yields [41] .", "Furthermore, preliminary structure-activity relationship evaluation of 1,2,3-triazole nucleoside phosphonates 3 and 4 suggested that this scaffold could be further optimised to afford selective inhibitors of HCV replication (Fig. 4) [28] ." ] },{ "paper_id": "9e8066b614f3db5212ebd32729dff2430cfc988a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The Chi-square test was used with Yate\u00b4s correction when applicable. Calculations were perfomed with Statgraphics, version 2.6, Statistical Graphics Corporation, STSC, USA.", "Ach\u00e1 SJ, K\u00fchn I, Jonsson P, Mbazima G, Katouli M, M\u00f6llby R: Studies on calf diarrhoea in Mozambique: Prevalence of bacterial pathogens. Acta vet. scand. 2004, 45, 27-36." ] },{ "paper_id": "9e8a62fc036d8dc6b63def0a7812b07e11021d51", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9ea9c0517c3f57dd4eeab9d0b6bb64f785ce36dc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To analyze the distribution of Middle East respiratory syndrome coronavirus (MERS-CoV)-seropositive dromedary camels in eastern Africa, we tested 189 archived serum samples accumulated during the past 30 years. We identified MERS-CoV neutralizing antibodies in 81.0% of samples from the main camel-exporting countries, Sudan and Somalia, suggesting long-term virus circulation in these animals.", "MERS-CoV antibody-carrying dromedaries were present in all 3 countries in 1983, 1984, and 1997 ( Figure; Tables 1, 2). The high seropositivity in camels from Egypt (35 [81.4%] of 43), a country that imports camels from Sudan and Somalia, was consistent with previous studies (7, 10) . Strikingly, camels sampled in Somalia and Sudan >30 years ago were identified as MERS-CoV antibody positive with seropositivity of up to 86.7% in Sudan in 1983.", "MERS-CoV sequences from camels in Saudi Arabia and Qatar were closely related to sequences found in humans and did not show major genetic variability that would support long-term evolution of MERS-CoV in camels (10, 11) . The MERS-CoV sequence from a camel in Egypt was phylogenetically most distantly related to all other known camel-associated MERS-CoVs but closely related to the early human MERS-CoV isolates (10) . An urgent task would be to characterize the diversity of MERS-related CoV in other camels in Africa to elucidate whether the current epidemic MERS-CoV strains have evolved toward more efficient human transmissibility." ] },{ "paper_id": "9eab3344aca02a78b6a81ebda1666faff0561e39", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Stratified random sampling provides for a lower variability within subgroups than the variability for the population as a whole and with the possibility of making meaningful inferences among subgroups.", "Worldwide, around 1.1 billion people have no access to clean water sources, and 2.4 billion have no basic sanitation. Each year, there are approximately four billion cases of diarrhoea worldwide, and infectious diarrhoea is widespread throughout the developing world (1) . Poor quality of water, sanitation, and hygiene account for some 1.7 million deaths a year, mainly due to infectious diarrhoea. Nine of 10 of such deaths occur in children, with a significant majority of deaths in developing countries (2) .", "All the 40% of the households investigated completed the questionnaire. Each household had a pit-latrine which was in use, and none had a flush toilet. Water collected from the abstraction-points for domestic use, such as drinking, cooking, and laundry, was not treated in any way before use in any households. Generally, water collected was stored in jerry-cans or buckets for several days before refilling.", "Tshikuwi is located in Makhado municipality in Vhembe district, Limpopo province, South Africa. The geographic grid of the study area is located between 22 o 55'S and 22 o 57'S latitude and 29 o 54'E and 29 o 59'E longitude. The population size is approximately 5,300, with a high unemployment rate and limited clean potable water infrastructure." ] },{ "paper_id": "9ef828a2fe98eb0aebae134bd073051c659a8560", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "RNA interference (RNAi) is now widely used to knockdown gene expression in a sequence-specific manner, making it a powerful tool not only for studying gene function, but also for therapeutic purposes, including antiviral treatments (1) (2) (3) (4) . Currently, the replication of a wide range of viruses can be inhibited successfully using RNAi, with both short interfering RNAs (siRNAs) and siRNA expression vectors (5) .", "These sequences were downloaded from the Los Alamos HIV Sequence Database (http://hiv-web.lanl.gov/), the Los Alamos HCV Sequence Database (12), the NCBI Influenza Virus Sequence Database (http://www.ncbi.nlm.nih.gov/ genomes/FLU/FLU.html), and NCBI GenBank (13), respectively. siVirus will be updated continuously as these databases are revised. We also plan to incorporate other viruses if sufficient numbers of their sequences are available.", "To test the validity of siVirus, 35 siRNAs satisfying the guideline by Ui-Tei et al. (6) were designed against the conserved regions of HIV-1 genomes using siVirus and were assayed for inhibition of viral replication. Among them, 31 siRNAs effectively inhibited HIV-1 replication by >80% when each siRNA duplex was transfected at 5 nM (Y. Naito, K. Ui-Tei, K. Saigo and Y. Takebe, unpublished data)." ] },{ "paper_id": "9f08226b10da36589025f4b568fa4734be47f0c1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Emerging Infectious Diseases \u2022 www.", "To determine whether nonhuman primates are infected with infl uenza viruses in nature, we conducted serologic and swab studies among macaques from several parts of the world. Our detection of infl uenza virus and antibodies to infl uenza virus raises questions about the role of nonhuman primates in the ecology of infl uenza.", "As part of our decade-long longitudinal studies, \u2248200 serum samples were collected from macaques. These included pet macaques (Macaca nigra, M. nigrescens, M. hecki) from Sulawesi, Indonesia; performing macaques from Java, Indonesia (M. fascicularis) and from Bangladesh (M. mulatta); M. fascicularis macaques from the Bukit Timah and Central Catchment Nature Reserves in Singapore, where they freely interact with wild avian fauna and visitors (occasionally entering residential areas) (7); M. sylvanus macaques from the Upper Rock Nature Reserve in Gibraltar, where international tourists frequently use food to entice the macaques to climb about their heads and shoulders (6) ; and free-ranging macaques (M. fascicularis and M. nemestrina) at temple shrines or M. fascicularis macaques that range throughout a wildlife rescue center and nearby villages in Cambodia ( Figure 2 ). Serum was collected and stored as described (8) . All samples were stored on cold packs in the fi eld and transferred to dry ice for shipment to the United States, where they were then stored at \u221280\u00b0C." ] },{ "paper_id": "9f290aa8269c9b4f281f2e0757e22a4a72ac867d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9f2eacde02bfd34993a2eab9d87c2643fcfd17e2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CD3+4+ T-helper cells and CD3+8+ T-cytotoxic cells were enumerated using commercial monoclonal antibodies (Beckman Coulter; Miami, Florida, USA) by dual color flow cytometry (EPICS XL-MCL, Coulter). White cell and differential counts were performed by standard methods.", "[33] The effect of IL-4 on HIV in culture merits further study." ] },{ "paper_id": "9f5b88ccb461ad00982bfad6778331faf6840982", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9fa81d8d9b302402c54cefce4885df1317658c13", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "Data availability. The genome sequences of RV-C56 strains USA/2016/CA-RGDS-1002 and USA/2017/CA-RGDS-1003 have been deposited in GenBank under the accession numbers MG950178 and MG950179, respectively.", "We report here two genome sequences of a newly designated rhinovirus genotype, RV-C56, which were obtained from respiratory specimens of three patients with acute respiratory illness in 2016 and 2017. To our knowledge, these sequences represent the first near-complete genomes for RV-C56 strains." ] },{ "paper_id": "9fa838a7ec9e083660848bf720e4d13d7d6f372f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dr. Wilder-Smith is a resident physician in infectious diseases with a special interest in travel and international health. Her research interests include meningococcal disease, travel-related problems, dengue, and SARS.", "AWS was responsible for blood-taking, data analysis and interpretation and writing the paper. MDT and BHH were responsible for the questionnaires and data entry, AEL for SARS serology, AE for data analysis, and YSL for initiating and leading this study. All authors critically reviewed the final paper.", "T he patterns of spread of severe acute respiratory syndrome (SARS) suggest droplet and contact transmission (1, 2) . Close proximity of persons and handling of human secretions (respiratory secretions, feces, and the like) enhance the risk for transmission. These facts, together with the fact that transmission is more likely in more severely ill people (who end up in hospitals), have made the hospital setting particularly vulnerable to the rapid amplification of SARS (1) (2) (3) (4) ." ] },{ "paper_id": "9fbbae703d150466db0f5312aa28bb4f449a1f9d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sequencing Data Analysis. We used the Adapter-Removal, 27 BWA, 28 SAMtools, 29 and in-house python scripts to analyze read counts, sequencing depths, and uniformities of each library.", "The genome sequence of EcNR2 is already known; therefore, we were able to calculate the uniformity values " ] },{ "paper_id": "9fe474e7623a88324431ac74e778e8403e263465", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9ffccb5731f62e6c18e8c6b4411204407cc4df1d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a03cd1ddfd40e68547016fef7e8442d123156870", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a04f95dd2586d12bce1fab7cf5208046923da10a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Lewis Rubinson 1 and Tara O'Toole 2 1 Senior Fellow, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA 2 Chief Executive Officer and Director, Center for Biosecurity, University of Pittsburgh Medical Center, Baltimore, Maryland, USA modify them as deemed necessary, and prepare to implement rational, modified medical protocols in the wake of a significant disease outbreak that overwhelms current capacities to deliver 'traditional' critical care.", "In natural disasters or terrorist attacks resulting in traumatic injuries, a roughly accurate number of surviving casualties requiring medical care is usually quickly ascertained (within hours). Epidemics differ from other disasters in that they unfold over days or even months and years. The scope and impact of epidemics (whether natural or deliberate) are not immediately apparent. If a bioattack is discovered to have occurred (e.g. if several people within a community present with inhalational anthrax), then it may be impossible to determine quickly whether there has been one attack or several or to ascertain rapidly who else is at risk. It is usually not possible to predict accurately how big an epidemic will become or how fast it can be quenched. This uncertainty has important implications for the medical mass casualty response. How is the decision made to initiate mass casualty protocols or to turn them off? How do hospitals and other health care providers plan for and implement sustained emergency responses unless they know whether an epidemic is waning or expanding?", "A major challenge during an epidemic or other mass casualty emergency will be to determine when, and on what basis, traditional standards of critical care are modified to accommodate emergency conditions, and when modified standards revert to traditional modes of care. Medical professionals, hospital staff, and the affected patient community should actively participate in the development and review of mass care triage standards and protocols. If engagement of care givers and the community is neglected, then mass casualty standards could be misinterpreted and generate distrust or fail to be implemented during a disaster. Medical personnel and community members must understand and agree with the triage plans and be assured that implementation will be fairly applied to all victims. Extensive efforts must be undertaken to guarantee that vulnerable populations will receive equal treatment. Coordination of all affected hospitals to facilitate implementation of similar measures under similar conditions and to reinforce the reality of fairness would be useful, but there is no such 'organizing authority' within the fragmented and mostly private US health care system." ] },{ "paper_id": "a06b054ac060108a8563363fa40ce617eb7af258", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Rural hospital approximately 2 hours from Taipei City. were often configured with HEPA filtration. Some facilities installed ultraviolet germicidal irradiation (UVGI) lamps in HEPA filter banks, although the efficacy of using UVGI for control of SARS-associated coronavirus was uncertain.", "From a facility, personnel, environmental and occupational health perspective, the response to SARS in Taiwan had a profound impact on the healthcare system of the nation. The Taiwanese government responded in a swift and comprehensive manner to contain the outbreak.", "Most of the simple isolation rooms had been designed for isolating patients with infectious diseases such as scabies. These rooms lacked an anteroom, generally had window-mounted air-conditioning units, and small (1,000-2,000 ft 3 /min) window-mounted vane axial fans for negative pressure. Wall penetrations were typically not sealed, manometers were generally not present, and ceilings were not hard. Unfiltered room air was exhausted outdoors through windows." ] },{ "paper_id": "a0839bf8f94d79c1253bf89f170c22f9342fc095", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a0aed635308ebac3b0e430d3c7722756638b1510", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a0cc0dc42e116ed81ab681809e67edadda9663c8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Most eukaryotic mRNA contains a 5\u2032 Cap 0 (7mGpppN) structure with a methyl group at the N-7 position. In higher eukaryotes, methylation of cellular mRNA occurs additionally at the 2\u2032-O site of the penultimate (7mGpppNm, Cap 1) and antepenultimate (7mGpppNmNm, Cap 2) 5\u2032 nucleotides in the nucleus and cytoplasm, respectively 3,5. Many viral mRNA also contain Cap 1 and 2 structures, but cap acquisition occurs distinctly among virus families 2,6. RNA and DNA viruses that replicate in the cytoplasm cannot use the host nuclear capping machinery, and thus, have evolved MTases to facilitate N-7 and 2\u2032-O capping or mechanisms to \"snatch\" the cap from host cell mRNA 1. It remains unclear how 2\u2032-O methylation contributes to viral infection or cellular mRNA homeostasis 2,3.", "C57BL/6 wild type and immunodeficient (IFN\u03b1\u03b2R -/-, IFIT-1 -/-, IRF-3 -/-, IRF-7 -/-, IRF-3 -/-\u00d7 IRF-7 -/-, and IPS-1 -/-) mice were bred at Washington University. Infection experiments were performed with approval of the Washington University and Saint Louis University Animal Studies Committees. Viral titers in blood and organs were quantified as previously described 11.", "Refer to Web version on PubMed Central for supplementary material. " ] },{ "paper_id": "a0d46c310512552aeb8e88f5a5d0c11f42fffcc8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Lungs harvested for virus titer were weighed and homogenized in 1.0 mL PBS at 6000 rpm for 60 s in a MagnaLyser (Roche, Basel, Switzerland). Virus titers were determined by plaque assay on Vero cells as previously described 40 .", "Virus containing the ExoNI inactivation and mouse-adapted mutations within the viral coding sequence was produced using the infectious cDNA assembly strategy for SARS-CoV as previously described 39, 40 . ExoN viruses were kept at low passage (one passage past virus rescue, P1) to minimize the accumulation of mutations in cell culture. For this study, an equivalently low-passaged MAwt virus was used for comparison.", "Mouse sera were heat-inactivated for 30 min at 55 \u00b0C and were then serially diluted to 1:100, 1:200, 1:400, 1:800, and 1:1600 in PBS to a volume of 125 \u03bcL. Next, 125 \u03bcL of PBS containing low-concentration MAwt (40 PFU) or high-concentration MAwt (240 PFU) was added to each serum dilution. The virus-serum mixtures were incubated at 37 \u00b0C for 30 min. Following incubation, virus titers of the mixtures were determined by plaque assay as described 40 . Finally, we calculated the 50% plaque reduction neutralization titer (PRNT 50 ) values, the serum dilutions at which plaque formation was reduced by 50% relative to that of virus stock not treated with serum." ] },{ "paper_id": "a0ed0d8eecbfe77dad7e8c46acba3e9524422d66", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "required for membrane fusion. Our studies indicate that nAbs targeting this pocket could provide broad protection against both seasonal and pandemic influenza A infections.", "The recent spread of highly pathogenic avian influenza (HPAI), H5N1, across Asia, Europe and Africa raises the specter of a new pandemic, should the virus mutate to become readily transmissible from person-to-person. The evolution of H5N1 into a pandemic threat could occur through a single reassortment of its segmented genome or through the slower process of genetic drift12,13. Nearly 400 human H5N1 infections have been reported since 1997 from 14 countries, with a case mortality rate in the immunocompetent population above 60%4.", "New therapeutic strategies that provide potent and broadly cross-protective host immunity are therefore a global public health priority. Human monoclonal antibody (mAb)-based \"passive\" immunotherapy is now being used to treat a number of human diseases, including Respiratory Syncytial Virus infection, and we have proposed how immunotherapy could be used strategically in a viral outbreak setting14.", "H5-F10 complexes were formed by incubating the two purified components with an excess of F10 (See Supplementary methods), and isolated by Superdex 200 in TBS buffer. Peak fractions were pooled and concentrated to ~11 mg ml -1 . The integrity of the H5 trimer was examined using Gel filtration and SDS-PAGE. Crystals grew at 22\u00b0C by equilibrating equal volumes of protein and reservoir solution (12.5% PEG 1K (w/v), 25% ethylene glycol (w/v), 100 mM Tris, pH 8.5) using the hanging drop vapor diffusion technique." ] },{ "paper_id": "a0f886e37b6c1b0dbce48aa05a6a7638368110d4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a14cdb0e8beba648720b8bde6e97915fcaae0142", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dr. Toth is an assistant professor in the Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA. His research interest is applied mathematics, specifically mathematical modeling of infection and transmission of pathogens to support risk assessment and intervention planning for public health.", "Our framework quantitatively characterizes worst-case Ebola outbreaks resulting from an introduced Ebola case to a region with relatively effective control measures. Our results", "In another study, Rainisch et al. (18) calculated the estimated number of beds required to treat Ebola patients in the United States by using estimates of importation frequency and subsequent transmission. These researchers reported a high estimate of 7 beds (95% CI 2-13) required at any 1 time; they also provided no numerical probabilities for their estimates." ] },{ "paper_id": "a1533dacc01547792d22032e0781a7ea7632f0cb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a1f353aafa8d3dfc2e76c6d3d75df0342c8a9e6e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "RNA extraction, a 10-\u00b5L aliquot of the extracted preparation was mixed with 15 \u00b5L of reverse transcription-PCR (RT-PCR) master mix, which containing 12.5 \u00b5L of 2\u00d7 reaction mix, 0.5 \u00b5L of SuperScript III RT/ Platinum Taq Mix (Invitrogen, Carlsbad, CA, USA), 5 pmole of each forward and reverse primer, and adjusted to a volume of 15 \u00b5L with nuclease-free distilled water. For influenza A H1, the reaction condition was 30 min at 45\u00b0C for reverse transcription followed by 2 min at 94\u00b0C, and 30 cycles of 1 min at 94\u00b0C, 1 min at 52\u00b0C and 1 min at 68\u00b0C; and a final extension of 10 min at 68\u00b0C. The reaction condition for influenza A H3 was similar, except that reverse transcription was carried out at 50\u00b0C and the annealing temperature was 55\u00b0C. The PCR products were separated by gel electrophoresis and visualized by SYBR safe DNA stain (Invitrogen) under gel documentation system. The product size of influenza A H1 was 431 bp; the influenza A H3 product was 232 bp.", "Enterovirus RNA was detected by one-step real-time RT-PCR (3, 4) . Amplification is specific for the 5\uf0a2 untranslated region. Enterovirus RNA extracted from cell-culture fluid of clinical isolate confirmed by immunofluorescent was used as the source of positive control. RNA from the plasmid pAW109 was used as internal control for nucleic acid extraction as well as for the presence of inhibitors in the clinical samples. Primers and probes used were as follows: primer for enterovirus (EV), 5\uf0a2-ACATGGTGTGAAGAGTCTATTGAGCT-3\uf0a2, respectively. The performance of the assay was demonstrated by analysis of 3 replicates of quality control samples at 3 levels. The coefficients of variation (CV%) during the analysis of OP were 4.1%,1.9% and 2.1% at 3 ng/mL, 20 ng/mL, and 150 ng/mL, respectively (limit of detection of OP, 0.25 ng/mL). The coefficients of variation (CV%) during the analysis of OC were 2.3%, 0.5%, and 3.1% at 30 ng/mL, 400 ng/mL, and 4,000 ng/mL, respectively." ] },{ "paper_id": "a21078272350d16ee144e2c00faf0d68de89152d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a2132636acb6782dd23b7e691b8f847ad6d883d0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a22d836f2da3eb697e877de9bddcb4785d2e8b1e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "By December 2016, CDC had trained 39 fellows from 25 countries. As leaders within their respective organizations, returning fellows facilitate the expansion of PHEM within their countries and have assumed key roles as leaders and managers of emergency response units in Africa, Asia, and the Middle East.", "The PHEMF curriculum is guided by a global PHEM Core Competency Model, currently in development, which encompasses 7 competencies: leadership, emergency management frameworks, emergency management functions, emergency management communication, partnership and collaboration, training development and facilitation, and evaluation. With mentorship from CDC subject matter experts, fellows apply their learning to develop a personalized toolkit of products to be used by their ministries of health. Specific products in the toolkits may include standard operating procedures (SOPs), draft all-hazards or hazard-specific plans, or Web-based systems for EOC messaging.", "Providing technical assistance to countries during an outbreak or public health emergency is important; however, CDC encourages countries to invest in preparing for emergencies by highlighting the effect of an effective PHEM program on a response. CDC is focusing on regional workshops to bring together neighboring countries for trainings to increase communication and collaboration to leverage expertise across nations with similar threats and hazards.", "Because of the benefits gained through the visits to CDC, several countries expressed interest in comprehensive fellowship opportunities to learn how CDC manages public health emergencies. In 2011, through a cooperative agreement between CDC, the Chinese Center for Disease Control and Prevention, and the National Health and Family Planning Commission of the People's Republic of China, CDC hosted fellows from China for a year-long study tour. As Chinese institutions became more advanced in their S184", "In the years leading up to the 2012 self-assessment on IHR 2005 capacities, worldwide need increased for guidelines and standards for building PHEM capacity. In fact, by June 2012, only \"42 of 193 [21.76%] States Parties declared that they had met their core capacity requirements\" (4), and most countries had requested a 2-year extension. To fill this need, CDC and other international organizations focused their global technical assistance on countries' IHR 2005 requirements. However, after 2 years of such support, in 2014, WHO reported that \"at the time of\u2026[the] second Review Committee meeting, 64 States Parties [33.16%] had indicated that they met the minimum core capacity standards\" (4), which indicated that additional effort was needed." ] },{ "paper_id": "a2373788b3199f709c0686dec692ec9030a2ac0c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a23739aba0ae99bdf7e687731f4c61770cb6569d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All statistical analyses were conducted using stata \u2044 ic 11AE1 (StataCorp LP, College Station, TX, USA).", "currently and previously has been the principal investigator for clinical trials sponsored by Abbott, Baxter, CSL, GSK, MedImmune, Merck, Novartis, Sanofi-Pasteur, Wyeth, and Pfizer." ] },{ "paper_id": "a2e717e550d63d5519146d4b94fd7f71468e0a1a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a334bbb2a7fe8f65dccde53a8d0234d524bf10f7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a3935942e50683102c5f4f15da7563931648e329", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Viral infections are common causes", "Viral spread is by droplet transmission, although many cases suggest that airborne and contact routes also occur [39] . Spread to health care workers who wore appropriate personal protective equipment suggests an airborne mode, and additional spread by aerosol-generating procedures, such as resuscitation (cardiopulmonary resuscitation), medication nebulization, and noninvasive ventilation, further supports this mode [39, [50] [51] [52] . The treatment for SARS is largely supportive with low tidal volume mechanical ventilation [40, 53] . Numerous treatment strategies, including corticosteroids, ribavirin, immunoglobulin, and interferon, have been investigated in SARS: none has been demonstrated to provide clinical evidence of benefit.", "Transmission appears to occur through contact with nonhuman primates and infected individuals [95] . No specific therapy is available and patient management includes supportive care [92, 93, 95, 98] . In a few cases in the Zaire outbreak of Ebola in 1995, whole blood with IgG antibodies against Ebola may have improved outcome, although subsequent analysis suggests that these patients were likely to survive even without this treatment [100] ." ] },{ "paper_id": "a3ef5e2ffb31783af550c32f7512c0330ab9bc93", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a410689981eddf53ed0073a2310941bb37913ab9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All data are presented as mean \u00b1S.E.M. The difference among all groups was analyzed with ANOVA, and the correlations between 2 variances were analyzed with linear correlation regression. P<0.05 was considered statistically significant.", "p38 mitogen-activated protein kinase \u2022 chronic obstructive pulmonary disease \u2022 CXCL8", "Full-text PDF:" ] },{ "paper_id": "a43bb56b5b1f3c5d5f30023ce701f33d670bc5ce", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Blood was collected from healthy aged (65-90 years) and young (20-35 years) donors. Aged subjects were of middle-class socio-economic status and were living independently. Cohort description is provided in Table 1 . The Institutional Review Board of the University of California, Irvine, approved this study.", "Peripheral Blood Mononuclear Cells were separated from the blood using Ficoll density gradient centrifugation. PDCs were then positively selected using BDCA-4 PDC purification kit from Miltenyi Biotech. This kit contains magnetic beads coupled to BDCA-4, which is expressed exclusively on PDCs. We routinely recovered approximately 0.5-1\u00d710 5 PDCs from 40 ml blood. Purity of the PDC population was >90%." ] },{ "paper_id": "a43dc2a14f1a0ea6e5203a062f130693f5fd2a4d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a452e108006dbd4db3375ce517ab1b7b35425197", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a49355dcd1dfe17df391674f41b4134a88e3c92e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dr. Li is a veterinary virologist at the National Research Center for Veterinary Medicine, Luoyang, China. His research interests include epidemiology and the pathogenesis of new and emerging infectious diseases.", "We collected tissue samples to test for seal parvovirus, phocine distemper virus, influenza A virus, coronavirus, canine distemper virus, canine adenovirus, pseudorabies virus, rabies virus, and JEV using commercial real-time PCR kits (Beijing Anheal Laboratories Co. Ltd., http:// www.anheal.com). PCR results were negative for all tested pathogens except JEV, indicating this virus might have infected these seals.", "Our data indicate that the causative agent of these 2 seal deaths was JEV. Why and how disease developed is unclear. In humans, young children are susceptible to JEV infection and often have fatal outcomes. Because the 2 seals that died were in their adolescence and the others with no clinical signs were older, age might have contributed to the fatal outcomes seen with these seals." ] },{ "paper_id": "a4b7fac91178fae8acd884c584fbbb525b883c65", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a510ff06475118256003b81fbc9abdaa33242da1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ingen effekt av homeopatisk behandling av kalvdiarr\u00e9 i en klinisk studie.", "En dubbel-blind och placebokontrollerad klinisk studie av homeopatisk behandling av sp\u00e4dkalvsdiarr\u00e9 beskrivs. Fyrtiofyra kalvar fr\u00e5n 12 mj\u00f6lkkobes\u00e4ttningar ingick i studien. Kalvarna behandlades med antingen det homeopatiska preparatet Podophyllum D30 (n=24) eller placebo (n=20). Varken kliniskt eller statistiskt signifikanta skillnader mellan de b\u00e5da grupperna kunde p\u00e5visas. Kalvar som behandlats med Podophyllum hade diarr\u00e9 i medeltal 3,1 dagar j\u00e4mf\u00f6rt med placebogruppens 2,9 dagar. Nedsatt foderlust, p\u00e5verkat allm\u00e4ntillst\u00e5nd och feber registrerades i samma utstr\u00e4ckning i b\u00e5da grupperna. Resultaten styrker \u00e5sikten att vetenskapliga bevis f\u00f6r homeopatisk effekt saknas. Att, som i l\u00e4nder inom EU, f\u00f6rorda homeopatisk behandling i ekologiskt jordbruk inneb\u00e4r d\u00e4rmed en risk f\u00f6r djurens h\u00e4lsa och v\u00e4lbefinnande.", "No statistically significant difference between the calves treated with Podophyllum and calves treated with the placebo was demonstrated." ] },{ "paper_id": "a5c784a31fe00d8790017dae8081e5000e1323fa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a618a87ac05377d6f665251c756bc2e8f77d34e6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Holm et al.", "OR, odds ratio; CI, confidence interval; P-value, Pearson chi-squared. *Reference category." ] },{ "paper_id": "a6223e7c69d8d8404a4576a0a6968cbf010c426d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a67212b1e5d4cac7cd2deb4a3b065e7aac6d8aea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a6e86c94af0d5da2d07a4d4047823ba8f829dad1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We used the MERS-CoV standardized serologic investigation protocol developed by WHO and the Consortium for the Standardization of Influenza Seroepidemiology (18) ", "Infection in Closed Setting, Riyadh, Saudi Arabia, 2015", "Bivariate analyses indicated significant assocations between MERS and the following risk factors: having direct contact with a known MERS patient (RR 10.9, 95% CI 6.7-17.6); sharing a bedroom (RR 25 " ] },{ "paper_id": "a6fe0efaddf824480cd89f3940ad0109e74453b6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a7413d2d2f103768cb45b13fc91c8f96568eaccb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Article diaminobenzoic acid, the mixture was stirred at 85\u00b0C for 72 h under argon. The resulting dark-violet solution was cooled at r.t. to induce precipitation of the product. The crude powder was filtered and purified by HPLC chromatography, (CH 3 CN:H 2 O 0.1%TFA) according to analytical method A and preparative method B, affording the title NDIs 6 (27%) and 7 (30.5%).", "Article dynamic so that a clear protection/exposure could not be observed.", "Nucleophilic " ] },{ "paper_id": "a750d0302fd2e1684bb414f2e81a1f5b4322da42", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a7517a8506234e015417206358feca31adbf21a2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Technical Note DNA encoding the designed STAR which contained the target viral sequence. In this way, we anticipated that combining the CDO-encoding reporter construct and RPA amplified DNA into a cell-free gene expression reaction 12,17 would lead to the production of a detectable colorimetric output signal.", "Here we have demonstrated a novel scheme for combining isothermal amplification and custom synthetic biology viral sensors for the detection of the important plant pathogen CMV from infected plant lysate. Building off of previously elucidated STAR design rules, 15 we have shown that our molecular sensors can be efficiently designed, built, and ", "S ynthetic biology has recently contributed to multiple advances in point-of-use nucleic acid diagnostic (PoUD) technologies. 1 These technologies leverage isothermal strategies to amplify target nucleic acids, with new advances in detection of these targets using strand-displacement, 2 or CRISPR-based methods 3,4 that produce fluorescent readouts, or RNA toehold switches that control translation of enzymes that produce colored compounds. 5 Overall these technologies can be used for sensitive detection of pathogen-derived nucleic acids in complex matrices in field-deployable formats that significantly improve upon current laboratory-intensive PCRbased approaches." ] },{ "paper_id": "a77badb297bf4927419481e660ea8f1806ed91b1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Though the 9 \u00c5 model provides a partial explanation for why mRNA pseudoknots promote programmed \u00c01 ribosomal frameshifting (\u00c01 PRF) more efficiently than simple *To whom correspondence should be addressed. Tel: +1 301 405 0981; Fax: +1 301 314 9489; Email: dinman@umd.edu \u00aa The Author 2005. Published by Oxford University Press. All rights reserved.", "Pseudo-pseudoknots stimulate frameshifting, and frameshifting efficiency changes with the degree of pseudo-pseudoknot rotational freedom", "The structure of an RNA molecule is widely recognized to play a role in many processes, including structurally organizing complex RNAs, the assembly of ribonucleoprotein complexes, and in translational recoding and regulation [reviewed in (1) ]. One common RNA folding motifs is a pseudoknot, the folding back of a single-stranded RNA onto itself to form two helical structures with single-stranded loops joining them (2) . Many such structures can be inferred from RNA sequences and frameshifting function has been demonstrated for some of these [reviewed in (3) (4) (5) ]. However, though much theoretical progress has been made in understanding how mRNA pseudoknots promote efficient \u00c01 ribosomal frameshifting (6), a complete understanding of this mechanism remains untested." ] },{ "paper_id": "a7b821c27f0e48460b838afa289ab348f672b5aa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a829488e75a4af749d8fc997fcf24ebeb907228b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a8341c6a373e27741446456bce5aae29fa926c52", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a83597bafe4870a3b5bf41a3012cb7c94d79a7ff", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a8aa723ba5e98887cee2b63ca3cfe956c4a5933b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a8c1928d0295a8f2f13a679f4536ceff03508bde", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The EM techniques discussed above have all made use of the standard transmission electron microscope (TEM). There are indications that the scanning electron microscope (SEM) may also eventually be of use to the diagnostic virologist. At present, its practical application, albeit a valuable one, is limited to screening cell cultures for mycoplasma contamination [38] .", "The following brief review will examine some of the ways in which virus morphology can serve as an important aid for rapid virus diagnosis, some of the limitations of this approach, and current and future developments in electron microscopy relating to diagnostic virology. For detailed information on electron microscopy in diagnostic virology, the reader is referred to more comprehensive reviews [1, 2] .", "The commonly practised laboratory methods to detect the presence of a virus in clinical material have changed little in the past 25 years. A specimen is inoculated into a host system (tissue culture, eggs, animals), and subsequent detection and identification of an isolated virus depends on indicators such as cytopathic effect, hemagglutinin, complement fixation, etc. Results obtained by these procedures usually take several days-if not weeks-to complete. Thus, although they continue to serve as the backbone of most virus laboratories, current procedures are rarely capable of providing a rapid diagnosis." ] },{ "paper_id": "a8fcb5f33a550dbbf4e54a3ce58f45e4a3e17567", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a998defbe9236dc5f7880910ccb4b2c6f350879d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "pEF-IFITM1, 2, 3 were cloned by PCR amplification and inserted into a pEF6-BSD vector. All mutants of IFITM3 were generated by using the QuikChange Multi Site-Directed Mutagenesis Kit (Stratagene). The pCAS9 plasmid and gRNA basic vector (pGL3-U6) were gifts from Dr. Wensheng Wei (Peking University) 51 .", "For genomic sequencing of IFITM clones, total genome was extracted by genome extraction kit from QIAGEN. The target genomic site was amplified by gene-specific primers. The amplified fragments were added dATP at 3' end by taq polymerase and then ligated with T vectors. After transformation, ten bacteria colonies were picked randomly and sent for sequencing.", "Lysosomal protease activity assays." ] },{ "paper_id": "a9ef59df236cebc1284670d073d8724ca360ac6a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "aa37211ba5110e94e0eb66faeab05d0e9a407c53", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We report a serologic survey for immunoglobulin (Ig) G against SARS-CoV in a representative sample of close contacts of all SARS patients in Hong Kong (>76% had laboratory confirmation of SARS by either paired serology or repeat reverse transcription-polymerase chain reaction (RT-PCR) according to World Health Organization [WHO] criteria [2] ).", "A total of 1,068 asymptomatic close contacts of patients with severe acute respiratory (SARS) from the 2003 epidemic in Hong Kong were serologically tested, and 2 (0.19%) were positive for SARS coronavirus immunoglobulin G antibody. SARS rarely manifests as a subclinical infection, and at present, wild animal species are the only important natural reservoirs of the virus.", "The extent of seroconversion in close contacts of confirmed patients should provide the upper limit of SARS-CoV antibody seroprevalence in the general population, given the relatively intense exposure history of these persons to SARS patients. Our finding of the near absence of transmission resulting in asymptomatic infection in this representative high-risk group of close contacts indicates that the prevailing SARS-CoV strains in Hong Kong almost always led to clinically apparent disease. Whereas some SARS patients, especially healthcare workers, might have been initially admitted to reduce transmission to family members, virtually all SARS patients (perhaps with very few exceptions in children [4] ) had severe disease requiring inpatient treatment; thus, we can infer that infection with SARS-CoV inevitably caused severe disease requiring hospitalization." ] },{ "paper_id": "aa71e82c7e8fb18305287a5bccd724d35d238db6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As described, DENV isolations were attempted from acute-phase plasma or serum samples from Thai children by inoculation into C6/36 cells or intrathoracically in mosquitoes (Toxorrhynchites splendens) (12) .", "DENV was identified in C6/36 cells by an antigen-specific enzyme-linked immunosorbent assay (ELISA) with a panel of monoclonal antibodies against DENV (13) .", "In Bangkok, HAI antibody against DENV types 1-4 and Japanese encephalitis virus were measured in all sera (15) . A fourfold increase was considered positive for acute flavivirus infection. The infection was diagnosed as primary if titers >1 week after onset of illness were <1:1,280 or as secondary if antibody titers were >1:1,280 (16) ." ] },{ "paper_id": "aa8016f871841b6899dac58441f6f8de93f30ffa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "aacbe6a4b7636a58ee07716296eae9ec499bbc3f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Hematological analysis was carried out following standard protocols. The total white blood cell count, lymphocyte, platelet, reticulocyte, and red blood cell counts, hemoglobin, hematocrit values, mean cell volume, mean corpuscular volume, and mean corpuscular hemoglobin concentrations were determined from EDTA blood with the HemaVet 950FS+ laser-based hematology analyzer (Drew Scientific).", "For measures of gene expression dynamics, the array data were normalized using NeONORM 34 and subjected to SVD-MDS analysis 35 . In parallel, the data for each individual were merged using weighted averages to generate combined profiles. These were visualized using SVD-MDS.", "Refer to Web version on PubMed Central for supplementary material. " ] },{ "paper_id": "aaced93f65162e95222aee866dd1248133cb4e0b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ab10fed7d8688da4c396efac79aa05d8d6b8f300", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Evaluation of the role of other classes of anti-SARS-CoV antibodies in the diagnosis of SARS-CoV infection is needed.", "In addition to hospitalized patients, a healthy group was included as non-SARS controls. This group comprised 635 medical students 19-31 years of age (mean 23.5, SD 2.2); 41.9% were female. Their blood samples, which had been submitted for pre-varicella-zoster virus vaccination screening in 2000, were retrieved for this study.", "Anti-SARS-CoV IgG antibody was detected by the indirect immunofluorescence technique. Vero cell monolayer at 90% confluence was inoculated with SARS-CoV. The coronavirus stock used was the third passage of an iso-late grown from a SARS patient. The full genome sequence of this isolate has been published (GenBank accession no. AY278554). Infected cells were harvested when cytopathic effect was observed on 70% of the cell monolayer. With our laboratory conditions, this event occurred consistently at 96 to 100 hours after virus inoculation. Infected cells were mixed with noninfected Vero cells at a ratio of 1 to 1. After being washed three times with phosphate-buffered saline (PBS), cells were spotted onto 12-well, Teflon-coated glass microscope slides. The slides were allowed to air-dry and then fixed for 10 minutes with 100% pre-chilled acetone, and stored at -70\u00b0C until use." ] },{ "paper_id": "ab343259d4d09f7bc3e154063755e18d3ffed609", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "RNA extraction: Viral RNA was extracted from 140\u00b5l of clinical specimens or virus ICF using a QIAamp viral RNA mini kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions. The initial processing of specimens was performed at biosafety level 3 containment facilities. The extracted RNA was eluted in a total volume of 60\u00b5l of elution buffer and stored at -70 C until further use.", "The nine H5N1 influenza virus strains used in this study were isolated from humans in 2004, 2005 and 2007. Two of them belong to clade 1 (HN3040 and HN30408) and the others to subclade 2.3 (BM 196, HN 30850, HN 31203, HN 31242, HN 31244, HN 31312 and HN 31323) . The viruses were isolated using MDCK cells, and the virus titer in the infected culture fluid (ICF) was examined by plaque assay using MDCK cells according to the standard protocol. Briefly, confluent MDCK cells were incubated in a 24-well plate for 1h at 37 C with 10-fold serial dilution of virus ICF. The cells were then overlaid with minimum essential medium (MEM) containing 1.5% agar and 1\u00b5g/ml of TPCK trypsin. The plaques were visualized after incubation at 37 C for three days by staining with 0.1% crystal violet solution containing 10% formaldehyde.", "The RT-LAMP reaction was carried out in 25\u00b5l total reaction volume using the Loopamp RNA amplification (RT-LAMP) kit (Eiken Chemical Co. Ltd.; Tochigi, Japan) containing 40 pmol each of FIP and BIP primers, 20 pmol each of loop-primers, 5 pmol each of F3 and B3 outer primers, 1.4 mM concentrations of deoxynucleoside triphosphates, 0.8 M betadine, 0.1% Tween 20, 10 mM (NH4)2SO4, 10 mM KCl, 20 mM Tris-HCl (pH 8.8), 8 U of Bst DNA polymerase (New England Bolabs), 0.625 U of avian myeloblastosis virus reverse transcriptase (Invitrogen), and 5\u00b5l of extracted RNA. The reaction mix was incubated at 62.5 C for 90 minutes in Loopamp realtime turbidimeter LA-200 (Teramecs, Japan). Positive and negative controls were included in each run, and all precautions to prevent cross-contamination were observed." ] },{ "paper_id": "ab394df8160904be82c09bfacf72f690a8004a0c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ab50cf0159a56f447825137b6100ce061f2a745a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ab6b6eba28fd72e9bf01d2821cc00762411b6a07", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All other chemicals were purchased from Sigma (St. Louis, MO) and used without further purification, unless stated otherwise. Unless otherwise noted, all solutions were prepared with ultrapure Milli-Q water (18.2 M\u03a9 cm) from a Millipore Milli-Q system (Bedford, MA).", "Microfluidic platform fabrication: Polydimethylsiloxane (PDMS, Sylgard 184) was obtained from Dow Corning (Midland, MI); Whatman#1 chromatography paper and Epoxy glue were purchased from Sigma (St. Louis, MO) and ITW Devcon (Danvers, MA), respectively.", "A chromatography paper disk (diameter 2.0 mm) cut by a laser cutter (Epilog Zing 16, Golden, CO) was placed inside each LAMP zone, as a 3D storage substrate for LAMP primers." ] },{ "paper_id": "ab9ebe0a429625b365db7684fca907c5fd2c5e31", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ac20dcb832b6cd6ea92dd87915d8520a91cef2b2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ac45f663ed3b7143b944a5385b5d82754087a6af", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ac6642c9936e8c0291bba6f5b6e812c891d2b072", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ac6ab25f83e79fc2c1794b69c8bbfe0616f527ad", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "acc553c568c83d482c22c85f280ea92a5afccdab", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "B at species worldwide have been implicated as reservoirs for several emerging viruses, such as lyssaviruses, henipahviruses, severe acute respiratory syndrome-associated coronaviruses, and filoviruses. Bats have several physiologic, cellular, and natural history characteristics that may make them particularly suited to their role as reservoir hosts (1, 2) .", "All bats received care that included antimicrobial drugs and nutritional and fluid support. However, minimal or no clinical improvement was observed, and the bats showed progressive joint swelling and increased lethargy. All bats were eventually euthanized. In all instances, gross lesions were limited to the joints.", "Although the 2 viruses are nearest neighbors, levels of shared nucleotide and amino acid identity between them suggest they should likely be considered separate genera (Table, Appendix, wwwnc.cdc.gov/EID/article/19/6/12-1713-T1. htm). We propose that the bat-derived isolate be distinguished as part of a new lineage with the suggested genus designation Chiropoxvirus. Further efforts should be undertaken to determine whether Cotia virus should be included in this genus. The bat-derived virus requires a new species designation for which we propose Eptesipox virus because of its isolation from an Eptesicus fuscus bat specimen.", "Chordopoxviridae is a subfamily of Poxviridae that contains large double-stranded DNA viruses that replicate in the cellular cytoplasm and are known to infect a wide range of vertebrates. Many of these viruses cause zoonotic disease in humans. Although poxviruses are known to have incorporated host genes into their genomes to subvert the host immune system (3), bats and poxviruses may also serve as facilitators in the horizontal transfer of transposable elements to other species (4) (5) (6) . We report the isolation and characterization of a viable poxvirus from bats." ] },{ "paper_id": "ad2b2d668217156f73fb821ae1228b662724b76a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ad512ced9c178a408dba4c56b96034fc7e894678", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A few separate experiments were conducted using MyIR.", "For this campaign, on November 21st, 2017, an email was sent to 7,772 users that asked them a simple question, \"Did you get your flu shot?\" If they selected Yes, they saw a funny meme and received positive affirmation. If they clicked No, the message was an encouragement to get their flu shot before Thanksgiving 2017.", "A 7.1% increase in returning users were tracked and a 9.1% increase in engaged users, again defined as logging in more than once a month. There was also a 6.7% increase in average session duration." ] },{ "paper_id": "add01845567b1c863e734710038329e3545aa3dd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The National Health and Family Planning Commission of China determined that collection of data for this patient was part of a public health investigation of an emerging outbreak. Therefore, informed consent was not required. This study was approved by the ethical committee of the First Affiliated Hospital of Guangzhou Medical University.", "parallel with similar efforts in Europe, strategies need to be developed to protect commercial and pet rabbits." ] },{ "paper_id": "ae259a3fbe7fe1269fb1fa49803adb40316e3c3e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ae267a98af103856a22932cac54e9208b34da846", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Transgenes that induce and maintain a latent state of the virus; -do not allow activation of a virus from its natural latent state.", "Many viral mRNAs are capped, in that they contain a single major initiation site near their 5' end, and their translation is similar to that of host mRNA. However, inhibition of host mRNA translation provides the virus with increased availability of ribosomal units. Thus herpes simplex and poxvirus degrade cellular mRNA to decrease its translation (Inglis, 1982; Fenwick and McMenamin, 1984) .", "Expression under the control of metallothionein of a single glycoprotein D gene from herpes simplex virus (HSV-1) rendered cells resistant to infection by HSV but not by other viruses (Johnson and Spear, 1989) . The mechanism of this resistance is not known but it seems likely that D interacts with a cell surface component required for viral penetration." ] },{ "paper_id": "ae453f1b3f495c4cea808f1ab92de2c7fb80b72d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Staff wore clean suits, disposable gloves, bonnets, and face masks. Mice were transferred to new individually ventilated cages (IVCs, VentiRacks TM ; BioZone, Margate, UK) in class II laminar flow changing stations with disinfected forceps padded with silicone tubing. All materials were autoclaved before use.", "PCR products (10 ll) from both virus groups and the controls were mixed with 2 ll loading buffer (MBI Fermentas), electrophoresed on a 1.5% agarose gel, stained with ethidium bromide and visualized under UV light.", "Outbred Crl:CD1(Icr)/Dcm (Dcm = Department of Comparative Medicine) mice were bred in a full barrier unit at our animal facilities. Breeding colonies were kept in filter-topped Type II Makrolon \u00d2 cages at a temperature of 20-24\u00b0C, humidity of 50-60%, 20 air exchanges per hour and a 12/12-h light/dark cycle. Wood shavings (Altromin, Lage, Germany) were provided as bedding. Mice were fed a standardized mouse diet (1314, Altromin) and provided drinking water ad libitum." ] },{ "paper_id": "ae5583765a6a5c11926b7d4b3820d4ee98defe64", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "aeae3e593ea4d3d0b59c83839837be75d2ea47d5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Toll-like receptors were initially identified through their homology to Drosophila Toll protein, a critical component of Drosophila's innate immune system (Rock et al. 1998 ).", "Despite the wealth of new and exciting information concerning TLRs and RLR pathways, many questions remain to be answered. Specifically, what is the physiological significance of each of these systems and which viral triggers are responsible for their activation. The problem of how a cell manages to differentiate between self and non-self remains one of the fundamental questions in virology and immunology.", "LGP2" ] },{ "paper_id": "aeb2fd035cedb1adb0f4498c351310f5f2fea5a8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The two N-terminal domains of human CD4 were cloned into vector pHCMV3 with an Nterminal Ig-kappa secretion signal and a C-terminal hexahistidine tag for expression in HEK293F. One liter of 293 Freestyle cells was transiently transfected with 0.5 mg of DNA. After 7 days, the supernatant containing the secreted protein was applied to a 5ml HisTrap ", "Number of atoms in deposited model gp120 10,341 9,150 n/a n/a n/a gp41 3,312 3,270 n/a n/a n/a b12 5,547 n/a n/a n/a n/a 17b n/a 5,514 n/a n/a n/a SCD4 n/a 4,113 n/a n/a n/a glycans 1,551 1,689 n/a n/a n/a MolProbity score 1.92 1.93 n/a n/a n/a Clashscore 5.54 6.27 n/a n/a n/a EMRinger score 2.44 2.38 n/a n/a n/a RMSD from ideal Bond length (\u00c5) 0.010 0.010 n/a n/a n/a Bond angles (*) 1.13 1.18 n/a n/a n/a Ramachandran plot Favored (%) 86.95 88.80 n/a n/a n/a", "B41_CD4_17b B41_LF B41_CD4 B41_PGV04" ] },{ "paper_id": "af13aa4011a57e2670ce8204394e3a11f173109d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Appropriate controls (free siRNA and dendriplexes \u00b1 RNase A, and \u00b1 heparin treatments) were included in these experiments. Heparin decomplexation assay is described in SI.", "Moreover, the fact that the cohesive force for mannitol in HFA is relatively lower compared to other those of other sugars, such as lactose, 67 indicates an enhanced solvation of that surface in the propellant, but this is a relative observation, and no quantitative comparison with the cohesive interaction between CSLA particles and those with mannitol is available.", "Statistical Analysis. OriginPro 8 SR0 v8.0724 (B724) was used to perform statistical analysis. Data were compared using One-Way Analysis of Variance (ANOVA) followed by Tukey's posthoc test. Means were considered statistically significant different with a p value <0.05." ] },{ "paper_id": "af6f36f6996b3cbbe64dc659b12f5b2ea5d41fb1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "af80c32eafcea0399e640e11e913412f298e1aae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "af8bd3576468e8c80a70d8ed5a07e4b2be7a6b80", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A clinical severity score (CSS) was adapted from the severity score described by Martinello et al. (11) . Two points were assigned if the patient required positive-pressure ventilatory support during the illness, and one point was assigned for each of the following: hospital admission, hospitalization for >5 days, oxygen saturation <87% (at least one measurement), and any use of supplemental oxygen. Therefore, CSS ranged from 0 to 6. Medical records from all patients were abstracted and scored by a reviewer who did not know the patient's HMPV status.", "In 2001, van den Hoogen et al. reported the isolation of a novel paramyxovirus, human metapneumovirus (HMPV) from children with respiratory tract disease (2) . HMPV has been identified worldwide (3) (4) (5) (6) (7) and appears to have a seasonal distribution (winter and spring) (8) . Since the circulation of HMPV may overlap with that of RSV, simultaneous infection with both RSV and HMPV may contribute to severe disease. Greensill et al. (9) reported that 70% of RSV-infected children who required admission to the Pediatric Intensive Care Unit (PICU) in Liverpool, U.K. were co-infected with HMPV.", "RNA extraction and reverse transcription-polymerase chain reaction (RT-PCR) were performed as previously described (4) . Primers used for the amplification of the RSV L gene were as follows: forward primer 5\u2032-GGTA-GAATCTACATATCCTTACCTAAGTG-3\u2032 (genome location 14881-14909, [reference strain RSV A Melbourne, Australia/2/'61] GenBank accession no. M74568), reverse primer 5\u2032-CGAGATATTAGTTTTTGACAC-3\u2032 (genome location 15190-15210, GenBank accession no. M74568). The HMPV forward primer, 5\u2032-GCGCGTTCTGAG-GACAGGTTGG-3\u2032 (HMPV genome location 3163-3180, GenBank accession no. AF371367, G/C clamps are underlined) and reverse primer, 5\u2032-GCGCTCAAGCCGGATG-GTTTTGG-3\u2032 (3425-3444, GenBank accession no. AF371367, G/C clamps are underlined) used for the amplification of the HMPV F gene were based on regions of the F gene conserved in New Haven, Netherlands, and Australian strains (4). PCR reactions were performed by using HotStar (Qiagen, Inc., Valencia, CA) and amplification cycles were as follows: 95\u00b0C for 15 min followed by 35 cycles of 94\u00b0C for 1 min, 55\u00b0C for 1 min, and 72\u00b0C for 1 min, and a final 10-min cycle at 72\u00b0C. Each set of reactions contained appropriate negative (water) and positive control samples for the RT (HMPV-positive nasal wash) and the PCR (HMPV cDNA) steps." ] },{ "paper_id": "afb0a74705b6788ca4c0f9a1dc056200000d7f0f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We studied antibody response in 9 healthcare workers in Jeddah, Saudi Arabia, who survived Middle East respiratory syndrome, by using serial ELISA and indirect immunofluorescence assay testing. Among patients who had experienced severe pneumonia, antibody was detected for >18 months after infection. Antibody longevity was more variable in patients who had experienced milder disease.", "In conclusion, our results indicate that MERS-CoV antibody persistence depends on disease severity. Further studies are required to determine the role of the virus-specific T-cell response in MERS patients and determine whether patients with mild infections are at risk for reinfection and would therefore benefit from vaccination. Our data also show that potential donors of MERS-CoV convalescent-phase serum samples are limited to patients who recover from severe pneumonia.", "Patients' medical records were reviewed for information on demographic characteristics, comorbidities, clinical presentation, intensive care unit admission, and outcome. Patients were classified into 4 categories according to their clinical presentation: asymptomatic, upper respiratory tract infection, pneumonia, or severe pneumonia. Patients with severe pneumonia were those who required intubation and ventilatory support and were treated in an intensive care unit. Serial ELISA and IFA testing was performed at 3, 10 and 18 months after illness onset (online Technical Appendix). Specimens were considered to represent previous infection only when ELISA and IFA test results both were positive. Microneutralization testing was not available in the KFSHRC-J laboratory." ] },{ "paper_id": "afcc1a28b96721fb9f9544943254ab73d656b635", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Fraser (34) White (36) Yang (29) Yang (29) Tuite (35) Yang (29) Suess (28) Cowling (21) Leung (25) Lessler* (22) Hahn\u00e9 (32) SG-Spain* (30)" ] },{ "paper_id": "affa4df43665fb042bffde141c288050aa99ed47", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Quarantine led to financial and psychosocial stresses, risk communication, compensation, and workforce staffing issues for persons, families, employers, and governments. Legal appeals and defiance of quarantine orders were rare (2, 6, (8) (9) (10) (11) (12) (13) ." ] },{ "paper_id": "b01edd6c71207f4ab7f514a7e39267ee2eb8d029", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "F ood markets that offer both poultry meat and live birds either for sale or for slaughter are collectively referred to as live-bird markets (LBMs). LBMs are part of the supply chain and are essential for maintaining the health and nutritional status of rural and urban populations, especially in developing countries (1, 2) . However, LBMs provide op-timal conditions for the zoonotic transfer and evolution of infectious disease pathogens because they provide major contact points between humans and live animals (3, 4) .", "Thirteen viruses were isolated from LBMs, most frequently from the slaughter zone (7 of 13 viruses isolated, Table 1 ). All isolated viruses came from 6 LBMs, from which 1-4 viruses were isolated per LBM.", "Markets, Indonesia", "RNA extraction, cDNA synthesis, and real-time reverse transcription-PCR (RT-PCR) were used as described (15) . Virus isolation methods have also been described (16) but in general involved supernatants from a 1,000-\u03bcL sample homogenized by vortex and centrifuged at 2,500-3,000 rpm into 9-to 10-day-old specifi c pathogen-free eggs. Those positive in the hemagglutination assay were tested by hemagglutination-inhibition test with reference antiserum (A/chicken/West Java/Hamd/2006)." ] },{ "paper_id": "b022e6ee1e7b9a0a822b1255c2fa12f81ddc52fd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The colonies of full-length cDNA were screened by PCR. Human Testis Large-Insert cDNA Library (Clontech, Calif) was first converted into plasmid cDNA Library, and then an arrayed cDNA library in 96-well plates was made according to the method of Munroe [13, 14] . In this arrayed cDNA library 1.54 \u00d7 10 6 colonies were screened by PCR.", "After PCR amplification, the results can be shown as a pattern (00000000100010100000011000001000000011 000001000001000001001000000010000000000100100100 0001). Retrieving results from the Stanford genome center web server shows that HSE is localized in the human 11q24 ( Figure 4) .", "G N F T Y M S A V C W L F G R Y L Y D T L Q Y P I G L V S S S W G G T Y I E V W S S R R T L K A C G V P N T 143 m-Lse 181 A G N L G H G N F T Y M S A V C W L F G R Y L Y D T L Q Y P I G L V S S S W G G T Y I E V W S S R R T L K A C G V P N T 240 h-Lse 181 S E N L G H G Y F K Y M S A V C W L F G R H L Y D T L Q Y P I G L I A S S W G G T P I E A W S S G R S L K A C G V P K Q 240 m-Cse 144 R D E R V G Q P E I K P M R N E C N S E E S S C P F R V V P S V R V T G P T R H S V L W N A M I H P L Q N M T L K G V V 203 m-Lse 241 R D E R V G Q P E I K P M R N E C N S E E S S C P F R V V P S V R V T G P T R H S V L W N A M I H P L Q N M T L K G V V 300 h-Lse 241 G S _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ I P Y D S V T G P S K H S V L W N A M I H P L O N M T L K G V V 274 m-Cse 204 W Y Q G E S N A D Y N R D L Y T C M F P E L I E D W R Q T F H Y G S Q G Q T D R F F P F G F V Q L S S Y M L K N S S D Y 263 m-Lse 301 W Y Q G E S N A D Y N R D L Y T C M F P E L I E D W R Q T F H Y G S Q G Q T D R F F P F G F V Q L S S Y M L K N S S D Y 360 h-Lse 275 W Y Q G E S N I N Y N T D" ] },{ "paper_id": "b029cd7b3c8216e1e78a56afcc5ed30fdc8d812d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We identified hospitalizations of adult patients from January 1, 2004, through December 31, 2012. Hospitalizations were included if the patient was admitted through the ED with any combination of cough, fever, or shortness of breath.", "We excluded hospitalizations resulting from a transfer from another health institution (such as a long-term care facility or another regional hospital). If a patient had been seen in the ED with respiratory symptoms but was not subsequently admitted, the patient was also excluded from the study.", "Our findings should encourage hospital administrators and infection control practitioners to reevaluate current practices, so that viral test results are used appropriately to modify subsequent treatments and guide provision of isolation precautions. This study sets the foundation for further research to ensure that current policies and practices result in efficient resource utilization and prevent infection transmission in hospitals." ] },{ "paper_id": "b0b8ac292312c6642c37e502d2fd803955084c17", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b14030110db9acc99c663c87643a6754ab25b6d8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b1760223f473dfc2a2249653a66292a89332b7e4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b18e1ab81f9263fe8f2ec5bec5c54c31371f4a4c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "These results indicate that intramers may be an alternative to RNAi by specifi cally suppressing the activity of gene products instead of inducing degradation of mRNAs coding for these proteins.", "In oncology, direct delivery of siRNAs and viral delivery of small hairpin (sh)-RNAs to tumors have been shown to successfully inhibit xenograft growth in mouse models.", "However, the effects of NA drugs on human exposition must be completely understood, with emphasis to unforeseen long-term effects. There is yet little knowledge about pharmacokinetics of NA-based drugs. The greatest challenge facing the therapeutic utility of NAs is to overcome the low cellular absorption inherent to their highly polar molecular structure. The innate ability of these drugs to cross membranes is minimal in normal circumstances. In addition, their low biostability results in unpredictable pharmacokinetics. NA molecules that happen to enter the cell are subsequently subjected to intracellular degradation by nucleases effectively narrowing the drug's activity time-span." ] },{ "paper_id": "b19a21295cdc5bb0be8ddc6688268147a0a6d510", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The rated mean values of the answers to \"how do you like the mask?\" were 5.4 and 4.8 for facemasks A and B, respectively, suggesting that facemask A can be accepted and facemask B came in as a close second acceptance.", "An infl uenza pandemic has the potential to cause more death and illness than any other public health threat (DHHS 2005) . Since January 2004, a total of 240 human cases of avian infl uenza A (H5N1) have been reported to the World Health Organization (WHO) and of these cases, 141 were killed by H5N1 (WHO 2006) . Therefore, Monto (2005) pointed out that the greatest concern is that human-to-human transmission may begin if there is a change in the vital genome of avian infl uenza.", "A study comparing the effects of wearing different kinds of facemasks (N95, surgical, and facemasks A and B) on the ear canal temperature, heart rate, and clothing microclimates was carried out simultaneously (Guo et al 2006 (Guo et al , 2008 . In addition, after wearing the facemask for 100 min, the subjects were asked \"how do you like the mask?\" The scales ranged from 0 to 10, with \"0\" representing \"not at all\", \"5\" representing \"acceptable\", and \"10\" representing \"very fond of\"." ] },{ "paper_id": "b19c7828106ac7bcff5511ee3fc7189123e0cc4c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b1e9d1c6ab23addf3775583442376e4d5e63e44e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sequences were analysed using Sequence Navigator Software version 1.0.1 (Applied Biosystems) and MacVector\u2122 version 10.6.0 (Oxford Molecular Group), followed by manual adjustments. After the alignments of all Mamuand Mafa-B exon 1-4 sequences using the MacVector software, version 10.6.0, phylogenetic analysis was performed with the phylogeny.fr pipeline (Dereeper et al. 2008 ) using maximum likelihood (ML) of the software PhyML 3.0 with the substitution model HKY85 with 4 categories, the gamma shape parameter of 0.407, a transition/transversion ratio of 2.130, and a SH-like approximate Likelihood-Ratio Test (aLRT) for statistical test of branch support. For tree rendering the pipeline uses the program TreeDyn 198, and the output tree is rooted using the mid-point rooting method.", "Furthermore, expanding the lexicon of Mafa-B alleles may provide more insight into the organisation of the macaque B-region, and may help in the definition of different lineages and loci, resulting in a more appropriate nomenclature.", "cDNA, cloning, and sequencing For all animals used in this study RNA was isolated from lymphoblastoid B-cells (Rneasy kit, Qiagen) and subjected to One-Step RT-PCR, as recommended by the supplier (Qiagen or Promega). The primers 5\u2032MBS: AATTCATGGCGCCCCGAACCCTCCTCCTGC and 3\u2032 MBS: CTAGACCACACAAGACAGTTGTCTCAG were used that anneal specifically to Mhc-B transcripts in macaques (Boyson et al. 1996) . Furthermore, for a subset of the animals the generic class I primers 5\u2032 GGACTCA G A A T C T C C C C A G A C G C C G A G a n d 3 \u2032 TCTCAGTCCCTCACAAGGCAGCTGTC were used. The final elongation step was extended to 30 min to generate a 3\u2032dA overhang. The RT-PCR products were cloned using the InsT/Aclone kit (Fermentas) or the PCR cloning kit (Qiagen). After transformation, 32 to 48 colonies were picked for plasmid isolation. Sequencing reactions were performed using the BigDye terminator cycle sequencing kit, and samples were run on an automated capillary sequencing system (Applied Biosystems Genetic Analyzer 3100)." ] },{ "paper_id": "b1f59bdfada5dfed801691b8499168baf8b5c67f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b27455411400dcb41fbfb8df4cd9a0976e352426", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b27597f4106492dc77eb8e3e6ae832cc5a8262be", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors declare that they have conflict of interest.", "In conclusion, AnExILs present a new platform for DNAbased vaccines which combines antigen production, adjuvanticity and delivery in one system and which offer several advantages over existing vaccine formulations." ] },{ "paper_id": "b27756adff17efe99584415760407f3feb51014c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b277e521eb43fedeb50a08be126e76dd9bc7314a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b2893c753d19c6596ebcda65230f65b6935d18ba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b2afa8848026171f770c7154e8ff44c432ca23b7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b2b148720d1cf79fbeac9a409962bf9e2e190c4a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For immunohistochemistry, the sections were treated with 3% H 2 O 2 in PBS for 20 minutes and subsequently incubated with horseradish peroxidaseYlabeled polymer-conjugated anti-mouse antibody (Ab) reagent (EnVision+ reagent; Dako, Tokyo, Japan) for 30 minutes at RT. Finally, peroxidase was visualized using 3-amino-9-ethylcarbazole (AEC) substrate as the red color. The sections were counterstained with hematoxylin and analyzed by light microscopy.", "Apoptotic cells were detected with antiYactive caspase-3 Ab or antiYsingle-stranded DNA Ab by light microscopy and confocal laser scanning microscopy. The cells were also detected with TdT-mediated dUTP nick end labeling method according to the manufacturer's instructions (ApopTag Millipore, Billerica, MA).", "Previous studies reported that the HTLV-1 antigen is hardly detected in PBMCs (30, 31) , despite a high proviral (12) . We also failed to detect any HTLV-1 proteins by the immunohistochemical or flow cytometric study in PBMCs from 20 HAM/TSP patients, even though the proteins became detectable after short-term culturing ( Figure HTLV-1Yinfected cells could express viral antigens anywhere in the body of the infected individuals (14, 32) , the expression of HTLV-1 proteins in vivo has remained elusive so far." ] },{ "paper_id": "b2eb07b13c059c3bc0907d5e3f38424dcd7fcd84", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b31b7e11a6cf05cf0132d92bc09ee5911e7672f0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b32b26b8d44120d0daaa6fa57f5fd73234085837", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The classical symptoms of human influenza include cough, malaise, and fever, often accompanied by sore throat, nasal obstruction, and sputum production, which resolve spontaneously in most healthy individuals, although immune compromised and elderly individuals tend to be more vulnerable. Complications may include bronchitis and pneumonia, and exacerbation of asthma, and chronic obstructive pulmonary disease (COPD) [16, 18, 20] .", "All three EP preparations exhibited dose-dependent antileishmanial and trypanocidal activities after 24, 48, and 72 h incubation, although their relative potencies varied somewhat between extracts and target species. In general the ethanol extract was the most effective.", "However since we do not know the exact mechanisms of the EP antiviral activity, or the nature of the active \"compounds\", then we cannot explain these phenomena. But the lesson is obvious, namely, that some EP preparations by themselves can be potent antiviral agents and should not be mixed with unknowns.", "Another problem with the specific antiviral target approach, especially in the case of compounds directed at specific viral genes or their products, is the inevitable emergence of virus resistant mutants [14, 15] and their subsequent spread through the community and environment. The conventional answer to this problem has been to use combinations of two or more antiviral drugs, with distinct molecular targets, notwithstanding the likely increase in undesirable side effects. However, a logical alternative approach is the use of a noncytotoxic agent that has the capacity to inhibit many different respiratory viruses simultaneously, and recent evidence indicates that certain herbal extracts could fulfill this requirement [15] [16] [17] .", "EP-treated rats were assessed for spleen and lung macrophage-related functions, including phagocytic activity and cytokine stimulation, both of which were stimulated in the treated animals [107] , in agreement with the studies on mouse cells cultured in vitro." ] },{ "paper_id": "b333e890955fbc28fc246b5e97467a0312f4def3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b34652cd7c52b16dc961e00da7f2b64599aba91a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "a The sequence of peptide dens25, KHAILLVAVSFVTLITGNMS-FRDLGR, is underlined. See text for details.", "where F is the fluorescence intensity, F max the maximum fluorescence intensity, [P] the concentration of peptide, K d the dissociation constant of the membrane binding process, and n the Hill coefficient." ] },{ "paper_id": "b3bf0cacc79b216fa4d6218521b5730e9023ac00", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "did not constitute phylogenetic outliers (Figure 2 , panel A). The analyzed fragment had 6 aa exchanges, but they were insufficient for drawing conclusions about protein function because the fragment did not include domains putatively relevant for receptor binding (online Technical Appendix Figure 2 ).", "Because cell culture experiments may not show the full host range of a specific virus, we tested serum samples collected in 2008 from Sus scrofa domestica pigs in Goul\u00e9ako, the rural village where GOLV and HEBV were first isolated from mosquitoes in C\u00f4te d'Ivoire (5, 6) . The 28 tested samples represented nearly all the pigs kept in Goul\u00e9ako at that time, all of which were constantly exposed to mosquitoes. We also tested 108 serum samples collected in 2011 from mosquito-exposed swine in Kumasi, Ghana, where mosquitoes were found to be infected with HEBV (6) and GOLV (S. Junglen, unpub. data).", "The finding of genome fragments of GOLV and HEBV in swine in South Korea needs to be more fully explored. However, with no further independent proof of infection of swine or other vertebrates, HEBV and GOLV should not be considered epizootic pathogens or arboviruses. Search past issues of EID at wwwnc.cdc.gov/eid" ] },{ "paper_id": "b3c9cb39f0bb957864906c7710cbbc349380face", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Keywords: ARDS, extracorporeal membrane oxygenation, ECMO, Qatar, SRF", "The authors thank the Hamad Medical Corporation Leadership for facilitating the training of the Qatar ECMO team and the Guy's and St Thomas' NHS Foundation Trust team for delivering outstanding training. They are also very grateful to the ECMO team of doctors, nurses, perfusionists, respiratory therapists, physical therapists, clinical pharmacists, nutritionists, critical care paramedics, and their simulation expert Prof. Guillaume Alinier, who put effort, time, and dedication into making this program successful. They are particularly grateful to the support of their colleagues in cardiothoracic surgery, vascular surgery, blood bank, anesthesia, internal medicine, Hamad International Training Center, and the Ambulance Service for supporting the ECMO program all the way. The authors acknowledge the help and support of everyone, without whom this success could not have been achieved or lives could not have been saved.", "one patient per month. The survival rate was 100%. The first ECMO retrieval occurred in October 2014. This was carried with no recorded incidents. The year 2015 saw ECMO team size expansion and consolidation through in-house simulation courses and the HMC ECMO center joining ELSO. By the end of 2015, the center had treated 25 patients with a recorded survival rate of 70%. The year 2016 witnessed the introduction of VA ECMO modality, and the first aeromedical ECMO transfer occurred in June that year. Towards the end of 2016, the center began an ECMO fellowship program and registered its participation in multicenter ECMO trials. By the end of 2016, the center had carried out 50 runs of ECMO, with 10 patients dying while on ECMO (20% mortality). The ECMO patient survival to ICU discharge was 70% and to hospital survival was 68%. The future direction of the HMC ECMO program is to play a role of an adult regional center of excellence with not only land, 8 but also aeromedical transport capability, and to consolidate on ECMO education and training, through simulation courses, for both static and transport modalities. 7 Other future directions are, through local partnership, build on pediatric and cardiac ECMO, to introduce neonatal ECMO programs." ] },{ "paper_id": "b3fd1c9139c31dc46f7b65873260adcb21f47192", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Initial contact for recruitment took place through participating childcares, and following receipt of the information and consent document by mail, families interested in participating were screened and enrolled by telephone.", "We collected ILI impact data in a prospective cohort study in the southern hemisphere winter season in 2010. From 24 January 2010, healthy children aged \u22656 months to <3 years (as at 01 March 2010) were recruited from 90 childcare centres and one paediatric-focussed GP clinic in metropolitan Sydney, Australia. Exclusion criteria included any known allergies to influenza vaccine, history of Guillain-Barr e syndrome and haematological disorders. Informed consent for participation was obtained from parents or legal guardians.", "Ethical approval was given by the Human Research Ethics Committee of the Children's Hospital at Westmead, Sydney, Australia." ] },{ "paper_id": "b411919ba9575cf0fb503965275a640a116edfb0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We sampled small mammals at 5 (21) .", "Conference summaries/reports are published online only. Manuscripts submitted for online publication may include illustrations and relevant links." ] },{ "paper_id": "b4415bd2dea3b83efaf8cd097c8911614814ef6e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To determine travelers' actual and subjective knowledge about risk for Ebola virus disease, we surveyed travelers from France. Actual knowledge did not prevent irrational perceptions or promote safe behavior. Rather, readiness to adopt protective behavior depended on subjective knowledge and overconfidence in ability to self-protect.", "Our results indicate that not considering subjective knowledge and positive illusions can lead to the erroneous conclusion that increasing actual knowledge will necessarily translate into behavioral change and good practices. EVD communication would benefit from research showing that promoting behavioral change requires changing subjective evaluations of risk to make it self-relevant and to induce a reappraisal of the perceived benefits of (or costs of not) performing safe behavior (10). ", "Our observations of suboptimal actual knowledge about EVD replicated findings of past knowledge, attitudes, and practices studies (3-6); however, we went further by showing that relationships between actual versus subjective knowledge and perceptions of risk for EVD differed. The fact that subjective knowledge and positive illusions, but not actual knowledge, were associated with protective behavior intentions is problematic, especially because actual knowledge was low. Persons' belief that they know how to protect themselves when they actually do not and the feeling of knowing added to a feeling of overconfidence in how to self-protect might result in risky rather than safe behavior (7) ." ] },{ "paper_id": "b44258fb9be12d1ddecb77617f2cf7914313d35c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As the sequencing revolution continues to gather steam, and the rate of viral genome sequencing increases, reference databases will be pressed to serve growing community needs. Meeting these will require further collaboration with individual viral communities and across public databases. Data models will also need to shift to better represent the extant sequence universe and provide better standardized sequence annotation.", "A new emphasis has been placed on initiating annotation collaborations at the beginning of a large genome sequencing program so that reference annotations, isolate naming schemes and other standards can be established prior to sequence submission (42) (43) (44) . These collaborations often include members of the UniProt Viral Protein Annotation Program (45) (9), and/or curators from sequencing centers and other databases (46) in addition to members of the relevant viral communities and effectively ensure both well annotated references and consistently annotated INSDC sequence records. Such arrangements underscore the extensive impact of viral genome annotation issues--from public databases to sequencing centers to individual researcher communities--and were formalized within the Viral Genome Annotation Working Group, which brings together stakeholders and provides a forum for the discussion of annotation issues (29, 47) . In addition to protein annotation and isolate naming issues, this group is working to define standards for viral genome sequence data.", "The growing cloud of viral genome sequences also poses significant barriers to the maintenance of reference genome records. The pace of experimental discovery and the number and breadth of viral genomes make it increasingly difficult to provide well annotated, up-to-date reference sequences. To counter, we must leverage community knowledge and activities against the goal of better RefSeq viral resources and must collaborate with viral communities to maintain well annotated reference sequences, develop community-accepted gene and protein naming standards and define community-established subspecies classification schemes. Though collaborations have been initiated within D576 Nucleic Acids Research, 2015, Vol. 43, Database issue some communities (29, (42) (43) (44) 47) , they need to be scaled to include more groups. As a public resource, we serve a range of communities--from the public health to the basic research--and rely on them to both better inform our mission and help support it. Only by engaging our stakeholders and working together on shared goals can we provide the rigorous resources necessary to support viral sequence data activities.", "Once annotated, large-scale genome sequence data will need to be presented in ways that facilitate human data sorting and discovery operations. This will require semiautomated metadata capture and standardization, as well as innovative interfaces and tools that leverage metadata in discovery operations. Many of these approaches and processes are currently being tested within the NCBI Virus Variation Resource (25) where users can readily find sequences based on specific, standardized sequence descriptors, greatly improving the accessibility and utility of viral sequence data. While currently limited to a handful of human pathogens, our intent is to expand the Virus Variation data model to include more viruses from more viral communities. This should open up a number of possibilities and will support the aggregation and retrieval of sequences based on community-defined criteria like genotypes or complete genome sets as is currently possible for influenza virus sequences (11, 25) ." ] },{ "paper_id": "b44c16070a980ad9258249edfc99db4f17149d99", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Two cases are possible:", "In the biological field, several tools may be used to color species in taxonomic tree. 4, 7, 8 In particular, PhyloView 4 has been specially designed to display taxonomy and other analyses (phylogenetic trees) together. Strictly speaking, however, these tools are not automatic coloring tools: the user has to define the colors for taxonomic groups that are relevant from his point of view." ] },{ "paper_id": "b45b6c2d890f204bd14f8140605ded987336b791", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b45eb2cb079ef2489165f86686645b88c2bac2bb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b48d63ad65555f3c41a482332d3a9971ab28bc00", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Infectious diseases remain a leading cause of morbidity and mortality in humans. Rapid and accurate identification of the aetiological agent, be it an old or an emerging pathogen, can influence prognosis by enabling appropriate interventions, such as drug treatment, to be promptly initiated.", "We sought to devise a protocol that maximizes the advantages of all these approaches, while minimizing the less desirable characteristics. We describe here a generic, highly parallel method to rapidly identify multiple pathogens and their genetic elements in an unbiased manner and without the need for a specific hypothesis.", "The description of the experimental procedures resides in Appendix S1 in Supplementary material." ] },{ "paper_id": "b499a41ad1d85a0e071b59e60065c874e534911d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We have listed the human proteins analysed in this work in a table (Table 1 ).", "Seven full-length coronavirus genomes were retrieved from the GenBank database [33] with the following acces- ", "Very conserved positions will then get tall columns with the height of individual residue symbols reflecting the amino acid distribution." ] },{ "paper_id": "b4ac66a59b0e40c10a447b7a90f5c03d03eb58dc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b4b8f10ccc235f72d842eec82c9e6f5a5afd56cc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Transcription System\" kit from Promega. The recombinant human POLRMT and transcription factors mitochondrial transcription factors A (mtTFA or TFAM) and B2 (mtTFB2 or TFB2M) were purchased from Enzymax. RSV ribonucleoprotein (RNP) complexes were prepared according to a method modified from Mason et al. 29 .", "CC 50 (\u03bcM) *", "Statistically significant P-values (P < 0.05) are highlighted in bold. Table 4 Statistical summary of selected clinical pathology parameters ", "Transcription reactions contained 25 \u03bcg of crude RSV RNP complexes in 30 \u03bcL of reaction buffer (50 mM TRIS-acetate [pH 8.0], 120 mM potassium acetate, 5% glycerol, 4.5 mM MgCl 2 , 3 mM DTT, 2 mM EGTA, 50 \u03bcg/mL BSA, 2.5 U RNasin, 20 \u03bcM ATP, 100 \u03bcM GTP, 100 \u03bcM UTP, 100 \u03bcM CTP, and 1.5 \u03bcCi [\u03b1-32 P]ATP [3,000 Ci/mmol]). The radiolabeled nucleotide used in the transcription assay was selected to match the nucleotide analog being evaluated for inhibition of RSV RNP transcription." ] },{ "paper_id": "b553ae7b38c105bfb4182ec31b51c9a24ed501cf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b59de45467bf403971b02fc44bc84f4e75bfbdfa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The solution algorithm for our dynamic predictive simulation optimization methodology is given below.", "The instantaneous force of infection applied to contact i at time t (Eq. 2) was modeled as", "A schematic of the disease natural history is shown in Figure 2 .", "The authors disclose no conflicts of interest. " ] },{ "paper_id": "b5f7f394b121c84ea076571e10b4a4b1bad7e344", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Many researchers who have developed smallpox models have been optimistic about residual vaccine-induced immunity and assumed a case-fatality ratio (CFR) of 30%, whereas estimates of outbreaks in nonimmune populations suggest a CFR of 50%-70% (6) . Given the absence of smallpox in the world for nearly 40 years and loss of immunologic boosting from wild-type infection, the CFR of an epidemic today might be higher.", "Dr. MacIntyre is professor of Infectious Diseases Epidemiology at the University of New South Wales, Sydney, and leads a research program on biosecurity, bioterrorism, and emerging infectious diseases, which are her primary research interests.", "We constructed a modified SEIR (susceptible, exposed, infected, recovered) model for smallpox transmission (online Technical Appendix Table 2 ). The population was divided into vaccinated and unvaccinated compartments, which were then further subdivided into 3 categories of immunity: immunocompetent, mildly immunosuppressed, and moderate-to-severely immunosuppressed. The model used ordinary differential equations to move populations into epidemiologic states related to their smallpox infectious status: susceptible, infected, prodromal, infectious, recovered, or dead. Once infected, populations were moved into the next state on the basis of disease duration rates.", "In the United States, including New York, widespread smallpox vaccination occurred until 1970 (32). In contrast, in the geographically isolated island continent of Australia, quarantine was used to protect the population because smallpox was never endemic (32) . Widespread vaccination never occurred in Australia; only the armed forces and healthcare workers were vaccinated, which occurred until 1979, although reactive vaccination campaigns had been conducted during a smallpox outbreak in Sydney in 1917 (33) ." ] },{ "paper_id": "b60d9bb4f4f516bdf9e4e376e536c07111a940f4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b60e2996ec59f48cb2376f9c791d7253d0f220cd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Mr Dare is a microbiologist in the Division of Viral and Rickettsial Diseases at the Centers for Disease Control and Prevention. His research focuses on developing molecular diagnostic assays for respiratory viruses. ", "I nvestigation of a suspected Legionnaire's pneumonia outbreak in 1992 led to the isolation of a new microorganism from a water cooling tower in Bradford, England. This pathogen was thought to be a bacterium because it resembled small gram-positive cocci; however, in 2003 it was correctly identifi ed as a virus (1) . Acanthamoeba polyphaga mimivirus (APM), named for its ameba host and bacteria-mimicking characteristics, is a double-stranded DNA virus with the largest viral genome described to date (1.2 Mb) (2) . Mimiviridae is the newest member of the nucleocytoplasmic large DNA virus (NCLDV) group, which also contains Poxviridae, Iridoviridae, Asfarviridae, and Phycodnaviridae (1) . APM encodes specifi c translation proteins that are more commonly associated with cellular organisms than with viruses (2) .", "If we assume an APM prevalence of 0.2% (1 case in the study sample), the estimated probability of obtaining our results by chance, based on binomial analysis, would be 0.37. Most of the specimens we tested were from the upper respiratory tract, whereas the only reported APM PCR-positive sample was from a lower respiratory bronchoalveolar lavage specimen (3) . Moreover, the patient populations sampled may not represent those at highest risk for APM infection. Nevertheless, our study supports the fi ndings of an Austrian study that failed to detect APM in 214 nasopharyngeal specimens from hospitalized children with respiratory symptoms (8) ." ] },{ "paper_id": "b62751438aa94a45829290ba4e6144afc95f4755", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b62b8267bb53def16c93b7e566c780f7ab70456c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b639036a443e2dd13f9c37556011232ff35375ed", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b6641c661abc4e253dac263e658506b83995ec46", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b69fe5e231d41629e4620b18e90999022c72474d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b6b194382723f8c929c36eb1e7e80394f0a105fd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Proportion of female participants was higher among the respondents than among the non-responders (57.9% versus 45.4%, p < 0.01).", "Methods" ] },{ "paper_id": "b6ed892b894ed62251a8cb78b5bca37318a03a4d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All results are expressed as means \u00b1 s.e.m. We analyzed the data with unpaired two-tailed t tests (Prism 5).", "albopictus5, that survives in temperate climates and is widely distributed6. CHIKV continues to cause substantial morbidity resulting in significant economic losses, and vaccine development remains a high priority." ] },{ "paper_id": "b70352cde76b15b3f8eb60a492ad27bd0a8c4a20", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The mean incubation period was 6.4 days (95% CrI 5.2-7.9 days) for 36 patients who died compared with 7.1", "Our study had some limitations. Our estimates of the incubation period were based on self-reported exposure data, which could be affected by recall bias. Moreover, 61 patients (36%) included in our main analysis had missing exposure data, and inclusion in a Bayesian framework with a wide interval of 0-21 days was necessary. Both of these limitations could have reduced the statistical power of our study to identify an association. Finally, we did not have information on underlying medical conditions or the geographic location of cases, or the treatments that were given to cases, and these variables could have been associated with clinical outcomes.", "In conclusion, we found an association between shorter incubation periods among patients with MERS-CoV infection and a higher risk of death subsequently, similar to the association previously reported for severe acute respiratory syndrome coronavirus (9) . This association might occur because the duration of the incubation period is an early reflection of disease pathogenesis. ", "MERS-CoV also has higher replication rates and shows broader cell tropism in the lower human respiratory tract than severe acute respiratory syndrome coronavirus (13) . These results suggest that a shorter incubation period could be related to a higher initial infective dose and consequently to faster or greater pathogen replication. This finding could lead to a more severe disease induced by more aggressive and damaging inflammatory responses (14) . Closer monitoring of patients who have a shorter incubation period could be considered during such outbreaks." ] },{ "paper_id": "b703a12d98e44bc45d958bc7e15e38f570393e5c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b7089fc75836770d44da4bc7d6200e81426b2d4e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b75374ebf027be698e5ce4e721a4840dc4384240", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Antiviral activity and induction of ISG expression were evaluated for three formulations of IFN\u03b2: IFN\u03b2-1a sc, 44 \u03bcg (Rebif, original formulation, lot number Y09B7770V, Industria Farmaceutica Serono, Rome, Italy); IFN\u03b2-1a sc NF, 44 \u03bcg (Rebif, serum-free formulation, lot number Y09B0227, 290 C. Scagnolari et al. Industria Farmaceutica Serono); and IFN\u03b2-1b sc, 250 \u03bcg (Betaferon, lot number 1560, Bayer Schering, Berlin, Germany).", "For each of four different concentrations of each IFN\u03b2 formulation, MxA gene expression activity was measured in three replicates, and ADAR1 and ISG56 expression were measured in six replicates. Since the concentrations differ by factors of 10, a logarithmic scale was used to present the results so that they could be displayed meaningfully on the same graph. Student's t-test was used to compare relative gene expression of MxA, ADAR1, and ISG56 among the three IFN\u03b2 formulations at the same amount of dilution.", "Induction of ISG expression was assessed using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) for myxovirus resistance protein A (MxA), ADAR1 (adenosine deaminase, RNA-specific), and ISG56 mRNAs. A549 cells were incubated with various concentrations of IFN\u03b2 formulations for 24 hr. At the end of the incubation, total cellular RNA was extracted from the cells using Trizol \u00ae (Gibco BRL, New York, NY, USA) according to the manufacturer's instructions. RNA was dissolved in 50 \u03bcL of RNase-free water, and the quantitation of ISG mRNA was performed by a real time 5' exonuclease RT-PCR Taqman assay using an ABI 7000 sequence detector (Applied Biosystems, Foster City, CA, USA) after generation of cDNA as previously described. [27] The following primer pair and probe -MxA (MxA F: 5'-CTGCCTGG CAGAAAACTTACC-3'; MxA R: 5'TCTGTTATTCTCTGGTGAGTCTCCTT-3'; MxA P: 6-carboxifluorescein (FAM)-5'CATCACACATATCTGTAAATCTC TGCCCCTGTTAGA3'-6carboxy-tetramethylrhodamin (TAMRA) [28] ); ADA R1 (ADAR F: 5'-CCGGCAGGATGACACAGAC-3'; ADAR R: 5'-GCTTGGC AATATTCCAAGGC-3'; ADAR P: 5' FAM-CACTTCCCAGGGAGCACGG GCA-3' TAMRA); ISG56 P56 F: 5'-TGAAGAAGCTCTAGCCAACATG TC-3'; P56 R: 5'-GAGCTTTATCCACAGAGCCTTTTC-3'; P56 P: 5' FAM TATGTCTTTCGATATGCAGCCAAGTTTTACCG-3' TAMRA [29] ) -were added to the universal PCR master mix (Applied Biosystems, Foster City, CA, USA) at 300 nM and 100 nM, respectively, in a final volume of 50 \u03bcL. Coamplification of the beta-glucuronidase gene (GUS; Assay-On-Demand, Hs99999908_m1; Applied Biosystems) was used to normalize the amount of total RNA present using the threshold cycle relative quantification according to the supplier's guidelines (2 \u2227 -Ct method). The threshold cycle (Ct) value is the PCR cycle in which the amplification plot crosses the threshold line. The Ct values of each amplification reaction performed in A549 cells before and after in vitro IFN\u03b2 treatment were used to calculate the difference " ] },{ "paper_id": "b7f1dcfe8b12d6b8a548db0de597cbef95712d9c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical tests were performed by using the Statistical Package for the Social Sciences software (SPSS 10.1.0, Inc., Chicago, IL). The chi-square test was used to analyze categorical variables. All statistical tests were two-tailed and p values <0.05 were regarded as significant.", "The same RNA extraction method was used in laboratory B. The RT-PCR was carried out in a single-tube system (Superscript One-Step RT-PCR with Platinum Taq, Invitrogen, Carlsbad, CA), in a 25-\u00b5L reaction mix containing 0.6 \u00b5mol/L of each COR-1 and COR-2 primer, 0.2 mmol/L of each deoxynucleoside triphosphate and 1.2 mmol/L magnesium sulphate. The reverse transcription was conducted at 54\u00b0C for 30 min. After the mixture was held at 94\u00b0C for 3 min, it underwent 45 cycles of amplification at 94\u00b0C for 45 sec, 60 o C for 45 sec, 72\u00b0C for 45 sec, and final extension at 72\u00b0C for 7 min. The PCR amplicon was also detected by agarose gel electrophoresis as in laboratory A." ] },{ "paper_id": "b846eb629d90098884d798cbfe4132db5f63562c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Serologic studies of domestic livestock in Jordan, Saudi Arabia, Qatar, United Arab Emirates, and Egypt have found high seroprevalance to a MERS-like CoV in dromedary camels but not in other domestic animals (7) (8) (9) (10) (11) . An investigation of domestic animals in the vicinity of 2 persons with related infections detected fragments of viral RNA in dromedary camels in contact with these persons but whether this represented transmission from a unidentified source to humans and dromedaries, transmission from humans to dromedaries, or vice versa is not clear (12) .", "Using a previously described pseudoparticle neutralization assay (8), we detected antibodies against MERS-CoV (titer >20) in 48 (92.3%) of 52 dromedary serum samples with titers ranging from 20 to >640. Dromedary NRCE-HKU205 had a serum antibody titer of 640, possibly indicating a developing serologic response, as was noted previously (7), or the possibility of re-infection. Serum was not available from the other 3 animals with MERS-CoV RNA-positive nasal swab specimens.", "M iddle East respiratory syndrome (MERS) is a pneumonic illness caused by a novel lineage C betacoronavirus (CoV). During September 2012-January 20, 2014, a total of 178 confirmed cases in humans resulted in 76 deaths (1) . Primary infections have originated from countries within the Arabian Peninsula, although travelassociated cases and some secondary transmission have been reported in other countries. Limited human-to-human transmission has resulted in clusters of cases, some associated with multiple rounds of human-to-human transmission (2); the remaining sporadic cases in humans are presumed to be of zoonotic origin." ] },{ "paper_id": "b85fb3c87b048a1ead4177bf01e987ed23f87c33", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "However, in large-scale studies, copy number variation of total b-defensin gene number positively correlates with HIV load in Ethiopian and Tanzanian patients [107] . The authors suggest that the chemoattractant nature of bdefensins may bring the target Th17 cells into mucosal sites where they can be readily infected by virus. Other work, however, has recently shown that exposed but seronegative individuals have much higher HBD2 and 3 copy numbers in oral mucosa (but not vaginal mucosa) than healthy controls, indicating a role for these defensins in combating infection [108] .", "Acknowledgments DJD is supported by a MRC Senior Non-clinical Research Fellowship (G1002046). SMC is supported by a University of Edinburgh College of Medicine and Veterinary Medicine Studentship. The authors have no conflicts of interest that are directly relevant to the content of this article.", "Viral diseases are a leading cause of morbidity and mortality worldwide, particularly of children [1] , and yet development of effective therapies is slow. In particular, progress is hampered by the fact that the majority of antiviral drugs are specific for only one virus. Current approaches are expensive, require rapid identification of the virus before therapy and, at the initial stages of development, involve enormous redundancy of research effort. This also results in efforts being concentrated on a few viruses; of the 60 antiviral drugs that have so far been approved by the US Food and Drug Administration (FDA), almost half target HIV-1; the remaining half are used for the treatment of hepatitis B virus (HBV), herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), influenza (IAV) and hepatitis C virus (HCV) infections [2] .", "There is a pressing need to develop new antiviral" ] },{ "paper_id": "b8c816b6461d1c8bf4603f85f6e9841c172a8bc1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b8cce26d679d7fe229d2694978be17b229508320", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The study's limitations included the inability to assess real responses, inability to generalize findings to all university students and the general public, and the use of scales that had not been validated. Also, some students might have given exaggerated responses.", "DOI: http://dx.doi.org/10.3201/eid2201.150898" ] },{ "paper_id": "b8d17f3628650e4b6ab0d9068e9e25aa26857569", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Chronic diseases are the leading cause of death in Tianjin, China. China should commit additional resources to supporting chronic disease prevention and control programs, including proven special health promotion projects.", "We analyzed trends of major causes of death in Tianjin, China, from 1999 through 2004 to better inform disease prevention and control programs and policies.", "Tianjin is the third largest city in China, and its population ( through 2004 if they had formal residential household registration in Tianjin and a completed death certificate. Practicing clinicians in hospitals and community medical centers in Tianjin complete death certificates and enter the data into a computer linked with the local disease prevention station and the TJCDC. Deaths outside a hospital are added to the database on the basis of home surveys conducted by community doctors. TJCDC screens, sorts, and analyzes submitted data. TJCDC holds periodic training to improve the quality of death certificate reporting.", "Our study is limited in that mortality was derived primarily from deaths reported by hospitals, and mortality is approximately 10% underreported outside the hospital system (unpublished data). Nevertheless, this study presents the first data from a provincial surveillance system on all-cause mortality in China. It provides basic information for developing health policy and health promotion activities that can improve the health and life expectancy of the Chinese people. ", "We calculated mortality rates according to ICD-9 or ICD-10 classification; age-standardized mortality rates are based on the World Health Organization world standard population in 2000 (2) . We used \u03c7 2 tests for significance (\u03b1 = .05) to compare the change and difference between the mortality trend and mortality distribution, respectively (3). All analyses were done in SPSS version 11.5 (SPSS, Inc, Chicago, Illinois)." ] },{ "paper_id": "b8fc960573a817a8bdd0dc42420ef61f3073330d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "IH, et al. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol. 2004;136:95-103. 5", "Of 41 samples (40 SARS and 1 H5N1) received for testing, 26 (63%) samples were not tested because clinician responses failed to satisfy the screening criteria. The remaining 15 (37%) samples met criteria for testing and all had negative results. In the absence of positive results, no confirmatory testing was indicated.", "To the Editor: In August 1999, the Laboratory Response Network (LRN) was established to better integrate and improve laboratory capacity for responding to public health threats (1) . However, while experts have focused on clinical indications for testing for agents of bioterrorism, laboratory methods for microbial identification, and needs for integrated communication networks (2) (3) (4) , little attention has been given to how sentinel laboratories can effectively screen clinicians' requests for testing pathogens designated as global health threats." ] },{ "paper_id": "b9b4213574ea78c40397f25bd72806df09c05013", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b9b56a7b507acbddb2122ecc330a8d331c5ff33c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "N. caninum infection causes neuromuscular disease in dogs and reproductive disorders in ruminants, causing fetal loss due to vertical transfer of parasites during acute infections or reactivation of chronic infections. Clinical neosporosis in animals resembles the disease outcome of toxoplasmosis (1) .", "We thank Ben M. Hause for the viruses used in the study." ] },{ "paper_id": "b9e13e3c31f4361833a9c3ac5647d3f3d3aea670", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b9fbd0773ea09b1ad96a7746601d7a8e2125313d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All sampled tissues were examined by IHC analysis to detect viral antigen. Briefl y, 5-\u03bcm tissue sections were subjected to antigen retrieval (20) and were then incubated in 10% normal goat serum in PBS for 30 min to block nonspecifi c binding sites. Slides were further incubated with chicken anti-IBV hyperimmune serum at 1:500 dilution in PBS for 2 h, followed by incubation with a horseradish peroxidase-conjugated rabbit chicken IgG for 1 h. The reaction was visualized by the addition of 3,3-diaminobenzidine (DAB; Sigma, St. Louis, MO, USA) for 15 min. After IHC staining, sections were counterstained with hematoxylin, air dried, and examined by light microscopy.", "A vian infectious bronchitis virus (IBV), a member of family Coronaviridae, order Nidovirales, causes a highly contagious respiratory and sometimes urogenital disease of chickens that is characterized by respiratory signs, nephritis, or reduced egg production and quality in layer chickens. IBV is a major poultry pathogen that is endemic worldwide and leads to serious economic losses.", "The amplifi ed DNA products were purifi ed by using an AxyPrep DNA Gel Extraction Kit (AxyGEN, Union City, CA, USA), and the purifi ed products were ligated to the pMD18-T Easy Vector system (Promega). Recombinant plasmids were extracted from positive clones by using the E.Z.N.A.R. Plasmid Miniprep Kit (Omega, Norcross, GA, USA) and identifi ed by EcoRI restriction digestion (Promega). Nucleotide sequencing reactions were performed by Sunbio Biotech (Bejjing, China).", "To better control IBV in China, more detailed analysis of the biologic and antigenic characteristics of the predominant IBV isolates is warranted, and assessments of the effi cacy of current vaccines against these isolates are needed. ", "Clinically, some birds appeared depressed with ruffl ed feathers; these birds had increased water intake and huddled together in YN-inoculation group at 2 days postinfection (dpi). At 4 dpi, IB-like signs became obvious in all infected chickens, and some birds were euthanized because of severe disease. Deaths occurred until 21 dpi; the death rate reached 65% (Figure 3, panel A) . No deaths or clinical signs were observed in the control group." ] },{ "paper_id": "ba085942946a4ef42509d21445021f1bcdbe3b7e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Introdu\u00e7\u00e3o: A tosse \u00e9 o sintoma respirat\u00f3rio mais comum em crian\u00e7as e adultos. Objetivo: Apresentar uma revis\u00e3o sobre a neurofisiologia e os m\u00e9todos para estudo do reflexo da tosse, bem como a farmacoterapia e terapia fonoaudiol\u00f3gica da tosse, baseada nos trabalhos publicados entre 2005 e 2010 e indexados nas bases Medline, Lilacs e Biblioteca Cochrane sob os unitermos \"tosse\" ou \"antituss\u00edgenos\". S\u00edntese dos dados: O reflexo da tosse envolve ativa\u00e7\u00e3o de m\u00faltiplos receptores vagais nas vias a\u00e9reas e de proje\u00e7\u00f5es neurais do n\u00facleo do trato solit\u00e1rio para outras estruturas do sistema nervoso central. T\u00e9cnicas experimentais permitem estudar o reflexo da tosse ao n\u00edvel celular e molecular para desenvolver novos agentes antituss\u00edgenos. N\u00e3o h\u00e1 evid\u00eancias de que antituss\u00edgenos isentos de prescri\u00e7\u00e3o m\u00e9dica tenham efic\u00e1cia superior \u00e0 do placebo para o al\u00edvio da tosse. A terapia fonoaudiol\u00f3gica pode beneficiar pacientes com tosse cr\u00f4nica refrat\u00e1ria ao tratamento farmacol\u00f3gico, sobretudo quando coexiste movimento paradoxal das pregas vocais. Coment\u00e1rios Finais: A abordagem multidisciplinar tem papel fundamental no diagn\u00f3stico etiol\u00f3gico e tratamento da tosse. O otorrinolaringologista deve informar os pacientes sobre os riscos dos antituss\u00edgenos de venda livre a fim de prevenir intoxica\u00e7\u00f5es e efeitos adversos, especialmente em crian\u00e7as." ] },{ "paper_id": "ba1b2eea863c7a93bdeb49f6062d3660b793e2c5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ba31adca4b7af49cd5e209dd5ad53a1ca30723c6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We tested samples collected from camels, camel workers, and other animals in Sudan and Qatar in 2015 and 2017 for evidence of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. MERS-CoV antibodies were abundant in Sudan camels, but we found no evidence of MERS-CoV infection in camel workers, other livestock, or bats.", "Other livestock were also seronegative for MERS-CoV in our study, a finding in agreement with most serosurveys, although some sheep, goats, and donkeys and 1 cow have been reported to have MERS-CoV antibodies (3, 10) .", "2 These authors were co-principal investigators." ] },{ "paper_id": "ba57dd74c557de7638d8c30c1622de799edc65cd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In Figure 1 , exposure variables and their suggested coding include date (DD/MM/YY), source (whether the source is already identified and included in the data table as an observed patient with an assigned ID or whether the source is unknown), duration of exposure (<30 minutes, 30-59 minutes, or >60 minutes), and locale (whether exposure occurred at home, in a hospital, or some other location). The same variables are measured for each exposure, and the table can be expanded to collect information on all known exposures." ] },{ "paper_id": "ba581dc8851307204bba0a4d63c9e1bf10ff6e26", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ba59b6a25e1ed76527b1876c403372afda76f4d1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The study protocol was reviewed and approved by the US Naval Medical Research Unit", "Diarrheal disease is the second leading cause of childhood illness and death and is responsible for \u22482 million deaths annually in children <5 years of age (6, 7) . Frequent and prolonged episodes of nonfatal diarrhea can lead to malnutrition, stunting of growth, and absenteeism in schoolage children (8, 9) . In Egypt, where child mortality rates have been reduced in recent years, diarrheal diseases still account for 13.9% of deaths in children <5 years of age.", "Campaign materials were developed for 3 groups (students, teachers, parents). The teachers' guidebook included a detailed description of the students' activities and methods to encourage students to practice these activities. Posters were placed near sinks in the classrooms and on the playground. The primary message was to wash hands with soap and water upon arriving at school, before and after meals, after using the bathroom, and after coughing or sneezing.", "Acute respiratory infections (ARIs) and diarrheal diseases cause substantial illness and death worldwide. Most of the estimated 5.5 million deaths associated with ARI and diarrhea occur in children from resource-limited countries. In these settings, where access to health services is often lacking, effective prevention methods are paramount. ARIs cause >4 million" ] },{ "paper_id": "ba905b2783008a9ceb817d60ead70d937fb002a4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "bada3cc0577a226694617d77f95ac443c6431969", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This work was funded by Grant SEP-2004-C01-47122 from the Consejo Nacional de Ciencia y Tecnolog\u00eda (CONACYT).", "Most authors thus argue that a successful Leishmania vaccine is likely to be based on multiple antigens.", "An alternative way to broaden vaccine immunogenicity and increase its efficacy has been to use combination of plasmids encoding various antigens. For examples, cysteine proteinase (CP) a and b DNA vaccines are not protective when used individually, but immunization with a combination of both plasmids induces long-term protective immunity [34] . Alternatively, gene fusion has also been successively used to achieve expression of an antigenic fusion protein from a single plasmid construct [33] . Overall, expression of several antigens mostly resulted in increased efficacy, but this also depended on the antigen combination [13, 22, 23, 41, 45] ." ] },{ "paper_id": "bae793db127cecb4f94b4964d3ecad045b793848", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Murine B16 melanoma, CT26 colon carcinoma and A20 B cell lymphoma lines were purchased from American Type Culture Collection. Mouse dendritic DC2.4 cells were originally from Dr. Kenneth Rock (University of Massachusetts Medical School, MA). Highly metastatic clone of K1735 melanoma (C4) was kindly provided by Drs. S. Huang and J. Fidler of M. D. Anderson Cancer Center (Houston, TX). The stably transduced A20-Luc cell line was provided by Dr. Defu Zheng (City of Hope, Duarte, CA). The generation of transgenic C57BL/6.CEA mice and MC-38.CEA cell line was previously described 50 .", "EMSA and Western blot analysis to detect Stat3 DNA-binding and protein expression were performed as described previously 18 . The protein levels of Stat3 detected by Western blotting were later quantified by densitometry using AlphaEase FC software (Alpha Innotech).", "We prepared single-cell suspensions of spleen, lymph node or tumor tissues by mechanic dispersion followed by collagenase D/DNase I treatment as described before 10 . For extracellular staining of immune markers 1 \u00d7 10 6 of freshly prepared cells suspended in PBS/2% FCS/0.1% w/v sodium azide was preincubated with Fc\u03b3III/IIR-specific antibody to block non-specific binding and stained with different combinations of fluorochrome-coupled antibodies to CD11c, I-A b (MHCII), CD40, CD80, B220, CD11b, Gr1, CD3, CD8 or CD4 (BD Biosciences). Prior to intracellular staining with antibodies to TLR9 (eBioscience), Dicer (Santa Cruz) or FoxP3 (eBioscience), various immune cell subsets were fixed in paraformaldehyde and permeated in methanol. Fluorescence data were collected on FACScalibur (Beckton Dickinson) and analyzed using FlowJo software (Tree Star)." ] },{ "paper_id": "bafafd9f8218f31163be864df6a1a0681ad0d16c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical Analysis. All experiments were conducted in triplicate. Data are all expressed as mean \u00b1 SEM (standard error of the mean). Comparison of means using student's t test was utilized to analyze the statistical differences between SNAP-doped catheters and control catheters. Values of p < 0.05 were considered statistically significant for all tests.", "(2)", "The authors declare no competing financial interest." ] },{ "paper_id": "bbb82b5cc6363d7e376af1d92e30ea59c0807f7b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "bbe2e49fac5f007f3313b35f9b264bb4219aa67d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Consequently, even though M cells constitute only a very small percentage of mucosal epithelial cells, they are the major point of attachment and/or entry used by numerous mucosal pathogens including bacteria (e.g., S. typhimurium, Shigella flexneri, Yersinia enterocolitica and Vibrio cholerae), viruses (e.g., reovirus, HIV-1 and polio virus) and parasites (e.g., Cryptosporidia) [72, 79, 80] .", "ates the adhesion of S. typhimurium to murine Peyer's patches [21] . LPF was first described in S. typhimurium, and is found in numerous pathogenic E. coli strains [22] . Although its specific receptor remains unclear, extracellular matrix proteins (ECMs), which comprise an interlocking mesh of fibrous proteins and glycosaminoglycans, may act as a receptor for LPF of enterohemorrhagic E. coli O157:H7 (Fig. 3 ). ECMs are modified by various carbohydrate moieties, and the addition of mannose inhibits LPF-ECM interaction. Then mannose-containing carbohydrates may participate in bacterial adhesion by LPF [23] .", "Epithelial mucins are a heterogenous family of large complex glycoproteins containing a dense array of Olinked carbohydrates typically comprising over 70% of their mass. The carbohydrate structures present on mucosal surfaces vary according to cell lineage, tissue location and developmental stage [58] . Mucin glycosylation can alter in response to mucosal infection and inflammation, and this may be an important mechanism for unfavorable changes in the niche occupied by mucosal pathogens. The O-linked glycans of muchin proteins contain 1-20 residues, which occur both as linear and branched structures [58] .", "Long polar fimbriae (LPF) and plasmid-code fimbriae (PEF) are categorized as type 4 fimbriae (Fig. 2) . Std fimbriae are categorized as \u03c0-fimbriae [2, [13] [14] [15] . A previous report showed that when one of the fimbriae carried by Salmonella typhimurium was deleted, only virulence for mouse was moderately altered, and that multiple fimbrial adhesins were required for full virulence [16] . For Salmonella and assortative bacteria, type 1 fimbria is the Std fimbriae are categorized as \u03c0-fimbriae. Bacterial flagella are the moving apparatus of bacteria, but their components can also contribute to the binding to sugar-containing molecules.", "Moreover, the host gastrointestinal tract cell surface, which is the object of microbial infection, is composed of glycoproteins, glycolipids, and proteoglycans. These molecules are potential targets for carbohydrate drugs used in the treatment of infectious diseases." ] },{ "paper_id": "bc3575cce4fb95a77596f85eec9ad9e75137e06e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This work is supported by the National Institutes of Health (R01 AI135937; R21 TW010635-01), NIH/Fogarty International Center (D43 TW009348), the Bill and Melinda Gates Foundation (OPP1123092), and Vanderbilt University through the Laboratories for Innovations in Global Health Technologies. C.F.M. and K.A.R. acknowledge support from the National Science Foundation Graduate Research Fellowship Program (DGE-1145197). We gratefully acknowledge Shellie Richards for her tireless proofreading efforts that sharpened the manuscript.", "These questions should be answered carefully and systematically. Given the greater number of microspheres bound to eggs in the high affinity group, the populations should be separable using external magnetic fields of differing strengths. Egg-microparticle binding mechanisms for each population could be interrogated by determining solution properties (e.g., pH, salt, surfactant, chelators, blocking proteins, etc.) required to interrupt the interactions. Additionally, functionalizing microspheres in a way that systematically varies their zeta potential and hydrophobicity could determine the role these physiochemical properties play in binding. These studies will be crucial if the Helmintex method aims to determine infection intensity using quantitative egg enrichment. This is particularly important for schistosomiasis surveillance and morbidity control campaigns, which aim to quantify and reduce the prevalence of high-intensity infections.", "Review diagnostic sensitivity and specificity can lead to more complex tests, potentially requiring more user steps, expertise, and time to complete." ] },{ "paper_id": "bc652839250b03af000623dec894399f63d8203b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Tissue sections were mounted on 3-aminopropyltriethoxylane-coated slides (Fisher Scientific, Pittsburgh, PA, USA). A 25-nt oligomer (CTCAGACAGAGACAC-CGTTGCTATG) complementary to a segment of ORF2 (capsid) was 3\u2032-end labeled by the addition of a single digoxigenin-II-dideoxy undine (Eurofins MWG Operon, Huntsville, AL, USA). A manual capillary-action work station (Fisher Scientific) was used to perform colorimetric DNA in situ hybridization. Tissue sections were deparaffinized and digested by incubation at 37\u00b0C for 10 min in 0.25% pepsin in 1\u00d7 Tris-buffered saline (pH 2.0); pepsin activity was stopped by a 5-min incubation at 105\u00b0C. Nucleic acid was denatured by 5-min incubation at 105\u00b0C in 100% formamide. Tissue sections were then incubated at 37\u00b0C in 10 \u00b5mol of the digoxigenin-labeled probe in hybridization buffer (22.5% deionized formamide, 7.5% chondroitin sulfate, 5\u00d7 saline sodium citrate, 0.25% blocking reagent, and 50 mmol phosphate buffer). Sections were incubated in an antidigoxigenin antibody solution (500:1 dilution) containing 2.5 mL buffer 1 with 5 \u03bcL of antidigoxigenin Fab fragments conjugated with alkaline phosphatase (750 U/mL) (Roche). Sections were then washed and developed according to manufacturer instructions before counterstain with 1% fast-green FCF for 5 min. Slides were mounted with ImmunoHistoMount (Immunobioscience, Mukilteo, WA, USA) and coverslipped with SHUR/Mount (Triangle Biomedical Sciences, Durham, NC, USA). No background hybridization was seen when replicate tissue sections were incubated with an unrelated digoxigenin-labeled probe with similar guanine-cytosine content or when matched tissue from unaffected dogs were incubated with the DogCV-specific probe (23) (24) (25) .", "Of \u224810,000 squesnce reads, 5 contigs and singlets composed of 52 sequence reads from the liver tissue had significant similarity to the Rep protein of circoviruses (Evalue <1 -10 ). Two bocavirus sequences were also detected. Because circoviruses have a circular genome, the full viral genome was then amplified by inverse nested PCR and the amplicon sequenced by primer walking. The assembled genome was named DogCV strain UCD1 (DogCV-UCD1).", "A liver tissue sample (\u224825 mg) were immersed in 1 mL cold Hank's balanced saline solution and disrupted with a tissue homogenizer for 30 sec on ice. The resulting homogenates were placed on dry ice for 5 min and then thawed at room temperature (18) . Freezing and thawing were repeated twice. Samples were clarified by centrifugation at 10,000 \u00d7 g for 3 min; the supernatants were then filtered and underwent nuclease treatment as described (19) . Viral nucleic acids were extracted by using the QIAamp Viral RNA Mini Kit (QIAGEN, Valencia, CA, USA) and stored at \u221280\u00b0C.", "C ircoviruses are nonenveloped, spherical viruses with a single-stranded circular DNA genome of \u22482 kb; they group as a genus within the family Circoviridae, together with the proposed genus Cyclovirus and the phylogenetically more distinct genus Gyrovirus (1) . Most of the known species in the genus Circovirus infect birds and cause signs including malformations and necrosis of the integument, lymphoid depletion, and immunosuppression (2) .", "Phylogenetic analyses based on aligned amino acid sequences from full-length replicate (Rep) proteins were generated by using the neighbor-joining method in MEGA4 (22) , using amino acid p-distances with 1,000 bootstrap replicates. Other tree-building methods, including maximum parsimony and maximum likelihood, were used to confirm the topology of the neighbor-joining tree." ] },{ "paper_id": "bce0050667b80e7ff893094d6d7ff84a005d14e3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "bd04b79a0dba1a6f912d0ee7604ab62f84b6734c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "bd42860179bf3032b5da35bf4cba948603f8dc10", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "bdd29bc2544c4db266bcec6b7b404e5c360ca35f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "be602928156cf0ace9899c1c8569eb4f4ea4597b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "During the severe acute respiratory syndrome outbreak in Toronto, Canada, patients with the infection were frequently alone between brief contacts with staff , and some had worsening psychological symptoms during their stay, including panic attacks. Nearly one-half of hospital employees reported diffi culty in communicating with patients through the enhanced infectious precautions [35, 36] .", "Taken together, these studies suggest that isolation of patients for infection control purposes may have a deleterious eff ect on the quality of medical care received and perceived by these patients.", "Ignaz Semmelweiss, a Hungarian physician and contemporary of Holmes, consolidated these theories through his epidemiologic work at a Viennese hospital with the realization that frequent contact with cadavers among medical students was associated with transmission of particles to women in labor, leading to puerperal fever and even sepsis. He is credited with introducing hand disinfection prior to vaginal examination, with a subsequent dramatic decrease in mortality [4] . Th is practice was reinforced in Florence Nightingale's 1859 treatise, in which she called for 'every nurse \u2026 to be careful to wash her hands very frequently during the day' [5] .", "outcomes? To address this question, we present a discussion on the merits, concerns and costs surrounding enhanced precautions for critically ill patients, the latter of which was found to be lacking in a systematic review of the literature performed within the last 5 years [6] ." ] },{ "paper_id": "bf417a4d999dae8d6ad38e62fc69f2a578c58f16", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In order to provide evidence to support this commissioning aim, our research objectives were as follows:", "Epidemiological, corporate and comparative healthcare needs assessments were performed from an NHS perspective.", "Limited criteria were agreed against which to value the options, including accessibility, GP practice opinion, user opinion, ease of staffing, ease of management, capacity, quality of environment and time to implement. These criteria were independently weighted by members of a DXA Advisory Group in order of importance and a mean weight was calculated for each criteria. The options were then scored against the criteria and assessed on a range of one to five as follows -1-Very poor 2-Poor 3-Average 4-Good 5-Very good -to produce weighted benefit scores." ] },{ "paper_id": "bf5c9b9133105871316b57136a6d2926303d3ebe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data were analysed using expressionSuite Software v1.0.3 (Applied Biosystems \u00ae life Technologies\u2122). Baseline and threshold settings were manually adjusted for each individual gene. The comparative C T (\u0394\u0394C T ) method was used to calculate relative quantities (rQ). Normalisation of C T values was based on five reference genes (18sRNA, X03205; Gapdh, NM_017008; Hprt1, NM_012583; Pgk1, NM_053291; Ppia, NM_017101). A detailed description of gene and TaqMan \u00ae array specifications is provided in Supplementary Table 4 ." ] },{ "paper_id": "bf73a62e8d870d8edd2bd1fb2ca68424e2e8b7d9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In all cases, written informed consent was obtained from the participants (or guardians of participating children) before inclusion in the study. ", "Sequence data of the monoclonal antibodies isolated in this study have been deposited in GenBank (https://www.ncbi.nlm.nih.gov/genbank/) with the accession codes indicated in Supplementary ", "Scripts for Illumina and MinION sequence analysis are available at https://bitbucket.org/ mathildefog/switchillumina and https://bitbucket.org/mathildefog/switchminion, respectively.", "Kenyan plasma samples were obtained from adults living in a malaria-endemic region within Kilifi County. Tanzanian serum and plasma samples were obtained from healthy male volunteers, malaria negative at study enrolment and during PBMC collection, HIV and Hepatitis B and C negative, age 25.4 \u00b1 2.8 (mean +/-SD)3. The Mali study was conducted in the rural village of Kalifabougou where intense P. falciparum transmission occurs from June through December each year. 610 individuals (310 males and 300 females) were enrolled, age ranging from 1 to 26 years (mean 9). The cohort has been described in detail elsewhere4. Smaller numbers of sera were also obtained from adults in the Fulani and Dogon ethnic groups in Mant\u00e9ourou, Mali. 48 individuals (28 males and 20 females) were enrolled, age ranging from 21 to 57 years (mean 39.7)." ] },{ "paper_id": "bfc30febb21caaeca4b083ee15c7b36f94d8b3b4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Emerging Infectious Diseases \u2022 www.cdc.gov/eid \u2022 Vol. 14, No. 10, October 2008 1521 ", "Methods" ] },{ "paper_id": "bfebea5629eb128672f452ba095d7b2057401410", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c09a10b1d2e8dedabdc06617cff5c3d86b111d18", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Screen-printing technology is a kind of low-cost thick film technology which allows to deposit thick films (a few to hundreds micrometers) and is well suited for mass production and portable devices [10] . They allow both real time and in situ monitoring. For example, disposable screen-printed enzyme strips are widely used by diabetic patients for self-monitoring of their blood glucose levels [11] . Such a microfabrication route offers high-volume production of extremely inexpensive and yet highly reproducible disposable enzyme electrodes.", "Microsensor arrays for glucose sensing were fabricated using photopolymerization of poly(ethylene glycol) diacrylate (PEG-DA) with 2-hydroxy-2-methyl phenyl-propanone as photoinitiator to encapsulate the enzyme GOx using cross-link method. The redox polymer was found to exchange electrons with GOx in biocompatible PEG-DA hydrogels [41] . And other hydrogel was utilized to cross-link the enzyme [42] .", "Nanomaterials have become an extremely popular theme in recent electrochemical sensing research, due to their electrical conductivity, unique structural and catalytic properties, high loading of biocatalysts, good stability and excellent penetrability." ] },{ "paper_id": "c128cbe506d417582e13e50a2028a34d13c6b2fb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All fly stocks were raised on standard corn meal-agar medium supplemented with live baker's yeast. For aging experiments flies were maintained at 25uC on standard corn meal-agar medium but the vials were not supplemented with live bakers yeast. A single fly was maintained in a vial and each vial was tipped on every 1-3 days. Prof. Paul Salvaterra, Stanford University provided w; Cha-GAL4 (19B), UAS-GFP S65T and the tau-lacZ enhancer trap line, 3,358, was obtained from Prof J. Thomas at the Salk Institute [26] .", "Heads were fixed in 4% paraformaldehyde for 4 hours at room temperature, after an overnight dehydration step in methanol they were cleared in BABB for at least six hours. The heads were mounted with a raised coverslip in a small amount of BABB. To achieve maximum fluorescence heads were visualized using the following emission filters: LP650 BP500-530 BP 565-615.", "The efficient bleaching and clearing of Drosophila makes it an ideal organism to be imaged by OPT, and may be of use for other microscopy techniques, and so we specifically show the utility of this procedure for confocal microscopy. Additionally OPT may assist in imaging large numbers of Drosophila lines that express GFP or b-galactosidase reporters. Large-scale genetic screens have dominated Drosophila research for many years. Originally reverse genetics in Drosophila relied upon random P-element insertions that induced mutations [15] [16] [17] . Now mutations can be specifically targeted by homologous recombination [18] [19] [20] or specific gene products can be depleted by expressing siRNAs to genes in specific tissues or cells [21] [22] [23] . Cell or neuron specific gene silencing, driven by GAL4, currently underlies the functional dissection of neuronal networks in Drosophila and relies upon detailed spatial and temporal expression data on the neuronal GAL4 driver lines. Moreover these expression patterns must be referenced precisely and consistently to specific points in the standard Drosophila brain [24, 25] ." ] },{ "paper_id": "c12f447d8fe4cc4602b52a31f1715e0cadedb6a1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "vaccinia and AIDS-associated complications that culminated in death of the recruit 18 months after vaccination.", "In patients without underlying disease, cowpox infections manifest as self-healing diseases. However, in the absence of vaccination and among a population with increased numbers of immunocompromised persons, the risk for human poxvirus infections is increasing. Early diagnosis is essential for differentiating cowpox from illnesses and skin reactions with similar signs and symptoms, such as smallpox, monkeypox, generalized vaccinia virus infection, disseminated herpes zoster and herpes simplex virus infections, drug-associated eruptions, erythema multiforme, enterovirus infections, secondary syphilis, scabies, insect bites, impetigo, and molluscum contagiosum. The oral drug tecovirimat (previously known as ST-246), as well as cidofovir, CMX-001 (an antiviral substance), and vaccinia immune globulin, should be considered for use as postexposure therapeutic treatment for orthopoxvirus disease (10). References 1. Olson VA, Laue T, Laker MT, Babkin IV, Drosten C, Shchelkunov SN, et al. Real-time PCR system for detection of orthopoxviruses and simultaneous identification of smallpox virus.", "Further studies on the epidemiology of MERS-CoV infection among camelids from central Asia are warranted." ] },{ "paper_id": "c135b16e3b78c0c09c16de6287ddb1233acf9bd3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Artiklen beskriver de kliniske, patologiske, serologiske og virologiske fund i kalve fra 2 st\u00f8rre danske slagtekalvebesaetninger i forbindelse med udbrud af alvorlig lungebetaendelse. Kalvene var vaccineret med en inaktiveret vaccine mod bovine respiratorisk syncytial virus (BRSV) to m\u00e5neder tidligere. De kliniske symptomer omfattede nasal fl\u00e5d, feber, hoste og for\u00f8get respirationsfrekvens. I alt 28 kalve d\u00f8de i de to besaetninger. Laboratorieunders\u00f8gelser viste at BRSV var involveret og formodentligt udl\u00f8ste begge udbrud. Ydermere viste resultaterne af de serologiske tests, at vaccinen kun inducerede lave maengder af antistoffer; formodentlig p\u00e5 grund af tilstedevaerelse af maternelle antistoffer p\u00e5 vaccinationstidspunktet. Obduktion af fem kalve viste forandringer typisk for lungebetaendelse for\u00e5rsaget af BRSV. P\u00e5 baggrund af de beskrevne fund kunne det konkluderes, at vaccination med en inaktiveret BRSV vaccine ikke beskyttede kalvene mod alvorlig og fatal lungebetaendelse to m\u00e5neder efter sidste vaccination.", "Bovine respiratory syncytial virus; BRSV; vaccination; enzootic pneumonia; serology, calves." ] },{ "paper_id": "c13a9965ccf255b75e8c2d08b3da78f73e77fbc5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c160b476d630126321658e6cd0d00276af4875d1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Tissue samples were dissected and lysed in 0.5 mL of extraction buffer (0.5% Triton X-100, 5 mM Tris, pH 7.5; 20 mM EDTA, and 100 \u03bcg/mL proteinase K) for 20 min on ice. DNA was extracted twice with phenol followed by chloroform/isoamyl alcohol extraction to remove proteins and residual traces of phenol. The DNA was then precipitated for 24 h in two volumes of ethanol at 20 o C, resuspended in Tris-EDTA (pH 8.0) containing 20 \u03bcg/mL RNase (Takara, China), and incubated at 37 o C for 1 h. The DNA fragments were separated by electrophoresis on a 1.5% agarose gel and visualized under UV light after staining with GlodenView (SBS Genetech, China) staining. The fragments were compared to a 100-bp DNA ladder marker (Tiangen, China).", "Positive was judged as the result was over 0.3 after subtracting the apoptotic ratio (per 0.1 mm 2 field) of control gosling from that of the infection gosling. And the result less than 0.3 was considered negative. Three goslings were tested per time point. So, if there were N goslings judged positive, which was recorded as N/3. ", "At intervals of 0 ", "The experimental group (n = 100) and observation group (n = 30) were orally inoculated with 0.2 mL of a NGVEV-CN strain suspension containing 1,000 LD 50 , while the control group (n = 16) received oral doses of sterile 0.2 mL PBS (0.15 M, pH 7.2) instead of the viral suspension. After infection, the virally-challenged goslings were monitored for clinical signs of disease. The experimental, observation, and control groups were maintained in different isolation units in a bio-secure animal housing building (Sichuan Agricultural University, China) and fed a commercial diet ad libitum. The research was conducted in accordance with the internationally accepted criteria for the care and use of laboratory animal as outlined in the National Institutes of Health guidelines, USA." ] },{ "paper_id": "c164cfe5a21b1f6a0efb61aa0e8bdf34efb93867", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c16fecd2784f334dbf3265085fa2fc4d20ea19ae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c1a03657b225afb8628f4806530db7f57645ad54", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Another distressed transapical sodium transport occurs in injured lungs, for example, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) (please see classical reviewes [47] [48] [49] [50] [51] . Apical ENaC contributes to up to 60% of transepithelial sodium transport in mammalian lungs under physiological conditions. This critical process is sensitive to aspirated pollutants, allergens, pathogens, and bacterial endotoxins. In addition to increased leaking through alveolar microvascular endothelium (indirect ALI), lung edema ususally results from reduced edema fluid resolution via ENaC (direct ALI). ENaC is a promising target for developing new therapeutical strategies to alleviate lung edema, at least for the phenotype of direct ALI 52, 53 .", "CPT-cAMP to activate ENaC. These cell permeable compounds, when applied in vivo or in vitro, will stimulates ENaC activity by both acting as an external ligand to release self-inhibition and as a cytosolic signal molecule to phosphorylate cGKII that subsequently activates ENaC.", "Cyclic guanosine monophosphates (cGMP) are important cyclic nucleotides, playing a critical role in signal transduction in many different organisms 1 . Signal transduction in eukaryotic cells is essential for moderating the transmission of information through the cell membrane, and as a second messenger, cGMP regulates numerous essential processes in cells by amplifying external signals, for example, from hormones and neurotransmitters. Cytosolic cGMP binds to cyclic nucleotide-gated ion channels 1, 2 and phosphorylates protein kinase G (PKG) directly [3] [4] [5] ." ] },{ "paper_id": "c20b07555abfd0ee9bb51260bbbb997f30a95031", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Following an insurmountable number of e-mails and telephone calls, it was recognized that the Toronto critical care community would benefit from regular teleconferences for several reasons. Because SARS was a new illness, a great deal was gained by providing a forum for the [4, 5] .", "As a result, thrice weekly teleconference calls involving critical care clinicians, and invited representatives from public health, infection control, infectious diseases, government, and hospital administration were held. Participants were identified by searching individual e-mail contact lists, personal communication, and announcements to hospital administrators through the Ontario Hospital Association. During the calls clinical information and therapeutic challenges were discussed. In addition, we were able to dispel rumors, clarify media reports, synthesize the barrage of faxes and government directives, answer questions, and support those feeling isolated. The discussions generated new ideas about how to deal with this previously unknown illness, and identified leaders to focus on specific tasks.", "Other communication initiatives included a group of tertiary care intensivists making themselves available to provide 24hour on-call clinical support and advice to any critical care provider. These individuals were available through a government sponsored toll-free line. In addition, software specific to SARS was developed for handheld computers and made available for broad distribution free of charge [7] . Finally, on a more personal level, ICU leaders needed to communicate regularly with critical care staff in quarantine and those who were admitted to hospital with SARS. At many institutions ongoing emotional support was provided to all levels of ICU staff through regular meetings and psychologic intervention [8] ." ] },{ "paper_id": "c26343b1cf5dfc83c01af64179530a7cfa69c5c8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c275276d1cebcac93a5964d79f4b7174ed4afcf9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The specimens were placed in centrifuge tubes filled with gadopentetate dimeglumine (1:50 dilution) and 10% gelatin by weight. MRI was performed using a 1.5T MRI scanner, using a 1-channel loop coil (Signa HDxt; GE Healthcare, Little Chalfont, UK). Imaging was achieved using the three-dimensional (3D) first-spoiled GRASS protocol. The parameters used were: TR, 11.8 ms; TE, 4.1 ms; flip angle, 30\u00b0; FOV, 5 \u00d7 5 cm; matrix size, 512 \u00d7 512; slice thickness, 1 mm. Source images were made available for analysis on a workstation that enabled interactive multiplanar reformatting of the data sets.", "All experimental protocols were approved by our Animal Experimentation Committee. All experiments were conducted in accordance with the Animal Care Guidelines of Shiga University of Medical Science." ] },{ "paper_id": "c289f35b5482b7a6d778503a6360704d59cbc7da", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c2bd5bf1038d976b60d86a81c00d886c1af3c0da", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ethics approval was obtained from St. Jude Children's Research Hospital Institutional Animal Use and Care Committee (Memphis, TN, USA) . Swabs and tissues were tested by RT-PCR, and positive samples were sequenced. ", "The second round forward and reverse primers were to sequence the purified DNA amplicons using a BigDyeR Terminator v3. GenBank accession nos.: KT220528-KT220562, KT368821, KT581588-KT581603. Serology A pseudo-particle neutralization assay was used to test bat serum against MERS-CoV as previously described (5) .", "Viral RNA was extracted by using the Qiaamp viral RNA minikit (QIAGEN, Hilden, Germany). The RNA was eluted in 60 \u03bcL AVE buffer and was used as a template for further detection by a pan-coronavirus nested PCR targeting the RNA-dependent RNA polymerase (RdRp) gene. First-round reverse transcription PCR (RT-PCR) was conducted by using forward primer 5-GGKTG-GGAYTAYCCKAARTG-3 and reverse primer 5-TGYTGTSWRCA-RAAYTCRTG-3 and QIAGEN 1-step RT-PCR kit. A 25-\u03bcL reaction mixture contained 5 \u03bcL of" ] },{ "paper_id": "c35675e5426c3a70835a0ce56c2921b4416f8686", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Disaster response medical simulation approximating actual scenarios enables disaster planners and responders to test procedures and technologies, and to incorporate the lessons learned from past disasters [17] . This simulation has been shown to be effective [16, 18] . The level of realism is much higher than in facility-based exercises, where time and personnel utilization are compressed and usually do not adequately teach disaster resource management.", "Engendering enthusiasm for sustainable disaster critical care response: why this is of consequence to critical care professionals?", "Saqib I Dara 1 , Rendell W Ashton 2 and J Christopher Farmer 3 Taken together, this means that we do not need a major disaster like a terrorist attack or an emerging infectious disease epidemic to tip the strained balance between the supply and demand of critical care resources. Disasters of a local scale alone can tip the balance, such as when a fire broke out at a nightclub in Rhode Island in 2003. The local hospital immediately received 40 critically-ill patients, most requiring intensive care support [14] .", "Pre-emptive education is the single most effective tool we can employ to mitigate the future effects of a disaster. In terms of impact, the education of healthcare professionals is at the top of the list [15] . The educational initiatives we propose to accomplish this goal are as follows: heightened disaster response awareness, enhanced skill sets, understanding of roles and responsibilities, alternate communication methods, self-preservation training, and experience in how to cooperate and coordinate during mayhem." ] },{ "paper_id": "c35f1a6432bd9d7f5bce38e59661f93b1aa13060", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sequences of the 17 mAbs characterized in neutralization and binding studies. Figure S1 showing potential roles of 16F6 combining site residues in the interaction with GP SUDV . This material is available free of charge via the Internet at http:// pubs.acs.org.", "T he ebolaviruses and Marburg virus (MARV) comprise the family Filoviridae of enveloped negative-sense RNA viruses that cause severe hemorrhagic fever. 1\u22124 Based on nucleotide sequence and outbreak location, isolates of Ebola virus are classified into five species: Zaire (EBOV), Tai Forest (TAFV), Sudan (SUDV), Reston (RESTV), and Bundibugyo (BDBV). There are two MARV variants (Marburg and Ravn). Severe human disease, Ebola or Marburg Viral Disease, is associated with EBOV, SUDV, BDBV, and MARV with 30\u2212 90% case fatality rates in large outbreaks. 2 EBOV and SUDV are the most pathogenic among the ebolaviruses, and both have been associated with recurring outbreaks. 5 Among the 13 documented EBOV outbreaks and the six SUDV outbreaks from 1976 to 2012, the average human case fatality rates are 70% and 52%, respectively. Together, EBOV and SUDV have accounted for over 95% of Ebola virus-related deaths; 5 these statistics do not include the ongoing large outbreak in West Africa, which is of unprecedented scope and geographic distribution. 1,6 Many studies have been directed at understanding EBOV entry and inhibition of virus entry with antibodies and other agents; 3,4,7\u22129 however, considerably less is known about MARV and SUDV despite the increasing prevalence of these two species.", "Corresponding Authors *E-mail: john.m.dye1.civ@mail.mil. *E-mail: sachdev.sidhu@utoronto.ca. *E-mail: jon.lai@einstein.yu.edu. ", "PRNT assays with complement were performed using Low-Tox Guniea pig complement (Cedarlane). The lyophilized complement was resuspended with 1 mL of ice-cold water and then diluted 1:18 in ice-cold PBS and filter sterilized. This complement mixture was incubated in a 1:1 ratio with 65 \u03bcL of 2,400 pfu/mL virus stock 37\u00b0C for 1 h (this gave a final viral titer of 1,200 pfu/mL). Vero-E6 cells were exposed to 100 \u03bcL of the virus/antibody/complement mixture at 37\u00b0C for 1 h with gentle rocking every 15 min. The remaining steps were identical to the PRNT assay without complement as described above." ] },{ "paper_id": "c3942c841518e9b2e2097dea7ee813e968000303", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c3cb6dbc8f9856954962672e54253ab8fe627446", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Evaluation of the Stryker T4 Personal Protection System indicated an average removal efficiency of 68% for particles >0.5 \u00b5m in diameter and 54% for particles >5 \u00b5m. This equates to a reduction factor (i.e., particles outside of the hood would be reduced in number by this factor) of 3.1 and 2.2, respectively.", "Policies must be developed that consider all high-risk exposures or emergency situations and not just individual procedures. Policies that are too focused are of little value in dealing with the hundreds of unforeseeable possible situations that may arise. Conversely, policies that educate healthcare workers to assess the risks of a task and empower them to take appropriate protective action will be more effective. These policies should be crafted at each healthcare facility by a team that involves key stakeholders, including persons involved in the clinical response along with infection control practitioners and infectious disease experts.", "The powered air-purifying respirators (PAPRs) most commonly used in healthcare settings have a disposable full hood with face shield covering the healthcare worker's upper body (Figure 2) . This device provides a higher level of protection against airborne infectious agents (any PAPR equipped with a hood or helmet with any type of particulate air filter has an assigned protection factor of 25 [32] ), and it may be faster and easier to apply in an emergency situation. Finally, ensuring that a hospital has adequate " ] },{ "paper_id": "c3d3ee0b012a09d8de42c13d046f42ebd291e76e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We identified a convenience sample of 256 nasopharyngeal (NP) specimens from children younger than 18 years of age admitted with respiratory symptoms between November 1, 2006 and May 31, 2007 . The specimens were obtained by a NP wash or swab based on the admitting physician's discretion. After routine testing by direct fluorescent antibody (DFA) and/or culture for RSV, parainfluenza viruses 1-3, influenza viruses A and B, adenovirus, and rhinovirus, the NP specimens were frozen at -70\u00b0C and later subjected to nucleic acid extraction using the EasyMag system (bioM\u00e9rieux, Durham, NC, USA) and following the manufacturer's protocol with slight modifications. Two hundred microliters of each specimen were pre-treated with 20 units of DNase (New England Biolabs, UK) at 37\u00b0C for 45 min before extraction. Extracts were used as the template for detection of hMPV using the NucliSense real-time analyte specific reagent (ASR) assay performed on the EasyQ instrument (bioM\u00e9rieux). A proprietary internal control containing the same primer binding sites as the hMPV target with unique internal sequences targeted by a separate molecular beacon probe were spiked into each specimen before extraction to monitor amplification integrity.", "Respiratory specimen testing data were linked to patient demographic and clinical data. Laboratory personnel were blinded to the clinical data and the clinical investigator was blinded to the laboratory results. Only the first specimen from which a virus was identified per admission was considered. The c 2 -test was used for analysis of categorical variables, comparing hMPV-positive patients to RSV-positive patients as well as patients who were negative for both hMPV and RSV. The Student's t-test was used for an analysis that compared continu ous variables. Data were analyzed using SPSS version 16.0 for Windows.", "While several studies have shown that hMPV occurs more in older children than does RSV, other reports showed no difference in age predilection, gender predominance, or presence of underlying medical disorders. 23, 36 In our study, the majority of hMPV-positive patients were aged 13-24 months (n=7, 43.8%), whereas most RSV-positive patients (n=35; 71.4%) were younger than 12 months of age (P<0.01). No statistical significance in gender predomin ance was found. The proportion of children with underlying medical disorders was similar across all three groups. Underlying medical disorders considered were prematurity, chronic lung disease, bronchopulmonary dysplasia, asthma, congenital heart disease, congestive heart failure, immunosuppression, immunodeficiencies, hematological and solid organ malignancies, diabetes, and renal failure. We also found that children attending daycare or school were not at increased risk of being positive for hMPV or RSV or for having a respiratory illness not associated with either of these viruses (Table 1) ." ] },{ "paper_id": "c411d679c075271c621362069cea8014264d6c67", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "E pidemiologists are warning against an impending pandemic of avian influenza that could kill several million people (1) . This possibility raises an urgent and thorny ethical question: Are healthcare professionals obligated to care for patients during virulent epidemics of infectious disease?", "As potential participants in the drama and as holders of a duty of care toward healthcare workers, the general public also should be involved in setting limits to duty. Some form of dialogue between the public and the medical profession, through the media, public consultations, and educational establishments, could help establish a mutually acceptable set of limits.", "Daniel K. Sokol*" ] },{ "paper_id": "c43a5466719bd6f3d36d415fdceb244e53d811a0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c4f1924395fe010018f7e83f71f5a0ba744dcf2e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Mean (+/\u2212 SD) pg/ml 1989 (3116) 7907 (26830) 3069 (5567) Median pg/ml 644 2153 866", "a P value was calculated by Pearson correlation test using natural log transformation of the LDH and cytokine concentration values." ] },{ "paper_id": "c50308992db0a3aac3f2624668e5708d221ba230", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Pneumonia is a major global health problem; it kills more children under 5 years of age than any other disease 1. The burden of disease is aggravated by old age, chronic lung disease, immunosuppression and viral co-infection. Secondary pneumonia following pandemic and seasonal influenza virus infection is a significant cause of mortality worldwide 2.", "Neutrophil killing capacity was evaluated as previously described with minor modifications 54. Briefly, neutrophils were isolated through density gradient centrifugation, followed by 45 min incubation with serotype 6B pneumococci (inoculation strain, MOI 100:1), baby rabbit complement (Mast Group, Bootle, UK) and human intravenous immunoglobulin (IVIG; Gamunex, Grifols Inc, Spain). In some experiments, recombinant TNF or CXCL10 (Biotechne) was added.", "Purified blood neutrophils were stored in RLT buffer (Qiagen) with 1% 2-mercaptoethanol (Sigma) at -80C until RNA extraction as above. The single cell immunology v2 kit (Nanostring) was used with 20 pre-amp cycles for all samples. Hybridized samples were prepared on a Prep Station and scanned on a nCounter\u00ae MAX (Nanostring). Raw counts were analysed using DESeq2 using internal normalization, which gave lower variance than normalizing to included housekeeping genes. DEG were identified using a model matrix correcting for repeated individual measurements." ] },{ "paper_id": "c5131e5f5c6000ec84139edc64778a6f1d391b83", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A large multicenter trial is underway to look at the effectiveness of some of these simple measures to reduce transfusion. The role of blood substitutes remains futuristic.", "58 ARDS = acute respiratory distress syndrome; HGMB1 = high mobility group B1; ICU = intensive care unit; IL = interleukin; MOF = multi-organ failure; NDD = neurological determination of brain death; PaO 2 /FiO 2 = arterial oxygen tension/inspired oxygen ratio; SARS = severe acute respiratory syndrome; VAP = ventilator-associated pneumonia.", "Several targets for modulation of the inflammatory response have been identified and are a source of ongoing investigations. One such treatment target is the high mobility group B1 (HGMB1), a nonhistone chromosomal protein.", "Stein has presented these thoughts to deputy ministers in the Canadian government and has received what she interpreted as a less than receptive response. However, Stein provided the audience with a sound argument for the development of an action plan and the notion that the health care sector cannot afford to ignore the 'back up' of systems and human resources -the next time we may not be so fortunate." ] },{ "paper_id": "c54608c457676be2a819a1879a14df08074082d1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c5557ff86a3d5630f341285081a5d39089964ab3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c5d0bce44486081ea768a33f90828d3ef996af07", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c5fa97f3c08e5b88b1081d261c675cf9f0fea73b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "RNA extraction and real-time PCR were performed by following specimen-handling procedures established for Hendra virus (8) and were used to identify shedding patterns after each challenge. After initial challenge, (Table 1) .", "Notwithstanding these limitations, we believe that the alpaca might be a useful model that could greatly facilitate the development and testing of vaccine candidates. We recommend further research and trials to substantiate this potential. Experimental Infection of Alpacas with MERS-CoV", "The animals remained clinically healthy except for a reduced condition score that occurred by day 18 in 1 animal (alpaca 2); no signs of upper or lower respiratory tract disease appeared in any animal. Increased temperature was noted in alpaca 2 during days 17-20, but fever (rectal temperature >39\u00b0C) was not recorded. Gross abnormalities at postmortem examination were found only in alpaca 2 and comprised extensive adhesions of the caudal sac of compartment 1 of the stomach to the umbilicus; clinical findings in this animal were attributed to this lesion.", "We obtained 3 adult female alpacas (Vicugna pacos) from a commercial supplier in Victoria, Australia, and housed them in the Biosafety Level 3 containment facility at the CSIRO Australian Animal Health Laboratory. Before experiments, the alpacas were allowed to acclimatize for 6 days; during this time, intrauterine temperature data loggers were implanted according to a previously published procedure (8) . We found no previous MERS-CoV challenge trial reported in alpacas, so we chose a preliminary dose and rechallenge time on the basis of our experience with other virus infection trials for other emerging infectious diseases (8) ." ] },{ "paper_id": "c60e9faaf8d025d3cf00b275de051fc9bc3b5bd4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Seven germ-free piglets (Groot Yorkshire 9 [Cofok 9 Large White]) were obtained by caesarean section and housed in isolators, fed with sterilized condensed milk till the age of 14 days and thereafter with pelleted feed (sterilized by X-ray radiation) and water ad lib. On day 21, three of the seven piglets were transported to the necropsy room and served as uninfected control piglets.", "With an estimated death rate of more than 400,000 per year, mainly affecting children less than 5 years of age in developing countries, rotavirus is recognized as one of the major infectious diseases of the gastrointestinal tract [38] . Rotaviruses are members of the family Reoviridae, viruses with segmented double-stranded RNA genomes [17] .", "Equal amounts of total RNA (5 lg) were separated on a denaturizing 1% (w/v) agarose gel. After several washes with RNase-free water, the gel was blotted on Hybond-N membranes (Amersham), and blots were hybridized with 32 P-labeled DNA fragments homolog to the mRNA in question, in the same manner as was described in an earlier study [34] . After post-hybridization washes, the blots were scanned using a Storm phosphor-imager (Molecular Dynamics, Sunnyvale, California, USA).", "The same collection of pig probes (ESTs) used in earlier studies [34, 35] were spotted in triplicate on Corning Ul-traGAPS slides. Briefly, this collection consisted of 2,928 probes prepared from jejunal mucosal scrapings collected from 4-week-(672) and 12-week-(2,256) old pigs, probes coding for porcine cytokines (IFN-c, TNF-a, GMCSF, IL-2, 4, 6, 8, and 10) and lung surfactant proteins SFTPA and SFTPD, and 110 Marc1 and Marc2 probes (porcine ESTs) homolog to trefoils, collectins, defensins, and glycosyltransferases [34] . A list of the probes already sequenced/ annotated is accessible on the website of Arch Virol (gene list Hulst et al. pdf)." ] },{ "paper_id": "c6463593f45c19d4989336f52905704d1ec9b74e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Novel respiratory infectious diseases (RIDs) such as severe acute respiratory syndrome (SARS), avian influenza A/ H5N1 and most recently pandemic influenza A/H1N1 represent serious public health threats. For influenzas, antivirals enable treatment of infected individuals and chemoprophylaxis of exposed individuals throughout the first wave until vaccines are developed. Non-pharmaceutical interventions may also delay local transmission and mitigate the impact of local epidemics [1] . Although A/H5N1 is predominantly a disease of domestic fowl [2, 3] and rarely occurs among humans, its very high mortality rate and high potential for mutation to readily transmit between humans remain of great concern. In contrast, A/H1N1 is highly contagious among humans but has in most cases a relatively benign clinical profile and low mortality rate [4] .", "This study utilized data collected in 2006 during high levels of A/H5N1 activity in southern China [39] and during the 2009 A/H1N1 pandemic [40] to test the hypothesized model. Comparing the model in these two different epidemic situations helps to validate the model's robustness under different, but not unrelated circumstances.", "Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. s , where P 0 (i) and P 1 (i) are the observed proportions in the ith category from the by-census data and survey data, respectively Values reported outside the brackets refer to effect size of A/H5N1 sample while values reported inside the brackets refer to effect size of A/H1N1 sample Pearson's correlation with age, which is a continuous variable e T-t test to compare the differences between males and females for H5N1data and H1N1 data (within parentheses), respectively" ] },{ "paper_id": "c64895008556e2b29bdd88524b8be2e54ed5abe9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c657dee5652708f18918e1c24b24d2f98cc1c4af", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The choice of a relatively broad CRI definition was dictated by our interest in interrupting transmission of a wide range of respiratory viruses, which in adults may or may not be accompanied by fever. Also, all respiratory pathogens share a similar transmission mechanism namely aerosol, droplet and fomite spread, although the relative role of these factors may vary between different viruses and in different clinical situations. Other endpoints included adverse effects, measured using a semi-structured questionnaire and adherence.", "We analysed compliance as wearing the mask for >80% of the shift.", "The small number of randomization units along with the small numbers of cases means that estimation of multivariate models would not necessarily converge. In the post hoc multivariable analysis, we could not adjust for all of the factors because of high correlation among some of them." ] },{ "paper_id": "c67b2bd9b0311fefe3b3d7371e01828fb248adfa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c67da0716b299594f705eaae2945f8d1c72b7927", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "LETTERS thrombocytopenia, hepatomegaly, and recent exposure to ticks. Although Amblyomma americanum, the main known vector of E. chaffeensis, has not been reported in Venezuela, Rhipicephalus sanguineus and A. cajennense are abundant in rural areas of Venezuela; their ability to be vectors should be investigated.", "We found a novel Borrelia in bat ticks that is closely related to, but distinct from, the other known species of tick-borne relapsing fever spirochetes in North America. The human health implications of the new relapsing fever group spirochete are not yet known. The willingness of C. kelleyi to feed on humans and the fact that infection with bacteria closely related to true relapsing fever spirochetes occurs in ", "We are grateful to Jacqueline Dawson for providing the DH82 cell lines infected with E. canis and E. chaffeensis. We also thank Guillermo Comach for performing serologic testing, isolation, and PCR techniques for dengue virus." ] },{ "paper_id": "c6a34c64f00ecea47bb8b62a5e0c66dc173cd299", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c6b99ab3de10ff656a6892c41510df092ea76ef4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "SAMN04490241, internal reference IRF0137. RNA was isolated from virus preps in 1:4 supernatant: TRIzol after RNA extraction with cleanup using RNeasy MinElute cleanup kit (QIAGEN).", "ThermoFisher Scientific, Pittsburgh, PA), cell culture supernatants were collected and clarified by centrifugation at 650 \u00d7 g for 10 min at 4\u00b0C. RNA was isolated from cell-culture supernatant using the QIAamp MinElute virus spin kit (QIAGEN) for isolated VEEV particles." ] },{ "paper_id": "c6e964e7a3f4cb45e146546ae2aef10017fe69d4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Here, we report the full coding sequence of rhinovirus C47 (RV-C47), obtained from a patient respiratory sample collected during an acute respiratory illness investigation in Butte County, California, in January 2017. This is the first wholegenome sequence of RV-C47 to be reported.", "family of nonenveloped single-stranded positive-sense RNA viruses. RV-C was first described in 2006 in patients with influenza-like illness, defined as fever of \u03fe38\u00b0C with cough and/or pharyngitis (1, 2) . RV-C has been associated with more severe respiratory illness (3) than have RV-A and RV-B species and is also distinct from RV-A and RV-B in not being culturable by conventional cell culture methods (4).", "Based on the VP1 region, CA-RGDS-1001 shares 96% nucleotide identity (NI) with the only other available RV-C47 VP1 sequence (PNG7254-3947) (GenBank accession number JF519760); CA-RGDS-1001 has \u03fd80% NI with VP1s from other RV-C genotypes. The rhinovirus genome can be divided into one structural (P1-capsid) and two nonstructural (P2 and P3) regions. The P1, P2, and P3 regions of CA-RGDS-1001 share 67 to 79%, 65 to 79%, and 65 to 80% NI with other RV-C genotypes, respectively." ] },{ "paper_id": "c723a1d259891519fd489b94a7ff128f9a5555aa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We propagated the bacteriophages using host bacteria, Escherichia coli and Pseudomonas syringae, and standard culture methods. Concentrations in stock suspensions were 10 8 \u221210 10 plaque-forming units per milliliter (PFU mL \u22121 ).", "We tested four bowl-shaped materials commonly used in wastewater systems: porcelain, PVC, polypropylene, and concrete. The Supporting Information provides further details about the containers used in this study." ] },{ "paper_id": "c776741a382b4b6a00d9deb5f97bc2fb113bef74", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "After a person made a healthcare visit, we simulated the syndrome assigned to the person by using probabilities that reflect the distribution of clinical presentations for inhalational anthrax reported in the literature (25, 26) . Because we considered only respiratory syndromes for surveillance, we varied directly only the probability of being assigned a respiratory syndrome to persons in the prodromal disease state.", "We used records of ambulatory visits in the Norfolk, Virginia, region acquired from the TRICARE health maintenance organization as a baseline onto which we superimposed simulated outbreak records. The data covered the period 2001-2003, and the simulation region included 17 clinical facilities within an \u2248160-km \u00d7 200-km area that encompasses 158 ZIP codes from 2 states. Over the 3 years of available data, 427,634 persons made >5 million visits. We classified the records into syndromes by using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) to syndrome mapping defined by the ESSENCE system (7) and used only 351,749 records for which persons were classified as having a respiratory syndrome. The Human Subjects Panel at the Stanford School of Medicine approved the use of these data for this study. We examined 3 scenarios defined by the amount of spores released: 1 kg, 0.1 kg, and 0.01 kg. For each scenario, we performed 1,000 simulations.", "Results from analyses of additional release scenarios (data not shown) indicated that the trends in sensitivity and timeliness across release amount were mediated to some extent by the number infected. Sensitivity was a nonlinear function of the number of persons infected, with sensitivity increasing more quickly when fewer persons were infected. At a specificity of 0.975, an increase of 10,000 infected persons resulted in a decrease in time to detection of \u22486 hours." ] },{ "paper_id": "c7bc90f329faeba483338d68f8cda2b59506da57", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Author Information: The coordinates and structure factors for the P[14] VP8* structures are deposited in Protein Data Bank under accession numbers 4DRR (apo), 4DRV(with A-type trisaccharide) and 4DSO (with A-type tetrasaccharide). Raw glycan array data are available at www.functionalglycomics.", "Crystallization conditions for P [14] VP8* (13.5 mg/ml) were screened by hanging-drop vapor diffusion using the Mosquito crystallization robot (TTP LabTech) and visualized using Rock Imager (Formulatrix) at 20\u00b0C. The crystals from one of the conditions (30% PEG 1500, sodium acetate trihydrate, pH 4.5) were harvested with the screen condition containing 18% glycerol. To obtain crystals of VP8 * -HBGA complex, VP8 * was cocrystallized with A-type trisaccharide or tetrasaccharide (purchased from Dextra labs), with a 1:52 or 1:46 excess molar ratio of ligand under similar condition as the unliganded P [14] VP8*." ] },{ "paper_id": "c7c4b98517819b787b89bfeee835280593dbf035", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c817b976b111658ac342f938c26c72c0bf1c6e61", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Abbreviations: AIDS: acquired immune deficiency syndrome HIV, human immunodeficiency virus IA: immunoassay IEM: immune electron microscopy IF: immunofluorescence Address reprint requests to:", "The earliest laboratory diagnoses of viral infections were made by microscopy just after the turn of the twentieth century. Animal and egg inoculation were the methods of choice until tissue culture and serology accelerated the field of diagnostic virology during the fifties and sixties. More rapid methods, including electron microscopy, immunoassays, and nucleic acid probes, are now available and influencing laboratory decisions and patient care. This review discusses changes in science and society which have influenced diagnostic virology and how the discipline has responded to these influences.", "What about the future? More rapid and accurate technology can be anticipated, with particular emphasis on polymerase chain reaction enhancement of viral nucleic acid detection [11] . New and more effective treatment, more commercial kits, and better quality control as well as office and home testing can be expected. These changes in turn will set new courses and directions in the laboratory diagnosis of viral infections." ] },{ "paper_id": "c842b8c5487911096f23f2894b690620e511c522", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "T he first case of severe acute respiratory syndrome (SARS) in Taiwan was reported from the National Taiwan University Hospital (NTUH) in mid-March 2003 (1) . An infected businessman returning from mainland China was the source of a cluster of infections involving his family and a physician. Thereafter, a number of sporadic cases or small outbreaks emerged in the following month, mostly imported from abroad.", "This study not only highlights the presence of mild and asymptomatic infection in healthcare workers during a SARS epidemic but also indicates lower antibody response and earlier seroconversion. Controlling this highly infective emerging disease requires meticulous preparation and vigilance by every worker in the emergency department.", "Approximately 30% of emergency department workers without SARS-CoV infection in this study had clinical symptoms and signs similar to those of SARS during this epidemic. These illnesses might have been due to influenza or other upper airway infections; however, differentiating between SARS and other respiratory tract infections in these patients was difficult." ] },{ "paper_id": "c85ac6dc2c53a16be7fcdbb1523954da3e053d25", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The Yates corrected chi-square test and the Fisher exact test were used for comparison of groups.", "F ever is one of the first signs of severe acute respiratory syndrome (SARS) (1-3). Persons with fevers initially attributed to other illnesses have caused outbreaks of SARS in hospitals and the community (1-7). This finding highlights the need for early recognition of cases." ] },{ "paper_id": "c88784fa43f85c65f163931de7eb149e6e6dd8ba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c905423410ad459a067d65c11efbb89fa196d751", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Reprints may be obtained from: Camilla Bj\u00f6rkman, Department of Ruminant Medicine and Veterinary Epidemiology, Swedish University of Agricultural Sciences, P.O. Box 7019, SE-750 07, Uppsala, Sweden. E-mail: camilla.bjorkman@idmed.slu.se, tel: +46 -18671778, fax: +46 -18673545.", "i prover fr\u00e5n kalvar mellan 7 och 84 dagars \u00e5lder och under hela \u00e5ret. Resultaten bekr\u00e4ftar att C. parvum f\u00f6rekommer i svenska mj\u00f6lkkobes\u00e4ttningar och kan ha klinisk betydelse. G. intestinalis var det agens som p\u00e5visades hos flest kalvar, men parasitens betydelse f\u00f6r kalvh\u00e4lsan \u00e4r oklar. Fynden \u00e4r intressanta d\u00e5 b\u00e5da parasiterna anses ha zoonotisk potential. Resultaten styrker \u00e4ven tidigare iakttagelser att rotavirus \u00e4r den vanligaste infekti\u00f6sa orsaken till kalvdiarr\u00e9 i Sverige." ] },{ "paper_id": "c963e012bdc62568b37159f8a60ab687c8489e3c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c96e2b9d86911b1bc2bc67cd49081b64065764c0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c9877ae6ac5465d45291db9429e8e2b0976c8c48", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ca18e923f1cd6532ba1a7f05ca8e2abfa940834a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "If a randomized trial is not considered justified, feasible, or ethical, therapeutic agents of unknown efficacy should not be used without attempts to systematically document illness severity, clinical course, treatment, adverse events, and confounding factors in a standardized manner to facilitate analysis. At a minimum, comparisons of cohorts of patients treated differently may yield information that can inform subsequent trials.", "The initial case definitions for SARS are examples of this problem. Based on the World Health Organization's initial case definition, persons presenting with fever, respiratory symptoms, and an epidemiologically defined exposure are considered to have SARS (14) . This definition is non-specific, as all patients with febrile respiratory illnesses, regardless of etiology, will be included if they have any exposure history. This was particularly problematic in returned travelers with respiratory illness. Because direct SARS exposure was uncommon among travelers, even to high-risk areas, inclusion of travel-related cases in our trial would have resulted in a low positive predictive value for the case definition.", "Due to the unknown size of an outbreak, the use of composite endpoints is a reasonable strategy to maximize the number of observed outcomes and minimize the required sample size, provided every component of the composite endpoint is clinically relevant and can be measured in a standardized manner.", "These agents should be used in the setting of randomized trials, to determine their efficacy and prevent therapies of unknown efficacy (e.g., corticosteroids for SARS) from becoming \"standard of care\" in the absence of good evidence.", "After the SARS outbreak in 2003, thousands of patients were treated with agents of unproven efficacy and definite toxicity; data on these agents' efficacy were not gathered. To prevent this situation from repeating itself, we must be prepared to conduct prospective, randomized controlled trials in the event of future outbreaks of novel pathogens." ] },{ "paper_id": "ca3eeb26589ebc7faeeec6943a4340583d6a467f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ca7208e80e01498b6aa51efded32283f2827a634", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cabbf64c0fcdcb3cfff6df2101a6b8c77c02e4f6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "caf34dc95f513eba16331c99fbe0a1cbf1fe2557", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "S evere acute respiratory syndrome (SARS) is a new infectious disease, first recognized in November 2002 (1) . SARS has spread rapidly around the world: >8,400 cases have been reported from 30 countries on five continents (2, 3) .", "NTUH is a 2000-bed, university-affiliated medical center located in northern Taiwan. The center provides both tertiary and primary care for patients. It was also the primary hospital caring for SARS patients during the SARS outbreak in Taiwan.", "All statistical analysis was performed with SPSS version 10.0 (SPSS, Chicago, IL). Logistic regression was used for univariate and multivariate analysis. Continuous variables were compared with the t test. Categorical variables were compared by using the Fisher exact test. A p value < 0.05 was considered significant." ] },{ "paper_id": "cb42cda59259c534f30ab688560eceec6cc27a7a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Please cite this paper as: Szczawinska-Poplonyk et al. (2013) Fatal respiratory distress syndrome due to coronavirus infection in a child with severe combined immunodeficiency. Influenza and Other Respiratory Viruses 7(5), 634-636.", "Coronaviruses have been demonstrated to contribute substantially to respiratory tract infections among the child population. Though infected children commonly present mild upper airway symptoms, in high-risk patients with underlying conditions, particularly in immunocompromised children these pathogens may lead to severe lung infection and extrapulmonary disorders. In this paper, we provide the first report of the case of a 15-month-old child with severe combined immunodeficiency and coronavirus HKU1-related pneumonia with fatal respiratory distress syndrome.", "Intensive therapy and mechanical ventilation conducted in the Department of Pediatric Anesthesiology and Intensive Care did not contribute to either clinical or radiological improvement and the child died because of multiorgan failure." ] },{ "paper_id": "cb70928ef1e8112feb2a802c88996237f95a524e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acscentsci.7b00104. Molecular cloning, protein expression and purification protocols, protein sequences, and other molecular characterizations (PDF) \u25a0 ACKNOWLEDGMENTS", "From Obligate Dimers to Star Proteins. Having established that AXB and BXA are both very efficient in forming protein catenanes, we further investigated how the introduction of various proteins would affect the catenation efficiency. The protein can be added either to the N-terminus ", "Research Article exclusively as cyclic monomers (\u223c8%). It indicates that the monomeric rings are the major side product in both cases, which could result either from premature ring closure or from the formation of noncovalently associated rings after chain entwining. The catenation efficiency is thus evaluated as the product of dimer contents determined individually from SEC profile and SDS\u2212PAGE. It is (64% \u00d7 92%) for AXB and (96% \u00d7 92%) for BXA, respectively." ] },{ "paper_id": "cbb912f90a472343d8910eb0e4c02b5d8811269c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cbbc88f97eeb4e11fadea3ea628092195e608018", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cbbf2c867d16605a4802dfeea0b9a2b21d8ccb47", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cbe361acc62c98bc529a37614761fe15f49f0f95", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To accomplish the feasibility of targeting and imaging, we used QD605 conjugates having an RNA oligonucleotide for SARS-CoV N protein with an emission wavelength as the optical imaging probe.", "The production of designed RNA oligonucleotide and primer with T7 promoter sequence were synthesized by Bioneer Co Ltd (Seoul, Republic of Korea) and amplified by polymerase chain reaction (PCR). Template RNA was prepared by in vitro transcription using T7 RNA polymerase (Promega, Madison, WI). All RNA transcript products were separated by 8 M Urea 6% polyacrylamide gel electrophoresis (PAGE) after phenol extraction and ethanol precipitation procedures. The produced RNA oligonucleotide was solved in 0.1% diethylpyrocarbonate (DEPC) solution and stored at -70\u00b0C for further experiments." ] },{ "paper_id": "cc2e7594049d91279f4e3d69d27b440ddd8de1f9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The mean values of two groups were considered significantly different if * P < .05, * * P < .01, or * * * P < .001.", "Myofibroblast \u03b1-SMA: \u03b1-smooth muscle actin G3PDH: Glyceraldehyde-3-phosphate dehydrogenase MMP: Matrix metalloproteinase OPN:", "Osteopontin." ] },{ "paper_id": "cc343d904a45985b94b97900c462674c4c8ed237", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cc44d4c57c66a9c62c60fa0e3908462e812987c1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Norepinephrine is the vasopressor of first choice for patients with septic shock, and should be administered to achieve a mean arterial pressure of at least 65 mm Hg after excluding hypovolemia as a cause for hypotension. The selection of a second line vasopressor, such as vasopressin, dopamine, phenylephrine, epinephrine or angiotensin-2, depends on patient factors such as underlying cardiac dysfunction, presence of arrhythmias, and current response to vasoconstrictor or inotropic agents. Dopamine should not be used for renal perfusion or protection and it should be avoided in patients with tachyarrhythmias.", "Sepsis clinically manifests as life-threatening organ dysfunction due to a dysregulated host response to infection. 1 Optimal fluid resuscitation is relevant for all sepsis patients, and perhaps it is most important for those with septic shock. Septic shock is defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greatest risk of mortality, and septic shock is clinically identified as sepsis patients with serum lactate level .2 mmol/L and who require vasopressor infusion to maintain a mean arterial pressure $ 65 mm Hg in the absence of hypovolemia. Sepsis is among the most common conditions in the intensive care unit (ICU), accounting for up to half of all hospital deaths and being the third leading cause of death overall in the United States. 2", "Sepsis and septic shock are medical emergencies for which treatment and resuscitation should begin immediately. The goals of fluid resuscitation for these patients are: a) to rapidly replace intravascular volume and restore tissue perfusion, and b) to minimize organ dysfunction through timely interventions that either halt or reverse the physiologic derangements. If hypoperfusion is present, at least 30 mL/kg of IV crystalloid fluid should be given rapidly, and additional fluids should be guided by frequent reassessment of hemodynamic status, preferably using dynamic indices to indicate the likelihood of a beneficial response to fluid administration. Fluid administration should be targeted to achieve a MAP of at least 65 mm Hg, and to normalize lactate in patients with elevated lactate due to hypoperfusion. 3 Balanced crystalloids are the fluid of first choice for sepsis resuscitation based on ready availability and taking medication costs into account. Use of 0.9% saline compared to a balanced crystalloid, such as lactated Ringer's or PlasmaLyte, produces more kidney dysfunction and with a greater risk of dying. 4 The individual side effect profiles may best differentiate the natural and synthetic colloids. Albumin may be considered for administration to sepsis patients with refractory shock or who have received substantial amounts of crystalloid fluids, but should not be administered to patients with severe traumatic brain injury. 5 Hydroxyethyl starch (HES) products should not be administered to patients with sepsis because of increased risk of acute kidney injury and death. Gelatin solutions are not recommended in sepsis." ] },{ "paper_id": "cc50f83beb4dae7f0a60291c3e1d4868d0884c5a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Total RNA extraction. Total RNA was extracted from the leaves of PVX-infected or non-infected N. benthamiana using the easy-Blue RNA extraction kit (Intron, Republic of Korea) as directed by the manufacturer's instructions.", "Preparation of PVX-infected plant material. A pSPVXp31 binary vector, containing PVX full-length cDNA, was kindly provided by Dr. Kim from Seoul National University, Seoul Korea (Park and Kim, 2006 ). An Agro-infiltration method previously described by English et al. (1997) has been applied for PVX infection to Nicotiana benthamiana. After two or three weeks, the treated-leaves were collected from healthy and diseased plants.", "Using the Maxime TM RT-PCR PreMix Kit (iN-tRON Biotechnology, Korea), an one-step RT-PCR reaction was conducted. The mixture was incubated at 45 o C for 30 min and denatured at 94 o C for 5 min, followed by 30 cycles of 94 o C for 30 sec, 50.7 o C for 30 sec and 72 o C for " ] },{ "paper_id": "cc698ffabf545da2fd7ee6a5cb4f25d9102a856a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "First, the editorial board of eCAM is one that is diverse, and to ensure one aspect of creativity, many of us have never worked together, thus allowing for the infusion of different points of view. Our first purpose in establishing the eCAM editorial board has been to gather a mixture of experienced biomedical scientists and to combine them with newcomers from a variety of fields who are willing to embrace CAM and to extend themselves beyond their better known academic classifications or 'pigeonholes'. As one of our bases is in Japan, our search for diversity began in Asia at biomedical conferences and research centers in Japan,", "Finally, despite these examples of diversity in numbers, geographical origins and disciplines and scientific approach, there is the difficulty of reconciling the very nature of CAM with certain realities, i.e. the palpable need to undergird CAM with evidence-based results that can, through rigor, occupy the pinnacle of the experimental triangle devoted to immunological benefits as proposed by Goldrosen and Strauss (24) . For, as has been pointed out in previous editorials, there is a need for rigorous science if CAM and indeed eCAM are to be taken more seriously, thus ensuring less skepticism from its adherents and disciples and also from the traditional medical establishment and pharmaceutical industry. Now and in the near future, eCAM is discussing ways to consider seriously case reports, not the ideal within an acceptable scientific context. An excellent example devoted to Alzheimer's disease has led the way (25) ." ] },{ "paper_id": "cccc6d4345633099ad5574b4bbe23727e0e5edd0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cd12db30cf8d039ec120a0766259d9311d9a466d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cd492bb5d19539c9666aaa080e941f1e6e35f923", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Immunological methods. These are widely used methods based on an application of specific antibodies targeting proteins or carbohydrate moieties unique to the pathogen. Such methods include agglutination test, ELISA, and Western blot analysis. Immunoassays are very sensitive but require special conditions for the storage and handling of antibodies to prevent their denaturation.", "HIV-1 can also be inhibited by aptamers directed to nonviral targets. For example, human cyclin T1 (CycT1) together with cyclin-dependent kinase 9 (Cdk9) are the components of positive transcription elongation factor b (P-TEFb), which activates viral transcription after interaction with Tat protein.", "Microbiological method (isolation, growth, and microscopy of pathogens from clinical samples). This method, although highly specific, has several limitations. First, the method requires at least 24 h incubation of the pathogen culture. Second, some microorganisms cannot easily grow in culture (for example, Mycobacterium tuberculosis). The application of this method for the identification of viruses is even more restricted due to the small size of viral particles which cannot be studied by conventional optical microscopy and requires the use of electron microscopy for visualization." ] },{ "paper_id": "cd69df65ac1b519f8032fcc29c7c2506094e0fcf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cd72303957519f8ec6ea7df1d21c1fd6c330fe90", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Since 1994, when the isolation of Brucella spp. from marine mammals was reported for the first time, such infections have been detected in a wide range of marine mammal species and populations. The pathologic role of marine Brucella spp. in animals remains unclear, as does their zoonotic potential. In 2003, two human cases of community-acquired granulomatous central nervous system infections caused by marine Brucella spp. were reported (32) .", "Information and communication are key components in any prevention and control strategy. Public education and behavioral change are also important factors for successful intervention. Implementing restrictions on anthropogenic animal movement is another important preventive measure. For vector-borne zoonoses, vector control should be an integral part of any intervention strategy.", "Dr. Kruse is the head of the Norwegian Zoonoses Centre and a deputy director at the National Veterinary Institute, Norway. Her research interests include the epidemiology of zoonotic diseases and antimicrobial resistance.", "A good example of a zoonotic agent with many different transmission modes is F. tularensis. Rodents and hares constitute the main sources of infections, and hunters are at particular risk of acquiring the disease. The transmission mode also affects the clinical manifestation in humans. The agent can be transmitted by direct contact through the handling of an infected carcass and through tick or mosquito bites, which cause initial skin symptoms such as ulcers. Infection may also occur after eating insufficiently cooked meat from an infected animal or contaminated drinking water, causing symptoms from the digestive tract, and by inhalation of contaminated dust, causing a pneumonialike illness.", "Recognition and emergence of human tickborne ehrlichiosis are recent and continuing events, beginning with human monocytic ehrlichiosis and human granulocytic ehrlichiosis, reported first in the United States in 1987 and 1994, respectively. The causative agents, Ehrlichia chaffeensis and Anaplasma phagocytophilum, are intracellular bacteria that are maintained in zoonotic cycles involving persistently infected deer and rodents (30) ." ] },{ "paper_id": "cdb29ec7a9029d22f6fbf7ee04543819591acdc2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cdb6748d297a7329b905186e48611af6d932b62f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The follicular route", "An excellent review on the use of liposomes and similar vesicles for mucosal and transcutaneous vaccination purposes has recently been published and the reader is referred to there for further detail (Lilia Romero and Morilla, 2011) .", "Despite the great potential of barrier disrupting techniques they also raise concerns as the vital skin barrier is weakened more or less temporarily which may open the door for the invasion of pathogens. Also, some of the techniques mentioned require expensive equipment. Both points will have to be considered especially for mass vaccination campaigns in developing countries with poor hygiene standards and low funds." ] },{ "paper_id": "cdbf113c93f807ee1853027325c17d3d00dd871c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cdcd1d3772530b841701af3e7c01226fed60655a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To determine the relationship of ABVV to other rhabdoviruses, a phylogram was created based on the amino acid sequence encoded by the nucleoprotein (N), polymerase (L) gene, as well as the five gene concatenated alignment. The deduced amino acid sequences were aligned using Mafft 5.8 (6) with the E-INS-I alignment strategy and previously described parameters (4, 7) .", "Purified viral RNA was amplified with random primers using the TransPlex Whole Transcriptome Amplification kit (Sigma-Aldrich) according to manufacturer's instructions. The resulting shotgun libraries were sequenced using 454 pyrosequencing with GS FLX+ Titanium, as well as Solexa Illumina sequencing. A total of 100 thousand pyrosequences and 13.5 million Illumina sequences were generated. Sequences were trimmed and those sharing at least 95% nucleotide identities over 35 bases were assembled into contigs (3). Assembled contigs were compared to the GenBank non-redundant protein database using BLASTx with an E-value cutoff of 10 \uf02d4 (4)." ] },{ "paper_id": "cdfa82e974f1631bc2e4afb8132180ee84bc4b5e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ce40c2d0956a6167604ab1a0955fd47f22b55111", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ce4796d011abc721c271d969b7f3802e263a80b0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For real-time PCR, amplifi cation primers WU-TAB02-F 5\u2032-TGTTGCATCCATTTGTTACATTCAT-3\u2032 and WU-TAB03-R 5\u2032-GAAAGAACTGTTAGACAAATATATAG-GCCTTA-3\u2032 and the minor groove binder probe WU-TAB04-pro 5\u2032-6FAMATGTCAGCAAATTCMGB-NFQ-3\u2032 were used with a commercially available universal TaqMan real-time PCR master mix and ABI 7500 Real-Time Thermocycler (Applied Biosystems, Foster City, CA, USA). All WU polyomavirus-positive specimens were screened for 17 additional viruses (infl uenza A and B; RSV A and B; PIV 1-4; human metapneumovirus; adenovirus subgroups B, C, and E; rhinovirus; and coronaviruses OC43, 229E, and NL63) by using the EraGen MultiCode-PLx respiratory virus panel as described previously (1) .", "The 3 oldest patients positive for WU polyomavirus in this cohort were immunosuppressed. They included a 12-year-old with Evans syndrome and a 15-year-old with severe combined immunodefi ciency syndrome (both postbone marrow transplant) and a 14-year-old with end-stage renal disease and asthma.", "WU polyomavirus is a recently described polyomavirus found in patients with respiratory infections. Of 2,637 respiratory samples tested in St. Louis, Missouri, 2.7% were positive for WU polyomavirus by PCR, and 71% were coinfected with other respiratory viruses. Persistent human infection with WU polyomavirus is described.", "Each clinical specimen was assigned a code. Collection of clinical data was approved by the Washington University Human Research Protection Offi ce. Pertinent demographic, historical, and clinical information, when available, was collected by using a standard collection form. Statistical signifi cance was determined by using 2-tailed Fisher exact \u03c7 2 tests with Epi Info software version 3.4 (Centers for Disease Control and Prevention, Atlanta, GA, USA ) Seventy (2.7%) of the 2,637 tested specimens were positive for WU polyomavirus; 71% of the positive samples were also positive for >1 other respiratory virus. Of the 70 positive samples, 5 were omitted from analysis because of chart unavailability. The remaining 65 samples were collected from 60 individual patients (5 specimens were serial samples associated with distinct clinical syndromes in 2 immunocompromised patients)." ] },{ "paper_id": "ce964d964ab6d20bf9ba948f00f613084d10b6de", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ceabb750f6de4f2e3527db125ed62b4528ac958e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cf085d7780e024e54db7c45b4ca64900e5713a5e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cf2af5e2c7b504fe693f5d5a70c42bf97ed4faec", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Results from the outcome studies could provide evidence for efficacy and might be used to design more future comprehensive studies.", "There was no significant change in different parameters of the renal function test (sodium, potassium, urea creatinine) and liver function test (total protein, albumin, total bilirubin, alkaline phosphate, alanine transaminase) during the study period. All these parameters were generally within the normal range both before and after study.", "Publish your work in this journal " ] },{ "paper_id": "cf3640a2e06457c47beac679ac651bc69f7c9521", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The aim of.this suy was to dete if common commeial cosmetic prd&coaning mal oil could induce arthrtis in th higWy suseptbe DA (DarkAgouti) rat", "All rats were followed for at least 1 month after initial treatment.", "Examination for autoantibodies was performed without knowledge of the treatment given.", "Histology. Ankle joints of Natusantreated animals (ID) were fixed in 4% phosphate-buffered formaldehyde and decalcified with 14% EDTA in 0.36 M NaOH for 4 weeks. After dehydration, clearing, and impregnation, the tissues were embedded in paraffin blocks, sectioned, and stained with H&E." ] },{ "paper_id": "cf692fd14d468eaca2c460132802463f0747411e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cf811730e853bc23b3ce2978034940208bfa37f5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In January 2001, a 27-month-old girl was admitted to an upstate New York area hospital for a 5/6 human leukocyte antigen-matched cord blood transplant from an unrelated donor. The patient had been born by normal vaginal delivery after 40 weeks of gestation. Her medical history included leukocytosis at 3 months and splenomegaly at 6 months of age. Refractory juvenile myelomonocytic leukemia was diagnosed when she was 16 months of age, and she underwent splenectomy in September 2000. She had multiple infections before 2 years of age, including otitis media, a central vein catheter infection, and a urinary tract infection. She also demonstrated failure to thrive, developmental delay, mild pulmonic stenosis, and gastroesophageal reflux.", "Multiple segments of the WUPyV genome were amplified and sequenced by using overlapping primer sets ( ", "Lung tissues were fixed in formalin and then postfixed in 2.5% glutaraldehyde/0.1 mol/L Millonig phosphate buffer before processing into epoxy resin for sectioning and film photography. Microscopic examination was performed with a Hitachi 7100 transmission electron microscope (Hitachi High-Technologies Science America Inc., Northridge, CA, USA)." ] },{ "paper_id": "cfd6f06653c31766de27f2b499d1557c82ba1733", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Other possible contributors to the high rate of false positives include contaminated viral transport media or applied topical preparations, such as emollients to the neonates' nares. Aliquots from all infant nasopharyngeal specimens were provided to the RRADT manufacturer without personal identifying information for validation and verification; testing of these specimens was conducted by the manufacturer, and the hospital laboratory RRADT results were replicated." ] },{ "paper_id": "cfe0fc219225651d68cd409b66bfe522f6482403", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cff0235863f34320b1b684ee7b3469900d0576cf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The plasmid was amplified in and purified from Escherichia coli competent cells using standard plasmid preparation protocols. The purified plasmid was linearized overnight by SmaI restriction endonuclease (New England BioLabs) at 25\u00b0C. RNA was transcribed from the linearized plasmid with T7 High Yield RNA Synthesis Kits (New England BioLabs), with 1 \u03bcg of plasmid per 20 \u03bcL reaction mixture. After transcription mixtures had been incubated for 12 h at 37\u00b0C, 5 \u03bcL of 100 mM EDTA was added to stop reactions. A sample with 15 N-and 13 C-labeled rGTP and rUTP (Sigma-Aldrich) was synthesized with a similar protocol.", "The authors declare no competing financial interest.", "We thank the following individuals for their contributions to this work: Prof. Marty Serra for synthesizing r(GU-GAAUUUAC) 2 " ] },{ "paper_id": "d01690bafbc4c042dd47c6aa77801b56071493d2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "By sequencing of M2 gene, we confi rmed that almost all Japanese ORVs belonging to clade 2B retained sensitive genotype to M2 inhibitors, consistent with previously reports that recent clade 2B viruses are sensitive to M2 inhibitors, but clade 2C viruses are resistant (27) .", "The chemiluminescent NA inhibition assay was per-Emerging Infectious Diseases \u2022 www.cdc.gov/eid \u2022 Vol. 16 formed by using the NA Star Kit (Applied Biosystems, Tokyo, Japan) with slight modifi cations of the instructions provided by the manufacturer. The fi nal drug concentration ranged from 0.03 nmol/L to 6,500 nmol/L for oseltamivir and from 0.03 nmol/L to 12,500 nmol/L for zanamivir. Chemiluminescent light emission was measured by using an LB940 plate reader (Berthhold Technologies, Bad Wildbad, Germany). Drug concentrations required to inhibit NA activity by 50% (IC 50 ) were calculated by a 4-parameter method using MikroWin 2000 version 4 software (Mikrotek Laborsysteme GmbH, Overath, Germany).", "The phylogenetic tree of NA and HA1 genes was constructed by neighbor-joining methods. The phylogenetic tree was described by representative ORVs and OSVs isolated from several prefectures in Japan. Sequence information for isolates from other countries was obtained from the Global Initiative on Sharing Avian Infl uenza Data and the Los Alamos National Laboratory database. All amino acid positions in the phylogenetic tree were described by N1 numbering." ] },{ "paper_id": "d01a3aa9bfabf76255cad83bb3aef2e5773f2d1c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This atmosphere of concern motivated an intense effort to develop new surveillance methods (6) . Public health officials are now augmenting traditional disease surveillance, e.g., laboratory-based methods, with nontraditional analysis of electronic medical records for more timely monitoring of infectious disease patterns. The Centers for Disease Control and Prevention (CDC), along with many health departments, universities, and government organizations, has participated in research and development of syndromic surveillance systems. Some of these systems have been designed for local surveillance in a single metropolitan area, while others cover broad geographic areas, including multiple jurisdictions (7, 8) .", "Emerging Infectious Diseases \u2022 www.cdc.gov/eid \u2022 Vol. 13, No." ] },{ "paper_id": "d02034376ac45efa3806785215aa2d9619c7abfa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "At the time of collecting blood, respiratory specimens, or chest radiographs, surrogate specimens (venipuncture tube containing water, water-moistened swabs, and archival chest x-ray, respectively) were substituted by the accompanying study observer. Surrogate blood and respiratory specimens were followed to the laboratory, where infection control practices were observed until specimens were sent to the reference laboratory for molecular testing.", "The critical importance of effective PPE in hospital infection control was demonstrated during the outbreak of SARS in 2003 (10) (11) (12) (13) (14) . Nosocomial transmission of SARS was a prominent feature of the epidemic (15) and played a large role in the initiation and maintenance of outbreaks. As reported in a case-control study by Seto et al. (13) , staff who used masks (in particular), gowns, and performed hand hygiene were less likely to become SARS infected than those who did not. Similarly, Lau et al. (14) noted that inconsistent use of PPE by HCWs working on wards with SARS patients in Hong Kong was associated with a signifi cantly higher risk for nosocomial disease transmission. Provision of adequate PPE stock is therefore likely to be important in controlling the spread of API.", "of current stockpiles. This study aimed to estimate the resource needs that a hospital might face in the fi rst few hours of management of a single patient who sought treatment with possible avian or pandemic infl uenza (API) or similar highly virulent respiratory infection.", "Detailed observations were collated on infection control practice, clinical resources used, sequence of donning and removing PPE, time spent by the patient in each clinical area, and close contacts and exposures generated. The observation period could be stopped at any time if an actual patient's care was judged to be compromised by continuation of the simulation." ] },{ "paper_id": "d03888523e81c821f95247b544bdfac0c94a8b0c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d050ed9690b0179835dca97985ab7ef2c843f230", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Based on these initial analyses, we believe that further work is indicated to investigate the impact of anthropogenic landscape changes on mosquito distribution and accompanying arbovirus infection.", "Mosquito-borne infections cause some of the most debilitating human diseases, including yellow fever and malaria, yet we lack an understanding of how disease risk scales with human-driven habitat changes.", "(n = pool size, k = number of infected mosquitoes, p = infection probability). For each negative pool, we estimated the probability that no mosquito in the pool was infected as" ] },{ "paper_id": "d0610fbc985c67974c9182498173b3b91c176072", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Using clinical samples from patients with severe acute respiratory syndrome, we showed that the sensitivities of a quantitative reverse transcription-polymerase chain reaction (80% for fecal samples and 25% for urine samples) were higher than those of the polyclonal (50% and 5%) and monoclonal (35% and 8%) antibody-based nucleocapsid antigen capture enzyme-linked immunosorbent assays.", "We compared the detection rates of 2 ELISAs and realtime qRT-PCR using the McNemar test and studied the correlation between the optical density values at 450 nm (OD 450 ) of the 2 ELISAs and log 10 viral concentrations, as determined by real-time qRT-PCR, by linear regression (SPSS version 11.0, SPSS Inc., Chicago, IL, USA). A p value <0.05 was regarded as significant.", "SARS-CoV can be detected during the late phase of illness. Since SARS-CoV cannot be readily isolated from SARS patients after week 3 of illness (14) , the detection of SARS-CoV beyond this time may be due to prolonged shedding of nonviable viruses in these patients or the presence of neutralizing immunoglobulins in clinical specimens, which has prevented viral replication in cell cultures." ] },{ "paper_id": "d07a12c15f26f94f6b1d0fc1ab61730140e8c7d2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "HSPA8 motifs 2 (nt 620-624) and 3 (nt 669-673) are located in an unstructured single-stranded region forming the internal loop (nt 612-625, nt 662-674) of a hairpin preceding the GFP sequence ( Figure 4A ). Importantly, the GFP sequence base pairs independently (Supplementary Figure S2) .", "The assay was repeated twice. In three wells on each plate, cells were transfected with a negative control siRNA (NT, siCONTROL Non-Targeting siRNA #2, Dharmacon D-001210-02).", "Here, these are referred to as HSPA8-binding motifs 1, 2 and 3, respectively.", "Host DNA topoisomerase 1 (TOP1) facilitates EBOV genome transcription and replication (33) . In the case of retroviruses, such as human immunodeficiency virus-1 and Rous sarcoma virus, TOP1 interacts with their viral genome through a genomic RNA stem-loop, suggesting that the TOP1-viral genome interaction directly regulates transcription and replication (34) (35) (36) . Whether a similar interaction occurs with EBOV remains unclear, although, EBOV NP and L genes both contain a potential TOP1 target sequence (TCCTT) (33, 37) ." ] },{ "paper_id": "d086f62864fb6b39416bad3b5a969668b1791acb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The invasion threshold is easily found in our model. Extending result (1b) above, the pathogen invades if dI/ dt > 0, or", "Feline calicivirus (FCV) is an RNA virus of domestic cats. A large variety of FCV strains is known to circulate concurrently, with sequence divergence in the variable region of the capsid protein gene ranging as much as 50% between strains ). Virulence varies among isolates, from asymptomatic to highly virulent, the latter being as high as 50% mortality (termed VSD strains, for 'virulent systemic disease'). Multiple strains often circulate within a local cat population. Vaccines are available, but vaccination neither prevents viral infection nor prevents viral replication within a cat, so it appears that cross immunity among strains is only partial .", "As an aside, the lack of 'escape' mutants capable of infecting immune hosts is puzzling, as both viruses have RNA genomes, which are thought to be prone to rapid evolution. Furthermore, three antigenically distinct polioviruses are known (and each is included in the vaccine), yet no others have evolved in response to vaccine pressure (Macadam et al. 2006 ). These two viruses highlight the point that, contrary to common perception, some parasites may not be able to adapt to altered environmental conditions.", "The addition of recovery does change the interpretation of the preceding model somewhat. The derivations above remain the same, but the d term (now denoted d\u00a2) is no longer just host mortality. Instead, the d terms are replaced by d\u00a2, where" ] },{ "paper_id": "d09b79026117ec9faebba46a8d13aa9b23ec751e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Human adult brain library 10\u00d796 well plates with 100 cDNAs per well and Gold TNT SP6 ", "To confirm the interaction with p62's UBA domain, the final resulting individual proteins were used in the coupled TNT/p62 UBA pull down assays. The cDNA inserts were sequenced in the Genomics Core Facility at Auburn University and the sequences were compared with known sequences in NCBI database by BLAST analysis.", "In addition to the important role in recycling of amino acids from damaged or misfolded proteins, ubiquitin-protein conjugation also has functions unrelated to proteasomal targeting. For example, polyubiquitination is required for the internalization of several yeast and mammalian cell surface proteins into the endocytic pathway (15, 16) . Interestingly, p62 appears to sequester ubiquitinated substrates into a cytoplasmic structure referred to as a sequestosome, into which excess ubiquitinated proteins are segregated (17) . In addition, p62 is an immediate early response gene product for a variety of signals (18) . Thus, p62 appears to play a novel regulatory role for polyubiquitinated proteins and may have an essential function in cell proliferation and differentiation. We have developed a method that will enable identification of protein(s) that interact with p62's UBA domain." ] },{ "paper_id": "d0c33264c3dc13c6c5f3a3d83bdde246bdc82165", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A new parvovirus, human bocavirus (HBoV), was dis-", "Because most continuous data were skewed (by Kolmogorov-Smirnov test), they were analyzed by using regression analysis and generalized linear models after logarithmic transformation. Logistic regression analysis was used for categoric data. Statistical analyses were conducted by using SAS/STAT(r) software version 9.1.3 SP4 (SAS Institute Inc., Cary, NC, USA)." ] },{ "paper_id": "d0e1735b8e1aa2448475c0e317ad01cac96f0701", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We found 5 cases of histoplasmosis complicating an allogeneic HSCT in the English literature [1] [2] [3] [4] [5] . The pertinent case details are summarized in Table 1 along with our patient. Both disseminated and isolated pulmonary infections were reported between 5 weeks and 18 months posttransplantation. All 4 patients with reported outcomes died. A notable common feature of most cases including ours is the recent receipt of corticosteroids for GvHD treatment.", "Per the 2007 Infectious Diseases Society of America management guidelines for histoplasmosis, treatment is not recommended for asymptomatic pulmonary nodules [12] . However, we chose to treat in this case because there was evidence of active inflammation on histology and PET scan, because the patient had an altered immune system after HSCT, and because of the dismal prognosis of histoplasmosis in this patient population (Table 1) . Because monitoring of itraconazole levels in the patient's home country was difficult, the choice of voriconazole treatment was made after establishing levels of 1-2 \u03bcg/mL before discharge.", "Keywords. allogeneic; Histoplasma; histoplasmosis; pulmonary; transplantation." ] },{ "paper_id": "d12482c6be35334fcb33c74a2f0740b230d8c32e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cotton swabs were weighed before and after collection to determine virus titers per 100 mg nasal secretions. Swabs from both nostrils were suspended in 1 ml of phosphatebuffered saline supplemented with 10% fetal bovine serum, 100 IU/ml penicillin, and 100 lg/ml streptomycin and mixed vigorously at 4\u00b0C for 1 hour. Tissue samples were weighed and ground in PBS containing 10 IU/ml penicillin and 10 lg/ml streptomycin to obtain 20% (w/v) tissue homogenates. Nasal swab samples and tissue homogenates were clarified by centrifugation (16 000 g for 3 minutes) and stored at \u00c070\u00b0C until titration. All samples were titrated on Madin-Darby canine kidney (MDCK) cells in serum-free medium with trypsin. Briefly, confluent monolayers of cells were inoculated with 10-fold serial dilutions of samples. Cells were washed 2 hours after inoculation and subsequently observed for development of cytopathic effect over 7 days. Virus titers were expressed as log 10 50% tissue culture infective doses (TCID 50 ) per 100 mg (nasal swabs) or per gram (tissues).", "Nasal virus shedding in each group was quantified by calculation of the area under the curve (AUC), which is obtained by plotting viral titers versus each time point of sample collection. Samples that tested negative for virus were given a numeric value of 1\u00c16 log 10 TCID 50 per 100 mg or gram. Samples that tested negative in the serological assays were assigned a value corresponding to half of the minimum detectable titer. Mann-Whitney tests were used to compare virus titers and antibody levels between any two experimental groups. P < 0\u00c105 was considered statistically significant. GRAPHPAD PRISM 5.0 software (GraphPad Software, Inc., San Diego, CA, USA) was used for all analyses." ] },{ "paper_id": "d12f22eb235332248406e89f3badacc97a0c2cbc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data was collected on demographics, bat cave-associated activities, contact with bats, bites and scratches from bats and the use of bats for food, medicinal or ritual purposes. An exposure to bats was defined as a bite or scratch from a bat or circumstances such as direct skin contact with a bat, bat urine or guano.", "Quantitative data from questionnaires were recorded using EPI INFO version 5 (2), and imported into Microsoft\u00ae Excel. Subsequent analysis was performed using R statistical software version 3.0.2 (3). Categorical variables were analyzed using Chi-square or Fischer's", "The study site was divided into four areas based on the major roads. Social centers in each quadrant were identified, and every other adjacent house starting from the social center was marked and respondents were interviewed using structured questionnaires. Respondents were from 13 years and above." ] },{ "paper_id": "d1501d93b454fa850a635ceed555f5266bc1db6a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d1e1e8dba793fcab2ab717c2b9e34009768a699c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Imiquimod (1-(2-methylpropyl)-lH-imidazo [4,5c] quinolin-4-amine) has a structural formula indicative of a novel compound.", "Imiquimod (1-(2-methylpropyl)-lH-imidazo[4,5c]quinolin-4-amine) has a structural formula indicative of a novel compound." ] },{ "paper_id": "d1e4a15d8ddab3043d3727443599a6ab43765bd3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d20952c61aec1485523305c6c24fb757b5c27dba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d21c15c55bc1ec4daa906cdd848ad037e20c925c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(2) to identify through network analyses the multilocus genotypes (MGs) that most closely resemble those that were first introduced into California, using historical samples collected around the time when P. ramorum was first identified in Californian forests;", "Keywords Emergent forest disease \u00c1 Genetic epidemiology \u00c1 Microsatellite \u00c1 Coalescent analysis \u00c1 Network analysis Peter J. P. Croucher and Silvia Mascheretti contributed equally to this paper." ] },{ "paper_id": "d22dce4d19758350089a8bca54f25e5b602e58b7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d24c57228f54ec5f1ac1f075a265eff7b80b8b71", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d283e04661726366d5eb583ddbb927d630d89852", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d2e50891500031a482f95969c3657a6ef253b22a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d2f5ff7d542090b94032fa81f1e22ec4c3c4ffef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The mode of transmission of SARS is unclear, but evidence suggests it may be spread by large-and mediumsized droplets spread within 3 feet (5, 10) . Some studies show use of any mask was associated with lower odds of infection in healthcare-related clusters (10) .", "Sixty-six healthcare workers (65%) reported that the patient was coughing during one or more patient-worker interactions. Of these, 40% had at least one exposure without a respirator and 52% had at least one without gown, gloves, and eye protection. Eleven (11%) reported interaction with a patient who had active diarrhea, and 1 (1%) reported exposure during patient vomiting (Table 4) . Healthcare procedures with high potential to generate droplets and aerosols were infrequent: 5 healthcare workers (5%) reported manipulating an airway, (i.e., performing endotracheal intubation or suctioning), and 4 (4%) reported being present during administration of aerosolized medications (Table 4) .", "Data were entered into Microsoft Access and statistical analysis was performed with SAS version 8.2 (SAS Institute, Cary, NC). Univariate analysis was performed by using two-sided Fisher exact or Mantel-Haenszel chisquared test, as appropriate. A p value of <0.05 was considered significant." ] },{ "paper_id": "d2fc91c08f376138ab8783e627db3f2e27d8c796", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d32e506b9bb4c99bc79e4231c0db5f2581bf8a17", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d349613c2d95360358af0b2c3d576e9ad21dd0c5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d36eb475d88c70eea0f81e38a0aa0811f91b2dc3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In the previous issue of Critical Care, Salluh and colleagues [1] suggested evidence-based recommendations for corticosteroid therapy in community-acquired pneumonia. Corticosteroids have been used as an adjunct therapy for severe infection for roughly half a century. Contrasting with the clinical practice, researchers are continuing to argue the pros and cons of this therapeutic approach [2] .", "The use of corticosteroids for the treatment of community-acquired pneumonia has been reported for almost 50 years. A recent systematic analysis of the relevant literature suggested that corticosteroids reduce the critical illness associated with communityacquired pneumonia. There is little doubt that a prolonged administration of a moderate dose of corticosteroids may alleviate the systemic inflammatory response and subsequent organ dysfunction in severe infection. Whether these favorable effects on morbidity may translate into better survival and quality of life needs to be addressed in additional adequately powered randomized controlled trials.", "In theory, corticosteroids may favor the onset of gastroduodenal bleeding, superinfection, metabolic disorders, and muscle weakness. A recent systematic review on the use of corticosteroids for severe sepsis and septic shock, however, failed to show any evidence for an increased risk of bleeding, superinfection, or neuromuscular weakness, whereas hypernatremia and hyperglycaemia occurred more frequently in treated patients (D. Annane, personal communication). It is important for physicians to implement preventive measures and to perform daily screening for possible complications. A specific surveillance of potential sites of superinfection and control of blood glucose and serum sodium levels should be systematically performed." ] },{ "paper_id": "d3a675bfc74c8ebef84c248dca0b8cc05f5b3ce1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For categorical data we used the Chi-square test to compare distributions. To compare mean values between groups we used paired t-test and analysis of variance (ANOVA).", "Refer to Web version on PubMed Central for supplementary material. " ] },{ "paper_id": "d40e933624cc2b3006d8998924d79e103cf06fe0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d4147c3df65fb378821ec21f5171668cdd76ceae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The chi-square test was used for intergroup comparisons of differrent age groups in specific virus groups. The results were analyzed by using SAS software (version 8.2, SAS Institute, Cary, NC).", "The study was supported by the Academy of Finland, the Pediatric Research Foundation, and the Foundation of Jalmari and Rauha Ahokas.", "Typical of the situation in Finland, a minor RSV epidemic occurred during the spring of 2000, followed by a major epidemic during the winter of 2001 to 2002 ( Figure 2 " ] },{ "paper_id": "d450fc8885843d48772df9a898552302f8c80b98", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We are working to eliminate this issue in future versions of the software.", "The sequencing analysis pipeline uses the DNA and protein signature pipelines", "The intermediate quality simulated draft is consistent with error rates for draft sequencing cited in the literature (1,3) ." ] },{ "paper_id": "d45eca08453374762035363feb89e80b414f6105", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The inflammation of lung tissue, secondary to radiation therapy, is localised in the tissue within the radiation field and depends on the interval since completion of treatment.", "Although the patient had no history of bird exposure, serum precipitins against pigeons were elevated. To resolve this paradox, an open long biopsy was performed. Histology demonstrated interstitial pneumonia with lymphocytes, plasma cells and foamy macrophages in the interstitium. Epithelioid granulomas without caseation were also seen. There was no fibrosis (Fig. 3c) .", "A 56-year-old woman with increasing dyspnoea.", "A 46-year-old man presented with a 1-week history of progressive dyspnoea. He also complained of a cough and the production of white mucus in the morning. He reported a smoking habit of one pack of cigarettes per day with no further information regarding his past smoking history." ] },{ "paper_id": "d46d2f01a570bfb6e3b2e65ec50972d1649b6a3d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We saw a variety of chest x-ray changes in these patients (Tables 3 and 4 ). The primary abnormalities were Cough ", "From March 13 to May 5, 2003 , we identified all epidemiologically linked patients whose disease met the Centers for Disease Control and Prevention's case definition of SARS issued on April 29, 2003 (2) . Initial investi-gations included a complete blood count (with a differential count), serum biochemical measurements (including electrolytes, renal and liver function values, creatine kinase, and lactate dehydrogenase), and a chest x-ray. Since the cause of the virus was not known at the onset of the outbreak, routine microbiologic cultures of sputum, urine, and blood were done to rule out common bacterial causes of pneumonia. In addition, mycoplasma serology and urine Legionella antigen testing were carried out. When reverse transcriptase-polymerase chain reaction (RT-PCR) kits for coronavirus detection became available, later patients also provided samples for RT-PCR.", "Probable SARS was diagnosed in 14 patients and healthcare workers at National University Hospital. The median age of the patients (five men and nine women) was 58 years (range 21-84). Detailed patient characteristics, including background, medical histories, symptoms, and signs, are shown in Tables 1 and 2 ." ] },{ "paper_id": "d47bd477b5abdf117bc2e03d5ddfba990fc21e1b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We thank Ernest Gould for the extensive time he took to provide guidance and insight with this paper. We additionally thank Gordon Burleigh, Susan Perkins, and Susanna Remold for providing thoughtful comments. We thank the NSF library for all their support during this endeavor and especially the NSF librarians, Maura Mullins, and Brock Temanson without whom we could not have accomplished this exhausted literature search." ] },{ "paper_id": "d4bff180d69fcc96bc31299183a498820fbca3ea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study was supported by USDA CRIS project 6040-32000-072.", "The mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture.", "Data availability. The complete genome sequence of the GA/1359/1994 isolate of the ArkDPI-like strain has been deposited in GenBank under the accession number MN566147. The raw data were deposited under SRA accession number SRR10742607, BioSample number SAMN13020879, and BioProject number PRJNA556282." ] },{ "paper_id": "d4fa60c6535f776f6350942c3636069ed04b2771", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A major determinant of outbreak dynamics is the ecologic cycle of the virus and its vector. This cycle in Reunion probably follows a denguelike model characterized by the absence of an animal reservoir and the ability to spread rapidly among humans through peridomestic mosquito bites. We suspect that direct transmission to healthcare workers may have also occurred in diseaseendemic countries, but it was not identified.", "In January 2006, a 75-year-old female patient (patient 4) returned from Reunion with a sudden-onset fever, asthenia, arthralgia with wrist pain, and diarrhea. Two days later, blood specimens were collected at the patient's home by a 60-year-old female nurse (patient 5). At this time, patient 4 had high fever (temperature 40\u00b0C). Three days later, fever, skin rash, and arthralgia with pain at wrist pressure developed in the nurse. Interview and examina-Emerging Infectious Diseases \u2022 www.cdc.gov/eid \u2022 Vol. 12, No. 10, October 2006 tion did not show recent travel abroad, mosquito bite, accidental skin puncture during blood sampling, skin lesion, or eczema. The nurse washed her hands with a hydroalcoholic solution before and after drawing blood, but she did not wear gloves. She noted direct contact with patient 4's blood during hemostasis.", "A 1,044-nt sequence of the E1 gene was used for comparative genetic analysis of sequences from Indian Ocean CHIKV and reference strains from diverse geographic and temporal origins (23) . Indian Ocean strains formed a sublineage that is closely related to but distinct from viruses belonging to the East/Central African evolutionary lineage ( Figure 3 ). The E1 nucleotide sequences of the 4 CHIKV isolates from 2006 (GenBank accession nos. DQ451149-DQ451151) were 100% identical, while ranges of 2.1%-3.3%, 14.8%-15.8%, and 5.5%-6.4% of nucleotide divergence were observed when compared with isolates from Central/East Africa, West Africa, and Asia, respectively.", "In 1 year, >250,000 persons have been infected by a new CHIKV variant on the Indian Ocean islands. Although major differences in the fitness or virulence of CHIKV may be associated with minor genetic differences, the most likely explanation for this devastating outbreak is the penetration into a region where the population is immunologically naive for CHIKV and where Ae. albopictus proliferates. As this outbreak has spread, we believe this type of outbreak could occur in other regions of the world where competent vectors are prevalent. Because of high viremia, the virus could also be directly transmitted to healthcare workers. We must be prepared for the possibility of similar arboviral epidemics in such places. " ] },{ "paper_id": "d5448306c493aaa77174e9140427688e0f9c1824", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d58be1bc0e9893f61c4fb1f2fa632821ecfac98d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d5cfc9cea824e7282fc781c7295d0cbeed69dd1c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d5e52547df25abfc489429e1cd693f5c70876de9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d6186af12acb48dec863ecc4ec38450630e32807", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ethical approval (018 \u2044 2004) was granted by the Research Ethics Committee of the Faculty of Health Sciences, University of Cape Town, South Africa." ] },{ "paper_id": "d624310854291e71dfd4af21d00cc0406d52c7a3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "tries had reported 8,098 probable cases of SARS and 774 deaths (2) .", "We observed that the time from symptom onset to admission decreased during the outbreak (data not shown).", "Our findings in regard to treatment are nonspecific. Proven treatment options must await proper clinical trials in other centers.", "The mean age of SARS patients was 40.8 years (median 43, range 20-76 years) and 39 (62.9%) were female. A detailed description of the epidemiology of the SARS outbreak in Vietnam will be published separately." ] },{ "paper_id": "d6303899bb27b192349eb8f8a8f5498cdc963ccd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d64ec639ed9aee0bbfb01e5fbeaeb8c88c6d810e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Toxin profiling was by PCR detection of the toxin A (tcdA), toxin B (tcdB), and binary toxin (cdt) genes (7, 8) .", "Samples were cultured directly onto cycloserine cefoxitin fructose agar and incubated anaerobically at 37\u00b0C for 48 h. The swabs were then inoculated into a Robertson's cooked-meat selective enrichment broth and incubated anaerobically at 37\u00b0C for 7 days; spores were then selected by alcohol shock (1:1 with anhydrous ethanol). The spores were then cultured onto cycloserine cefoxitin fructose agar with 0.1% taurocholic acid added. Putative C. difficile colonies were subcultured onto prereduced blood agar and identified by Gram stain, characteristic colony morphology, and smell.", "In vivo virulence was assessed by using a mouse model of CDI (12) . Specifically, 6-8-week-old male C57/B6 mice (5 mice per strain) were force-fed 1 \u00d7 10 7 spores of the same C. difficile strains used in the Vero cell assays. Mice were housed in separate cages to avoid cross-contamination and monitored daily for weight loss and signs of disease." ] },{ "paper_id": "d66d18ad33170f29a2279d8cc4ca3e31bdee67f0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Good agricultural vaccines provide protection from disease despite lack of a close antigenic match between the vaccine and circulating strain and reduce the virus load below the level of transmissibility. They do not provide sterilizing immunity: vaccinated birds may excrete low levels of virus after challenge infection. Sentinel unvaccinated birds are kept in each house to monitor for virus shedding, antigenic drift, or both.", "Early detection and aggressive control measures allowed Japan, South Korea, and Malaysia to eradicate H5N1 virus soon after its introduction into those countries' poultry flocks, demonstrating that rapid and determined responses can keep the virus from gaining a foothold. In other countries in Asia, delayed detection and response caused the virus to become entrenched across a wide region, and eradication at this stage has become a formidable undertaking.", "I nfluenza is an ancient disease that has infected humans at irregular intervals throughout recorded history (1) . While the 1918 \"Spanish\" influenza is the best recorded catastrophic influenza pandemic, similarly severe pandemics occurred earlier, when the human population of the world was much smaller, and they will occur again. Our challenge is to understand all aspects of the influenza virus, the hosts and their response, and the virus' global impact so that we may be better prepared to face the inevitable next influenza pandemic." ] },{ "paper_id": "d6a5a00ad9468ae27a3a1c7cc33c2131297fbaa9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Enzyme-linked immunosorbent assay (ELISA) for serum \u03b1-D3 IgGs", "The titers of serum \u03b1-D3 IgGs were measured by indirect ELISA, as described previously. 29 Briefly, 96-well microtiter plates (Nalge Nunc International, Rochester, NY) were coated with 1 \u00b5g/well of the E. coli-expressed recombinant D3 protein, and blocked with 10% (w/v) skimmed milk in bicarbonate buffer. Serially diluted antisera and horseradish peroxidase (HRP)-conjugated rabbit anti-mouse IgG (1:4000; Sigma-Aldrich, St Louis, MO) were added to wells, followed by HRP substrate. After 20 minutes of incubation at room temperature, the reaction was stopped by adding 1 N sulfuric acid, and the absorbance was measured at 450 nm (OD450) using a microplate reader (Bio-Rad Laboratories, Redmond, WA).", "submit your manuscript | www.dovepress.com" ] },{ "paper_id": "d6a8375529a761648f605f507786e218d0bd558a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For each dog tested, data was collected regarding age, sex, breed, nature of diarrhoea (haemorrhagic or nonhaemorrhagic) and CPV vaccination history and recorded accordingly. The data was analysed using SPSS version 23 and was subjected to Chi-square test at confidence level of 95%.", "The authors declare no conflict of interest." ] },{ "paper_id": "d6bc3b70f8ee04ee9bb00e4aa98c89c4290b125a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In ", "pneumonia 2015 Volume 6", "Most swabs (n \u0441\u03ed\u03ef\u03f3 \u03f5\u03f0\u0358\u03f1\u0439\u037f \u01c1\u011e\u018c\u011e \u0189\u017d\u0190\u015d\u019f|\u011e \u0128\u017d\u018c \u0102\u019a \u016f\u011e\u0102\u0190\u019a \u03ed organism ( (Table 3) ." ] },{ "paper_id": "d6f24e997f0b166dba199b275aaeb5d1f4f6c44c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dr. McDonald is a medical epidemiologist in the Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention (CDC). He led both CDC teams that assisted in the investigations in Toronto during the SARS 2003 outbreak.", "To facilitate the complicated process of donning and removing personal protective equipment, officials developed videos, computer presentations, and posters to train and remind healthcare workers. In addition, changes in shift duration and rearrangement of nursing stations in SARS wards were needed to minimize lapses in infection control. However, as mentioned, even with fully protected healthcare workers, SARS transmission continued among patients, precipitating the second outbreak phase in Toronto. Glove use outside the immediate care environment was not recommended, but officials needed to emphasize the importance of removing gloves and washing hands after leaving SARS areas to prevent contaminating the environment or infecting patients.", "Emerging Infectious Diseases \u2022 www.cdc.gov/eid \u2022 Vol. 10 ", "In contrast, experiences with SARS in the United States and several other countries have not shown similar super-spreading patients or events despite opportunities for transmission (12) . The reasons for such variable communicability are uncertain but may be due to innate characteristics of infected patients (13) , high virus concentrations in secretions during peak illness (8) , or exposures to aerosolgenerating procedures such as intubation or positive-pressure ventilation (10) . Because these procedures are considered high risks for SARS transmission, guidelines were developed that emphasize use of PPE and, if needed, furlough for healthcare workers with unprotected exposure to these procedures (14) ." ] },{ "paper_id": "d7011047894121dc7f115cbeb1f355b76c33f80d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Primary cell culture of bovine [108] [109] [110] , ovine and porcine [111] origin has exhibited susceptibility to FMDV from infected tissues. However, the most sensitive culture system for virus isolation is primary bovine thyroid cells [109] but cryopreservation of bovine thyroid cells directly after trypsinization results in the loss of susceptibility to FMDV [110] . Some stable cell lines, like IBRS-2 [112] , MVPK-1 clone 7 [112, 113] , LFBK cell line and Veterinary Medicine International 5 BHK-21 [114] are also susceptible to FMDV and so are most desirable for diagnostic system but these are less sensitive than primary cells for detecting low amount of infectivity [115] .", "Revenson and Segura [116] reported that FMDV grew well on BHK-21 cell line enabling large-scale production of antigen with good complement fixing properties. The BHK-21 cell culture provides better growth for FMDV than the suspension culture [115, 117, 118] . It has also been reported that with subsequent passage in BHK-21 clone 13 cell line, the titre of FMDV increased significantly [108] . Nair [112] reported that the susceptibility and infectivity titers of IBRS-2 and MVPK cell lines were less as compared to BHK-21 cells, and thus had no advantage over BHK-21 cell line for vaccine production. Mishra et al. [119] also adapted FMDV field isolates to BHK-21 clone 13 cells in 3-7 serial passage.", "Veterinary Medicine International 3", "In 1929, Ciuca was first to use CFT for typing antiserum and FMDV of guinea pig origin [13] . Later, virus of bovine origin was successfully typed by CFT using guinea pig antiserum [23] . Since then CFT has been used extensively for distinguishing different strains of FMDV [24, 102, 103] . Subsequently, a modification of CFT, micro-CFT was developed, in which 96 well microtiter plates were used instead of tubes [104] . In the years 1964-1965 CFT (tube test) was used to replace the virus type identification by guinea pig cross-protection test [105] . Subsequently, the micro-CFT was adopted for this purpose [106, 107] . Although CFT was a fast method it needed high virus load and results were sometimes affected by pro-and anticomplementary activities of the test sample [26] .", "The distinction among mutants of the same virus is becoming increasingly necessary in view of the extensive variation among representatives of most virus groups [207] , the quasispecies population structure of RNA viruses and some DNA viruses [208] , and the increasing recognition that one or a limited number of mutations in a viral genome can have a profound effect in its biological behavior [209, 210] ." ] },{ "paper_id": "d754e10693704ae712d206a81db8c7e68037ebc9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "However, pandemic preparedness plans should guard against all possibilities of spread. This would include the possibility of a 2 nd or 3 rd wave, the absence of effective vaccines, and increased infection rates for high-risk sub-populations such as HCWs. We assumed that sufficient treatment doses are available as planned in current prophylaxis strategies, because prophylaxis is always over and above stocks available for treatment. This may necessitate having 100% treatment coverage for all HCWs.", "Policy makers must also consider additional preventive measures in addition to antiviral drugs. Public health and infection control measures must be emphasized together with anti-viral use, and not superseded by treatment or prophylaxis strategies.", "given by Mills et al (3) . The equation is reproduced below, using our chosen notation for growth rates, and latent and infectious periods:", "Figures A5 to A10 reinforce the fact that for pandemics of shorter durations, shorter durations of prophylaxis are effective because they are sufficient to cover most of the pandemic's duration. It is during these pandemics (shorter duration and high peak absenteeism) that the impact will be greatest and where prophylaxis strategies will be effective." ] },{ "paper_id": "d785df22b7e40dd293869c502877d0af4e5b1821", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d7c1bff961955e099a23dd51fd2a7734069bd942", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "a The results were determined by analysis of cloned sequences; + represents that nucleotide substitution at the variant site is detected and -represents that the nucleotide at the site is identical to the one of BJ01 reference sequence in all analyzed sequences. b SARS, severe acute respiratory syndrome; SW, throat swab; PL, plasma; SP, sputum; ST, stool. c The numbers represent the ratio of reference to variant nucleotide detected at the site from the analyzed cloned sequences.", "RNA extraction was performed in a biosafety level 3 (P3) laboratory. RNA was extracted directly from plasma samples. Sputum samples were shaken for 30 min with an equal volume of 1.0% acetylcysteine and 0.9% sodium chloride, followed by isolating supernatant by centrifuging (10,000 g x 3 min). Throat swab and stool samples were", "In conclusion, we report here some new variant sites in the S gene of SARS coronavirus and possible existence of SARS-CoV quasispecies in some patients, though in limited numbers. This knowledge furthers our understanding of this emerging virus." ] },{ "paper_id": "d7f5e5abde02015d22f7738d6db889db53fe5863", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d80a7090ab5c8141c7dbedb3b8bf302b1bdcee40", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In conclusion, we suggest that an accurate NGSbased prediction requires an integrative approach to all relevant information obtained by in silico analysis of a given genome locus. In particular, not only presence of CRISPR spacers but also presence and location of potentially interfering IS6110 insertion(s) should be considered for correct NGS-based assignment to internationally recognized spoligotypes.", "of drug resistance. However, knowledge of strain genotype is no less clinically and epidemiologically relevant. A superspreading strain might be marked with other pathobiologically important features. In the case presented here (indeed emerging and MDR), the NGS-based in silico spoligotyping would confuse the MDR/extensively drug resistant SIT266 with \"less dangerous\" SIT264. To be precise, the revealed discrepancy is not inherent to the NGS technology itself. Although the general limitation of the use of short sequencing reads to infer repetitive genome regions is known, it did not pose a problem in our study. However, both bioinformatics tools predicted the spoligoprofile solely from the presence or absence of spacer sequences and did not take into account a \"hiding\" effect exerted by a putative IS6110 insertion on adjacent spacer under classical spoligotyping.", "The herds were located at a distance of \u2248200 m from each other within the barn complex and were cared for by the same animal workers, who lived in a common house between the herds at the complex. Both the alpacas and camels were kept as hobby animals." ] },{ "paper_id": "d81ae79ebc6462fd3de075e220992f1aae1f06ae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Corda also provides a handy SARS worldwide infections/ recoveries/deaths time line graph ( Figure 2 ). The graph allows users to visually monitor and appreciate the epidemic's progress at a glance.", "However, according to Monmonier, it is not just easy but also essential to lie with maps. The cartographer's paradox is that to avoid hiding critical information in a fog of detail, the map must offer a selective, incomplete view of reality [22] . Map users always need to be alert for \"lies\" that can range from legitimate and appropriate suppression of some details selectively to help the user focus on what needs to be seen to more serious distortions in which the visual image suggests conclusions that would not be supported by careful epidemiological analysis. Sound epidemiological and statistical principles and methods should provide the foundation for all data analyses to be displayed on maps [23] .", "Location-based services draw heavily on geoinformatics, blending information about a person's location with other useful content to provide relevant, timely and local information to consumers when and where they need it [14] .", "it has become evident that carefully planned and designed maps can be very powerful decision support and spatiotemporal analysis tools [10] . In the case of infectious disease epidemics, they allow public health decision makers, travellers and local populations at risk to visually monitor and appreciate at a glance changes, trends and patterns buried in large datasets that are continuously varying with time (like SARS datasets -see below). This kind of support is vital for making well-informed decisions when designing and following up epidemic control strategies or issuing and updating travel advisories.", "The maps were created with ESRI ArcIMS, a GIS-driven Internet map server, and feature a handy toolbar that provides the sort of functionality found in the standard ArcView GIS desktop interface (e.g., zoom in, zoom out, pan, identify, measure, etc.)." ] },{ "paper_id": "d83a2c20f409e7be9dbe6e9c8c62ddaf2b506c48", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In conclusion, the epidemic of a new infectious disease, SARS, took firstly China and subsequently many other areas in the world completely by surprise. In the end, the consequences of this epidemic in terms of people afflicted and economic loss were not entirely catastrophic. Also, it turned out that SARS could be controlled relatively easily through standard interventions. However, the epidemic revealed some important weaknesses in the Chinese public health system, which has been dealt with efficiently by the Chinese government. At this point in time, China is better prepared than ever for epidemics, which may very well be worse than SARS in terms of speed of spread and number of deaths. As a matter of fact, SARS can justly be seen as a wake-up call.", "Second, there were long-term health consequences for those former SARS patients who were treated with corticosteroids. Lv et al. investigated the relationship between avascular osteonecrosis (AVN) and corticosteroid treatment given to patients with SARS through a longitudinal study of 71 former SARS patients (mainly HCWs) who had been treated with corticosteroids, with an observation time of 36 months. 22 Magnetic resonance images and X-rays of hips, knees, shoulders, ankles and wrists were taken as part of the post-SARS follow-up assessments. Thirty-nine per cent (39%) developed AVN of the hips within 3-4 months after starting treatment. Two more cases of hip necrosis were seen after 1 year and another 11 cases of AVN were diagnosed after 3 years, one with hip necrosis and 10 with necrosis in other joints. In total, a staggering 58% of the cohort had developed AVN after 3 years of observation. The sole factor explaining AVN in the hip was the total dose of corticosteroids received, which ranged from 1000 to 10 000 mg for the majority of cases, but was as high as 25 000 in some cases. 22 The use of corticosteroids as well as other drugs (e.g. rib- Lessons learnt and actions taken in China regarding epidemic preparedness", "SARS was caused by a novel coronavirus that was provisionally termed SARS-associated coronavirus (SARS-CoV). 3, 4 The earliest cases of SARS occurred in mid-November 2002 in Guangdong Province, China. SARS was first recognised in February 2003, when cases with an atypical pneumonia of unknown cause began appearing among hospital staff in Guangzhou, China. Within weeks, similar outbreaks occurred in Hanoi, Hong Kong, Toronto, Singapore and Taiwan. Soon thereafter, cases were reported from 32 countries and regions (later corrected to 29). After July 2003, SARS came under control thanks to enormous efforts made by national and international organisations. More than 8000 cases were reported worldwide, with over 5000 from mainland China, making the country the epicentre of the outbreak. 5 During the SARS outbreak in China, epidemiological and clinical information was obtained in difficult circumstances. The available data were only to a limited extent analysed and reported, and mainly in Chinese literature. There was a need for good documentation, accessible to the international scientific community. The first step in the collaboration was to integrate all existing Chinese SARS data into one final database. 6 With this comprehensive nationwide database it was possible to perform in-depth studies and dissect the SARS epidemic in mainland China, answering many questions that up to now were only studied in part or not at all.", "There were many obvious immediate consequences of the epidemic, such as substantial morbidity and mortality, fear for becoming infected, panic in the public domain, stringent quarantine measures, travel restrictions, etc. Also two important middle and long-term consequences of the epidemic were identified. First, there was the economic impact. This was studied for Beijing by Beutels et al. 21 through associating time series of daily and monthly SARS cases and deaths and volume of public train, airplane and cargo transport, tourism, household consumption patterns and gross domestic product growth in Beijing. It was concluded that especially leisure activities, local and international transport and tourism were affected by SARS, particularly in May 2003. Much of this consumption was merely postponed; but irrecoverable losses to the tourist sector alone were estimated at about US$ 1.4 billion, or 300 times the cost of treatment for SARS cases in Beijing." ] },{ "paper_id": "d84f1c9036052ca0d9f8216cac4c5118ad8cea19", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "soybean meal) and 12.9 + 0.6 days (organic soybean meal).", "The relative stability in feed may be the result of variable protein, fat, or moisture content among ingredients. Overall, the mean half-life for ASFV in all animal feed ingredients was 12.2 days.", "African swine fever virus is transmissible through animal consumption of contaminated feed. To determine virus survival during transoceanic shipping, we calculated the half-life of the virus in 9 feed ingredients exposed to 30-day shipment conditions. Half-lives ranged from 9.6 to 14.2 days, indicating that the feed matrix environment promotes virus stability." ] },{ "paper_id": "d8716057edc20cdcb232b1ce062ff2804bfd041d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data was expressed as mean \u00b1 SEM. Statistical analysis was performed with Student's t-test for data from MTT Proliferation assay, AO/PI staining assay, and flow cytometry. Differences were considered significant at P<0.05.", "NDV strain was propagated in allantoic fluid of 9-11 days-old embryonated chicken eggs at 37 \u00b0C for 48 hours. The allantoic fluid was harvested, and the presence of virus was confirmed by the haemagglutination test (Alexander,1988) . NDV strains AF2240 purified as previously described .", "When cells were viewed under fluorescence microscopy, it was observed that untreated cells had round intact nuclei and stained green indicating viable cells whereas the treated cells stained green and exhibited features of apoptotic cells, which had irregular shaped nucleus, shrinkage, condensed chromatin and cell membrane blebbing (Chan et al., 2006) ." ] },{ "paper_id": "d8932d954c612d2ef0220a53943c24e7b0920dac", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Our data should help design future clinical trials. A source control arm should be included in tests of mask and respirator effectiveness.", "The first series of experiments were performed with no masks on either manikin. This defined \"Maximum Exposure\" (Max Ex) reported as the percent of nebulized particles captured (i.e., inhaled) by the receiver.", "Aerosol exposure to the Receiver was quantified by placing a filter (model No. 041B0522; Pari, Starnberg, Germany) within the Receiver manikin, which captured all inhaled particles (Figures 2 A,B,C) . All inhaled gases and particles passed through the mouth to the filter via sealed tubing. No ventilation passed through the nose." ] },{ "paper_id": "d8a0a04161c4ee9b42ffddb705b21ab539098447", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Thin-section electron microscopy showed the typical features of intracellular CoV particles. Cells were engulfed with viral particles localized in cytoplasmic vesicles ( Figure 3A ). This feature is typical of all Coronaviridae viruses that bud intracellularly at membranes of the intermediate compartment between the endoplasmic reticulum and the Golgi complex, whereas newly assembled virions reach the cell surface by vesicular transport (16) . After the extracellular release, virus particles were found in large clusters adjacent to the plasma membrane, as evidenced in Figure 3B . Overall, the ultrastructural analysis documented that SARS-CoV cultivated in Vero cells behaved like a typical coronavirus, characterized by intracellular budding (Figure 3, panels C and D) .", "To have the most effective quantitative assay of virus infectivity and to compare the infectious titer with quantitative molecular assays, we optimized a plaque assay (determining the PFU/mL). Confluent Vero cells in 6 well plates (Falcon) were incubated in duplicate with 1 mL of PBS containing 100 \u00b5L of SARS-CoV HSR1 viral stock in 10-fold serial dilutions from -10e2 (1/100) to -10e8 (1/100,000,000). After 1 hour of incubation, the viral inoculum was removed and 1 mL of 1% carboxymethylcellulose (Sigma Chemical Corp., St. Louis, MO) overlay with DMEM supplemented with 1% fetal calf serum was added to each well. After 6 days of incubation, the cells were stained with 1% crystal violet (Sigma) in 70% methanol. The plaques were counted after being examined with a stereoscopic microscope (SMZ-1500, Nikon). The virus titer was calculated in PFU per milliliter.", "A n outbreak of atypical pneumonia, referred to as severe acute respiratory syndrome (SARS), was identified in the Guangdong Province of People's Republic of China at the end of 2002 and spread to other Asian countries and Canada (1, 2) from February through March 2003. Individual cases (all in persons infected in Asia) were diagnosed in Europe during the same period (3) . A novel human coronavirus (SARS-associated coronavirus [SARS-CoV]) has been isolated from the oropharyngeal specimens of patients with SARS (4, 5) . Experimental infection of macaques has confirmed that the SARS-CoV is the cause of SARS (6, 7) ." ] },{ "paper_id": "d8b36980251bf7abdc4d17ff7ef4baf1899f0540", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CMV reactivation was modeled as a time-dependent indicator defi ned as any antigenemia or positive PCR value, or antigenemia >10 cells per slide or >100 copies/mL by PCR. Neutropenia was modeled as a time-dependent covariate set to 1 when the absolute neutrophil count was <500 cells/mm 3 . When values were missing, the indicator for the previous day was carried forward. Lymphopenia was modeled similarly with 2 thresholds, 100 and 300 cells/mm 3 .", "Combined nasopharyngeal wash (or swab) and oropharyngeal swab samples were collected weekly beginning 1-2 weeks before transplantation until day 100; then every 1-3 months for \u22641-year after transplantation from allogeneic HCT recipients enrolled in a prospective surveillance study approved by the Institutional Review Board at Fred Hutchinson Cancer Research Center (Seattle, WA, USA) (22) . Participants provided written informed consent. Additional specimens were collected when respiratory symptoms were reported. Patients had \u22651 specimen collected during January 2006-December 2007. Participants completed surveys weekly for 1 year and reported any of 11 respiratory or 4 systemic symptoms. Clinical and laboratory data were obtained from medical records.", "Two other human polyomaviruses, BK and JC, cause mild or asymptomatic primary infections early in life, followed by persistent, subclinical infections in healthy persons (14) (15) (16) . However, these viruses can reactivate, primarily from the kidney, bone marrow, and lymphoid tissue, and cause serious disease in immunocompromised patients (14) (15) (16) . Similarly, reactivation of KIPyV and WUPyV from lymphoid tissue was described among immunosuppressed persons with AIDS, although clinical consequences of reactivation were not examined (17) ." ] },{ "paper_id": "d8ba6ed1922432420ce26e3be1fd1f97dbbb5f71", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d90a211ef31ec56091a8c30bb8ee39e9f07ca755", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d911768dd0b8ffceaa878966a9196a26eda89e42", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "SARS coronavirus injected intratracheally into chickens, turkeys, geese, ducks, and quail, or into the allantoic sac of their embryonating eggs, failed to cause disease or replicate. This finding suggests that domestic poultry were unlikely to have been the reservoir, or associated with dissemination, of SARS coronavirus in the animal markets of southern China.", "Domesticated poultry species are major commodities traded in the animal markets of southern China. Poultry have been shown to be reservoirs for H5N1 and H9N2 avian influenza viruses that have crossed over and caused infections in humans from 1997 to 2003, some with fatal outcomes (12) (13) (14) . Therefore, poultry should be examined as potential hosts for infection and amplification of SARS-CoV to determine any potential role they may have played during the emergence of human infections in southern China.", "To determine if SARS-CoV could grow in avian embryos, 9-day-old chicken eggs and 13-day-old turkey embryonating eggs were inoculated by allantoic sac route and 17-day embryonating turkey eggs were inoculated by yolk sac route; all were tested by virus isolation and realtime RT-PCR for SARS-CoV. All laboratory procedures and animal studies were conducted in biosafety level 3 agriculture (BSL-3AG) (15) facility with HEPA respiratory protection and barrier clothing procedures for personnel. General care was provided in accordance with the Institutional Animal Care and Use Committee." ] },{ "paper_id": "d931ca4a427c3ecfdc8608bc404a8a09c21d3bdc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "At the community level, signals were being recognized and reported from multiple sources. The most frequent EBS reporters were VHWs, teachers, community members, traditional healers, veterinarians, and representatives from industrial complexes (Figure 7) . Reported events included multiple suspected avian influenza poultry die-offs and human outbreaks of chickenpox, mumps, and foodborne disease.", "Thus, only a relatively small proportion (25%) of VHWs respondents were able to complete the survey, which might have limited the representativeness of some of the survey findings.", "A training of trainers workshop was conducted for the Regional Institutes and pilot provinces. These participants became master trainers and led cascade trainings in each province down to the commune level. At each level, a trainer from a higher administrative level provided mentorship and support." ] },{ "paper_id": "d9642448d10a480b44672fcdb066ca3deff8031e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d9d6c6f034dd3114696c0811a672bbd5c9c9dc18", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nina Marano,* Paul Arguin,* Marguerite Pappaioanou, \u2020 and Lonnie King* \u2021" ] },{ "paper_id": "da2fb4ffdc8824adeec5af4103d04667dc618b6a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Jay's patients worshipped him for his diagnostic acumen and ability to listen. Jay was always in a good mood; full of life; and a caring, warm, and compassionate teacher, mentor, physician, and research collaborator.", "Jay continued teaching and seeing his patients until a few weeks before his death. He worried about who would follow his cohort of delusional parasitosis patients, a group that few but Jay would listen to and treat with skill and compassion.", "Jay taught me to never take my work overly seriously yet to thrive by enjoying the meaning and relevance of contributions to the health of patients and of the increasingly mobile public. Jay's life was remarkable not only for his accomplishments and the inspiration that he engendered in others but also for his self-deprecating humor. He maintained close friendships with colleagues from all over the world, who surely share our feelings of loss." ] },{ "paper_id": "da445fcbe5ce291f6749c02784523b331c64baf1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We identified unusual rotavirus strains in fecal specimens from sheltered dogs in Hungary by viral metagenomics. The novel rotavirus species displayed limited genome sequence homology to representatives of the 8 rotavirus species, A-H, and qualifies as a candidate new rotavirus species that we tentatively named Rotavirus I.", "Rotavirus A has been detected in a wide variety of mammals and birds. In mammals, both endemic and epidemic forms of rotavirus B, C, E, and H infections have been described, whereas rotavirus D, F, and G have been identified only in birds (1) (2) (3) . Genetically diverse rotaviruses have been found in some viral metagenomics studies (4, 5) . Using the metagenomic approach and the VP6-based molecular classification scheme, we found evidence for a novel rotavirus species that we tentatively called Rotavirus I.", "During 2012, we collected fecal specimens from sheltered dogs in northern Hungary to detect enteric viruses. Of 63 samples obtained from 50 animals, 37 randomly selected samples (from 33 animals) were subjected to random primed reverse transcription PCR and semiconductor sequencing by using the Ion Torrent PGM platform (New England Biolabs, Ipswich, MA, USA) (online Technical Appendix). Bioinformatics analysis consisted of the mapping of reads >40 bases against \u22481.7 million viral sequences downloaded from Gen-Bank by applying moderately rigorous mapping parameters (length fraction 0.6; similarity fraction 0.8) within the CLC Genomics Workbench (http://www.clcbio.com/)." ] },{ "paper_id": "da692ee969d9c33986196372c3f7cb87fa6b6f8f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Molecular weights in PubChem were updated using the latest International Union of Pure and Applied Chemistry (IUPAC) recommendations for atomic mass and isotopic composition information (11, 12) . Increasingly the scientific community is recognizing complex issues with average atomic weight and isotopic data, as greater degrees of pre-Nucleic Acids Research, 2018, Vol. 46, Database issue D13 cision in atomic masses and variations in isotopic abundance are known. PubChem now uses the 'conventional atomic weights' described by IUPAC when available. In addition, PubChem is now restricting the allowed isotopes for a given element to those with a half-life of one millisecond or greater.", "In 2014 NCBI introduced the 'Identical Protein Report' to the Protein database to clarify the relationships between WP sequences and the set of individual Nucleotide CDS sequences they represent (8) . Now ", "The PubChem Data Sources page summarizes data contributors to PubChem, and this page was updated to provide new and improved capabilities to navigate as a function of data type, category, and country, while also including keyword searching, counts, and geographic visualization. In addition, the Data Sources page makes it easier to separate active data contributors from non-active ('legacy') data contributors." ] },{ "paper_id": "da6cb24186f59847fb1dcdb6614ab15b2bd3377c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The RT-PCR products were cut from the gel and purified using the Wizard SV Gel and PCR Clean-Up system (Promega, USA) according to the manufacturer's protocol. Purified RT-PCR products were sequenced in a forward direction using primer FOR1 and in a reverse direction using primer RE3. Sequencing reactions were performed with the ABI Prism BigDye Terminator Cycle Sequencing Ready Reaction Kit (Applied Biosystems, USA) as described by the manufacturer. Sequencing reactions were run on an ABI Prism 310 Genetic Analyzer.", "Viral RNA was extracted by using Viral Nucleic Acid Extraction Kit (Real Biotech, Taiwan) following the manufacturer's instructions directly from the supernatants of 10% w/v sample suspensions and from the allantoic fluid of embryonated chicken eggs used for virus isolation.", "Between January and June, 2008, thirteen poultry farms in the eastern part of Thailand had an outbreak of a mild-to-moderate respiratory disease (Table 1) . All flocks had been vaccinated against IB with commercial live attenuated H120. Chickens showed respiratory symptoms including gasping, coughing, sneezing, and tracheal rales. Sick chickens were selected and sent to the Department of Veterinary Medicine, Faculty of Veterinary Science, Chulalongkorn University. Necropsy was performed and gross lesions were evaluated. Gross lesions showed mildto moderated tracheitis and non-purulent airsacculitis. No gross lesion were found in the kidneys. The trachea and lung samples were taken as pools of chickens from the same farm. The samples were prepared as 10% w/v suspensions in phosphate-buffered saline (pH 7.4) and clarified at 1,800 \u00d7 g for 10 min; the supernatants were then collected for analysis." ] },{ "paper_id": "dab2d95da5307c840eb4a1e00f0186022541d63d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Another reason for the modeling of a pseudo-iodotyrostatin complex is that CLN2 is a tripeptidase, and that this inhibitor it represents the only experimental structure of a tripeptide analog bound to sedolisin." ] },{ "paper_id": "db055944a3acc538005fe7af772ec33c16b2fdd9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Structural information can also be exploited to generate chimeric proteins which contain protective epitopes deriving from multiple variants of the same antigen. This approach has been recently used for a novel MenB candidate vaccine that was rationally designed by assembling epitopes from three different variants of MenB factor H-binding protein (Scarselli et al., 2011) .", "We think that vaccinology of the future will be less empirical than it used to be and will learn more from human immunology. Antigen design will be directed by a deep knowledge of cross-protective epitopes in humans. Adjuvants and expression vectors will be selected based on the type of humoral and cellular immune responses which correlate with protection. A more rational vaccine design will hopefully allow the development of effective preventive vaccines for all remaining 'difficult' targets including HIV, malaria and tuberculosis.", "The identification of conserved epitopes in HIV and flu that are target of broadly neutralizing antibodies is only the first step for the development of universal vaccines. A lot of work needs to be done to rationally design and express the target antigens (e.g. HA or Env) in a form that stabilizes cross-reactive epitopes and makes them sufficiently immunogenic. The only way to achieve this goal is to have a deep structural knowledge of the candidate antigens (Fig. 1) ." ] },{ "paper_id": "db23b1ede65392b310b9152cf2999ec8f86ebd9b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "substantial kinetic barriers both leading into this intermediate and leading away from it toward the product (Fig. 2) .", "The accumulated evidence suggests that viral fusion proteins lower the various kinetic barriers and, hence, catalyze the membrane fusion process, as follows." ] },{ "paper_id": "db40a1dfdecdf2427c6d0a22c0affdbeda3cb25a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "db59c00ca304cff50531d66511fcf971f97a53ec", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Eggs of Toxocara spp. were recovered only in three of the parks.", "Samples were analyzed for the presence of rotavirus 11-segment RNA using polyacrylamide gel electrophoresis-PAGE (Herring et al., 1982) . NCDV group A rotavirus strain was used as the positive control.", "Chi-square test (Epi-Info, 6.4) was used to evaluate the differences in the presence of different pathogens in the parks, considering p <0.05 (Triola, 2005) .", "All samples were processed in the Laboratory of Microbiology and Infectious Diseases of Animals, Department of Veterinary Hygiene and Public Health, School of Veterinary Medicine, UNESP -Universidade Estadual Paulista, Botucatu, Sao Paulo, Brazil. Samples were kept under refrigeration (4-8\u00b0C) or frozen (-20\u00b0C) until they were analyzed." ] },{ "paper_id": "db5f07cca2e8c9d47193fa957565147e7fad8d10", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sequence analyses confirmed the identity of HMPV and influenza A RT-PCR amplification products. A BLAST (available from: www.ncbi.hlm.nih.gov/BLAST) comparison of five putative HMPV specimens showed identity to HMPV sequences in GenBank. Similarly, influenza A amplification products from 12 patients identified solely by RT-PCR showed homology to known influenza A viruses.", "From March 12, 2003 , through July 30, 2003, cases of possible SARS reported to the CDHS were classified as suspect, probable, or laboratory-confirmed, according to CDC criteria (3). Extensive diagnostic testing was performed at the CDHS Viral and Rickettsial Disease Laboratory on specimens from 165 patients, including those with conditions that did not meet strict CDC case criteria (Table 1) .", "In California, molecular testing was useful in decreasing suspicion for severe acute respiratory syndrome (SARS), by detecting common respiratory pathogens (influenza A/B, human metapneumovirus, picornavirus, Mycoplasma pneumoniae, Chlamydia spp., parainfluenza virus, respiratory syncytial virus, and adenovirus) in 23 (45%) of 51 patients with suspected SARS and 9 (47%) of 19 patients with probable SARS.", "Of the 165 patients tested, 51 (31%) met the criteria for suspect SARS, 19 (12%) met the criteria for probable SARS, and 2 had serologically confirmed SARS (Table 3) . A likely pathogen was detected in 23 (45%) of the 51 suspect and 9 (47%) of the 19 probable SARS patients ( " ] },{ "paper_id": "dbb74d7f7208f09f5c107ecc18d9b28fcbc4d67a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Physicochemical Characterization. Physicochemical characterizations of 4 were conducted to assess its solubility and chemical stability.", "Synthesis. Our initial attempts to prepare 4 in two steps from triptolide by either O-alkylation with chloromethyl phosphate diesters or direct alkylation of the hydroxyl group with chloroiodomethane were not successful. 35, 50, 51 Therefore, an alternative strategy 44 based on methylthiomethylation of the hydroxyl group was selected (Schemes 1 and 2) to furnish key ", "Dibenzyl ((((5bS,6aS,7aR,8R,8aS,9aS,9bS,10aS,10bS ", "Notes" ] },{ "paper_id": "dc02bc5e86dabe370331b032a7956db8660db1cc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Pandemic (H1N1) 2009 among Quarantined Close Contacts,", "I n early April 2009, human cases of infection with a novel infl uenza virus of swine origin, pandemic (H1N1) 2009 virus, were identifi ed in the United States and Mexico, and this virus spread rapidly across the world (1-3). On June 11, 2009 , the World Health Organization raised the pandemic level to 6, the highest level for pandemic alert (4) .", "For each close contact, before quarantine, a pharyngeal swab specimen was collected for reverse transcription PCR testing, regardless of symptoms. A second pharyngeal swab specimen was collected for testing for pandemic (H1N1) 2009 virus if any of the following symptoms developed in a close contact during quarantine: axillary temperature >37.3\u00b0C, cough, sore throat, nasal congestion, or rhinorrhea." ] },{ "paper_id": "dc91750f913c083da70bb7dd1816c0418eaf346d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "More than half of all admitted patients were admitted to medical specialties, such as general medicine and paediatrics. Decreases in patient attendance were evident for general surgery, orthopaedics, paediatrics, and gynaecology. General medicine admissions increased, but obstetric admissions were steady.", "Funding None.", "Conflicts of interest None." ] },{ "paper_id": "dca62735df89a3903dc137e511095984c2d9f21a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "dce54cded1eacab0a9aa40c210a4b27ea9fd2226", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Female BALB/cAnNCR mice were purchased from Division of Cancer Treatment, National Cancer Institute, Frederick, Maryland, USA. The institutions' Animal Care and Use Committees approved all protocols for animal experiments.", "One concern about M2 vaccines is the possibility of escape mutants. A study of forced escape mutants found limited diversity (13) , which indicates that structural constraints, perhaps due to requirements of the M1 structure encoded by the same segment, may limit drift.", "Y early development of influenza vaccines that are antigenically matched to circulating strains poses extraordinary challenges. A rapidly developing pandemic would shorten the time for strain identification and vaccine preparation; meanwhile, antigenic changes would continue. Moreover, the need to immunize an entirely naive population would exacerbate problems with vaccine production and supply.", "Priority is being given to developing vaccines that offer broad protection against multiple influenza subtypes, including H5N1. Indeed, development of conserved-antigen vaccines, and specifically M2-based vaccines, is part of the US Department of Health and Human Services Pandemic Influenza Plan (www.hhs.gov/pandemicflu/ plan/). We therefore evaluated M2-based vaccine efficacy against divergent challenge viruses." ] },{ "paper_id": "dd5f28bd9fee1733222b8816932316ad81964826", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "dd601ba03cbb74182fafd2290bc100bc5569e1c3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "dd6c1a719bd75ba7fb7c62291a676b39c99bb0bc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Each resulting product was gel purified and then cloned into pCR2.1 TA cloning vectors (Invitrogen, USA) according to the manufacturer's instructions. All the clones were amplified by transformation into competent DH5 \u03b1 cells. Clones with correct inserts were confirmed by restriction enzyme digestion of the recombinant vectors.", "The viral genomic RNA was extracted using the methods described by Joh et al. [8] . Briefly, GC1-infected cells were frozen and thawed 3 times and clarified by centrifugation. Viral dsRNA was then extracted with phenol and chloroform, followed by digestion with proteinase K. Seven primer pairs were used for reverse transcription-polymerase chain reaction (RT-PCR). The oligonucleotide sequences were deduced according to the published dsRNA sequences of the Western Buxton strains (AF078669) ( Table 2) .", "Virus and cell GC1 was isolated from the rockfish S. schlegeli, and it was grown in the Chinook Salmon Embryo-214 cell line supplemented with Eagle's minimum essential medium. The sources of VP1 sequence cited in this study are listed in Table 1 .", "The RT-PCR procedure used in this study was a modification of the method previously described by Joh et al. [10] . The RT-PCR solution was heated to 95 o C for 3 min and passed through 35 cycles under the following conditions: 1 min at 95 o C for denaturation; 1 min at 54 o C to 58 o C (depending on the primer) to allow annealing; 1 min at 72 o C for extension and final amplification at 72 o C for 3 min. The ethidium bromide-stained PCR products were electrophoresed on a 1.5% agarose gel and were visualized by UV fluorescence." ] },{ "paper_id": "dd798f4e35268f8ab935a299973627fc3082864a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "If a patient was unable to supply the information needed, the next of kin and/or the concerned hospital staff were interviewed. If a patient was not able to give informed consent, the next of kin was asked for permission.", "Specimens were kept at room temperature until nucleic acid extraction, which usually took place within 24 h and always within 48 h. PCR analyses were performed within the next 24 h or else the nucleic acid eluates were stored at \u221270\u00b0C until testing. Using monoplex (RSV and human metapneumovirus) or multiplex (influenza A/B, adenovirus/internal control and parainfluenza virus 1-4) PCR methods, the specimens were examined for, in total, nine different respiratory viruses (Table 2) .", "The study design was approved by the Norwegian Regional Committee of Research Ethics.", "In recent years, respiratory viruses have been established as significant causes of mortality and morbidity in the older population [1] [2] [3] [4] [5] . However, as respiratory pathogens may cause similar clinical pictures, the aetiological diagnosis depends on laboratory confirmation [6] ." ] },{ "paper_id": "de5e1374a67895eb515193eca9435d1ad8bce7e0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "de697e14b572a44814a93dabd82210bde299bdc2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "deff02a187178ad474a1c556ff4f134d48300ce9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "df5c297cca7c38328fdac4a3cfef5bda4e948e93", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "df806aba65548a95da899a9663ff3b37fadd3da8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In 2003, a 43-year-old white woman who had undergone a pulmonary lobectomy during childhood underwent bilateral lung transplantation because of severe chronic respiratory failure caused by bilateral bronchiectasis. The posttransplant period was complicated by bronchiolitis obliterans syndrome stage 1, with episodes of acute respiratory distress. The immunosuppressive regimen included tacrolimus (through level 10-15 ng/mL), low-dose steroids (0.10 mg/kg/day), and monthly courses of extracorporeal photopheresis that were initiated after a 3-month course of low-dose azythromycin (discontinued because of lack of efficacy).", "In the absence of specific therapy, the patient reported here underwent parenteral rehydration and nutritional supplementation; her general condition improved progressively, and her bowel movements were reduced to 2-3 per day, enabling her to be discharged within a month. However, her gastrointestinal symptoms persisted, and 3 fecal samples collected at 4, 6, and 7 months after discharge were positive for the same HCoSV strain (at a high titer of 10 5 -10 7 virus RNA copies/mL feces) but negative for other viruses, bacteria, and parasites. ", "Because the 5\u2032 UTR is not sufficiently discriminatory for typing, we sequenced the highly variable region encompassing VP3-VP1 genes, obtained according to a published protocol (6) . Phylogenetic analysis, performed with the maximum-likelihood method with parameters selected by the Model Selection tool in MEGA version 5.0 (15) , showed that the HCoSV VP3-VP1 sequence from Italy clustered with species E strains found in Australia and Bolivia and recombinant D/E strains circulating in Nigeria. Although homology was greatest (97% nt and 81% aa identity) with a strain from Australia (GenBank accession no. FJ555055) (Figure) , the hypothesis that this HCoSV strain might be a D/E recombinant strain (6) cannot be excluded because the recombination breakpoint between VP1 and the 2A gene was not investigated.", "I n 2008, a new virus was detected in fecal samples from children with nonpolio acute flaccid paralysis (1) . The genome structure of the new virus was closely related to those in the family Picornaviridae, but phylogenetic analysis showed that it diverged from known picornaviruses. Thus, a new genus of picornaviruses was proposed: Human Cosavirus (common stool-associated virus; HCoSV)." ] },{ "paper_id": "e00be029fff23d2dd375aa4f86cef9d79b1ac7c6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e02f049fee95cabc6dbd1795a61117b73bc084ec", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e03a59f8c651cd120e4c06a6c4f6e87b20d5e2d4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.6b00143.", "Experiments showing slide fabrication affected by different voltages and reaction times; conditions required to optimize surface thickness and roughness; mathematical modeling of surface response methodology; computer software design for surface fabrication; fluorescence intensity and homogeneity related to arraying conditions and protein\u2212glycan interaction (PDF) ", "Article can be estimated from the in-line electrical current measurement during the ACG slide fabrication." ] },{ "paper_id": "e05de9e9983b9e4ee063afa20cbe46a38243b9d1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e06405cc150773e699a28a474e50a5e579939f89", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e065a96a33ccdbcc23e9f7d0af9c5edf440cb478", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "RT-PCR assays were undertaken by using three sets of primers, one developed at the National Microbiology The highest dilution in which the virus or the RNA were detected is given in log10 .", "Six 4-week-old crossbred pigs were kept for 2 weeks to acclimatize before being inoculated. The pigs, obtained from a high health status herd (Sunnyside Colony LTD, Sunnyside, Manitoba), had preexisting antibodies against PRCV, likely of maternal origin (4), which decreased during the experiment, as determined by competitive enzymelinked immunosorbent assay performed by the Veterinary Services Branch of Manitoba Agriculture and Food.", "Preliminary tests to establish a sensitive cell system for virus replication were performed before animal inoculation and virus isolation. SARS-CoV replicated in Vero E6, Vero V76, and PT-K75 approximately to the same titer. QT-35 did not replicate SARS-CoV. Although CEKEC did not show any CPE, the virus replicated in those cells up to the approximate titer of 10 6 , based on positive RT-PCR results on lysed cells and cell culture supernatant harvested 54 h after inoculation." ] },{ "paper_id": "e0737ee93afe7b0bf06b1e3f9adf21d541dd10f0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "An aliquot of lung tissue from each animal was homogenized in 10% ice-cold DMEM utilizing a Polytron homogenizer (Fisher Scientific, Whitby, Canada). Viral titers were determined in L2 cells as described previously (25) .", "Refer to Web version on PubMed Central for supplementary material. " ] },{ "paper_id": "e159298c6d214ba5e950ef1cda327cf5a88326b8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Universal influenza vaccination of children is controversial, but its use has provided data that help assess the potential effect of reducing transmission by schoolchildren. For example, in 1968-1969, when 86% of its schoolchildren were vaccinated against influenza, the small town of Tecumseh, Michigan, had one third the illness rate of nearby towns where children were not vaccinated (18) . In Japan, when most schoolchildren were vaccinated against influenza , excess death in the entire population decreased 3-to 4-fold and rose again when the program was discontinued (19) .", "A 1959 WHO consultation concluded, \"In the Northern hemisphere at least, the opening of schools after the summer holidays seems to have played an important role in initiating the main epidemic phase\" (13) . Despite the propensity of influenza epidemics to be amplified in primary schools (14) , data on the effectiveness of school closures are limited. Apparently no data or analyses exist for recommending illness thresholds or rates of change that should lead to considering closing or reopening schools.", "A WHO consultation in 1959 concluded that the 1957 influenza pandemic tended to appear first in army units, schools, and other groups where contact was close. Also noting the reduced incidence in rural areas, the consultation suggested that avoiding crowding could reduce the peak incidence of an epidemic and spread it over many, rather than a few, weeks (13) .", "During a 2-week teachers' strike during an influenza epidemic in Israel in 2000, significant decreases were seen in the rates of diagnoses of respiratory infections, medication purchases, and other parameters for children 6-12 years of age; when school reopened, rates for these parameters rose again. The study did not report on illness in family members (15) . In 21 regions of France from 1984 to 2000, a temporal relationship was reported between school holidays and a decrease in the incidence of influenza diagnoses by general practitioners 10-20 days later and the daily death rate 30-40 days later, although the time delay raises the question of whether outbreaks may have been subsiding on their own (16) ." ] },{ "paper_id": "e194924017ffd82f926955f23ca6e30ef772b6de", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Wound cultures showed growth of Proteus mirabilis and Enterococcus spp. The urine culture grew >100,000 CFU Escherichia coli. The first set of blood cultures grew O. ureolytica in aerobic and anaerobic bottles, but another set drawn 30 min later showed no growth. The blood cultures were processed by using the Bact/Alert 3D (bioM\u00e9rieux, Marcy l'Etoile, France) and Gram stained. Identification was from the Vitek 2 compact system (bio-M\u00e9rieux). The O. ureolytica sample was sensitive to amikacin, ampicillin/sulbactam, ceftazidime, ceftriaxone, gentamicin, imipenem, levofloxacin, nitrofurantoin, trimethoprim/sulfamethoxazole, and chloramphenicol. No resistance was found.", "Because of the unique bacteremia, further diagnostics were conducted. The results of chest, abdomen, and pelvic computed tomography scans were unremarkable. HIV" ] },{ "paper_id": "e1a92eaaadeb57ad1273b68900ab659a34e1db12", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e1c75a638bdac1693aee9103d38374e401253704", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Legal guardians of study participants and healthy adult participants provided informed verbal consent for participation in this investigation. The Ethical Review Committee of icddr,b reviewed and approved the protocol for NiV surveillance and outbreak investigation.", "All case-patients, except 1, were either too sick or too confused to respond or had died, so the field team selected multiple appropriate proxy respondents for interview. We used standardized, structured questionnaires in the Bengali language. ", "To estimate the association between each exposure and NiV infection, we calculated the matched odds ratio (mOR). We used conditional logistic regression and considered any association to be statistically significant if the p value was <0.05. We analyzed data in STATA 10 (Stata Corp., College Station, TX, USA).", "The investigation team collected acute-phase and subsequent whole blood specimens from possible casepatients. Samples were centrifuged in the local government community clinic, and the separated serum was stored and transported to the IEDCR laboratory in liquid nitrogen. Samples were stored at -70\u00b0C." ] },{ "paper_id": "e1dc3ea3a7ad4303e6e57417de0daee78e31d5bb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.9b02900.", "Article flavonoids interacted and fitted more effectively in its pocket. This binding property of halogenated dihydrorugosaflavonoids with nsP3 invigorated us to screen these compounds for antiviral efficacy against CHIKV.", "The cases of chikungunya viral fever are burgeoning every year. Infections are not only limited to Asia and Africa; recently, the epidemics of chikungunya have been reported from Central and South America. 1, 2 Concerning the data obtained from the National Vector Borne Disease Control Programme (NVBDCP, India), the number of infected people identified in April 2018 was 9175, 4875 from Karnataka following 1375 from Gujarat and 966 from Maharashtra. Earlier research studies have shown that there is considerable resource burden from chikungunya outbreaks, which escalates in monsoon and post-monsoon seasons. Therefore, cases of chikungunya viral fever have increased in the continent of Asia and various parts of the world. The name chikungunya originates from \"Makonde\", meaning \"to become twisted\". It denotes the \"curved\" appearance of those going through joint ache as a result of chikungunya infection. Chikungunya virus (CHIKV) spreads by mosquito vectors Aedes aegypti and Aedes albopictus. The common eukaryotic hosts are primates and humans. In humans, the symptoms associated with CHIKV are nausea, fever, joint pain, vomiting, rashes, and persistent arthralgia.", "Clinical manifestation is one of the bases for the diagnosis of chikungunya infection, but the confirmation of disease can only be made after laboratory tests. Suspected cases are validated by positive anti-Chikungunya virus IgM or IgG results or by positive polymerase chain reaction (PCR) results. 3, 4 In Togaviridae family, CHIKV comes under the genus Alphavirus. Alphaviruses are configured as enveloped positivesense single-stranded RNA viruses. There are 29 members in the alphavirus genus; some members of the genus contain several animal and human viruses like Ross River virus, Sindbis virus (SINV), Western equine encephalitis virus (WEEV), Semiliki Forest virus (SFV), Venezuelan equine encephalitis virus (VEEV), etc. They are furthermore categorized into Old World and New World viruses reliant on the changes that occurred in their life cycle, fatality, and clinical manifestations. Basically, the Old World viruses CHIKV, SINV, SFV, etc. engage the protein nsp2 to downregulate the host cell transcription, have less demise percentage, and stimulate arthralgia. The New World viruses VEEV, WEEV, etc. use virus capsid protein (CP) to downregulate the host cell transcription, have high casualty frequency, and generate encephalitis." ] },{ "paper_id": "e1dd5b5b1884508b0e49421388eb658f9f9949e1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The model is a promising tool for future research because it induces reversible pharyngeal irritation, in controlled conditions, and is amenable to a crossover study design. It may provide a valuable research tool and an objective way of measuring the therapeutic potential of treatments. Furthermore, this procedure may also allow for research in occupational and environmental medicine where exposure limits for single potential irritants exist but interactions are not yet well established. In this way, a CDA stimulus may be combined with one or two potential irritants in order to generate comparable results in crossover study designs.", "Ambient air pollution is a common cause of sore throat. The factors implicated include ozone, nitrogen oxides, and fine dust.", "Ozone has an inflammatory effect on both the upper and lower respiratory tract, characterised by polymorph infiltration and release of pro-inflammatory cytokines [135] [136] [137] , although the specifics relating to sore throat are less certain. The underlying mechanism is proposed to include a direct effect of ozone on respiratory tract cell membranes and fluid, with lipid ozonation products activating specific lipases, triggering the release of endogenous mediators of inflammation [138, 139] such as prostaglandin E, IL8, thromboxane B2 and calcitonin gene-related peptide.", "There are some more specific animal models with objective endpoints. Pharyngeal inflammation was induced in a rat model by applying capsaicin directly to the pharyngeal mucosa [159] . Intubation has been used to induce pharyngeal inflammation in a swine model [117] and laryngeal inflammation in a rat model [160] , with analysis of biomarkers. Well-defined human models of pharyngeal irritation with objective endpoints are generally lacking. One that is in research use is the Tonsilliopharyngeal assessment (TPA) scale which is based on a clinical examination of the throat [158] , although this still depends on the clinician's judgement. Currently, any correlation between subjective and objective endpoints is therefore untested." ] },{ "paper_id": "e1f1806e2d4561bb8cd2f4025586b9b6278e5a72", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The regulation of r-gene transcription is tightly connected with ribosomal chromatin (r-chromatin; chromatin-containing rDNA/r-genes/rRNA genes) structure. The chromatin competence may be controlled by many factors (see \"Nucleolar chromatin\").", "Regardless of the differences mentioned in this section, the plant counterparts of animal FCs are termed FCs in literature according to nucleolar nomenclature (Jordan 1984) , although some researchers do not share this idea.", "Almost fully processed pre-rRNAs leave nucleolonema and enter GC where the terminal stages of processing and assembly of ribosomal subunits occur.", "Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.", "FCs together with DFC are structurally and functionally associated with nucleolonema (Fig. 2a) . This additional nucleolar component, although not always unequivocally described and discriminated, has already received the status of the fundamental nucleolar structure. Nucleolonema is built of a threadlike component which prevails in nucleoli and is generally characteristic of higher plants. In the animal nucleoli, this structure is often difficult to distinguish probably because of small content of DFC, however, nucleolonema is clearly visible in the animal reticulate nucleoli (Deltour and Motte 1990) ." ] },{ "paper_id": "e2619c76a8dde67ace5623870a263a365d2c944b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Suctioning negative pressure \u2264 -400 cmH 2 O ", "Return to pre-endotracheal suctioning FiO 2 , ventilatory mode and peak airway pressure alarm", "Different types of recruitment manoeuvre have been proposed for enhancing alveolar recruitment and improving arterial oxygenation in the presence of ALI [50] . A plateau inspiratory pressure can be maintained at 40 cmH 2 O for 40 s.", "It is recommended that the ventilatory settings be optimized before the patient is turned into the prone position [35] . If arterial saturation remains below 90% at an inspiratory fraction of oxygen of at least 60% and after absolute contraindications such as burns, open wounds of the face or ventral body surface, recent thoracoabdominal surgical incisions, spinal instability, pelvic fractures, life-threatening circulatory shock and increased intracranial pressure have been ruled out [56] , the patient should be turned to prone in accordance with a predefined written turning procedure [56] . The optimum duration of prone positioning remains uncertain." ] },{ "paper_id": "e26317772e5eefc6c0ca5e616b2073c65c00550e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e269ac6cbd3208b8f71892f9e1f8b9ccb225f472", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e29e17f37924d1d14edf56276a5dcca87851e62f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Density Functional Theory (DFT) Calculations. Structures depicted in Figure 2 were minimized with GAMESS 60 version 1 May 2013 (R1) using the B3LYP 61 density functional method and the 6-31g(d) basis set. van der Waals surfaces colored by electrostatic potential were visualized with Avogadro 1.1.1.", "The Supporting Information is available free of charge on the ACS Publications website at DOI: 10 ", "Peptide precursors to compounds 3\u22127 were synthesized in the solid phase using methods analogous to our previously reported results. 20\u221222 Synthesis of 1,4-triazole analogs also provided us with the first opportunity to synthesize and test nonsymmetrical N-methylation patterns (e.g., compounds 4, 5, and 6), as previous attempts to accomplish this using on-bead olefin cross-metathesis had met with modest yields, at best. The Cu(I)-catalyzed Huisgen cycloaddition was conducted on resin using methodology described by Meldal and co-workers. 38 In each case, this method provided the desired compound following cleavage from the resin and concomitant deprotection as a single major peak by analytical HPLC.", "Surface Plasmon Resonance. SPR was conducted using a Biacore X (Biacore, Inc.) instrument. Streptavidin was immobilized to 7500 RU in both flow cells using EDC/NHS coupling to a CM5 chip (GE). The surface was then blocked with ethanolamine. Next, 50 \u03bcM 5\u2032-biotin HIV-1 FSS (obtained as an HPLC-purified sample from Integrated DNA Technologies, Inc.) was refolded in 10 mM HEPES and 150 mM NaCl at pH 7.4 by heating at 98\u00b0C in a heater block for 2 min then cooled to RT and immobilized on one flow cell of the SPR chip to a density of 1100 RU. The control flow cell was then blocked with an injection of 50 \u03bcM biotin in 10 mM HEPES and 150 mM NaCl at pH 7.4. Compounds were injected at a flow rate of 50 \u03bcL/min in 10 mM HEPES, 150 mM NaCl, and 0.005% tween at pH 7.4 for 1 min. Each injection was repeated twice for consistency. Each trace was fit individually to a Langmuir model." ] },{ "paper_id": "e2d91b039a8a0d8631126c4eea4b82ff4510c70f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We identified from suckling piglets with diarrhea in China a new bat-HKU2-like porcine coronavirus (porcine enteric alphacoronavirus). The GDS04 strain of this coronavirus shares high aa identities (>90%) with the reported bat-HKU2 strains in Coronaviridae-wide conserved domains, suggesting that the GDS04 strain belongs to the same species as HKU2.", "S everal pathogens are thought to be responsible for porcine diarrhea, including porcine epidemic diarrhea virus (PEDV) (1), transmissible gastroenteritis virus (2), porcine deltacoronavirus (3), porcine group A rotavirus (4) , and emerging viruses like porcine kobuvirus (5) . To add to the list, we have identified from suckling piglets with diarrhea in China a new bat-HKU2-like porcine coronavirus (porcine enteric alphacoronavirus [PEAV] ).", "Furthermore, we designed specific primers of the n gene for the detection of the GDS04 strain. By using reverse-transcription PCR with these primers, we found that 97 out of 308 clinical intestinal or fecal samples were positive for GDS04. We collected all clinical samples from 25 farms in Guangdong Province during February-April 2017 and used 20 samples collected from healthy vaccinated piglets as negative controls." ] },{ "paper_id": "e315c421674f55c4e12287ff86314290f8965432", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The second tier of the LRN-B comprises referencelevel microbiology laboratories, typically state, city, or local public health laboratories, or military, veterinary, and agriculture laboratories (9) . LRN-B reference laboratories follow testing algorithms to rapidly identify specific presumed and confirmed bioterrorism pathogens.", "The third tier of the LRN-B comprises agencies such as CDC and the US Army Medical Research Institute of Infectious Diseases. The LRN reference-level laboratories can refer isolates that require further characterization to these laboratories.", "Emerging Infectious Diseases \u2022 www.cdc.gov/eid \u2022 Vol. 23, Supplement to December 2017 S129 " ] },{ "paper_id": "e32e94fd63e050881d16e0c938820df16fdeadb2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Serum specimens with sufficient volume were tested using 4 CDC serologic assays: 1) microneutralization (MN) assay (37); 2) spike (S)-specific pseudoparticle neutralization assay (VSV-MERS-S); 3) S ELISA (Ig-specific) (38) ; and 4) nucleocapsid (N) ELISA (Ig-specific) (37, 38) . Additional description is available in Appendix 1 (https://wwwnc.cdc.gov/EID/article/25/4/18-1595-App1.pdf).", "We reviewed epidemiologic interviews conducted at the time of case identification to include patient demographics, symptom history, and relevant exposures during the 2 weeks before onset. After patient death or discharge, we performed comprehensive medical chart reviews to collect medical history; symptoms before hospitalization; and daily information regarding symptoms during hospitalization, clinical course, treatments, medications, patient vital signs, diagnostic tests, and clinical outcome.", "We used Fisher exact, Kruskall-Wallis, or log rank tests to compare groups and exact logistic regression for multivariable analysis. We compared antibody titers with estimated viral load in different specimen types by using the Spearman test for correlation. All data were analyzed using Microsoft Excel 2016 (https://products.office.com) and SAS version 9.4 (https://www.sas.com).", "We retrospectively categorized patients into 3 groups on the basis of the need for supplemental oxygen, ventilation, and clinical outcome. Group 1 (G1) received room air throughout hospitalization; group 2 (G2) required ventilator support (mechanical or nonmechanical) and survived; and group 3 (G3) required ventilator support and died." ] },{ "paper_id": "e366e0d17ab75efbaaeeb16705d551d50a0c188a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Licorice was purchased from China. Glycyrrhizic acid (mono-ammonium salt hydrate) was obtained from Sigma Chemical Co. (St. Louis, MO) . Glabridin was purchased from Wako Pure Chemical Industries, Ltd. (Japan). Methanol, ethanol, acetonitrile and chloroform (HPLC Grade) were from Duksan Pure Chemical. Co., Ltd. (Korea). Water was twice distilled and filtered (FH-0.45 \u00b5m, Advantec MFS, Inc., Japan) by using a decompressing pump (Division of Millipore, Waters, USA).", "Licorice, the root of the glycyrrhiza plant species, has been used medicinally for more than 4000 years [1] . The genus glycyrrhiza consists of approximately 30 species, in which six species produce a sweet saponin glycyrrhizic acid (GA), and they are widely used in Asia countries [2] . These medicinal plants were used as flavorings, sweeteners and as herbal medicine, and they were also used for improving health, detoxification and cures for injury [3] .", "Glycyrrhizic acid (GA) (Figure 1 (A) ), the most studied active constituent of licorice, is a sweet-tasting material. The constituent is 50 times sweeter than sugar, making it a widely used as a sweetening additive in the food industry [4] . In many countries, GA is used as a major therapeutic agent to treat chronic viral hepatitis and allergic dermatitis [5] . It is also known to have anti-inflammation [6] , anti-ulcer [7] , anti-hepatotoxic [8] and antivirus activities [9, 10] ." ] },{ "paper_id": "e3af2ca43010f59c3d1bb731abd011e3dd0fc51c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For an ancestor sequence S 0 of a strain S, we can deduce for the assumptions above that" ] },{ "paper_id": "e3eb479eab9c4630958978752dfdd3c5ce08d35a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "NPA samples were collected from 235 children hospitalized with ARTI at the First Hospital of Lanzhou University, Gansu Province, China during December 2007-November 2008. All patients were <15 years of age, and informed consent was obtained from their parents. Demographic data and clinical fi ndings were recorded. The study protocol was approved by the hospital ethics committee.", "In addition, we designed HBoV2 forward (SN1: 5\u2032-ACCAGTGGGAGAACCACAAG-3\u2032) and reverse (SN2: 5\u2032-GGCATTTGTTTCCATGCTTT-3\u2032) primers, which produced a 563-bp fragment of the NP1 gene of HBoV2. Positive and negative controls were included for each PCR. Purifi ed PCR products were sequenced by using SinoGenoMax. ClustalX (ftp://ftp-igbmc.u-strasbg.fr/pub/ ClustalX) was used to align the obtained sequences with sequences available in GenBank.", "Of the 10 HBoV2-positive patients, 9 were male and 1 was female (\u03c7 2 = 1.957, p = 0.162). The median age was 8.5 months, and 9/10 (90%) were <3 years old. HBoV2 infections were detected throughout the year. Of the 18 patients who were HBoV positive, 11 were male and 7 were female (\u03c7 2 = 0.084, p = 0.772). The median age of patients was 11.5 months, and 16/18 (88.9%) were <3 years old." ] },{ "paper_id": "e400309a9601ccd52d0fbee511e868dfed9acef0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The clinical assessment after 16 months post operation revealed paraparesis of the lower extremities in neurological examination but the motor deficit was improved during this time. Patient was moving with a wheelchair.", "The above-mentioned viral diseases have been particularly noticeable in recent decades as diseases of civilization featured in mass media and also have constituted a high degree risk [1, 18, 32, 37, 38, 40] .", "There are also parasitical diseases, of which the most frequent in developed countries is trichinosis, caused when humans are infected with by eating infected meat. The reasons of zoonoses include also protozoa and helminths.", "In the human clinic also diseases of bacterial origin are present, to mention just the few most frequent ones: cat scratch disease, plague, anthrax, Lyme disease, brucellosis, tuberculosis, erysipeloid, salmonellosis, leptospiroses-Weil's disease, malaria, Stuttgart disease and listeriosis." ] },{ "paper_id": "e40be79a3cf1f325f186e5b8adb087211f5ebc56", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e4514865ab32606bac0018ad579fe143067874bd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e4a3696c1433c42badbd9cce9ec2721be357e02d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e4b48ce0579f908da6dd3289bb2cc262dbdeae72", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Detection of HCV RNA was performed by RT-PCR. The first strand cDNA was synthesized by Superscript\u2122 First Strand cDNA Synthesis kit (Invitrogen) using gene-spe-cific downstream primers targeting the HCV p22 core region [9] with minor modification of the upstream primer (406(m)5'-TAGACCGGTGCACCATGAGC-3'). HCV cDNA was amplified by PCR through 40 cycles of denaturation (94\u00b0C-1 min), annealing (55\u00b0C-1 min) and elongation (72\u00b0C-1 min). Subsequently, PCR products were resolved through 1% agarose gel electrophoresis, hybridized to 32 P-labeled internal probe (5'-AGGAA-GACTTCCGAGCGGTCG CAA-3'), and exposed to Kodak film." ] },{ "paper_id": "e4c93a18d68cdabdab5f1ed3ba9621f611f3aa9e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e5869f8b8ecda2894a0ac35dc2f50bf56f24e72f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e58c8d02a519cb271727a06b0b54ea39307cf9f8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e59218b42f783a547778cbf247cce2552f9a163a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e5a12d970ccbf27a26ddd5568214768342997cc9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The majority of available potential scores were developed as mortality indicators and perform less well for predicting critical care usage. Amongst ICU admissions with community-acquired pneumonia in Massachusetts in 1996 to 1997, 10/32 scored CURB-65 1 or 2 (that is, low risk) and 5/32 were classified as PSI (Pneumonia Severity Index) class III (intermediate risk) [40] . Even amongst patients with pneumonia included in the PROWESS study, only 90.5% were PSI class IV or V, and only 70.3% had a CURB-65 score of 3 or above [41] .", "There is no guarantee that pandemic influenza will be primarily pneumonic in its presentation; case reports have documented H5N1 influenza presenting with diarrhoea [42, 43] and coma [43] and a World Health Organisation summary has described absence of respiratory symptoms in a number of cases [44] . The utility of disease-specific pneumonia scores may also be limited by mortality from comorbidities such as cardiovascular disease." ] },{ "paper_id": "e5c898f447a574feb83e59b9c5dbb4deb1b267f0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e61dc248ce523ab72ae25a6974c9e10cc1dcdea7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e646b7a9960fc90325ceaf6bade3ab0bc2b237ef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All pediatric (from case-patients and controls) and adult (case-patients only) NPA specimens were previously analyzed by using a multiplex real-time PCR assay for infl uenza A and B viruses, human respiratory syncytial virus (hRSV), and human metapneumovirus (hMPV) (24, 25) . For symptomatic children, viral cultures and antigen detection assays were performed upon request by the treating physician. Remaining specimens were frozen at -80\u00b0C until subsequent HBoV PCR studies.", "Sequence analysis of the HBoV VP1/VP2 genes performed on \u224850% of HBoV-positive specimens showed 2 distinct clades of viruses (Figure) . These genotypes clustered with the original strains described by Allander et al. (ST1, GenBank accession no. DQ000495, and ST2, Gen-Bank accession no. DQ000496) (1). There was no temporal link between the clades because both were equally distributed throughout the study period. No obvious relationship was found between clades and the presence or absence of symptoms.", "Proportions of clinical characteristics in different groups of patients were compared by using the \u03c7 2 test or the Fisher exact test. The Wilcoxon nonparametric test was used to compare age distribution and length of stay. Analyses were performed by using SAS software version 9.1 (SAS Institute, Inc., Cary, NC, USA)." ] },{ "paper_id": "e6480c384c8c808c6d1215c72c4e540a09d944c8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e6721f956795bb264b2a66d30e5e6f2145a09193", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e69dfe25f7db4608216cabd383668302a49df586", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The basic reproductive number (R 0 ) is the average number of secondary cases generated by a primary case. If R 0 < 1, an epidemic can not be sustained. On the other hand, if R 0 > 1, an epidemic typically occurs.", "Taiwan, 94% of SARS cases occurred through transmission in hospital wards (6) , and similar effects occurred in Hong Kong and Singapore (7) . Although the SARS epidemic was eventually controlled, the measures used to achieve that control varied greatly in scope from one place to another. Control of an outbreak relies partly on identifying what disease parameters are likely to lead to a reduction in the reproduction number R 0 . Here we calculate the dependence of R 0 on model parameters.", "\u03b2 (a = 2, b = 2) \u03b2 (0.92), l (0.57), \u03b4 (0.53), \u03b3 2 (0.35), \u03b1 (0.32), k (0.13) \u03b2 (a = 1, b = 2) \u03b2 (0.90), l (0.60), \u03b4 (0.44), \u03b1 (0.39), \u03b3 2 (0.26), k (0.12) \u03b2 (a = 2, b = 1) \u03b2 (0.92), \u03b4 (0.60), l (0.51), \u03b3 2 (0.40), \u03b1 (0.22), k (0.11)" ] },{ "paper_id": "e6be23c89a2a35984244b66372f9ec6bcc549839", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The model generates a random number for each class of encounter between potentially contaminated or infectious and uncontaminated participants during each clinic appointment slot. If this random number is less than the contamination probability specific to the class of interaction being considered, the uncontaminated member becomes contaminated during the encounter.", "Improved hand hygiene, barrier precautions, patient use of hand sanitizers or facemasks, and avoidance of environmental fomites can each diminish dissemination risk. However, these measures depend on individual behavior, rendering them susceptible to implementation failure. Temporal segregation adds a system-based layer of protection to such behavior-based interventions, providing an additional barrier to pathogen dissemination that is not critically dependent on individual compliance. When additional data addressing pathogen transmission within the clinic become available (currently such data are sparse), mathematical models could help guide the allocation of resources required to support system-based infection-control measures. Moreover, numerical experimentation could help inform the design of infection-control strategies for pathogens that have transmission dynamics that are not yet well characterized.", "An infectious patient can also contaminate the 4 patients surrounding him or her in the clinic queue (2 preceding and 2 following patients). The model does not incorporate patient-patient transmission by contaminated patients, given the relatively low frequency of intimate patient-to-patient physical contact in the clinic." ] },{ "paper_id": "e6c4b7349bd9542b2aa4a58acc26c5a6adaf4ba0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We conclude that ordinary current workstations do not pose a limitation for rigorously determining the size-andshape distributions, neither with regard to available memory, nor with regard to processor capabilities.", "This highlights the nature of the problem being a standard nonnegative linear least-squares problem. The unconstrained problem can be solved with the method of normal equations (Lawson and Hanson 1974; Golub and VanLoan 1989) ", "or, formulated with normal equations," ] },{ "paper_id": "e70b0c3cfc63da354e09518073419ac8c670c89b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e7225a44e3ba71ff67dae1b7dcdaba98dbe4e22b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e73a6a49cecb243ce24b57182cd354db7922d7e0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Minimizing the delay between admission and beginning antimicrobial treatment is key to achieving a successful outcome.", "J-FD was an investigator in the PROWESS study and is a consultant for Eli Lilly and Company. Y-EC declares that he has no competing interests. ", "Whichever drug is selected, introduction of vasopressors should be considered after optimal fluid loading; these agents may allow therapies to be applied earlier and more aggressively in order to improve physiological parameters and ultimately outcomes [48, 62] ." ] },{ "paper_id": "e770da379851d0105fff14a6f509f152361d15e4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e776077dcfd93e49990ea94ab5f67e0c02cd3fca", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e7f311d3c752063f75f28de85abd5f82eacab413", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All epicatechins used in this study (Fig. 2) with 50, 60 or 100 mM of each epicatechin or with no epicatechin (control) in RPMI-1640 with glutamine (Invitrogen), 9% FBS, 0.54% HEPES buffer, gentamycin (5 mg%) and fungizone (0.5 mg%).", "Analyses of variance and Fisher's least significant difference (LSD) method were used for pairwise comparisons of values significant at the 0.05 level. " ] },{ "paper_id": "e85838ff5bf9ad259d3511d9e906950e9d0d1ede", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e88710cd7b238794bd75f21d308bc5442ad9713f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e8b5cb3fc6da16eb2ffe2830a159b3aa9c04577d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A putative target epitope for effector T-cells in the processes suggested above ('epitope No. 2') was identified in a short peptide from the HERV-W env gene complex: MPVPSAPST. It is predicted that this peptide is presented, though only subdominantly, by diverse HLA class I molecules including Ld, A*0201, B*0702, B*5101, as determined by reference to the SYFPEIHI database for MHC ligands and peptide motifs [47] .", "Thus these prior contacts could have induced populations of T reg s that have a crucial role in protection against MS but also cross-react with an epitope on EBV. A subsequent infection by EBV could therefore generate a dominant population of cross-reactive T-helper-cells which could suppress or delete the T reg s.", "The immunoregulatory pathways are based on populations of lymphocytes, termed regulatory T cells (T reg s), in which there is currently considerable interest. In the case of infectious disease, such populations may lead to rapid resolution, the establishment of latent or persistent infection or to tissue damage by autoimmune processes [28] . Accordingly, T reg s have been termed 'a dangerous necessity' [29] . This term implies that T reg s are neither 'good' or 'bad' per se but may, according to the overall pattern of responsiveness, participate in appropriate immune reactions leading to resolution of disease or in inappropriate ones resulting in immunopathology." ] },{ "paper_id": "e92e2d8ab6aedfa9c7486162c9520e4ea4485df2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sequences were aligned using MUSCLE with default setting in Geneious R6, and checked visually for errors 47 . The best maximum likelihood tree with and without the constraint tree were generated using RAxML-HPC2 on XSEDE via the CIPRES Science Gateway server v3.1 48 using a GTR model with parsimony seed, 1000 bootstrap replicates, and the following, specific parameters (raxmlHPC-HYBRID -s infile -n result -x 12345 -g constraint.tre -N 1000 -c 25 -p 12345 -f a -m GTRCAT).", "(1)", "Matrices of pairwise patristic distances between all species, including Homo sapiens, were calculated from the two phylogenies using the 'cophenetic' function in the R package ape 46 ." ] },{ "paper_id": "e93d3778e75fa7201f27b9c93b541a16b8f4393a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A PubMed search was completed in Clinical Queries using the key terms 'febrile convulsions' and 'febrile seizures'. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews.", "To provide an update on the current understanding, evaluation, and management of febrile seizures.", "Background: Febrile seizures are the most common neurologic disorder in childhood. Physicians should be familiar with the proper evaluation and management of this common condition." ] },{ "paper_id": "e9c78584c08ba79d735e150eff98297eb57f12dd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e9d184be19d186f0c3aa85806c7f1bb4d0107160", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e9e0611bd64fa36c1a87679f24e49e28b92951bc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ea0237728df0d0d6df8c9bf3623c7e696c03a7f3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ea36a40b76e233b4f7d69d38d9ce3741ccd710b4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "eaa32e6b91a42f8c79e06cb8ea2285295d3c1536", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "eac2d30bfd0231911f3879b0d57be63297e4f351", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "eac877909f4f306c9a7e1c2609fb5d73a6b8ba69", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "eaca17432584c7f2ecbb17e611df70deed0dbec3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The total costs, the number of QALYs gained, and the incremental cost-effectiveness of each strategy in the model is shown in Table 3 . The results of sensitivity analyses are shown in Table 4 and Figure 1 . Algorithms outlining optimal treatment strategies under different testing capabilities are shown in Figure 2 .", "Under each strategy, we considered the possibility that persons with FRIs seeking medical care might receive antimicrobial drugs during their evaluation. We estimated this probability by using data from the National Ambulatory Medical Care Survey (32) .", "A plausible range of high and low values for each variable was used to conduct sensitivity analyses, which examined the influence of parameter error on the results of the analysis. Selected variables in the model are listed in Tables 1 and 2 ." ] },{ "paper_id": "eaceb9c0b3330a958c786c5fa07673d744269070", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "eae82da25e8df59f046a3c31405984543b53dc2e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Possible sources of nonsampling errors for this survey include nonresponse bias, as well as specifi c wording of questions and the order in which questions are asked. The margin of error for the total sample was \u00b12.4%. To examine differences among subgroups, we compared responses by testing for differences in proportions, taking into account the effect of the study's design (20) .", "Researchers differ over the potential effectiveness of such community mitigation measures. Evidence to determine the best strategies for protecting persons during a pandemic is limited. Several studies based on fi ndings from mathematical models and historical analyses suggest that early implementation of multiple measures, such as social distancing, school closures, and isolation of sick persons, may be effective in reducing the transmission of the virus (2) (3) (4) (5) (6) . Other researchers cite uncertainty (7) or believe such measures may not be effective (8, 9) .", "Data reported here are derived from a survey by the Harvard School of Public Health Project on the Public and Biological Security. The survey was \u224820 minutes long and consisted of 85 questions. International Communications Research conducted the survey from September 28 through October 5, 2006.", "Independent studies have shown that the results of statistically weighted data from shorter duration surveys are similar to those based on the higher response rate in surveys of long duration and can be used without an unacceptable risk for bias (14) (15) (16) (17) (18) . Nonresponse in telephone surveys produces some known biases in survey-derived estimates because participation tends to vary for different subgroups of the population. To compensate for these known biases, sample data are weighted to the most recent Census data available from the Current Population Survey for sex, age, race, region, and education (19) . Other techniques, including random-digit dialing, replicate subsamples, callbacks staggered over times of day and days of the week, and systematic respondent selection within households, are used to ensure that the sample is representative." ] },{ "paper_id": "eb25ca46c7e411e952c63ded8455c9df1006bbd4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The optimal experimental humanized mouse model, in which all human immune cell lineages can develop and home to specific sites to perform optimal immune response, should be explored. ", "and CD69 were demonstrated in spleen, liver, lung, kidney and bone marrow of the recipients. [155] . Depletion of CD4 + CD25 + Treg cells from human PBMCs significantly exacerbated xenogeneic GVHD, whereas co-administration of this subset of Treg cells significantly inhibited the expansion of effector T cells and reduced the lethality of xenogeneic GVHD. Interestingly, the protective role was associated with a significant increase in plasma levels of IL-10 and IFN-\u2425, indicating the de novo development of Tr1 cells [155] .", "Malignant tumours can unlimitedly grow, escaping from human immune surveillance. Athymic nude mice, SCID or Rag \u03ea/\u03ea mice could be successfully engrafted with xenogeneic human tumours including a wide variety of solid human tumours and haematological neoplasms [163, 164] , in which human tumour biology, growth, angiogenesis and metastasis have been evaluated." ] },{ "paper_id": "eb682a5cbe2942e78f0ec4959adce8475d5723d5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This survey was conducted as a public health authorized outbreak investigation, and research ethics board review was not required. However, ethics review and approval were obtained prior to blood collection.", "13 ( ", "BC Centre for Disease Control." ] },{ "paper_id": "eba4fe7ae5e8a69de34227a077e2050f4a93cb2f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Electronic supplementary material The online version of this article (", "In contrast to bacterial pre-tRNAs-which are disrupted by self-splicing group I introns [12, 13]-archaeal and eukaryal pre-tRNA transcripts undergo enzymatic splicing. The latter achieves intron removal by endoribonucleolytic cleavage and subsequent ligation rather than by two consecutive transesterification events as employed by selfsplicing introns or the spliceosome.", "ASW has first been characterized in a genetic screen searching for genes differentially expressed in early neural specification in Xenopus laevis [127] . Although this study could demonstrate that alteration of ASW levels in X. laevis leads to severe developmental defects, it provided limited insights into mechanistic aspects of ASW function. ASW has been speculated to be specific for vertebrates as no homologous genes were detectable in Drosophila melanogaster or Caenorhabditis elegans [127] . Nonetheless, homologues of ASW are detectable in the genomes of at least some arthropods and nematodes (Fig. 5A) . Future studies might answer the question of whether the link between ASW and HSPC117 explains any of the developmental defects observed upon manipulation of ASW levels in X. laevis." ] },{ "paper_id": "ebed3cc5b0f4f9aa5a2dd3fd6f107c7a3a707914", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ec01394568507c47b7ef63f688ca9ca4c233964a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The bacterial tests were performed according to the standard procedures of the National Veterinary and Food Research Institute in Helsinki. The mycoplasma samples were kept frozen at -70 \u00baC until cultured. The media, culturing and identification methods used have been described elsewhere (Tanskanen 1984) . Species identification was based on growth characteristics and the selective use of an epi-immunofluoresence (IF) test; only antisera against Mycoplasma dispar 462/2, Mycoplasma bovirhinis PG 43 and M. bovis Donetta PG 45 were used.", "Results of the antibodies to viruses are presented in Table 1 . Antibodies to PIV-3 and BAV-7 were found in all 18 herds. Antibodies to", "Tracheobronchial lavage samples from 85 calves in 18 herds were tested for bacterial growth. Samples were cultured on blood agar (tryptose-soya-agar containing 5% bovine blood) aerobically and anaerobically as well as on selective agar for Histophilus somni (formerly Haemophilus somnus) in a CO 2 -enhanced atmosphere. More specific identification was made with biochemical tests. The susceptibility of different Pasteurella sp. isolates for selected antimicrobials was tested. The antimicrobials used were ampicillin, penicillin, trimethoprim-sulfamethoxazole, gentamicin, tetracycline and enrofloxacin or ciprofloxacin." ] },{ "paper_id": "ec1ffddf6d1cb1f2a96a599bf0d2b3c70d5dec58", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study was conducted exclusively at the Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital and Health Service, Brisbane, Queensland, Australia. The necessary ethical approval for this study was obtained from the Ethics Committee of the Royal Children's Hospital.", "Three MCPyV (MCV-B1/B2/B3)-positive samples were further investigated through bidirectional sequencing of their LT3 (FJ009185, FJ009186, and FJ009187, respectively) and VP1 (FJ009188, FJ009189, and FJ009190, respectively) assay amplifi cation products. The sequences of the 3 samples showed high homology to those of the 2 previously described MCPyV strain sequences, MCC350 (EU375803) and MCC339 (EU375804) (3); similarities in the LT3 and VP1 target regions ranged from 99.6%-100.0% and 99.0%-99.6%, respectively ( Table 2) .", "Analogous to MCPyV, both KIPyV (1,4) and WUPyV (2,4) have been found globally in respiratory specimens with a high prevalence of codetected viruses, but clear evidence for a causal association with respiratory illness has yet to be identifi ed. These PyVs may be merely transmitted through the respiratory route or detected during periods of reactivation (9) . Similarly, JC and BK PyVs are suspected of being transmitted by inhalation and are occasionally detected in respiratory samples, yet patients generally remain asymptomatic or exhibit nonspecifi c upper respiratory tract symptoms (10, 11) . Like these other PyVs, MCPyV may potentially be transmitted through the respiratory route and become latent in other sites, such as epidermal tissue, by systemic spread, in a similar fashion to murine PyV (12) . Clearly, further studies using larger sample populations, expanded respiratory pathogen detection methods, and control groups are needed to elucidate what role, if any, MCPyV plays in upper and lower respiratory tract illness.", "Clinical notes were available for 5 of the 7 MCPyVpositive patients and indicated that these patients exhibited a variety of upper and lower respiratory tract symptoms. MCPyV was the sole viral agent detected in 6 of the 7 samples (Table 1 ). However, due to limited remaining volumes, study samples were not screened for other known respiratory pathogens, including coronaviruses and rhinoviruses, which may have led to a higher codetection rate, similar to that for KIPyV (1, 4) and WUPyV (2, 4) ." ] },{ "paper_id": "ec36627d378bd763bd34105515a08f6f55f03da1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Interpretation of complete blood cell count was consistent with a stress leukogram. Mild leukocytosis (26.2 9 10 9 /L; RI, 5.5-19.5 9 10 9 /L) with mild neutrophilia (23.8 9 10 9 /L; RI, 2.5-12.5 9 10 9 /L) and mild lymphopenia (0.58 9 10 9 /L; RI, 1.5-7.0 9 10 9 /L) were present. Urinalysis disclosed the presence of granular casts (10 per 81 high-power fields, 4009), but was otherwise unremarkable. Urine specific gravity was 1.015 (after IV fluid therapy)." ] },{ "paper_id": "ec38b733b394029c900b0bf2b3ee8c186b7e9956", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ec3ef2cdfe11f6f475f0c193fe3c4dfe1066f277", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "No adverse events were observed or reported during or after either study. Controls and validations in both studies conformed to EN1499 requirements.", "A total of 15 healthy adult volunteers were screened and enrolled in each study. All volunteers were in general good health with normal skin (free of dermatoses, cuts, lesions, hangnails and other skin disorders), short fingernails (\\ 2 mm in length), no history of skin disease and had not used oral or topical antibiotics within the previous 2 weeks. All volunteers abstained from using antimicrobial products for 7 days prior to testing and during the whole study.", "The experimental design using EN1499 is applicable to viral testing with MNV as discriminatory and reproducible results were generated ( Table 2 )." ] },{ "paper_id": "ec6675c47e1dc4e4227c9ed3345103a82baaf09b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Additional limitations of the PAGEIA are similar to those of other serologic tests. PAGEIA can detect only seropositivity, which is not necessarily indicative of current infection or of current shedding of virus. It also binds only with high affi nity to IgG; thus, it is not useful for discriminating other immunoglobulin classes, such as IgM, the presence of which usually indicates recent infection.", "horseradish peroxidase enzyme-linked immunosorbent assay (PAGEIA) to detect antibodies to SNV in deer mice (7) . The test can be completed in \u22481 hour under relatively primitive fi eld conditions. The assay has advantages over more laborious assays used for similar purposes and, because it is mammal-specifi c rather than species-specifi c, we expect this assay will be applicable to serologic tests of mammals of many other species.", "Because of the broad mammalian species specifi cities of a protein-A and protein-G conjugate, the rapid PAGEIA likely can be used to test for antibodies to other antigens in other mammals. Lee et al. (7) characterized the reactivities of protein A and protein G with IgG from rodents of several species. They found that serum specimens from both sigmodontine rodent species (deer mice and hispid cotton rats, Sigmodon hispidus) they tested were recognized by protein-A and/or protein-G conjugates. Similar laboratorybased PAGEIAs have also been used to detect antibody to antigens of agents causing other infectious diseases, including severe acute respiratory syndrome coronavirus-like viruses and Nipah virus in bats (13) (14) (15) ." ] },{ "paper_id": "ec69d4cf6cbbee8eab930f347ca9ad135db8ef28", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ec7973e6d8b97caf18e06fa5b0150b47157fe45a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ec9040732c2587bf4776b0953905e8a87828e8cf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ecee696015fbe0e5ec5d1a7c560fc8d1191d95a1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Twelve IBVs were isolated and propagated from the kidney, trachea and cecal tonsil of suspected IB carriers between 2001 and 2003 using embryonated SPF chicken eggs according to the standard procedure [7] . The history of these isolates is shown in Table 1 .", "All procedures for RNA isolation and reverse transcriptase-polymerase chain reaction (RT-PCR) were previously described [14] . Viral RNA was isolated and purified from allantoic fluid collected from embryonated SPF chicken eggs inoculated with IBV isolates using the QIAamp MinElute Virus Spin Kit (QIAGEN, USA).", "The avian infectious bronchitis virus (IBV) causes economically important upper respiratory and urogenital tract diseases in chickens, resulting in tracheal rales, sneezing, coughing, reduced weight gain, and reduction of egg production [5] . IBV, the causative agent of infectious bronchitis (IB), belongs to the family Coronaviridae and is found worldwide [5, 15] . The genome of IBV consists of a single-stranded sense RNA genome encoding four structural proteins, which are envelope glycoprotein, integral membrane glycoprotein, phosphorylated nucleocapsid protein, and spike (S) glycoprotein [15, 22] . The S glycoprotein is cleaved post-translationally by cellular proteases into the S1 and S2 subunits [4] . The globular S1 subunit forms the tip of a spike, extending outward, whereas the S2 subunit anchors the S1 moiety to the viral membrane [1] . The S1 subunit is involved in viral infectivity, virus-neutralizing epitopes, serotype-specific sequences, and hemagglutinin activity [1] [2] [3] 11, 12] ." ] },{ "paper_id": "ed276d222dcdee71e13c0b46fdb9c70f06d5fcd9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ed2de3694f5580ea38f4adf24bd1c8b46862df1f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "MBL assays were performed at baseline in 1037 (91%) of the 1142 subjects enrolled in the azithromycin trial. Of these, 909 had experienced one or more AECOPDs in the year prior to enrollment. Duplicate measurements of MBL had coefficients of variations ,15% in all cases and ,5% in most.", "Azithromycin increases expression of the mannose receptor, and uptake of apoptotic cells by human alveolar macrophages, and decreases recovery of apoptotic bronchial epithelial cells. 27 Accordingly, MBL concentrations from patients randomized to receive azithromycin or placebo were analyzed both separately and together.", "Because we only found 20 subjects (1.9%) with MBL concentrations below the lower range of normal reported by the manufacturer of the assay, we cannot exclude the possibility that very low concentrations of MBL have an association with AECOPDs. However, the infrequency of this finding implies that even if this association were found, it would pertain only to a small minority of patients suffering AECOPDs." ] },{ "paper_id": "ed41111b7ec211ae5ad254835306b8a92567411d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(a) (b) (c) (d) (e) (f) (g) (h) (i) (j)", "Interdisciplinary Perspectives on Infectious Diseases", "MHV-2 H and E, d5" ] },{ "paper_id": "ed7a04f26d6e08daab64aa8f7fb5bac8da9e0bad", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Genus in the family Parvoviridae. Previously identified members of this genus are pathogens of bovines and canines. A parvovirus of human origin was recently discovered and called human bocavirus because it is closely related to bovine parvovirus and canine minute virus. Human bocavirus is associated with respiratory tract infections, particularly in infants and young children. ", "Of 40 HBoV-positive respiratory samples, 25 (62.5%) showed coinfection with other viruses (respiratory syncytial virus in 13, rhinovirus in 3, influenza A in 3, coronavirus OC43 in 2, adenovirus in 1, influenza B in 1, respiratory syncytial virus and coronavirus OC43 in 1, and influenza A and rhinovirus in 1). Of the 48 HBoV-positive fecal samples, 28 (58.3%) showed coinfection with another intestinal pathogen (Salmonella enteritidis in 1, Campylobacter jejuni in 5, rotavirus in 14, norovirus in 7, and C. jejuni and norovirus in 1).", "Articles should be no more than 1,200 words and need not be divided into sections. If subheadings are used, they should be general, e.g., \"The Study\" and \"Conclusions.\" Provide a brief abstract (50 words); references (not to exceed 15); figures or illustrations (not to exceed 2); tables (not to exceed 2); and a brief biographical sketch of first author-both authors if only 2. Dispatches are updates on infectious disease trends and research. The articles include descriptions of new methods for detecting, characterizing, or subtyping new or reemerging pathogens. Developments in antimicrobial drugs, vaccines, or infectious disease prevention or elimination programs are appropriate. Case reports are also welcome." ] },{ "paper_id": "edc0a7510a126ecbd0c7d43a489979bab36ceea1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "None.", "references:" ] },{ "paper_id": "ee13a8332bcf2df6a68e2190a337a0cbaa161281", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Genomic DNA was isolated from flash-frozen mouse lung tissues using a Qiagen DNeasy Blood & Tissue Kit (Qiagen) according to the manufacturer's instructions. Measurement of N-7-(2,3,4trihydroxybut-1-yl)-guanine (THB-Gua) was performed using liquid chromatography/positive ion electrospray ionization/tandem mass spectrometry (LC=ESI + MS=MS) as described by Goggin et al. (2009) , with minor modifications.", "Differentially expressed mRNAs and miRNAs were identified using the package DESeq2 v. 1.8.2 (Love et al. 2014 ) in R (version 3.2.3; R Development Core Team) with betaPrior set to \"false.\" For miRNAs, a minimum threshold of 10 reads in at least five mice from one strain was required.", "* Indicates a significant difference (p < 0:05) between the exposed and the control mice of the same strain. \u2020 Indicates a significant difference (p < 0:05) between the exposed mice from each strain [based on one-way analysis of variance (ANOVA) with Tukey's post hoc test]." ] },{ "paper_id": "ee46c9064c2ef4916ba7d54c80236d3cb1781635", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The replication protein A complex (RPA) plays a crucial role in DNA replication and various DDR processes.", "Transcription-coupled nucleotide excision repair (TC-NER) is a sub-pathway of NER that efficiently removes highly toxic RNA polymerase II blocking lesions on DNA. Defective TC-NER gives rise to the human disorders-Cockayne syndrome and UV-sensitive syndrome (UVSS) [101] . Recently, the UVSSA protein was shown to recruit USP7 to ERCC6 TC-NER complexes upon DNA damage, representing a critical regulatory mechanism in restoring gene expression upon damage [102] . As we describe in later sections, the efforts at targeting USP7 with small molecule inhibitors have been undertaken based on the fact that USP7 regulates p53 checkpoint activity [103] and also behaves as a key DUB for multiple DDR pathways." ] },{ "paper_id": "ee70b25804619797b5aeb8440a84203117ee36ef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The steps for cloning the NoV GII-4 (GenBank sequence database accession number AF080551) full-length capsid gene are described elsewhere [11] .", "Sucrose VLPs+H type 3", "Noroviruses (NoVs) cause sporadic acute nonbacterial gastroenteritis in all age groups [12, 13] . NoVs are divided into five genogroups, GI to GV, of which GI and GII strains mostly affect humans [21] . Recently, NoV genotype GII-4 has been responsible for the majority of sporadic gastroenteritis cases and outbreaks [13] . The NoV genome consists of a single-stranded RNA of about 7.6 kb, organized into open reading frames (ORF 1-3). ORF-1 codes for the RNA-dependent RNA polymerase, and ORF-2 and -3 encode the two structural proteins VP1 and VP2 [10] ." ] },{ "paper_id": "ee8a6b2db7d43dedd8668300d2e71587a3062f17", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Background Timely influenza surveillance is important to monitor influenza epidemics.", "With all these n \u00b7 N values, a one-tailed point 95% confidence interval is calculated.", "The median timeliness of epidemics detection was 1 week. The timeliness ranged from 0 (Belgium, Castilla y Le\u00f3 n, Portugal and Switzerland) to 4AE5 (Norway), and again, the lowest values appeared in countries where other statistics of performance appeared strongest. This lag was observed to be a week longer in the countries reporting ARI than in countries reporting ILI but this difference was not statistically significant (P = 0AE13)." ] },{ "paper_id": "eede431ba944ca208bf69d6c10e40dc7d52db655", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "While it is extremely likely that the human MHC is critical to immune response, both against foreign and self antigens, few experiments have yielded results as clear as those in mice. For most immunologic disorders where an association with the MHC has been sought, analysis of observations in populations have been hampered by MHC polymorphism, as well as by many confounding clinical factors such as ethnic variation in the distribution of MHC alleles, environmental factors, and the additive effects of non-MHC genes.", "Although the MHC is a complex system, the recognition of common gene combinations in humans, or extended haplotypes, has clarified, and sometimes identified for the first time, relationships between MHC genes and immunologic function and dysfunction. Many questions can be explored using this approach-the relationship between specific haplotypes and gluten-sensitive enteropathy [37] , pemphigus vulgaris [38] , and diabetes [39] , for example. Others merit possible consideration-for example, could unrelated bone marrow donors be chosen based on extended haplotype matching (which we would predict could be successful despite selective HLA-A allele mismatching)? The concept of extended haplotypes should provide a useful framework for interpreting data from a variety of studies of the immune system over the coming years.", "As they are in mice, the genes of the human MHC are highly polymorphic, including at least 24 variants of HLA-A, 52 variants of HLA-B, 11 of HLA-C, 20 of HLA-DR, nine of HLA-DQ, and six of HLA-DP [14] . Such polymorphisms may have been important in an evolutionary sense in the development of immunity, although, ironically, at the expense of a greater likelihood of graft rejection [ 12] ." ] },{ "paper_id": "eee925fdf6e8c99bb72678f1b413fd65cc78c585", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Recombinant human sRANK receptor is a 19.3 kDa polypeptide. It was electrophoresed on a 10% polyacrylamide gel and transferred to nitrocellulose membrane. On incubation with generated mAb, a band was detected between 15 and 20 kDa, after the chemiluminescent detection of anti-RANK IgG (Fig. 4) .", "KEY WORDS drug delivery system . monoclonal antibody . osteoclast . osteoporosis . post-traumatic osteoarthritis . RANK receptor . salmon calcitonin M. Newa : K. H.", "associated with differing classes of bisphosphonates, the most commonly prescribed medication for osteoporosis (23) . Estrogen hormone replacement therapy stimulates uterine and breast tissue, which predisposes the patient to neoplastic disease (24) . Leg muscle cramps, joint aches and deep vein thrombosis has been associated with selective estrogen receptor modulator therapy (25) . Similarly, conventional salmon calcitonin has shown limitations in antiresorptive efficacy, likely in part because of poor bioavailability to bone cells and the undesired uptake of the drug by calcitonin receptors present in tissues other than bone (26, 27) ." ] },{ "paper_id": "eef0cab385662b98975be9e90899f63f19243bce", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ef5660b91f755b280e59a60c59ea2eee570ee370", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ef58b4dc1fbd69df709cfb1bd5e80a1ba03bc97b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study was conducted under grant of research council, AJA University of medical sciences and IVO grant.", "In the set of coronaviruses NL63, 229E, OC43, HUK-1 the only detected virus was 229E (5.5%, is positive samples). Of positive samples for all three months, 85% were male with the range of age between 12-75 years old.", "Sampling. 270 nasopharyngeal swabs from suspected patients that show respiratory clinical signs were collected during October to December 2015 (9) . Samples were collected from three hospitals in Tehran city (Besat, Golestan, and Imam REZA). The patients suffered from respiratory syndrome such as coughing, gasping, and excessive lacrimation. The range of age was between 12-75 years old. In addition, the males and females were 65% & 35% of the cases respectively. RNA Extraction. RNA was extracted from swabbed samples using high pure viral RNA kit (Roche Co.,Germany) according to manufacturer's instructions. The purity of the extracted RNA was determined by taking the ratio of the readings at 260 and 280 nm. We used negative control during the extraction procedure." ] },{ "paper_id": "efac5c5025f1b54b65276fea345f3a2dc580d174", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "On July 10, the diagnosis of MHF was confi rmed; the next day, the patient died. A complete case history and the public health response have been reported (1).", "This study was determined to be part of the public health response to the imported case of MHF and followup of contacts. Therefore, explicit ethical evaluation was not necessary.", "Emerging Infectious Diseases \u2022 www.cdc.gov/eid \u2022 Vol. 18, No. 7, July 2012 ", "Despite being sent reminders, the response rate of participants was only 60.0%. This limits interpretation of results because motives for noncompliance remain unknown. As in most retrospective studies, we also need to acknowledge the chance of recall bias, which might infl uence recollection of experiences. Another limitation was inherent to the study design, which required answers only from contacts. Thus, consequences of control measures on members of the household could only be assessed indirectly. Despite the limitations of IFA (32), serologic fi ndings strongly suggest that none of the contacts who provided a blood sample had become asymptomatically infected.", "I n July 2008 in the Netherlands, an imported case of Marburg hemorrhagic fever (MHF) (1) was diagnosed in a person after possible exposure in a bat cave in Uganda. MHF is caused by Marburg virus, which belongs to the family Filoviridae (2, 3) . The main route of transmission is by direct contact with blood or body fl uids (4) . The virus was discovered in 1967 during a laboratory outbreak in Marburg, Germany (5, 6) . Apart from this person, since the outbreak in Marburg, MHF has been diagnosed only once outside Africa (7) ." ] },{ "paper_id": "efff85e4de5521d86c399aceb8ef44c55a7a1121", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "emergence of primateborne pathogens such as HIV/SIV and will form a scientific basis for guiding policies and programs to deter the spread of emerging zoonotic pathogens.", "Five hundred ng purified DNA from whole blood was combined in a PCR reaction mixture with a final concentration of 10 mmol/L Tris (pH 9.0), 50 mmol/L KCl, 0.1% Triton X-100, 2.5 mmol/L MgCl 2 , 200 \u00b5mol/L each dNTP, 0.15 mg/mL BSA, 1 U Taq polymerase, and 400 nmol/L of each primer in a total volume of 50 \u00b5L. The following primers were used: forward, 12SA, 5\u00b4 CTG GGA TTA GAT ACC CAC TAT 3\u00b4, and reverse, 12SO, 5\u00b4 GTC GAT TAT AGG ACA GGT TCC TCT A 3\u00b4 (35) . Cycling conditions were the following: initial denaturation at 94\u00b0C for 5 min, followed by 35 cycles of 94\u00b0C for 30 s, 55\u00b0C for 30 s, and 72\u00b0C for 5 min, with a final extension at 72\u00b0C for 5 min. The 101-bp product underwent electrophoresis and was processed for DNA sequencing essentially as described for SFV.", "Because SFV is not known to occur naturally in humans, detecting serologic or molecular evidence, or both, of infection in a human, along with a history of close contact with primates, constitutes strong evidence for primate-to-human transmission, i.e., a marker for crossspecies transmission (28) . Existing serologic and molecular techniques can sensitively and specifically detect human SFV infections (29) ." ] },{ "paper_id": "f0487c3f285a07a594aac45ed339968de0680c3f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Conditions under which these approaches would be useful include:", "\u2022 Protein-protein interactions that are resistant to characterization using standard GST fusion or yeast 2hybrid analyses;", "\u2022 A source of monoclonal antibodies (mAbs) or similar specific binding agents must be available. If mAbs cannot be made, single chain fragment variable reagents from phage display libraries could be used (15); \u2022 Analytical quantities of functional protein, obtained by purification from bacteria, in vitro translation, baculovirus infection of insect cells or other methods; and \u2022 A functional assay for protein activity." ] },{ "paper_id": "f0cd69cc5ce78e991615973043a3db23a29bab4a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f0f56c1e82c717ced3a4f2ca872dd303581ea750", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f11cea7250059fc4acd3955f7d66579d10c11d7e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Hong Kong", "The study, being a large-scale study investigating SARS transmission in the community setting, allows us to have a better understanding of the infectivity, modes of transmission, and prevention of SARS in a community setting. It also gives insight into the prevention of secondary SARS infection within the household.", "Of rather than secondary infection (4, 5) . Excluding the Amoy Gardens cases, the attack rates were 13.9% and 8%, respectively. The SARS attack rates in the households therefore were not negligible." ] },{ "paper_id": "f1382d2d476137ce89455675b6a2eb68a485ebac", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 Proper hand-washing hygiene after toilet use and before food preparation and feeding. \u2022 Safe disposal of human and other waste.", "Blood cultures are examined for evidence of bacteremia.", "The authors report no conflicts of interest in this work." ] },{ "paper_id": "f1446580f1091a33b07aad5ecbe7151c5895cafc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Among those who contract infl uenza, subsequent illness and death may be infl uenced by underlying factors and conditions and by the timeliness and effectiveness of various treatment modalities. Most infl uenza illnesses are self-limiting, and most infected persons during both annual infl uenza epidemics and infl uenza pandemics (including that of 1918-19) recover with only supportive care in the community. Even so, current planning efforts recognize the potential importance of reducing disease during a pandemic, through early treatment with antiviral drugs and through other forms of treatment such as respiratory support and antimicrobial agents to treat secondary bacterial pneumonia, among those with more severe disease.", "On a US government website for pandemic infl uenza (www.pandemicfl u.gov), a question asks which groups would be especially vulnerable during an infl uenza pandemic. The answer notes that people may be vulnerable for a variety of reasons, including limited access to healthcare; limited profi ciency in English; or being disabled, homeless, economically disadvantaged, or a single parent. The response calls for faith-based and community-based organizations to develop plans \"to care for dependent populations\" and to \"provide fi nancial aid to the poor who are unable to work and are in need of emergency income for housing, medicine, or other essential needs\" (www.pandemicfl u.gov/faq/pandemicinfl uenza/pi-0001.html), which implies that attention to the needs of economically or socially vulnerable persons is not primarily a public-sector responsibility but is more a matter for private charity. The 2005 HHS plan (37) itself acknowledges that some groups may need fi nancial assistance if they are unable to work but does not indicate how that assistance would be provided or who would provide it.", "The Pandemic Infl uenza Plan of the US Department of Health and Human Services (HHS) (37) does not adequately address potential social disparities in exposure, vaccination, or treatment; the possible effects of such disparities; or strategies for minimizing or eliminating them. The HHS plan (37) , the federal guidance on vaccine allocation (38) , and the recent Centers for Disease Control and Prevention (CDC) guidelines for community-level mitigation strategies (18) should be credited for calling for community engagement and inclusion of a wide variety of stakeholders in planning at the local level. Outreach to providers, community leaders, and organizations, particularly in disadvantaged communities, will be an important component of any strategy for addressing disparities during a pandemic. However, the available versions of offi cial plans do not call attention to the need for special efforts to overcome the greater barriers likely to be faced by socially disadvantaged groups." ] },{ "paper_id": "f1548a1bcf0d81c278b46d24408dc7e63d9ce09d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Director, Patient Relations (The Hospital Ombudsman), University Health Network, Toronto, Ontario, Canada avoiding meetings/gatherings, as well as kissing, hugging and even hand shaking. Clearly, these restrictions are reflective of a loss of civil liberties in the general population and render expressions of caring difficult at a time when people may need them the most.", "It is ethical to accept that public health protection trumps individual rights to liberal visitation. The rationale for this position must be fully outlined to patients, visitors and staff.", "It is difficult to expect that both standardization of approach and variability in approach can easily coexist, but the operational challenge is to exercise awareness of the ethical values discussed above and the appropriate due diligence in the implementation of processes." ] },{ "paper_id": "f15bfd75b9e2933456942b0f1867aade1586670f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f16e75ea1eeb18f86b4e113796cabc4c7c78621a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f194d114007cfcecb07bcfc17b26256ea82cc46e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f1d1b9694aa43c837d9b758cb2d45d8a24d293e3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For illustration purposes, local signatures are developed as vertical vectors and stacked together in genome order to give an overall picture of word usage variations along each genome. In such plots, horizontal lines show the variation in frequency of words along the genome, whereas local changes in word usage appear as vertical breaks ( Figure 1 ). Figure 1 . Signatures (4-letter words and 5 kb windows) along genome for Clostridium acetobutylicum, Deinococcus radiodurans and Mycobacterium tuberculosis. In this kind of displays, lines represent the frequency of words along genome, columns represent signature of windows.", "Finally, the gene content of all detected regions is analyzed with the help of species dedicated databases [Genome Information Broker, http://gib.genes.nig.ac.jp/]. A BlastN search (GenBank, default settings) is carried out for each atypical region in order to identify the origin of potential HTs if homology is high enough.", "\u00aa 2005, the authors", "We have observed that most genomic regions are typical of the genome they belong to, using the signature as endpoint." ] },{ "paper_id": "f1e47847b222b58ed3c6cc35c785b1136c388019", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Total RNA was isolated using RNA STAT-60. RNA was quantified spectrophotometrically and 0.5 \u00b5g of total RNA was converted into cDNA. Briefly, total RNA and random primers (Invitrogen, Carlsbad, CA) were incubated at 72 degrees for 10 minutes. Reverse transcription was performed using the Superscript II RT enzyme (Invitrogen, Carlsbad, CA) and followed the specification of the manufacturer. cDNA was diluted to 200\u00b5l with water and 4\u00b5l was used for quantitative real-time PCR using SYBR Green kit (Abgene, Epson, UK). The PCR parameters were 15 minutes for 95 degrees and 35 cycles of 95 degrees for 15 seconds and 60 degrees for 1 minute in ABI prism 700 (Applied Biosystems, Foster city, CA). The primers were used at 10 nM. Serial dilutions of cDNA containing a known copy number of each gene were used in each quantitative PCR run to generate a standard curve relating copy number with threshold amplification cycle (45). Gene expression levels were calculated during the logarithmic amplification phase by determining the initial mRNA copy number using the standard curve. Amplification of each gene specific fragment was confirmed both by examination of melting peaks and by agarose gel electrophoresis. The following primer pairs were used in this study: SHP-1 (BC002523) forward-TGGCGTGGCAGGAGAACAG and reverse-GCAGTTGGTCACAGAGTAGGGC, SHP-1 Promoter (I) (NM080548) forward-TGGCTTCCCCCTCCCTACAG and reverse-CCCTGGTTCTTGCGACTGG, SHP-1 Promoter (II) (NM002831) forward-ATCTGAGGCTTAGTCCCTGAGC and reverse-CTGAGGTCTCGGTGAAACCAC, CCL17 (NM002987) forward-CGAGGGACCAATGTGGGC and reverse-GGGTGAGGAGGCTTCAAGACC, CCL11 (NM002986) forward-CACTTCTGTGGCTGCTGCTC and reverse-GCTTTCTGGGGACATTTGC, CCR8 (NM005201) forward-CAGTGTGACAACAGTGACCGAC and reverse-GCAATAAAAGACAGCAAGGAGC, ADAM8 (NM001109) forward-ATCCCGAGAGACCCGCTAC and reverse-TGATTCACCACCTCCAGCAC, Arginase I (NM000045) forward-GACCTGCCCTTTGCTGACATC and reverse-TTGACTTCTGCCACCTTGCC, MCP-1 (NM002982) forward-GCTCATAGCAGCCACCTTC and reverse-GCTTCTTTGGGACACTTGC, Caspase I (NM033294) forward-CATCCTCAGGCTCAGAAGG and reverse-TGTGCGGCTTGACTTGTC, COX-2 (NM000954) forward-GCATCTACGGTTTGCTGTG and reverse-ACTGCTCATCACCCCATTC, GAPDH (NM002046) forward-ACCACCATGGAGAAGGC and reverse-GGCATGGACTGTGGTCATGA.", "Whole cell extracts were prepared as previously described (26, 30) . Briefly, macrophages were rinsed with PBS, and then lysed with RIPA buffer. 10 \u00b5g of protein per lane was electrophoresed through a 12.5 % polyacrylamide resolving gel and electroblotted to a polyvinylidene difluoride (PVDF) membrane (Millipore Corporation, Burlington, MA). Membranes were blocked with 5% nonfat dry milk for 1 hour, and then incubated with anti-SHP-1 (Upstate, Lake Placid, NY) antibodies followed by horseradish peroxidase conjugated rabbit IgG antibody. (DAKO Corporation, Carpinteria, CA) or anti-arginase I (BD Biosciences, San Diego, CA) followed by horseradish peroxidase conjugated mouse IgG antibody. Enhanced chemiluminescence (Amersham Life Sciences, Inc., Cleveland, OH) was used to visualize reactive protein bands on X-ray film. Western blot protein bands were quantified based on pixel density using the Scion Image software.", "Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system (CNS) that remains a major cause of disability (1) . Several studies demonstrated that MS lesions contain multiple leukocyte cell types including lymphocytes, macrophages, and dendritic cells all of which are believed to contribute to lesion formation by various distinct and interacting mechanisms (2, 3) . Among these leukocyte subsets, infiltrating macrophages have been identified as major effectors of demyelination in both MS and animal models for MS (4) (5) (6) (7) (8) (9) (10) (11) . In accord with these studies, it was recently described that a predominant mechanism of demyelination in MS is macrophage-mediated (12) ." ] },{ "paper_id": "f24c7d6af5f673b9dcb3258adf3cba74df3af1d6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Colonoscopy and barium enema were unsuccessful because of excessive fecal residue.", "From the throat swab, a weak band measuring 310 bp was found by using the Cor1/2 primer set only. Positive bands were seen with all three primer sets on the stool sample; the bands with the SAR1S/As and BNIoutS2/As primers measured 190 and 150 bp, respectively.", "The patient had multiple coexisting conditions including ischemic heart disease with atrial fibrillation, previous stroke with scar epilepsy, diabetes mellitus with nephropathy (creatinine 242 \u00b5mol/L), and peripheral vascular disease. He was not on steroids or traditional medications.", "Clinical signs and symptoms were melena and dizziness. He was pale, temperature was 36.5\u00b0C, blood pressure was 126/70 mm Hg, and pulse rate was 110/min. Chest examination was normal, and the abdomen was soft. Rectal examination showed melena. The patient also had a sloughy right heel ulcer. Laboratory values are shown in the Table. Antral gastritis was diagnosed on gastroscopy." ] },{ "paper_id": "f2caaa5a4a9ddb82c1324b28106e08b30ccc501d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f2cc8e8c4fa06d2af961fe2c2bab8c2d1e2849b3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "its inhibitory effect on HIV-induced cell fusion. J Immunol 149:1779-1787 Burkly L et al (1995) ", "SV40 Although SV40 represents a virus with a particularly well-studied entry pathway, recent evidence suggests that this well-characterised route is not as clear cut as it may initially have seemed. SV40 became of particular interest to virologists and cell biologists alike as being the first virus shown to enter cells via a clathrin-independent endocytic pathway (Anderson et al. 1996) . In fact it was, at least in part, the study of SV40 entry which led to the discovery of what we know as caveolar endocytosis and the caveosome, and as such, labelled SV40 is often used as a tool to study intracellular trafficking (Fig. 2) .", "Influenza A The entry process of Influenza A is a muchstudied topic and differs from the simple membrane fusion processes described for the majority of enveloped viruses. The first electron micrographs of influenza-infected cells demonstrated particles inside cytoplasmic compartments. Subsequently, the particles were seen to penetrate the membrane of this compartment followed by genome release in the cytosol (Dourmashkin and Tyrrell 1974) . While this evidence pointed towards an endocytic mechanism of entry, the images failed to show the fusion of viral and host cell membranes that is believed to play a critical role in escaping the low pH environment of the endosome." ] },{ "paper_id": "f2cf26f9c677482ee8e060ce7d9d73b6214fef52", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "H uman noroviruses (NoVs) are the most frequent cause of epidemic and sporadic acute gastroenteritis worldwide among humans of all ages (1, 2) . The virus is transmitted through ingestion of contaminated food or water or from person to person through the fecal-oral route. The close genetic relatedness of swine NoV with human NoVs of genogroup (G) II suggests the potential for transfer from animals to humans (3) (4) (5) . In addition, recent fi ndings of viruses genetically related to human NoVs, as well as to animal NoV sequences in pigs and calves, have raised concerns about the possible emergence of recombinant viruses (4) .", "For several reasons, our fi ndings should be interpreted with caution. Viral shedding from dogs without diarrhea could represent asymptomatic infection, a resolution stage of the disease, or detection of CPV-2 vaccine virus. In addition, other canine enteric pathogens for which we did not test could bias the results. Further research that includes electron microscopy or infectivity studies is needed to confi rm the existence of this new canine NoV.", "Two (2%) of the 105 fecal samples tested positive for NoV with primer pair JV12y/13i, whereas no RT-PCR products were found using the p289-p290 primer pair. The 2 JV12y/13i sequences were identical and contained the GLPSG amino acid motif characteristic of viral RNA polymerases." ] },{ "paper_id": "f2d1c4e958f633fefcb90c78a29c8c19bb0562ad", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Thirty-six (64%) hospitals responded. Of the 33 that completed the full survey, 3 reported they no longer maintained their HLIU capabilities. The 2 that provided qualitative information about their decision to close reported needing HLIU resources for other, more pressing areas and cited close proximity to at least 1 other HLIU as reasons for closing.", "In early 2016, we sent a 70-question survey to the original 56 designated US HLIUs, including the 10 RESPTCs. The survey queried challenges and concerns about the maintenance of capabilities. Results were collected through Adobe Acrobat Pro (https://acrobat.adobe.com/us/en/acrobat/acrobatpro.html) and analyzed by using descriptive statistics. The University of Nebraska Medical Center Institutional Review Board declared the study exempt (#172-16X).", "Renovated/expanded isolation unit 4 Separate, permanent isolation unit 3 Expanded training (e.g., increased frequency) 2 *Individual HLIDs self-reported data through an electronically administered survey administered in 2016. HLIU, high-level isolation unit." ] },{ "paper_id": "f2e0d9212887c0032b1887f34ee3b3042510d7f9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dr Reuss is an epidemiologist at the Respiratory Infections Unit, Robert Koch Institute, Berlin, Germany. Her research interests include emerging infectious respiratory diseases, pandemic preparedness, and influenza vaccination.", "76% also had >1 underlying chronic condition (4). The median age of case-patients was 50 years (range 14 months to 94 years). All cases were directly or indirectly related to countries in the Middle East or on the Arabian Peninsula.", "Data from the City Health Department's contact monitoring, the contacts' questionnaires, and the laboratory findings were integrated in 1 database. Results were validated and analyzed by using Stata version 12.0 (StataCorp, College Station, TX, USA)." ] },{ "paper_id": "f2e236f0458f86706985c627ef88d40c8f037492", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "for providing convalescent-phase serum samples from patients confirmed with SARS.", "Beginning in April 2003, delay in recognizing SARS cases and in implementing isolation procedures led to several nosocomial clusters of SARS-CoV transmission in healthcare facilities in Taiwan (17, 18) . The results from a retrospective serologic survey by the peptide ELISA of healthcare workers from facilities affected by nosocomial outbreaks are presented as a working example.", "Seroconversion panels were collected as serial serum samples from SARS patients at National Taiwan University Hospital in the course of treatment. These panels tested positive for seroconversion by IFA (24) and are used here to evaluate analytical sensitivity." ] },{ "paper_id": "f2ea312712d4e9fbe371d2ccb5cfdca0c6348c53", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "One gram of a poultry tissue was transferred into a polypropylene (PP) centrifuge tube and 4 mL of MeOH was added while shaking using a vortex mixer. Subsequently, the tube was shaken for 15 min on a rotary tumbler. After centrifugation (3,600 g, 15 min), the upper layer was isolated by decanting it into a PP centrifuge tube and acidified by adding 20 \u03bcL of FA prior to the tandem solid-phase extraction (SPE) procedure (Fig. 2a) .", "Influenza infections continue to pose a serious problem. Recent outbreaks of avian influenza (H5N1) have had a huge economic effect in the poultry breeding sector [2, 3] but besides the economic effect, human health is at stake because avian influenza can also infect mammals including humans [4, 5] . The increasing incidence of resistance to antiviral drugs is a major concern to public health. Because strains tend to become more aggressive, adequate therapeutic strategies are needed [6] .", "A full validation was carried out according to 2002/657/EC [1] . The following parameters were determined: linearity, trueness, repeatability, within-laboratory reproducibility, decision limit (CC\u03b1), detection capability (CC\u03b2), selectivity and robustness. The validation was carried out on three different occasions, by two different technicians, using different batches of SPE cartridges and including 21 different poultry muscle samples." ] },{ "paper_id": "f3042820ac417ec01ca0e15a4232e24b8d78ba74", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "HIV-1 is a major public health problem affecting an estimated 40 million individuals worldwide (www. unaids.org). Although it has been over 20 years since HIV-1 was identifi ed as the etiologic cause of acquired immune defi ciency syndrome (AIDS) an effective vaccine is not available. Thus, apart from public health measures that aim at HIV-1 prevention, the only effective strategy for controlling HIV-1 infections and lowering HIV-1 transmission is the use of antiretroviral drugs either for the treatment or prevention of infections.", "Ribosomal frameshifting 1,4-bis-[N-(3-N,N Small molecule (Hung et al. 1998) . dimethylpropyl)amidino]benzene tetrahydrochloride (RG501)", "Virus particle budding and egress is mediated by interactions of viral proteins such as the p6 late domain with components of the endosomal sorting machinery. Ion channels formed by viral protein U (Vpu) also facilitate viral particle egress from the host cell. Below we describe in more detail the" ] },{ "paper_id": "f33262c1f98b13eb814eb7359521fd4394f48ce0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The R&D Blueprint methodology was developed to mitigate numerous sources of bias, including flaws in study design, selection bias, interviewer bias, chronology bias, and recall bias (3). These efforts were largely successful; however, further work might be necessary to mitigate selection and recall bias.", "Disease prioritization is not a straightforward task and requires a defined set of criteria on which to base prioritization (7). These criteria can be qualitative, intangible, or", "Experts compiled an initial list of relevant diseases at an informal consultation in December 2015 (4) . A more robust methodology was needed, one that could be standardized and repeated regularly for reviewing and, if necessary, updating the list in the light of successful development of new interventions or the emergence of new disease threats." ] },{ "paper_id": "f3a7c66f75eba81e19ad7e1e05aa8ae1133a984c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors declare that they have no competing interests Authors' contributions NFD, MG, and AM were involved in drafting the manuscript and have given final approval of the version to be published.", "More recently, within days of the initial identification of the first cases of 2009 pandemic influenza A (H1N1) in spring 2009, scientists had identified the origin of all eight influenza virus gene segments. Within two weeks, the Centers for Disease Control and Prevention (CDC) began to distribute RT-PCR diagnostic test kits to public health laboratories under a quickly granted emergency use authorization by the US Food and Drug Administration [8] [9] [10] .", "In a recent editorial titled 'Epidemic science in real time', Fineberg and Wilson underscored the critical importance of 'conducting the right science and communicating expert judgment' to 'enable policies to be adjusted appropriately as an epidemic scenario unfolds' [44] . They emphasized that in times of diminishing public health resources, scientists from diverse disciplines -epidemiology, laboratory, social sciences -must work together to respond to immediate threats and follow through with research to understand key attributes of the affected populations and the disease process. The results of such research are needed to inform policy, to develop treatments and interventions, and to update and adjust recommendations as the state of knowledge changes." ] },{ "paper_id": "f3d353eb411034e59f379d03308d6afcfb7d6da1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Despite this impressive progress, clinicians have been left with several unanswered questions. However, these questions may never be answered because we hope that there will never be another patient with classical smallpox, and the best nonhuman primate model does not perfectly reproduce clinical smallpox.", "The Soviet Union allegedly inserted genes from other pathogens into variola major virus (21) . Researchers working with mousepox virus have created a recombinant virus capable of escaping the effects of prior immunization with vaccinia virus (22) .", "These patients might become severely ill if exposed to smallpox virus. Their immune conditions may make vaccination diffi cult or dangerous if they are exposed to smallpox virus.", "Evidence has shown that protocols for isolation of patients with fever and an undiagnosed rash are not rigidly followed in many general hospitals (18) . It might be better to bring medical care to patients in a remote location (e.g., motel or defunct hospital) than to risk spread of the disease in a hospital. Fairly sophisticated medical care can now be given at home or in remote locations (19) .", "Such work has obvious ethical problems, but would creating live smallpox viruses be something terrorists would really want to do? Although most Western nations have mechanisms for controlling smallpox outbreaks, most third-world nations do not. The experience with severe acute respiratory syndrome showed that even in the absence of a vaccine or antimicrobial drug, diseases spread by respiratory secretions can be controlled by vigorous identifi cation and isolation of patients (23, 24) . If widespread transmission occurs of a newly created or genetically modifi ed variola major virus, it is highly likely that it would spread to third-world nations, including homelands of terrorists. The resulting devastation would create a major public relations setback to terrorists. This likely blowback should inhibit the motivation of terrorists to recreate the variola virus or enhance its pathogenicity." ] },{ "paper_id": "f3ead6ffa56b8d94abfe97c81efa762233a7aa13", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f41bba1e37e13b899c10c8f2c21b10fdc91930c2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Vero E6 (4 \u00d7 10 4 ) and A549 cells (5 \u00d7 10 3 ) were incubated with different doses of synthetic peptides as indicated for 72 hours. Cell proliferation was detected using commercial XTT assay (Roche Diagnostics, Indianapolis, Ind, USA).", "tein showed sequence homology with bradykinin as indicated by bold letters here and in Figure 2 (b). The identity score is 27%; and the similarity score from conservative substitutions is 36%.", "analyzed using Student's t-test. A value of P < .05 was considered to be significant." ] },{ "paper_id": "f433bb9c63b678e5ff5c981a1bfe5aad92392218", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f4761a305755e1f614a75cc8ade098b09d005728", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "where \u03b3 r (\u03b8,\u03d5) is the radiative decay rate density at \u03bb em that is integrated over all polar \u03b8 and azimuthal \u03d5 angles in the denominator.", "Over the last years, we witnessed numerous implementations of PEF into already established laboratory technologies such as fluorescence microarray scanners, fluorescence microscopes, or microtiter plate readers as well as the development of entirely new compact devices that utilize this amplification scheme. PEF nanostructures were mostly combined with immunoassays which offer the advantage of commercial availability of antibodies against a large variety of analytes (see Table 3 ). In order to avoid direct labeling of target analyte, there are typically used sandwich [105, 106] or competitive [105] assay formats with detection antibody conjugated to a fluorophore (see Fig. 8a ).", "In summary, the coupling of fluorophores with intense fields of surface plasmons can amplify emitted fluorescence light intensity by several orders of magnitude. The highest enhancements were demonstrated in measurements with single fluorophores that were placed into plasmonic hotspots. In combination with low quantum yield dyes, several groups reported the fluorescence enhancement >10 3 for such configurations." ] },{ "paper_id": "f4d18f2beafa875cd4e30a9a237a64b9d3110856", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In conclusion, apart from the selection criteria defined above, the individual screening of different siRNAs for highly efficient and specific duplexes, or the pooling of multiple siRNAs, is the most effective approach to increase siRNAmediated targeting efficacy.", "previously as \"rate-limiting\" for tumor growth and angiogenesis in several tumors ( [82, 83] , see [84] for review)." ] },{ "paper_id": "f4d811f1ad17486fd10dad9a4a5cbbdc59b4d9ad", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f4dd6a079963031a5fc8012b659c9bff14e739a6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\"Lectin\" comes from the Latin word \"legere\", which means \"to select\", by William Boyd in 1954. Lectins have the ability to bind carbohydrates. Nowadays, proteins that can agglutinate red blood cells with known sugar specificity are referred to as \"lectins\". The name \"hemagglutinins\" is used when the sugar specificity is unknown.", "The lectin contents are low in some varieties and high in other varieties (Table 3) .", "Lectins-pathogen management strategies" ] },{ "paper_id": "f4efcd5ff6922b61877d1bc108dc4d3bc1d1302c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f4f7e73df95c1229f3498aad7bf9ef1ccc3180bc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f5311986a1c067ce79c82fd9a50cc1b185718ff6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "HeV outbreaks. Infection-control management guidelines and workplace health and safety regulations must consider the context in which services are feasibly delivered to the public and should be devised in consultation with the private veterinary professionals on the frontline of outbreaks.", "HeV remains a threat to the veterinary profession and public health in Australia. The experimental success of an HeV vaccine for horses was recently announced; if a vaccine becomes available, it may re-instill confi dence in existing and future equine practitioners (9) . However, the potential that emerging infectious diseases might dismantle the veterinary workforce should be considered when developing offi cial strategies for the management of *Average. \u2020The practice manager interviewed was not a veterinarian and did not wish to supply this information. \u2021Self-reported. \u00a7One female participant did not provide this information. \u00b6The 1 participant who was a practice manager but not a veterinarian had not spent any time with animals and therefore was not included.", "During 2009-2010, we conducted face-to-face, indepth interviews with 21 veterinarians and allied staff from 14 equine and mixed private veterinary practices from a range of urban and rural areas between Cairns and Brisbane, Queensland, Australia (Table 1) (10). We asked a series of open-ended questions to determine what HeVrelated infection-control and workplace health and safety issues confront equine practices (Table 2) . Interviews were recorded, transcribed, and analyzed for themes.", "Of the 20 veterinary professionals interviewed, 12 (60%) had dealt with >1 suspected cases of HeV, and 7 (35%) had dealt with a confi rmed case of HeV. Of the 18 veterinarians interviewed, 4 (22%) reported having ceased equine practice, and as many as 8 (44%) knew of >1 colleagues who had done so in the previous 12 months. The decisions to quit were mostly motivated by the HeV-related fear for personal safety and legal liability." ] },{ "paper_id": "f54b32b81436b336dfcae7660350b7f488756e0d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ethical approval was obtained from the Institute of Medicine, Kathmandu, Nepal prior to using the questionnaire in the target hospitals.", "Seven hospitals had a strong interest in cooperating with foreign hospitals. A particularly strong expectation was observed regarding research support, information supply, PPE provision, and guidance in constructing an effective control system (Table 3 ).", "rector in addition to the information obtained by the questionnaire.", "The 17 hospitals responded to most of the questionnaire items, but for some items, a response was obtained from only 16 hospitals.", "Among the problems observed in the study were weak ICC function, few training opportunities among the hospital staff, inadequate use of antibiotics, shortage of infection control staff, shortage of doctors and nurses and their overload in daily medical practice, shortage of fundamental equipment including PPE, inadequate practice of basic tech- " ] },{ "paper_id": "f553255dcfe8027bcf53bcb1147a0f8e1ccbe74b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 Can the use of transgenic animals containing the natural resistance gene(s) of mallard ducks prevent pathogenic influenza virus infection?", "Influenza in humans is considered a non-eradicable disease due to periodic introduction of viruses from their natural reservoir, wild migratory birds -mainly ducks. The culling of wild birds is not an option. The sole current option is biosecurity and eradication of HP influenza from domestic poultry. The longer-term goal will be to understand the genetics of natural resistance in ducks and to introduce these traits into domestic animals. ", "An area that has been surprisingly neglected is the genetics of ducks, the ultimate reservoir species of all influenza A subtypes. The wild duck reservoir contributes some or all of the genes of future pandemic strains in humans and future panzootic strains in domestic poultry. Immune mechanisms in ducks are currently understudied, and the molecular basis of resistance of some duck species to lethal infection is unresolved. Sequencing of the genome of the mallard duck is warranted, as it could provide insight into the factors that contribute to markedly reduced influenza virus pathogenicity." ] },{ "paper_id": "f55b2931d9176d19dad45d49aa691957a8587317", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f5a95ba3b592c46903d5f4a4c00bd15a2cbb74f9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f5cb9270ebde80bfaf1298576cb7c6fc7076f6b7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Offi ce,", "The bodies had been frozen at -17\u00b0C before the samples were taken.", "We report the presence of 3 species of the B. burgdorferi s. l. group in European hedgehogs from Germany. To our knowledge, this is the fi rst report of these species in hedgehogs in this country and the fi rst report of B. spielmanii (A14S) (6) from this host." ] },{ "paper_id": "f5f5f2c5e7570a4152e6bbdecada50edc34a786d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f602e1eac50b0f5ad85c09bc5feb5b8c496cab51", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f6323e7d11e94480fdd62e5caad023d4d2d7cf6d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:", "Protein samples were adsorbed to glow-discharged carbon-coated copper grids for 30 seconds prior to 2% uranyl formate staining. Micrographs were recorded using the Leginon software 72 on a 120kV FEI Tecnai G2 Spirit with a Gatan Ultrascan 4000 CCD camera at 67,000 nominal magnification. The defocus ranged from 1.0 to 2.0 \u03bcm and the pixel size was 1.6 \u00c5.", "Cell-free supernatants were harvested at 24 h after transduction, filtered through 0.45-\u03bcm membranes, and virus particles were purified and concentrated by sucrose cushion ultracentrifugation at approximately 100,000 \u00d7 g for 3 h. Pelleted virions were resuspended in PBS and stored at \u221280 \u00b0C until further use. Inoculation of HRT18 monolayers in 96-well format was performed with equal amounts of S-pseudotyped virions, as calculated from VSV-N content (roughly corresponding to the yield from 2 \u00d7 105 transfected and transduced cells), diluted in 10% FBS-supplemented DMEM. At 18h post-infection, cells were lysed using passive lysis buffer (Promega). Firefly luciferase expression was measured using a firefly luciferase assay system. Infection experiments were performed independently in triplicate, each time with three technical replicates. Pseudovirus incorporation of flag-tagged OC43 S was determined for the parental type and each of the mutants by Western blotting and by calculating the S content (measured with monoclonal antibody ANTI-FLAG \u00ae M2; Sigma) relative to that of VSV-N (measured with anti-VSV N monoclonal antibody 10G4; Kerafast)." ] },{ "paper_id": "f655ed958a5ba1036a9fa2ef6d370829d6ec8b9b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f660fc62642dc8cdac853e68b3d2427fc967a361", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Author The results of the blood viral RNA analyses did not affect clinical management. We assessed the relationships among clinical and molecular diagnostic factors with the IBM SPSS Statistics program 22.0 (SPSS Inc., Chicago, IL, USA). In each test, p<0.05 was considered statistically significant. The institutional review board of the National Medical Center approved this study (H-1508-057-002).", "M iddle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic, betacoronavirus lineage C RNA virus that was first identified in Saudi Arabia in 2012 (1) . MERS-CoV causes respiratory and renal illness in humans, and infection often progresses to severe pneumonia, acute respiratory distress syndrome, renal failure, or death in a subset of patients (2) . Risk factors, including patient age, preexisting health conditions, and high viral load in upper respiratory specimens, have been suggested to be related to disease severity and death (3, 4) . However, pathogenesis and clinical characteristics promoting recovery from infection or progression to serious organ failure have not been well elucidated.", "A large MERS-CoV outbreak occurred in 2015 in South Korea. This outbreak comprised the first imported case and subsequent infection of 185 patients (11) . Our study aimed to evaluate the diagnostic utility of blood specimens for MERS-CoV infection by using large numbers of patients with a single viral origin and to determine the relationship between blood viral detection and clinical characteristics." ] },{ "paper_id": "f71c5fc3040dbc1fa7419bf6004a53353f32590b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Potential LF T eff epitope (Juv-p120)", "Potential T eff epitope CEFT pool", "Strain: A B C D E F G H" ] },{ "paper_id": "f74d6f598edd77d5ececd51da9d900910b21186d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The epidemiological model", "The simulations of the stochastic model were carried out using Gillespie's direct algorithm (Gillespie 1977) . In short, the interevent times are sampled from an exponential distribution with parameter R 5 P 8 k51 r k (Renshaw 1991) . The specific event type that then occurs is obtained by drawing a random variate from a discrete distribution with probability p(k) \u00bc r k /R corresponding to event type k, k \u00bc 1-8, as defined above. Once the event type has been chosen, a similar sampling process is applied to determine the affected individual on the basis of its relative rate compared to that of other individuals belonging to the same category.", "In the simulations, infection was introduced into an initially fully susceptible population through one latent infected individual. The simulations were carried out for closed populations with no birth or death or removal processes and for which disease progression was not influenced by treatment effects. The model was run for a simulated time period of 3 years, after which the infection either died out or, as indicated by preliminary results, converged to equilibrium prevalence in all simulated scenarios. Ten thousand replicates were generated for each parameter combination." ] },{ "paper_id": "f76c950c5c0544362b9bc72614a3f318da4a4076", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "the Comp#1 compound, hold very high potential to become a new drug candidate.", "The program of QikProp embedded in Schr\u00f6dinger 2009 (Schr\u00f6dinger, LLC) is a quick, accurate, and easyto-use program for predicting the ADME properties of the compounds. 41, 72, 73 The QikProp program adopted here was featured by having the functions predict a total of 44 properties of compounds, including the principal descriptors and physiochemical properties.", "Virtual screening and core hopping" ] },{ "paper_id": "f76e23d2dce15bbfa44c92cb917bf718ade1472e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f7778201dec1d1cf942577562819fa9841b1db50", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The Mainz Emergency Evaluation Systems (MEES) was developed in Germany to assess prehospital therapeutic efficacy. It is based on seven variables: level of consciousness, heart rate, heart rhythm, arterial blood pressure, respiratory rate, partial arterial oxygen saturation, and pain. A MEES score is obtained before and after prehospital intervention to assess patient improvement or deterioration.", "Although it does not allow outcome prediction, it does provide an easy and reliable assessment of prehospital care [43, 69] . A recent study [70] showed that adding end-tidal carbon dioxide capnometry to MEES has significantly greater value than MEES alone in predicting survival after cardiopulmonary resuscitation in nontraumatic cardiac arrest.", "The Pneumonia Severity Index [56] is a measure of severity of community-acquired pneumonia, taking into account physiologic parameters, age, medical co-morbidities, and laboratory studies. Even though it was designed as an outcome prediction tool, the Pneumonia Severity Index is widely used as a determinant for site of care in conjunction with clinical judgment [57] and as a quality assessment tool [58] [59] [60] ." ] },{ "paper_id": "f7929dc28f24ccdc65e36f6b67d182adc6c4f2ba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Primary obstacles for achieving this in vivo include competitive uptake by nontarget cells, excretion in urine, degradation by nucleases, and endosomal trapping.", "Viruses are at present the most efficient gene delivery vectors. After cell binding they are capable of delivering their nucleic acid payload intracellularly in a proficient way along with nuclear localization. Although virus-mediated delivery methods are usually based on delivery of genes encoding shRNA, few approaches used viruses to deliver chemically synthesized siRNA in vivo [43, 44] .", "Uchida et al used expression of two separate siRNA strands against survivin by adenoviral transduction to inhibit tumor growth. Survivin is a protein that inhibits cancer cell apoptosis. Mice bearing subcutaneous U251 glioma tumors were treated with intratumoral injections of 10 10 viral particles on three consecutive days every twenty days, ultimately leading to four-fold smaller tumors at day 48 after start of treatment as compared to empty adenoviral vector and adenoviral vector expressing irrelevant siRNA [20] ." ] },{ "paper_id": "f7d1b521f0668811e2435b60cce4657ff769f457", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f7eac9466807a50cfa24455c4a8b79bbf8c3510a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A n emerging infectious disease is one that is either newly recognized in a population or involves a recognized pathogen affecting new or larger populations or geographic areas (1, 2) . Disease emergence is infl uenced by ecologic and environmental changes (e.g., agriculture, deforestation, droughts, fl oods), human demographics and behavior (e.g., population migration, urbanization, international trade and travel), technology and industry, microbial adaptation, and breakdown in public health measures (1, 2) .", "Rebuilding and rehabilitation efforts in postconfl ict Sierra Leone have placed aid workers, United Nations peacekeeping forces, and businessmen at risk for contracting Lassa fever and enabled importation of cases to industrialized countries. Deaths from Lassa fever occurred in humanitarian workers in 2000, including United Nations peacekeepers (36, 37) . An imported case of Lassa fever was confi rmed in Germany in July 2006, after the patient, a Sierra Leonean resident, fl ew from Freetown to Frankfurt through Abidjan and Brussels, 5 days after symptom onset (36) . A businessman born in Liberia and residing in the United States died of Lassa fever in 2004 after traveling between Sierra Leone and Liberia before his illness (38) . Aid workers and British soldiers have imported Lassa fever into the Netherlands (2000) and the United Kingdom (2000 and 2003) after postings in Lassa-endemic areas of Sierra Leone (36) .", "Malaria had been virtually eliminated in Tajikistan in the early 1960s, and before 1992 only 200-300 malaria cases were reported annually (3) . Civil strife during 1992-1993 led to massive population displacement and deterioration in living conditions. More than 100,000 persons fl ed to Afghanistan, reintroducing malaria parasites when they returned in 1994. An outbreak ensued, which reestablished Plasmodium falciparum malaria in Tajikistan for fi rst time in 35 years (4). By 1997, 29,794 annual cases were reported, although estimates were 200,000-500,000 for that year (3) . During 1998-1999, a reemphasis on malaria control activities reduced the incidence of malaria by 50% within 2 years (29,794 registered cases in 1997, 19,351 in 1998, and 13,493 in 1999) (5) ." ] },{ "paper_id": "f7f228117ed266bdd9f35510bec8011dfcef21a1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This section will briefly review the history of the key developments and is derived from Bulloch [4] , Foster [5], and Bellanti [64] . Only key original references derived from these sources will be cited.", "After viruses were discovered, it was found that the production of a demonstrable, specific immune antibody response occurred much more frequently in viral than in bacterial diseases and constituted a critical element of viral diagnosis. An important test to demonstrate humoral antibodies was the complement fixation test developed by Bordet and Gengou in 1901 [71] . This method is still used as one of the most common diagnostic procedures in viral diagnostic laboratories around the world.", "Another important arm of the immune response in that of cell-mediated or T-cell immunity, which is demonstrable by skin tests, and is useful in the clinical diagnosis of infection due to agents that cannot be grown in culture and/or for which an antibody response is not produced: The organism that causes leprosy, M. leprae, is an example." ] },{ "paper_id": "f82887cb4851069ac9a0eebd39ecda541dbd44d4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Beyond the conserved core", "Function of the conserved main structural elements", "Common and unique features of viral RNA-dependent polymerases 4405", "Function of the conserved aspartates and lysine in the polymerase catalytic site" ] },{ "paper_id": "f87281bef799be6149320996f90bccc2194d7652", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f898a667de6c7ad8916d2e542498e953589be8d7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The obtained results which identified the epitopes cover a significant number of strains with decent population coverage. To exert cellular and humoral immunity, the computer aided result has been found potential and expected to mount immune response upon further in vivo and in vitro validation. The step by step analysis and progression for maximum possible MHC coverage provides significant primary screening result against this fatal virus. ", "Coronavirus possess a non-structural replicase polyprotein and several structural proteins including spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins [4, 5] . Like other coronaviruses, the host cell recognition of MERS-CoV by CD26 receptor is mediated by its surface anchored S glycoprotein [6, 7] . This S glycoprotein has S1 and S2 subunits. S1 subunit contains RBD which mediates initial host cell recognition whereas S2 subunit mediates membrane fusion [8, 9] .", "Conclusion:" ] },{ "paper_id": "f8e19f9d339fc06f51381d54969121f75fcbaf0f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "D uring the 2003 epidemic of severe acute respiratory syndrome (SARS), large nosocomial outbreaks of SARS occurred in several hospitals in Singapore (1, 2) . Since then, concerns have been raised about how emerging infections, in particular respiratory infections, could result in transmission from patients to healthcare workers and vice versa, given the high frequency and intensity of healthcare worker contacts in the hospital environment (3) . For pandemic infl uenza, additional concerns exist that even mild disease might result in staff absenteeism and, subsequently, would reduce staff strength at a time of increased demand for health services (4) .", "We do acknowledge several limitations in our study. First, our fi ndings are based on data from healthcare workers from just 1 hospital. Moreover, the unexpectedly low seroconversion rates in our cohort reduced the power of the study to investigate exposures more weakly associated with the outcome. We were also unable to assess the usefulness of personal protective equipment due to the lack of appropriate control groups. The resolution of exposure data from what was a self-administered questionnaire survey was also lower than insights that may be gained from detailed case investigations or exposure diaries that have been used in the healthcare setting (3, 11) . Finally, the lack of randomization also leaves scope for bias in our results.", "Although defi nitively attributing the low infection rates in healthcare workers to improved infection control practices is diffi cult without the appropriate control groups, much evidence supports the effi cacy of the common bundle of measures used in hospitals to reduce spread of respiratory viruses (21) . Notably, there was a high level of preparedness and widespread implementation of airborne and respiratory droplet precautions and other pandemic (H1N1) 2009 infection control practices in healthcare institutions in the United States, Singapore, and elsewhere (11, 13, (22) (23) (24) ." ] },{ "paper_id": "f8fd65777b69f5f9b7177a709e22607eb96abfa6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Dr. Jiang is associate member and head of the Viral Immunology Laboratory, Lindsley F. Kimball Research Institute, New York Blood Center. His primary research interests include development of vaccines and therapeutic agents against SARS-CoV and HIV.", "safe vaccines is urgently needed to prevent a new SARS epidemic and for biodefense preparedness. Currently, 3 major classes of SARS vaccines are under development: 1) inactivated SARS-CoV (Figure 1 ), 2) full-length S protein (Figure 2A) , and 3) those based on fragments containing neutralizing epitopes ( Figure 2B ).", "Developing effective and safe vaccines is urgently needed to prevent infection by severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV). The inactivated SARS-CoV vaccine may be the first one available for clinical use because it is easy to generate; however, safety is the main concern. The spike (S) protein of SARS-CoV is the major inducer of neutralizing antibodies, and the receptor-binding domain (RBD) in the S1 subunit of S protein contains multiple conformational neutralizing epitopes. This suggests that recombinant proteins containing RBD and vectors encoding the RBD sequence can be used to develop safe and effective SARS vaccines." ] },{ "paper_id": "f906cbd97a70362b2645796aea712e3b5ce8dd7b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Female ICR mice at postnatal age of 3 months, obtained from Saitama Experimental Animals (Saitama, Japan), were used.", "We chose female mice because postviral olfactory disorder in humans occurs predominantly in women (Sugiura et al. 1998 ). They were housed in a temperature-controlled environment under a 12 h light-dark cycle with free access to food and water. All procedures were approved by the University of Tokyo Animal Care and Use Committee, and performed in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals.", "Preparations of stained sections were examined using a microscope (E800; Nikon, Tokyo, Japan) under bright-field illumination or fluorescent illumination using green (excitation wavelengths: 510-560 nm; emission wavelength: 515-555 nm) and red (excitation wavelengths: 465-495 nm; emission wavelength: 590 nm) filters and photographed using a digital microscope camera (AxioCam; Carl Zeiss, Tokyo, Japan). Digital images were processed in Adobe Photoshop (Tokyo, Japan), adjusting only brightness, contrast, and color balance." ] },{ "paper_id": "f92ea65fa3771a913f8e3d7aff52c03fed0ae833", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Lignans are diphenolic compounds that contain a 2,3-dibenzylbutane structure that is formed by the dimerization of two cinnamic acid residues (Fig. 2) . Several lignans, such as secoisolariciresinol, are considered to be phytoestrogens. The richest dietary source is linseed, which contains secoisolariciresinol (up to 3.7 g/kg dry weight) and low quantities of matairesinol. 9", "Stilbenes contain two phenyl moieties connected by a two-carbon methylene bridge. Occurrence of stilbenes in the human diet is quite low. Most stilbenes in plants act as antifungal phytoalexins, compounds that are synthesized only in response to infection or injury. One of the best studied, naturally occurring polyphenol stilbene is resveratrol (3,4',5-trihydroxystilbene), found largely in grapes. A product of grapes, red wine also contains significant amount of resveratrol.", "Phenolic acids are found abundantly in foods and divided into two classes: derivatives of benzoic acid and derivatives of cinnamic acid. The hydroxybenzoic acid content of edible plants is generally low, with the exception of certain red fruits, black radish and onions, which can have concentrations of several tens of milligrams per kilogram fresh weight. 7 The hydroxycinnamic acids are more common than hydroxybenzoic acids and consist chiefly of p-coumaric, caffeic, ferulic and sinapic acids." ] },{ "paper_id": "f9a4350a22b0ac2d527dbbea0b0d4ebde180e2bf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Porcine samples (including feces and intestinal contents) from piglets with severe watery diarrhea, dehydration and high mortality were collected from 55 farms in five provinces in China during February 2010 to March 2012. These samples were confirmed to be positive for PEDV by reverse transcription polymerase chain reaction (RT-PCR) [9] .", "The hydrophilic regions of the deduced amino acid sequences were analysed using DNASTAR software. The phosphorylation sites were predicted using NetPhis and NetPhos K analysis tools available at http://www.cbs.dtu. dk/services/NetPhos/ and http://www.cbs.dtu.dk/services/ NetPhosK/.", "Phylogenetic analysis based on nucleotide and encoded amino acid sequences of the N gene confirmed that all field strains fell into two groups (Fig. 2) . Group I consisted of Chinju99 (Korean), CV777 (Europe), LZC (China), and " ] },{ "paper_id": "f9a57bac5e3280f475b1e3ba90c7a5610e917aef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f9ba45c34f390b5c7d0579b641303de39860a329", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Any child presented with Influenza-like illness (ILI) symptoms the chest clinic Abo El Rish Pediatric Hospital, Cairo University was considered eligible. ILI was defined according to CDC criteria as having measured fever > 38\u02daC and cough and/or a sore throat [13].", "Data were collected by a self-designed questionnaire include demographic data, risk factors (smoking, passive smoking and contact with birds). Throat washes and nasal swabs were collected from each child as appropriate.", "Specimens then were cultured on blood agar, chocolate agar, MacConkey agar and Sabarauds dextrose agar (Oxoid Co. England). Isolates were identified by conventional methods such as culture characteristics and biochemical reactions." ] },{ "paper_id": "f9c05a5c33ef91bbf61d086c882b60a5e6510b21", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Refer to Web version on PubMed Central for supplementary material. representative of two or three independent experiments with 9-12 mice per group. (i,j) show data from one experiment with 10 mice per group. (h,l) are representative of two independent experiments with 4-5 mice per group. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 versus corresponding group; unpaired t test.", "Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms Correspondence: T Hussell (tracy.hussell@manchester.ac.uk; Tel: +44 161 2751537).", "GraphPad Prism version 5.04 was used for all statistical calculations. For multiple dataset analysis ANOVA with Bonferroni correction was applied. To compare two datasets paired or unpaired t tests were applied. Data are presented as the mean \u00b1 standard error of the mean (SEM). P values<0.05 were considered significant." ] },{ "paper_id": "f9cd3dff30e7874eda1680c8aff01511184b821c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The farm was a 3-site herd with a total of 6,000 sows. At the time of the outbreak, 55% of breeder stock were gilts or fi rst-or second-parity sows. Site 1 comprised 20 gestation barns and 19 farrowing barns, site 2 (nursery) comprised 9 barns, and site 3 comprised growing and fattening barns.", "The amplicons were purifi ed by using the QIAquick PCR purifi cation kit (QIAGEN) and sequenced on a Mega-Base 1000 DNA sequencer (GE Healthcare, Chalfont St. Giles, UK). The obtained sequence was analyzed by using NCBI BLAST (www.ncbi.hlm.hig.gov).", "Virus isolation was attempted by inoculation of PK-15 and SK-K cells with brains and tonsils from 5 pigs positive for PHE-CoV by RT-PCR. Five blind passages were performed at 7-day intervals. IHC testing was also performed on SK-K cells." ] },{ "paper_id": "f9e51b353d1f30a9dfbb30f0661bffa319c041eb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The study protocol was approved by the animal care committee of the Universit e de Montr eal." ] },{ "paper_id": "fa0c32f39abb602e0161bf738b5292e251c0c885", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "What are the implications for public health practice?", "Vol. 62 / No. 20 401" ] },{ "paper_id": "fa38f89cd6981199ac346529620337c743e4aada", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fa4407c76e151d9a802720724d5604436d44e68b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nucleotide sequences were aligned using Clustal X, ver. 1.83, implemented in BioEdit, ver. 7.2.5. Phylogenetic analyses were performed using MrBayes, ver. 3.2.6 [12] , under a GTR model of nucleotide substitution with 4 categories of \u03b3-distributed rate heterogeneity and a proportion of invariant sites (GTR + 4 + I).", "ORF4a ( " ] },{ "paper_id": "faa9aae68713e08818d4eaeb3a3f8c02f075d21b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "It is too soon to know whether generic agents could be used to confront the next infl uenza pandemic, yet developing countries lack realistic alternatives. For this reason, their leaders must convince scientists and international organizations, including WHO, of the urgent need for research to determine whether these inexpensive agents could mitigate the effects of a pandemic. Otherwise, developing and industrialized countries alike could be faced with an unprecedented global health crisis. ", "None of this research on generic agents will be possible without international coordination. Thus far, the topdown approach that has characterized vaccine and antiviral research and development has lacked an international system for coordination and management to ensure rapid progress (2) . Likewise, nothing has been done to ensure worldwide production and distribution of the vaccines and antiviral agents being developed. A similar approach must not be allowed to govern the research agenda for generic agents.", "While these studies are under way, an analysis should be undertaken for each candidate agent to determine which companies produce them, where each is manufactured, annual levels of production (and surge capacity), patterns of distribution to other developing countries, and costs for public markets (Table 3) . Special attention must be given to companies that follow Good Manufacturing Practices to minimize the risk that some of these agents might be counterfeit. When animal studies have defi ned 1 or more promising regimens, an international process must be set up to develop logistics for fi nancing, producing, and distributing each agent." ] },{ "paper_id": "fab11f842979b0ca95927e6919ed0740a5ccc3be", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.", "Lipopeptide vaccines based on a palmitic acid moiety may present an ideal strategy against pathogens that infect mucosal surfaces. Intranasal administration of a palmitoylated lipopeptide vaccine for human cytomegalovirus (a herpes virus) elicited both systemic and local mucosal cellular responses when administered intranasally [93] . Herpes simplex virus type 2 peptide epitopes conjugated to a palmitic acid moiety have shown the ability to prevent transmission and/or limit the severity of diseases [94] .", "Furthermore, Flt3 has been demonstrated as a safe adjuvant with nasal dendritic cell targeting properties that confer protection against fatal pneumococcal pneumonia in mice [109] . To this end, CpG ODN and Flt3 represent mucosal dendritic cell targeting adjuvants for the induction of antigen-specific, protective mucosal immune responses." ] },{ "paper_id": "fb6abbffcf23a7f85906627f2203c55e784cee09", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Predictions due to conservation (Sharan) 606 171 28.2 Predictions combining multiple evidence types 2047 279 13.6 All predictions 2516 378 15.0 Random pairs 2354 72 3.1", "For brevity we write this expression as .", "Using Bayes rule we get ) (" ] },{ "paper_id": "fbabb5fb318eb82681d448718a79bc44f11a7643", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Fischer's exact two-sided tests were used to assess risk factors. Exact confidence intervals (CI) were reported. A Kaplan-Meier survival curve was constructed. Data were analyzed by using EpiInfo 2000 (Centers for Disease Control and Prevention, Atlanta, GA) and SAS version 8.0 (SAS Institute Inc., Cary, NC).", "Emerging Infectious Diseases \u2022 www.cdc.gov/eid \u2022 Vol. 10, No. 2, February 2004 255 RESEARCH SARS TRANSMISSION Figure. Onset of symptoms for severe acute respiratory syndrome by number of shifts worked (dashed lines represent 95% confidence limits).", "S evere acute respiratory syndrome (SARS) was first recognized in Canada in early March 2003 (1) . Caused by a novel strain of coronavirus, the disease was reported in more than 8,400 people globally, with cases in Asia, Europe, and North America in 2003 (2) (3) (4) . SARS is associated with substantial illness and death. The case-fatality rate has been estimated at 13% for patients <60 years and 43% for those >60 years (5) . In Canada, disease transmission has occurred predominantly among healthcare workers within the healthcare setting (1). Preventing SARS transmission to healthcare workers is therefore an important priority (6) ." ] },{ "paper_id": "fbac14ed1b86f5accd35d9a3153591b938b7d72d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fbad43ecd53034861cf23c877f45ee6265bfc386", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fbcbe40a6873d2dabd90963c5a7c8e26531eb52f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fbe7dbef085278229c19cf79fc2c5590495960f5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Author . Samples from subcohort G1 (n = 66) and from all camel-contact cohorts were tested for antibodies to CoV OC43 S1, a common human CoV; all showed high seropositivity (range 89%-100%) (Figure) . All 498 samples were tested for reactivity to severe acute respiratory syndrome CoV S1; none reacted (Figure) .", "We used 498 anonymized serum samples from persons in Qatar with and without dromedary contact (online We used microarray technology as described (3, 5, 6) to analyze samples for the presence of IgG reactive with MERS-CoV S1 antigen (Table) . To avoid overinterpretation of data, we set the reactivity cutoff at 30,000 relative", "We determined the presence of neutralizing antibodies to Middle East respiratory syndrome coronavirus in persons in Qatar with and without dromedary contact. Antibodies were only detected in those with contact, suggesting dromedary exposure as a risk factor for infection. Findings also showed evidence for substantial underestimation of the infection in populations at risk in Qatar." ] },{ "paper_id": "fc00aeeb5cb014196c3a07fbd9db0c5e80b4a8c4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fc154cdab53513c3beb93049b93dcc34602c921a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Wildlife trade provides mechanisms for disease transmission at levels that not only cause human disease out-breaks but also threaten livestock, international trade, rural livelihoods, native wildlife populations, and ecosystem health (7) . Worldwide, an estimated 40,000 primates, 4 million birds, 640,000 reptiles, and 350 million tropical fi sh are traded live each year (7) . International wildlife trade is estimated to be a US $6-billion industry (20) .", "As suggested by Kuiken et al. (41) , it is time to form \"a joint expert working group to design and implement a global animal surveillance system for zoonotic pathogens that gives early warning of pathogen emergence, is closely integrated to public health surveillance and provides opportunities to control such pathogens before they can affect human health, food supply, economics or biodiversity.\" Major tasks that should be taken by the international community include better integration and coordination of national surveillance systems in industrialized and developing countries; improved reporting systems and international sharing of information; active surveillance at the interface of rural populations and wildlife habitats, especially where poverty and low income increase risks for pathogen transmission; training of professionals, such as veterinarians and biologists, in wildlife health management; and establishment of collaborative multidisciplinary teams ready to intervene when outbreaks occur.", "Dr Chomel is director of the World Health Organization/Pan American Health Organization Collaborating Center on New and Emerging Zoonoses at the University of California, Davis. His research focuses on zoonotic infections, especially those caused by Bartonella spp., in domestic animals and wildlife and their effects on human health." ] },{ "paper_id": "fc5396c4fb0587a9741ed6ab1bec5c6cd8da1b17", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "What the surgeon needs to know C. Bassi; Verona/IT (claudio.bassi@univr.it)" ] },{ "paper_id": "fc6ab4b693bda93d6d96fed4c7ffba6510d04e0e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The following symptoms most commonly developed in 9 HCP contacts: rhinorrhea (33%), odynophagia (22%), or headache (22%) within postexposure day 14; more than 1 symptom developed in some contacts. Fever did not develop in any of these contacts.", "Basic descriptive analyses were conducted for all contacts. When available, self-reported and GPS-monitored exposure time and number of visits were compared by calculating Pearson correlation coefficients.", "This investigation was part of a public health response, so it was determined by CDC to be a nonresearch investigation and not subject to review by the CDC Institutional Review Board. All participants provided verbal consent before interview; parental permission and assent from from minors were obtained as appropriate." ] },{ "paper_id": "fc7a909258427d608f8f8e3a4d2f3d7ef1dba473", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The entire functionality of the tool is placed within a single web page ( Figure 2 ).", "At this point users can add more conditions to the same query, such as specifying a zip code, changing the value for age, etc.", "Finally, the tool should be self-contained and generic. This allows most web-based disease surveillance systems to incorporate the AQT into their systems.", "In its 2007 annual report, the World Health Organization warned of the increased rate at which diseases spread in a world where 2 billion people travel by air [1] . The early detection of known and emerging illnesses is becoming more important. Automated disease surveillance systems have been in existence for over 10 years [2] [3] [4] . Most of these systems analyze data by syndrome and search for disease outbreaks. A syndrome in this context is defined as a group of diseases related in some fashion, such as respiratory diseases. This level of investigation is often sufficient, but a more dynamic level of control may be required to understand an emerging illness in a community." ] },{ "paper_id": "fc8d3fb52dee4d49c606650486461f71f313d02c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fc9f4ba0a657fb6fe7c562097f43162406151a7e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nucleotide and amino acid sequences were aligned by using MegAlign version 6.0 (DNASTAR, Madison, WI, USA). A neighbor-joining tree with bootstrap values was constructed to estimate phylogenetic relationships among sequences. Nucleotide positions were numbered based on the TOR2 SARS virus isolate (GenBank accession no. NC_004718) (8) .", "Samples from patients and animals were cultured in fetal rhesus kidney (FRhK-4) cells or Vero E6 cells for virus isolation as described (6, 7) . Cells with or without SARS-CoV virus infection were harvested and fixed in 2.5% glutaraldehyde (Electron Microscopy Sciences, Hatfield, PA, USA) for 4 h and post-fixed in 1% osmium tetroxide for 1 h. Cells were then transferred to a 1.5-mL tube and centrifuged at 1,000 rpm for 10 min. The supernatant was removed and a 2% agarose solution (55\u00b0C-60\u00b0C) was added to the cell pellet. After the agarose solidified, \u22481-mm cubes containing the cell pellet were cut and dehydrated in graded ethanol. The cubes were then embedded in epoxy resin. Ultrathin sections (70 nm) were prepared and stained with uranyl acetate and lead citrate.", "Sections were examined with a Philips (Eindhoven, the Netherlands) EM208S electron microscope." ] },{ "paper_id": "fcbbd69303b907ba92cb854b46dc2d571e7db2e3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fd82025c545a45eb4e5701d19effecf2388f613a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fd8fe2d13c545800ba5aa3b59356002d35f81027", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We used SAS 9.2 (SAS Institute Inc., Cary, NC, USA) to conduct Wilcoxon rank sum tests and Kruskal-Wallis tests to compare continuous data, chi-square tests to compare categorical data, Spearman's test to identify correlations, and Cochran-Armitage test to identify trends.", "The " ] },{ "paper_id": "fdc336253485b3b3e895271a27f3457611e826f4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:", "Single cycle infections were performed at a multiplicity of infection of one and whole protein was extracted and separated on a 7.5%-10% SDS/PAGE gel and transferred to nitrocellulose (Bio-Rad). Membrane was blocked for 1 h with 5% skim milk at 25 \u00b0C, and then incubated with the indicated primary antibody overnight at 4 \u00b0C. Antibodies specific for actin (PA5-17568 Thermoscientific), H5 HAlo (DPJY02 (3B2) NR-19870 bei Resources, works in HI, WB, IFA, ELISA), and NP (NR-4544 bei Resources) were added at a concentration of 1 \u03bcg/mL in 5% skim milk. Serum from H5 HAlo infected mice was used at a 1:5000 dilution. Secondary mouse antibodies (NA931V GE Healthcare) were used at a 1:5000 dilution for 1 h at 25 \u00b0C. Protein was detected using Immobilon Western Chemiluminescent HRP Substrate (Millipore) as directed by the manufacturer." ] },{ "paper_id": "fdf569ac878048dd7d684ff5c664c5774cd8704b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Each participant performed one test with each device. Each test measured the ability of the device to filter ambient dust particles, normally present in room air, by using a previously described standard, quantitative, fit-testing protocol (9) . In brief, the testing compared particle counts inside and outside the protective device during a series of activities-normal breathing, deep breathing, turning the head from side to side, flexing and extending the head, talking loudly, and bending over followed by normal breathing.", "The median ratios of ambient-to-device particle counts were compared by using the Mann-Whitney U test (Statview 5.0, SAS Institute, Cary, NC). A p value <0.05 was considered significant.", "S evere acute respiratory syndrome (SARS) is a highly contagious, potentially life-threatening condition that frequently affects healthcare workers caring for infected patients (1) . Healthcare workers may need to adopt additional infection control procedures when carrying out potentially high-risk procedures such as intubation and surgery (2) . These procedures can generate aerosols known to penetrate surgical masks, which may contaminate all staff in the operating room (3) (4) (5) . Furthermore, other viruses such as the human papillomavirus have been shown to be present in CO 2 laser and diathermy plumes (6, 7) ." ] },{ "paper_id": "fe33ff01234dd6a16c30bf14916d1b32c4a940fd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis. Statistical analysis was performed using Graphpad Prism 7.03 (Graphpad Software Inc.) as indicated in the text.", "Supplemental material for this article may be found at https://doi.org/10.1128/ mSphere.00540-18.", "TEXT S1, DOCX file, 0.01 MB. FIG S1, TIF file, 2.1 MB." ] },{ "paper_id": "fe6434ef100a24a5528ba225163380cf0131dfbe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fe88da3bc7a4ef88f2bd09b88ae8b08ddb37901e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fe96465c506e69345e10773221f72b871b4e742f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The Application of Clinical Genetics is an international, peer-reviewed open access journal that welcomes laboratory and clinical findings in the field of human genetics. Specific topics include: Population genetics; Functional genetics; Natural history of genetic disease; Management of genetic disease; Mechanisms of genetic disease; Counselling and ethical issues; Animal models; Pharmacogenetics; Prenatal diagnosis; Dysmorphology. 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. ", "Evidence supporting the essential role of functional ischemia in contraction-induced myofiber damage and a 'two-hit' mechanism in mdx mice was reported by Asai et al. 12 The vasoactive drug tadalafil, a phosphodiesterase type 5 inhibitor, administered to mdx mice ameliorated muscle damage, and this has prompted a study of tadalafil in selected BMD patients (Table 1) .", "Submit your manuscript here: http://www.dovepress.com/the-application-of-clinical-genetics-journal" ] },{ "paper_id": "fe9f6f9d341b4949a8216e59c3bbbe4ddc3a7d5f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Chikungunya virus (CHIKV) is an arthropod-borne RNA virus of the genus Alphavirus, family Togaviridae.", "A fragment of the CHIKV E1 gene (positions 10265-11158, GenBank accession no. DQ443544) was amplifi ed directly from patient plasma and sequenced. Sequencing was performed with a CEQ 8000 Genetic Analysis System (Beckman Coulter, Krefi eld, Germany) as recommended. Sequences were analyzed with Lasergene software package (DNASTAR, Madison, WI, USA).", "Its genome is single stranded, of positive polarity, and 11.7 kb long. Based on partial sequences of the envelope protein E1, CHIKV strains can be grouped into 3 distinct genetic lineages, which share a common ancestor in tropical Africa (9) . The virus is transmitted to humans by numerous Aedes mosquito species, including Ae. aegypti and Ae. albopictus (2, (10) (11) (12) . The latter is thought to be less competent as a vector (2) ." ] },{ "paper_id": "feadeaa76cdeba85792a28babff5332a83ea1c82", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In a molecular epidemiologic study at a TB hospital in Delhi, Bhanu et al. performed DNA fingerprinting on 83 M. tuberculosis isolates from patients in 2 adjacent wards (31) . Of these 83 isolates, 8 strains were grouped into 3 clusters (identical fingerprints) by using IS6110 restriction fragment length polymorphism and spoligotyping analyses. Within each cluster, epidemiologic data showed overlapping hospitalization periods, which raises the possibility of nosocomial transmission (31) .", "Evaluation of symptomatic healthcare workers for active TB is feasible and should be implemented routinely. In addition to the above measures, hospitals should make every effort to treat TB patients on an ambulatory basis (25) . If hospitalization is required, every effort should be made to segregate potentially infectious patients from immunocompromised patients, rapidly diagnose and initiate treatment, and discharge patients promptly with DOT on an outpatient basis.", "In conclusion, healthcare workers are essential in the fight against TB, and their health needs to be protected. India, with its vast human and intellectual capital, nearly countrywide DOTS coverage, and a large, well-funded, successful national TB control program, is well placed to tackle this problem and set an example for other highprevalence countries." ] },{ "paper_id": "feb25c9a9dbc1800d43c52b03616c7a4d3e2a709", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The National Ethics Committee of Gabon approved this prospective study (no. 0023/2013/SG/CNE). Written informed consent forms and questionnaires were completed by parents or legal guardians upon a child's enrollment in the study.", "Center of Lastourville, are in semiurban and rural areas, respectively, of Ogoou\u00e9 Lolo Province. The fourth center, the Medical Research Unit of Ngounie in Fougamou, is in a rural area of Ngouni\u00e9 Province.", "Search past issues of EID at wwwnc.cdc.gov/eid" ] },{ "paper_id": "fed59469020955a3f7dfe77ab7c593643d48f505", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ff1cf519f153e1ebcdb5922731b28ee4e92f827c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CLRs comprise a large family of receptors which bind carbohydrates, through one or more carbohydrate recognition domains (CRDs), or which possess structurally similar C-type lectin-like domains (CTLDs) which do not necessarily recognize carbohydrate ligands. CLRs are divided into 17 groups based on features including phylogeny and structure (Zelensky and Gready, 2005) . Discussed in this review are CLRs from groups II (calcium-dependent lectins with single CRDs), group V (calcium-independent receptors with single CTLDs) and group VI (calcium-dependent lectins with multiple CRDs) (see Table 1 ). Based on their signalling potential, CLRs can be further subdivided into (i) activation Syk-coupled CLRs with immunoreceptor tyrosinebased activation motif (ITAM) domains, (ii) inhibitory CLRs with immunoreceptor tyrosine-based inhibition motif (ITIM) domains or (iii) CLRs without clear ITAM or ITIM domains such as MR, DEC-205 and DC-SIGN (Zelensky and Gready, 2005; Sancho and Reis e Sousa, 2012) .", "Activation of CLRs can induce intracellular signalling pathways in two ways: firstly through indirect signalling, where receptors such as macrophage-inducible C-type lectin (Mincle or CLEC4E), Dectin-2 (CLEC6A) and C-type lectin domain family 5A (CLEC5A) associate with ITAM containing adaptor molecules such as Fc Receptor \u03b3-chain (FcR\u03b3) or DAP12.", "Recently, CLECSF8 was also shown to be important in the resolution of pneumonia caused by Klebsiella pneumoniae (Steichen et al., 2013) . CLECSF8 \u2212/\u2212 mice were more susceptible than wild-type mice to pneumonic sepsis, with increased bacterial burdens, hyperinflammation and severe lung pathology which correlated with a massive accumulation of neutrophils. These results suggest that CLECSF8 plays an important role in resolution of inflammation, and is the first report describing a physiological function for this CLR." ] },{ "paper_id": "ff304104b0e2e1f4c8318ec119a79721fe7a4467", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ff365ebbc0fc55476886b0abd129e227c1f8a527", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We assessed appropriate sampling of chains graphically by ensuring mixing on trace plots, and convergence by ensuring the Gelman-Rubin statistic was < 1.2. 34, 35 We used non-informative prior distributions." ] },{ "paper_id": "ff7d49ac4008f60ef9c5a437e0d504dcefd1246f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ffb381668d93248759ca3855425e05722cb9f562", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ffd3a93b927e221ded4cf76536ad31bef2c74b89", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Twelve patients with severe ARI were admitted to the NHP intensive care unit over 38 days during the cool months of December 2007-February 2008 (temperature 5\u00b0C-14\u00b0C). The 12 hospitalized infants (11 female) were 2-to 4-months-old. Most (10/12) were from 1 orphanage, which was selected for investigation. Two hospitalized children had a known underlying condition: congenital hypothyroidism (n = 1) and HIV infection (n = 1). Seven infants were underweight (sex-specifi c weight-for-age; z score <2 SDs). All exhibited cough, coryza, wheezing, and dyspnea, and 6 (50%) had a documented fever.", "Emerging Infectious Diseases \u2022 www." ] },{ "paper_id": "ffe133ed880d6c77ae340c5374817232e21f8315", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To determine the target peptides that can be considered to elicit immune response, the steps in the process are, briefly:", "Since the HPV virion capsomers are composed of five L1 proteins, and one L2 each, it is possible that a surface accessible antigen in one protein may get covered by the folds of a neighboring protein.", "Determination of epitope segments. Next, we consider which of the segments from the second-stage choice contains epitope regions to elicit necessary immune response. For this, we use two epitope-prediction tools, viz., the Immune Epitope Database (IEDB) and Analysis Resource server [32] [33] [34] [35] and ABCpred server, 36, 37 which, as mentioned earlier, 21 have given good results. These tools indicate binding affinities of T-cell epitopes and B-cell epitopes (with 66% accuracy), major histocompatibility complex (MHC) I, and also of discontinuous epitopes through Ellipro." ] }]