[{ "paper_id": "0015023cc06b5362d332b3baf348d11567ca2fbb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Mutations were then introduced into the replicon plasmid as described above.", "VP3, and VP0 (which is further processed to VP2 and VP4 during virus assembly) (6). The P2 64 and P3 regions encode the non-structural proteins 2B and 2C and 3A, 3B (1-3) (VPg), 3C pro and 4 structural protein-coding region is replaced by reporter genes, allow the study of genome 68 replication without the requirement for high containment (9, 10) ( figure 1A )." ] },{ "paper_id": "004f0f8bb66cf446678dc13cf2701feec4f36d76", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "00d16927588fb04d4be0e6b269fc02f0d3c2aa7b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For MinION cDNA synthesis, RNA was extracted from 500 \u00b5l of each clinical sample using Trizol-LS (Thermo Fisher Scientific, Waltham, MA, USA), per manufacturer's directions." ] },{ "paper_id": "013d9d1cba8a54d5d3718c229b812d7cf91b6c89", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Background: A novel coronavirus (2019-nCoV) emerged in Wuhan City, China, at the end of 2019 and has caused an outbreak of human-to-human", "The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. The corresponding authors attest that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.", "Relative netflow = (inflow -outflow) / population of each county", "It is expected that further international exportation of cases from China will occur and cases may appear in any country [30] . Thus, all countries should be prepared for containment, including active surveillance, early detection, isolation and case management, contact tracing and prevention of onward spread of the 2019-nCoV infection [6, 31] . Of additional concern is that the anticipated destinations of hundreds of thousands of travellers departing China are to low-income or lower-middle income countries, where inadequately resourced medical and public health systems might be unable to detect and adequately manage an imported case of 2019n-CoV, including possible subsequent community spread." ] },{ "paper_id": "01d162d7fae6aaba8e6e60e563ef4c2fca7b0e18", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Although TWIRLS only identified 623 CSSEs after collation, for human researchers, the information is scattered in words, which is limited for reconstructing understandable mechanistic models. Therefore, TWIRLS clusters CSSEs according to the rules defined by CSHG distribution, as genetic level research can accurately answer and solve physiological and pathological problems.", "virus to ACE2 may disrupt this balance, which causes a steady-state imbalance of RAS, leading to subsequent pathological changes.", "Although Ang II was originally described as an effective vasoconstrictor, there is growing evidence that it is closely involved in the inflammatory response of the immune system." ] },{ "paper_id": "01e3b313e78a352593be2ff64927192af66619b5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "8", "Genome-wide polymorphisms required to measure pN/pS at the scale of the proteome 20 have become available for humans (Abecasis et al., 2012) (1,000 Genomes Project) 21 (Table S5) , and chimpanzee, gorilla, and orangutans (Prado-Martinez et al., 2013)", "although VIPs represent only 13% of the orthologs in our dataset, we estimate that in 18 human evolution they account for almost 30% of all adaptive amino-acid changes. Note ", "The product of P-values is a good measure of whether a specific protein experienced ", "Although we already find a strong signal of increased adaptation, the amount of adaptive 18 evolution that can be attributed to viruses is probably underestimated by our analysis." ] },{ "paper_id": "02201e4601ab0eb70b6c26480cf2bfeae2625193", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Individuals are divided into children (c, age less than 19y) and adults (a, otherwise). Population size and age structure per municipality as of January 1, 2008 are obtained from Belgian Statistics [1] .", "where the element ij (i = a, c, j = a, c) is given by:", "C reg weekday C reg weekday C reg weekday = C cc C ca C ac C aa = 40.71 7.84 7.84 14.25 .", "School closure is often considered as an option to mitigate influenza epidemics because of its potential to reduce transmission in children and then in the community. The policy is still however highly debated because of controversial evidence. Moreover, the specific mechanisms leading to mitigation are not clearly identified. We introduced a stochastic spatial age-specific metapopulation model to assess the role of holiday-associated behavioral changes and how" ] },{ "paper_id": "0255ea4b2f26a51a3bfa3bd8f3e1978c82c976d5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To determine if SWNT adsorbed RNA is protected from nuclease degradation, we performed an agarose gel electrophoresis based RNA protection assay as described in (24) . 200 ng free RNA and RNA-SWNTs (carrying 200 ng RNA) were each incubated with cell lysate proteins obtained from one Nb leaf to mimic the intracellular degradation conditions for 1, 3, 6, 12, and 24 hours.", "Preparation of chemicals. Super purified HiPCO SWNTs (Lot # HS28-037) were purchased from NanoIntegris, and SWNTs samples were extensively purified before use (49) . Single-stranded RNA strands, Cy3-tagged single-stranded RNA strands and all primer sequences were purchased from IDT and dissolved in 0.1M NaCl before use.", "The target gene in our qPCR was mGFP5 (GFP transgene inserted into Nb), and EF1", "Quantification of the RNA bands from the gel was done using Image J gel analyzer tool.", "Therefore, any fluorescence localized in the cytoplasm follows the cytosolic cell contour shape ( Supplementary Fig. 3 )." ] },{ "paper_id": "029c1c588047f1d612a219ee15494d2d19ff7439", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "03ce432f27c7df6af22b92245a614db2ecb5de5f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Despite their undoubted importance, astroviruses still represent one of the least studied groups of human positive-sense RNA viruses. The genome contains three main open reading frames:", "ORF1b (RdRp) amino acid sequences were extracted and aligned, and a phylogenetic tree constructed (Fig. S1 ). We follow the genogroups defined in Yokoyama et al. 8 . Although the more-divergent CP sequences may provide a less robust phylogenetic analysis, we also constructed a CP-based phylogenetic tree to test for possible recombination (Fig. S2 ). At the level of genogroup the ORF1b and CP trees were consistent, although within genogroups there were some differences between the topologies of the two trees. For simplicity, we used the ORF1b tree to define astrovirus clades for full-genome analyses.", "Note that genogroup V -represented by a single partial sequence, FJ890355 (bottlenose dolphin astrovirus 1) -is one of these. Table S1 ). Similar to other overlapping genes, which generally evolve de novo 11 , the XP peptide sequences show little to no homology to known protein domains. Many XP sequences contain a predicted TM domain, and some other XPs contain a stretch of hydrophobic amino acids that resembles a TM domain despite being scored below threshold by Phobius (Fig. S8, Fig. S9 )." ] },{ "paper_id": "03ea3a614b56409d3f099c9ad764864293132540", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "These data support a heterogenous RNA model in which frameshifting occurs on a small subset of RNA with high probability.", "Such low-fidelity factories may benefit viral robustness, where mutations are desirable.", "Requests for further information and resources should be directed to and will be fulfilled by the corresponding authors, Brian Munsky (brian.munsky@colostate.edu) and Tim Stasevich (tim.stasevich@colostate.edu). Key plasmids will be deposited on Addgene." ] },{ "paper_id": "04030bba3035a58c7725ae267973206f6eb6c0b4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The recent outbreak of infections by the 2019 novel coronavirus (2019-nCoV), the third 36 zoonotic CoV has raised great public health concern. The demand for rapid and accurate 37 diagnosis of this novel pathogen brought significant clinical and technological challenges. 38 Currently, metagenomic next-generation sequencing (mNGS) and reverse-transcription PCR 39 (RT-PCR) are the most widely used molecular diagnostics for 2019-nCoV.", "Based on the three potential target sequences we identified, multiple sets of RPA primers 197 and CRISPR gRNAs were designed and screened. Among these, the set that targeted Orf1ab 198 showed the best overall performance of sensitivity and specificity, and therefore, was used to 199 develop CRISPR-nCoV in this study for further evaluation (data not shown). 200 We then sought to determine its analytical sensitivity by serial dilution at various 201 concentrations. As shown in Figure 2B , CRISPR-nCoV consistently detected 7.5 copies of 202 2019-nCoV in all 10 replicates, 2.5 copies in 6 out of 10 , and 1.25 copies in 2 out of 10 runs." ] },{ "paper_id": "05082393ba4c7ec530190dd887d99c74fd72f6d6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0562f70516579d557cd1486000bb7aac5ccec2a1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The study population included 41 hospitalized staff with confirmed COVID-19.", "Only 2 cases (4.9%) told contact with infected family members, but they had also contacted with suspected COVID-19 patients, making the clue questioning. (Table 1 )" ] },{ "paper_id": "05d99c07db59b6948e39bfa62c2cbbf62944059a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "An outbreak of a novel coronavirus, recently renamed CoVID-19, was first reported from Wuhan, China on 31 December 2019. During January 2020, the outbreak spread to multiple cities in China, and the first cases started appearing outside China. By the end of January 2020, 9,720 cases had been confirmed in China, with 106 confirmed cases outside China across 19 different countries (1) .", "is the magnitude of the seasonal difference in transmission, ranging from", "The model is coded in C and is available on github (http://github.com/ldanon/MetaWards). The data are freely available from the Office for National Statistics website, or can be downloaded with the code at the github repository.", "A key element missing from our model is morbidity, mortality and the treatment of cases. The model in its current form predicts the total number of infections in the community rather than diagnosed cases. Observations from China suggest that many cases have mild symptoms and that only around 5% of cases have been reported and diagnosed (3) . The parameter estimates we used from China appear to be substantially different to previous coronaviruses (6) . Should CoVID-19 continue spreading the UK it will become possible to get UK-specific parameter estimates and improve prediction accuracy." ] },{ "paper_id": "0624a12abfe85c8b5070850d912a2db4cd453236", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Abrupt changes in the coverage depth can be caused by alternative splicing events, duplicate k-mers, or sequencing bias in SR. These abrupt changes are termed split-coverage.", "To evaluate the efficiency of these algorithms, we made use of two publicly available and one in-house SR and LR matched real datasets. The first dataset comes from a MinION cDNA sequencing experiment of ERCC Mix1", "We wished to use the recently published evaluation tool, LC_EC_analyser (42) . Unfortunately, it does not scale to our real size datasets (seemingly because of AlignQC issues in memory management). Nonetheless, we used analogous criteria (see below). Scripts designed to perform our evaluation are avalaible at: https://gitlab.igh.cnrs.fr/lbroseus/TransAT." ] },{ "paper_id": "06a1002f9fbea7179ac3572843f66b14568af6e4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In the SIE, the \u0394G was calculated based on equation (2),", "The 5 ns production run was performed with pmemd.cuda." ] },{ "paper_id": "06c1b3535b83251cf92c01258b5048beeab7a460", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The network approach naturally accounts for heterogeneity, meaning that some individuals will cause more infections than others. The network approach also accounts for stochasticity explicitly: Even with R 0 > 1, there is a probability 1 \u2212 R(\u221e) that patient zero lies outside of the giant outbreak and therefore only leads to a small outbreak that does not invade the population.", ". CC-BY 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.", "and solving for u = G C 1 (u) yields", "because it contains all nodes except those with no edges leading to the GCC. This solution is exact in the limit of large population size." ] },{ "paper_id": "07e833d0917cace550853f72923856d0fe1a7120", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Human FGF2 was produced as described by Duchesne et al. 13 . Porcine mucosal heparin was biotinylated at the reducing end using hydroxylamine biotin (ThermoFisher, UK) as described by Thakar et al. 14 . Heparin (20 \u00b5L 50 mg/mL) was reacted with 20 \u00b5L hydroxylamine-biotin in 40 \u00b5L 300 mM aniline (Sigma-Aldrich, UK) and 40 \u00b5L 200 mM acetate pH 6 for 48 h at 37 \u00b0C. Free biotin was removed by gelfiltration chromatography on Sephadex G25 (GE LifeSciences, UK).", "It is noteworthy that even pharmaceutical-grade heparin preparations remain a polydisperse mixture of natural products, containing both anticoagulant and nonanticoagulant saccharide structures. The latter may prove to be an invaluable resource for next-generation, biologically active, antiviral agents that display negligible anticoagulant potential, whilst the former remains tractable to facile, chemical (and enzymatic) engineering strategies to ablate their anticoagulation activities.", "Heparin, the second most widely used drug by weight globally, is formulated as a polydisperse, heterogenous natural product. Unfractionated heparin, low molecular weight heparins and heparinoids are clinically approved as anticoagulants / thrombotic with excellent safety, stability, bioavailability and pharmacokinetic profiles. Crucially, heparin and its derivatives, some of which lacking significant anticoagulant activity 1 , are an under-exploited antiviral drug class, despite possessing broad-spectrum activity against a multitude of distinct viruses, including coronaviridae and SARSassociated coronavirus strain HSR1 2 , in addition to flaviviruses 3, 4 , herpes 5 , influenza 6 and HIV 7, 8 ." ] },{ "paper_id": "08660499ee722a74043f8417faee3e1eeb9d0f5f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Zika virus genomes (Supplemental File 2 and Fig. 3) .", "https://github.com/andersenlab/paper_2018_cuba-travel-zika.", ". CC-BY-NC 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/496901 doi: bioRxiv preprint" ] },{ "paper_id": "08a22278486e12768ce186677a6a89663d24586f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "branch's length corresponds to an average number of nucleotide changes per 100 nucleotides. 326 327 Figure 3 ." ] },{ "paper_id": "090b6c8b3df30bc248221869f673a2d970caa1b9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "LHS was used to take into account uncertainty in parameter estimates; 1,000 values for each parameter were sampled 105 from the assumed parameter probability distributions (Table 1) ", "20", "In the wake of the Rohingya population's mass migration from Myanmar, one of the world's largest 10 refugee settlements was constructed in Cox's Bazar, Bangladesh to accommodate nearly 900,000 new 11 refugees. Refugee populations are particularly vulnerable to infectious disease outbreaks due to many 12 population and environmental factors. A large measles outbreak, with over 2,500 cases, occurred among 13 the Rohingya population between September and December 2017. Here, we estimate key epidemiological 14 parameters and use a dynamic mathematical model of measles transmission to evaluate the effectiveness 15 of the reactive vaccination campaigns in the refugee camps. We also estimate the potential for subsequent 16 outbreaks under different vaccination coverage scenarios. Our modeling results highlight the success of 17 the vaccination campaigns in rapidly curbing transmission and emphasize the public health importance 18 of maintaining high levels of vaccination in this population, where high birth rates and historically low 19 vaccination coverage rates create suitable conditions for future measles outbreaks." ] },{ "paper_id": "091a8e9a61e19e88caeb039f0e3888d111b20439", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "That is, the probability density function (PDF) of \u03c4 can be written as", "Similarly, for the OLS estimation, \u00b5 and \u03c3 2 can be estimated from the following optimization objective function:", "(2.8)", "The age distribution of patients in the whole province or each region all roughly follows normal distribution ( Fig.2 D, E). Patients aged between 21 and 60 years old take up more than 81% (938 out of 1156). The main reason may be that people aged between 21 and 60 years old are the social main labor forces, there are many migrant workers in this age interval. Moreover, they may have wider social circles than the others. Therefore, people aged between 21 and 60 years old are key crowd with high risks of COVID-19." ] },{ "paper_id": "09b6706748f0c1ae0da436ac2dfac9052b84e4ea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CTDs only have the one-layer or two-layer core structure without obvious inserted 294 region.", "respectively. The newly identified porcine SADS-CoV isolates are also found to share 65 ~95% sequence identity with Rhinolophus bat coronavirus HKU2, and this further 66 stressed the severe results of coronavirus spillover from bats to domestic animals 5-10 ." ] },{ "paper_id": "09c9fcabc66a106e01ef42247cbd86b6d85bd67f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Encephalitis Virus (VEEV) by interfering with viral replication [7, 8]. In line with this, Zika virus 89 replication is restricted by ARTD12 [26] . In addition to these molecular and cell-based studies, 90 evolutionary analysis suggests a role for several ARTD family members at the host-pathogen 91 interface, among them the macrodomain containing ARTDs (ARTD7-9) and ARTD13 [27]. 92", "Further analysis revealed that ARTD10 and ARTD12 had additive repressing effects on 170 replication when analyzed 30 hpt (Fig. 1f) . 171" ] },{ "paper_id": "09ec8daa8e32168d92d05b86de1784c639685fb4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0a32446730827ad8152c6a61e4738e4e0b231412", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "0a43046c154d0e521a6c425df215d90f3c62681e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The underlying cause for the superior performance of PS relative to PTFE and PVC merits The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/441154 doi: bioRxiv preprint among experimental conditions. For the Trizol method, a visible RNA \"pellet\" was to be 289 observed after extraction, distinguishable from impurities in the sample. However, several 290 samples did not produce a visible pellet, making it more difficult to distinguish between the viral 291 RNA and the remaining impurities in the sample. Therefore, the Trizol method may have 292 resulted in additional loss of viral RNA. Viral recovery efficiency from each filter type was not 293 measured for each sample; therefore, it is unknown whether the differences in virus recovered 294 from the filter types in each sample had an effect on viral RNA copy variability.", "Introduction minimize the effects of sampling stress and maximize recovery. The SKC Biosampler has been 78 found to have greater viral recovery compared to other commonly used filter-based samplers; 79 however, the differences across samplers were not statistically significant. [13] [14] [15] 80 81 Filters are used frequently as a sampling media in personal samplers in the field of exposure 82 assessment. Filter based samplers have also been used in the collection of aerosolized viruses due 83 to their efficiency in collecting sub-micrometer particles 10, 16 , and ability to be used for longer 84 periods in the field compared to impinger based methods. 17,18 Polytetrafluoroethylene (PTFE), 85 polyvinyl chloride (PVC), polycarbonate, and gelatin-containing filters have all been used to 86 collect virus 10,19 , with PTFE and PVC being the most efficient among filter materials tested. 16, 19 87 Nevertheless, the viral recovery from PTFE and PVC filter materials remains inefficient. 10", "After washing the filters with either HBSS or PBS, aliquots for each extraction process were The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/441154 doi: bioRxiv preprint For this experiment, a target of 50% RH was established for all trials. Although the optimal 311 comfort level for humans is 40-60% RH 14 , and previous studies have found that higher RHs (i.e., 312 50-56%) have no effect on viral infectivity. 13 Relative humidity was measured using a single real 313 time measurement instrument in the chamber over the course of the experiment. We assumed the 314 experimental chamber was well mixed however, the RH may not have remained at 50% for all 315 sampling locations during the entire 30-minute sampling period. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/441154 doi: bioRxiv preprint" ] },{ "paper_id": "0ab795fc615df6457551a8e231dce1f268eef9d2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "JH and ZZ finished the manuscript and data interpretation. SJ had roles in clinical management of patients. ZS had roles in data analysis and data interpretation, TW helped the data collection. All authors reviewed and approved the final version of the manuscript.", "All the authors declare no competing interests.", "No funding sources supported this work.", "All data referred to in the manuscript are available from the corresponding author by request." ] },{ "paper_id": "0acc1f9a1c333a9a6b2dbba4a252d7576f024783", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Finally, complete content and organizational editing before formatting. Please take note of the following items when proofreading spelling and grammar:", "The database is available at" ] },{ "paper_id": "0aff00101d5ccc6592987185ab833f95d842f98b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The third one, Ponatinib (see Figure 3 ", "Consequently, a important property of boundary operator, \u2202 k\u22121 \u2202 k = \u2205, follows from that boundaries are boundaryless. The algebraic construction to connect a sequence of complexes by boundary maps is called a chain complex", "Persistent homology [18] is devised to track the multiscale topological information over different scales along a filtration. A filtration of a topology space K is a nested sequence of subspaces {K t } t=0,...,m of K such that \u2205 = K 0 \u2286 K 1 \u2286 K 2 \u2286 \u00b7 \u00b7 \u00b7 \u2286 K m = K. Moreover, on this complex sequence, we obtain a sequence of chain complexes by homomorphisms: C * (K 0 ) \u2192 C * (K 1 ) \u2192 \u00b7 \u00b7 \u00b7 \u2192 C * (K m ) and a homology sequence:" ] },{ "paper_id": "0b282573f5c63c943021c10ca39a1ed21acfb429", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data description Resident population. The statistics about the distribution of the population across 31 regions in China were obtained from the \"China Statistical Yearbook 2019\" [22] . This annual publication reflects comprehensively the economic and social development of China.", "I\u2192R: Infected individuals enter the removed compartment with a rate inversely proportional to the mean infectious period, T I .", "Several studies predict a much larger number of infections than the actual number reported by the authorities, claiming that only between 10% and 20% of the cases have been detected and reported [6] [7] [8] [9] . The reasons for such deviations between models and actual count of cases are diverse, for instance, the fact that the symptoms could be mild and similar to other flue-like diseases for some people, may induce infected individuals not to seek medical care [10] . On the other hand, on Feb. 13th, 14,840 new cases were reported [11] , in contrast to 2,022 cases counted during the previous day [12] . The reason was that previously to that day, only those cases that had been laboratory-confirmed were being recognized as so, whereas from that date onwards, also the clinically diagnosed cases are accounted for. Therefore, the model-based prediction of the numbers of infected individuals can plausibly be larger than the official reports." ] },{ "paper_id": "0b460e73926eb107001c95c0dfeae2362b4251b0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We highly recommend adding SARS-CoV-2 to routine diagnostic testing in capable hospitals to prevent misdetection of the virus.", "Laboratories in Qingdao and Wuhan adopted a similar protocol for detection of IgM- ", "At the beginning of December 2019, a cluster of \"pneumonia of unknown aetiology\" emerged in Wuhan, Hubei Province, China. The disease has soon developed into an outbreak posing a pandemic threat. Since no causative pathogen was identified at the onset of the disease, it was once called \"Wuhan pneumonia\" by the health officials and the public. On December 31, 2019, a total of 27 cases were reported; meanwhile, a rapid response team led by the Chinese Centre for Disease Control and Prevention (China CDC) was formed to conduct detailed epidemiologic and aetiologic investigations in Wuhan. 1 ", "Although the climate in Qingdao is drier and colder than Wuhan, major respiratory pathogens circulate in the two cities were quite similar." ] },{ "paper_id": "0b48e1bfcdff9a42c88cc80a98661feb2703390d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "It should be noted that individual replicate data were noticeably noisier for this surface than the other 153 surfaces tested ( Figures S1-S5) , so we advise caution in interpreting this result. ", "1 2700 words. Current = 2638, including references and table/figure legends 2 5 Tables and Figures. Current = 3 3 40 references. Current = 24 4 5 for use under a CC0 license.", "We found that the half-life of HCoV-19 on cardboard is longer than the half-life of SARS-CoV-1." ] },{ "paper_id": "0b4b4e5bb8d0d5167eec1e203b5dad283bd364a5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "3 Some of the most important findings in biogerontology are the evolutionarily conserved pathways that 34 regulate lifespan 1-6 . In model organisms, mutations affecting these pathways can often extend lifespan 35 by between 30% and 100% 7,8 . Combining different genetic mutations can result in synergistic lifespan 36 extension 9-11 . By contrast, the effect of pharmacological interventions are typically much weaker, even 37 when targeting the same pathways 2,12,13 , but this genetic synergy suggests a potential strategy for the 38 design of novel pharmacological interventions by simultaneously targeting multiple evolutionarily 39 conserved ageing pathways. To date there is little data on synergistic effects of pharmacological 40 interventions on lifespan 14 . Here we report an in vivo approach to design novel multi-drug ageing 41 interventions. We show how multi-drug interventions leverage pathway synergies to maximize effect 42 size, while minimizing side effects and detrimental developmental tradeoffs through targeting distinct 43 but interacting ageing pathways. Our ultimate aim was to design a purely pharmacological, adult-44 onset intervention with lifespan efficacy similar or better than those of canonical aging mutations did.", "Nematode Growth Medium (NGM) agar plates at 20\u00b0C using E. coli OP50 bacteria as food 6", "source unless otherwise noted. After plates were poured and dried, they were sealed and 7 stored at 4\u00b0C. E. coli were spotted on plates on the previous evening and allowed to dry. For 8 compound treatments, all agar plates were prepared from the same batch of NGM agar and 9 treatment plates were supplemented with the respective compounds or vehicle as a control. 10", "Fresh plates were prepared every week. The following worm strains were used: wild type N2, 11" ] },{ "paper_id": "0bd443591b5e10934beef050b516afeca6b668fe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "y= 70.0916+0.0054\u00d7x1+2.3455\u00d7x2 (n = 44, R 2 = 0.9330, P<10 -7 )", "Nanjing, Qingdao, Shenzhen and Foshan during the 2019 Spring Festival travel rush (40d) are from their Official website of the Transportation Commission. We estimate one Baidu Migration index is about equal to 56,137 travelers (Fig.6) .", "The only lesson that humans have learned from history is that humans have not learned anything from history.", "Obviously, COVID-19 greatly reduced the human mobility of China Mainland." ] },{ "paper_id": "0c27c0ddaa4761f6155838df81a88d24619720f8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In conclusion, the Genome Detective Coronavirus Typing Tool is a web-based and user-friendly software application that allows the identification and characterization of novel coronavirus genomes.", "The result of the phylogenetic and mutational analysis performed by AGA is available in a detailed report. This report contains an interactive phylogenetic tree and genome mapper (Supplementary Figure 1) . It also presents the virus species and cluster assignments and a detailed table that provides information about open reading frames (ORFs), CDS and proteins. This table can be expanded to show nucleotide and amino acid mutations that differentiate a query sequence from their species RefSeq or from a sequence in the phylogenetic reference dataset. All results can be exported to a variety of file formats (XML, CSV, Excel, Nexus or FASTA).", "The tool uses a novel and dynamic aligner, AGA, to allow submitted sequences to be queried against reference genomes, using both nucleotide and amino acid similarity scores. This allows accurate identification of other coronavirus species and the tracking of new viral mutations as the outbreak expands globally. It also performs detailed analysis of the coding regions and proteins. Moreover, it can easily be updated to add new phylogenetic clusters if new outbreaks arise or if the classification nomenclature changes. The tool has been able to correctly classify all the recently released nCoV-2019 genomes, as well as all the 2002-2003 SARS outbreak sequences" ] },{ "paper_id": "0cad40f50e41144e8b64744251515eca8cfac5f7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 the mean generation interval of the infection T c ;", "Firstly, Let us introduce some variables:", "\u2022 f 2 (t): the transition probability from infection to illness onset;", "Conjecture 2.1. The epidemic model for COVID-19 is SEIR if CCDC's data are correct.", "\u2022 : denotes the quarantine strategy, for example, specially, we consider this parameter as the isolation rate. Large value of suggests that the government more likes to control the spreading of COVID-19.", "One can also use the discrete system with each step representing one day just as we have implemented in the code:" ] },{ "paper_id": "0cb9c296684ca5e71462d825cab2827854a01544", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Animal work was conducted under a protocol approved by the University of Minnesota IACUC." ] },{ "paper_id": "0d7964c665ff0107c674bc6dab8f252cab08038e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Significant differences between treatments were tested by the Tukey-Kramer (HSD) test.", "RNAi could be divided into cell-autonomous and non-cell autonomous [5] . In cell-autonomous RNAi, silencing is restricted to cells that produce or were exposed to the dsRNA trigger. Initiation of local RNAi could develop in some organisms into a non-cell autonomous silencing signal, affecting cells and tissues which originally did not generate or were not introduced to dsRNA [6, 7] . The mechanisms that facilitate RNA export from donor cells, extracellular spread and import into acceptor cells are not fully elucidated, but under ongoing investigation in diverse biological systems.", "The genome of A. mellifera was downloaded from ensembl (release 32). Using in-house scripts (https://doi.org/10.5281/zenodo.1302437), the fastq files (R1 & R2) of each royal and jelly sample were converted into fasta files, which were then aligned to the A. mellifera genome using blat [54] . The best hit for each R1 mapped read was matched with the best hit for its R2 mapped read. Therefore determining the final mapping of the read as well as the size of its matching RNA.", "List of species used in the metagenomics analysis The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/299800 doi: bioRxiv preprint " ] },{ "paper_id": "0da2ec30d7dfdef624833a36890f0297f19d09ec", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Protein and solvent dielectric constants were set to 2.0 and 78.0, respectively. All structural figures were generated by PyMOL(W).", "Using the premise that effective variants are in linkage disequilibrium (LD) with common polymorphisms and haplotypes, linkage and association studies have identified genes involved in the development of traits and pathologies. Upon their identification, the regions flanking associated markers are sequenced to find the linked, penetrant mutation. However, rare variants are often not detectable using LD-based methods.", "[ Figure 1 near here]" ] },{ "paper_id": "0e2ba405f636e06821999876cd82c00e26404b43", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In Eukaryotes, the RNA cap structure is thought to be synthesized post-transcriptionally [5] .", "In any case, the type, diversity, and distribution of RNA MTases along the Nidovirales deserves a closer look : SAM-dependent MTases are ancient folds associated with RNA stability and evolution [47] . Their presence and properties in a phylogenetic tree may well give interesting clues regarding RNA genome evolution and its associated issue of host defense mechanisms.", "Two salient features of these viruses are, amongst others, their complex and still obscure replication/transcription mechanism as well as their broad genome-size range. Genomes of Arteriviridae (12.7 -15.7 kb in length), Mesoniviridae (\u223c20 kb), Medioniviridae (20.2 -25 kb), Euroniviridae (\u223c24.5 kb), Roniviridae (\u223c26 kb) Tobaniviridae and Coronaviridae (\u223c27-32 kb), Abyssoviridae (35.9 kb), and Mononiviridae (41.1 kb) members, share a similar genomic organisation generating viral mRNAs from a fixed genomic location, the 'nest', which has inspired the family name (Nido : latin for 'nest') [3, 4] . Nidovirales genomic and mRNAs are presumably capped, although direct demonstration of the presence of an RNA cap structure is still missing for many of these Nidovirales members.", "Nidovirales have attracted much attention in the past decades for being causative agents of serious diseases in humans and animals. In humans, Severe Acute Respiratory Syndrome (SARS) and the Middle-East Respiratory Syndrome (MERS) coronaviruses (CoVs) have been associated with high fatality/case ratios of \u223c10% and \u223c35 %, respectively (reviewed in [2]). In animals, pathogens of significant economical and societal impact include Equine Arteritis virus (EAV, Alphaarterivirus equid) and Porcine Reproductive Respiratory Syndrome virus (PRSSV 1-2, Betaarterivirus suid 1-2).", "Multiple sequence alignments (MSA) were generated using Muscle in SeaView [29] . For each sequence of unknown structure, secondary structures were predicted using Predict Protein [30] . The predicted secondary structures were used to validate the alignment with structural references. The MSA was rendered using ESPript 3.0 [31] , together with appropriate structural models as indicated, to assign secondary structures. When possible, structural 3D models were generated using Phyre 2.0 [32] . Conserved patches of amino-acids were generated using WebLogo [33] and mapped in the structural models rendered in Chimera." ] },{ "paper_id": "0eda8331214ca028350b07e2953702f3078a105e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The novel coronavirus that emerged in Wuhan, China at the end of 2019 quickly spread to all Chinese provinces and, as of February 6, 2020, to 24 other countries 1, 2 . Efforts to contain the virus are ongoing; however, given the many uncertainties regarding pathogen transmissibility and virulence, the effectiveness of these efforts is unknown.", "This work was supported by US NIH grants GM110748 and AI145883. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences, the National Institute for Allergy and Infectious Diseases, or the National Institutes of Health.", "Our findings underscore the seriousness and pandemic potential of COVID-19. The 2009 H1N1 pandemic influenza virus also caused many mild cases, quickly spread globally, and eventually became endemic. Presently, there are four, endemic, coronavirus strains currently circulating in human populations (229E, HKU1, NL63, OC43). If the novel coronavirus follows the pattern of 2009 H1N1 pandemic influenza, it will also spread globally and become a fifth endemic coronavirus within the human population." ] },{ "paper_id": "0eee9760aee0ca2fdf8d1d215c3689d5f8d84df5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Most of the patients were mild-moderate in disease severity (mild-moderate cases, n=18, 85.7%).", "The ", "On presentation, most patients (85.7%) had fever with a mean body temperature of 37.8 o C." ] },{ "paper_id": "0fa18c47543c3ce69a3c9e4d77958c4d3691b1ed", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "7. The process of fermentation of hemp seed protein extract was performed using the following materials a proprietary probiotic formula containing Lactobacillus salivarius, Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactococcus lactis, Bifidobacterium infantis, Bifidobacterium bifidum, Bifidobacterium lactis, Bifidobacterium longum, and proprietary cultured kefir grains whose peculiar microflora was recently described (8) . The fermented hemp seed protein extract caused inhibition of HCT116 cell proliferation that was statistically significant (p < 0.05). We attribute this effect to formation of bioactive peptides from edestin. Edestin is an hexameric globular protein that bears striking functional resemblance to DBP-MAF. We postulate that proteases secreted by the microbes of the probiotic formulation, together with the increase of acidity that is characteristic of fermentation, led to formation of peptides functionally very similar to DBP-MAF and, in", "Sodium-bile acid cotransporter, also denominated sodium-taurocholate cotransporting polypeptide (NTCP) is an integral membrane protein with multiple hydrophobic transmembrane domains. The third extracellular domain of NTCP presents a stretch of nine aminoacids (KGIVISLVL) that is characterized by pronounced hydrophobicity and serves as receptor for a protein, preS1, showing the hydrophobic epta-peptide sequence NPLGFFP. Vitamin D-binding protein macrophage activating factor (DBP-MAF) is a multifunctional protein that is characterized by two hydrophobic regions able to bind fatty acids and vitamin D, respectively. Here we demonstrate that NTCP and DBP-MAF show significant sequence similarities as far as hydrophobic stretches of aminoacids are concerned. Alignment of the sequence of seven aminoacids preceding the 157-KGIVISLVL-165 stretch of NTCP shows four aminoacids that are identical to those of the corresponding sequence of DBP-MAF, and two that are conserved substitutions. In addition, in the sequence of DBP-MAF that is aligned with the sequence YKGIVISLVL of NTCP, there are two contiguous negatively charged aminoacids (ED) and, in the preceding epta-peptide sequence, there are three negatively charged aminoacids (D-ED), whereas in the corresponding sequence of NTCP there are only two (D--D) that are not contiguous. This concentration of negatively charged aminoacids may be involved in binding of protein inserts characterized by high density of positively charges residues. The alternating hydrophobic and electrostatic interactions described in this paper may help elucidating the biological roles of these proteins as far as protein-protein interactions are concerned.", "The sodium-bile acid cotransporter, also defined the sodium-taurocholate cotransporting polypeptide (NTCP) or also liver bile acid transporter, is an integral transmembrane protein that is encoded by the SLC10A1 (solute carrier family 10, member 1) human gene and shows multiple hydrophobic transmembrane domains (1) . This transporter plays a critical role in maintenance of the enterohepatic recirculation of bile acids and hepatocyte function. The protein is constituted by 349 aminoacids with a resulting molecular mass of 56 kDa and works by binding two sodium ions and one (conjugated) bile salt molecule, in this manner determining hepatic influx of bile salts. Other molecules that may be transported by this protein comprise steroid and thyroid hormones, and xenobiotics of different origin (2) . NTCP also represents the receptor for Hepatitis B virus (HBV) and the interaction between the aminoacid sequences of NTCP and those of HBV surface proteins has been characterized in molecular details. The preS1 sequence of large envelope protein (L) is essential for interaction with a stretch of nine hydrophobic residues (157-KGIVISLVL-165) located in the third transmembrane domain of NTCP. The sequence of the preS1 L protein binding NTCP is constituted by a stretch of predominantly hydrophobic aminoacids (residues 2-48) and, within this stretch, there is a highly conserved motif (9-NPLGF(F/L)P-15) that is essential for binding (3) . It is apparent that knowledge of the mechanics of interaction at this level may be instrumental in developing strategies aimed at preventing preS1/NTCP interaction with consequent internalization. We therefore decided to use computational tools to investigate sequence similarities in other proteins that may interact with the preS1 sequence as well as with other surface proteins of viruses. To this end, we chose a well-characterized multifunctional serum protein that has the ability to work as a transporter, a hormone-and fatty acid binding protein, and an immune stimulating cytokine, the vitamin D-binding protein (DBP) macrophage activating factor (MAF). This is a serum alpha-2 glycoprotein constituted by a single polypeptide chain showing a molecular mass of 51-58 kDa. From the structural point of view, it is related to serum albumin and it is also known as Gc (Group-component) globulin. DBP synthesis occurs in the liver and its level in human plasma is around 20-55 mg/100 ml. DBP is a multifunctional protein that, in addition to vitamin D, binds actin, acting as an actin scavenger, and also binds fatty acids. The protein is constituted by 458 aminoacids and shows three domains that share limited sequence similarity with each other as well as with similar sequences of human albumin. The first domain contains the vitamin D-binding site that is located in a shallow cleft that allows interaction with the plasma membrane. DBP is present on the surface of several cell types that comprise yolk sac endodermal cells and T lymphocytes. In B lymphocytes, DBP is responsible for the linkage of surface immunoglobulins, thus contributing to the balance of the immune response (4). The de-glycosylated form of DBP is a powerful macrophage activating factor -hence the designation DBP-MAF -and shows a number of biological effects (5) . We demonstrated that, in addition to its presence in human serum, DBP-MAF is formed during fermentation of milk and colostrum (6) as well as during fermentation of hemp seed proteins (7). Here, we demonstrate that DBP-MAF shares significant similarities with hydrophobic sequences of NTCP that interact with the preS1 sequence of L protein. We also show that DBP-MAF, but not NTCP, shares similarities between the hydrophobic sequence of the fatty acid binding site and the domain IV of the same L protein. Finally, we show the . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.03.975524 doi: bioRxiv preprint differences in the distribution of negatively charged aminoacids in DBP-MAF and NTCP and we discuss their biological implications." ] },{ "paper_id": "0fbb18050e29ca78191625d42576b1c574027377", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We thank Dr. Guoping Ren for advice and assistance using the Luna Cell Ready Lysis Module." ] },{ "paper_id": "0fd300aefb704c20f32152b97b6194015f1c74e7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This study attempted to overcome these limitations by using the clinical information verified by several reports and relying only on the beginning and ending cases. Therefore, this model tended to reflect the real trend of this critical epidemic and it provides more convincing evidence to guide the control of this disease by the government.", "Simulation of \u03b2 for the time period from December 1 st to January 1 st in Wuhan. 135 was the number of infectious (I) on Jan. 1 st .", "A susceptible-exposed-infectious-quarantine model was used for transmission analysis and prediction of epidemiological spread,", "To effectively fight and end the COVID-19 epidemic, the transmission of the disease and zoonotic source of origin must be accurately identified, leading to the discovery of an optimal strategy to control this outbreak. By studying the cases and clinical features from early reports, this paper illustrates rigorous epidemiological models and the associated statistical methods to estimate the transmission rates in different stages and scenarios and predict the outcomes for different control strategies.", "The outbreak of the novel coronavirus disease, COVID-19, originating from Wuhan, China in early December, has infected more than 70,000 people in China and other countries and has caused more than 2,000 deaths. As the disease continues to spread, the biomedical society urgently began identifying effective approaches to prevent further outbreaks. Through rigorous epidemiological analysis, we characterized the fast transmission of COVID-19 with a basic reproductive number 5.6 and proved a sole zoonotic source to originate in Wuhan. No changes in transmission have been noted across generations. By evaluating different control strategies through predictive modeling and Monte carlo simulations, a comprehensive quarantine in hospitals and quarantine stations has been found to be the most effective approach. Government action to immediately enforce this quarantine is highly recommended." ] },{ "paper_id": "0ff4ad5359ee2df3568605385a8616d8da66bf2c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We use weakly informative priors on hyperparameters:", "early estimates of R 0 rely on strong assumptions.", "\u00b5 r \u223c Gamma(mean = 1 week \u22121 , shape = 2) \u00b5 G \u223c Gamma(mean = 1 week, shape = 2) \u00b5 \u03ba \u223c Gamma(mean = 0.5, shape = 2) (\u03c3 r , \u03c3 G , \u03c3 \u03ba ) \u223c half-normal(0, 10).", "Since December 2019, a novel coronavirus (SARS-CoV-2) has been spreading in China and other parts of the world (World Health Organization, 2020d). Although the virus is believed to have originated from animal reservoirs (Centers for Disease Control and Prevention, 2020), the ability of SARS-CoV-2 ability to directly transmit between humans has posed a greater threat for its spread World Health Organization, 2020c) . As of February 27, 2020, the World Health Organization (WHO) has confirmed 82,294 cases of the coronavirus disease , including 3,664 confirmed cases in 46 different countries, outside China (World Health Organization, 2020a)." ] },{ "paper_id": "10138816c67a562b55bc9c2b882b62c81fc4b062", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "10424da2599f0258bfaf71a3186b999ab2d747d0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Naturalists from KTR confirmed the identifications based on scats. On five occasions, we had 123 permission from the KTR Forest Department to install camera traps (Capture IR, 5 MP camera, 124", "were from far villages. The recapture rate was lower for females (32% of 84) and juveniles (40% 184 of 84 recaptures) which were classified as adults in winter. 185 186 187" ] },{ "paper_id": "10525ac89e46be4cb9cb9fd1131d28411a902047", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Early detection and monitoring of infectious disease outbreaks through passive or active collection of surveillance data can help public health officials initiate interventions such as removing contaminated food sources, isolating affected individuals or launching vaccination campaigns. However, any data collection method involves trade-offs between speed, accuracy and costs. Data collected through traditional surveillance, for example via public health infrastructure, are generally reliable but are resource intensive and are therefore typically available for upstream analysis with an (understandable) delay [7] .", "Our analysis based solely on epidemic data available through ProMED/HealthMap provides a realistic appraisal of their strengths and weaknesses, especially if used in near real-time forecasting.", "A key feature of our model is that it provides, for each country identified as at risk, a map of where the risk comes from. Out of 5 observed instances of international spread of Ebola in West Africa, our model correctly identified the source of importation in 4 cases while in the remaining case, the model highlighted the source of importation while assigning it low relative risk. This could help translating data collected through digital surveillance into concrete operational outputs in real-time that could assist in epidemic management and control." ] },{ "paper_id": "107f0d5a47f48f85d6645cac0e7008edc4d9d8cd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "PCR gel products (1% agarose) of expected size were cloned into Strataclone PCR cloning vector, and twelve colonies were sequenced to confirm identity and detection of co-occurring viruses. Each clone was cross-referenced using the GenBank nucleotide database to confirm that sequences were indeed herpesviruses. Sequence data will be available at github.com/ARSjodin upon publication.", "Finally, OTUs were refined manually based on PID and affinity (see Results).", "A limit to working with viruses in an ecological context is the short viral lifespan or activation cycle (e.g. lytic stage), as compared to that in free-living or macroparasitic organisms." ] },{ "paper_id": "10abb3e977aa476a39bce4f1feda37c2e1250106", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Existing evidence suggests that MERS-CoV may be originated from bats. In particular, 49", "Tylonycteris-BatCoV HKU4 spike protein was shown to utilize MERS-CoV receptor, human 50 dipeptidyl peptidase 4 (DPP4). To better understand the potential infectivities of MERS-CoV in 51 bats, we developed 12 primary bat cell lines from seven bat species, including Tylonycteris 52 pachypus and Rhinolophus sinicus (host of Tylonycteris-BatCoV HKU4 and SARS-related-53", "CoV respectively). MERS-CoV demonstrated much broader cellular tropism than SARS-CoV 54 and HCoV-229E, being able to infect five cell lines, including R. sinicus but not T. pachypus 55 cells. The close phylogenetic relationship between bat and human DPP4 genes supported the 56 ability of MERS-CoV to infect bat cells, while DPP4 expression appeared critical for MERS-57" ] },{ "paper_id": "110b4b089bd757bd54587c2ab3262a374462c098", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Keywords: channel permeabilization/ free diffusion / plasma membrane/ sugar transport 32 33 All rights reserved. No reuse allowed without permission.", "As the initial step in carbohydrate catabolism in cells, the substrate-specific 19 transporters via active transport and facilitated diffusion play a decisive role in passage of 20 sugars through the plasma membrane into the cytoplasm. The SecY complex (SecYEG) 21 in bacteria forms a membrane channel responsible for protein translocation. This work 22 30 31", "The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. " ] },{ "paper_id": "111b9a6e91c938696fcdb4cb128b8ae739dbe11c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The gynecologic history, clinical characteristics, laboratory findings, chest computed tomography (CT) and outcome data were obtained from patients' records. To ascertain the authenticity and integrity of the gynecologic history, especially the sexual behavior history, we also directly communicated with patients or their families.", "All information was obtained and curated with a standardized data collection form.", "Two researchers also independently reviewed the data collection forms to double check the data. Sample collection, processing, and laboratory testing complied with WHO guidance.", "Positive confirmatory cases of COVID-19 infection were defined as those with a positive test result from either laboratory." ] },{ "paper_id": "114ed64f52f503d9d2e2ba1fd1ee62b0a168cd84", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The widespread outbreak of the Coronavirus Disease 2019 (COVID- 19, previously known as 2019-nCoV) in China is a big challenge for public health and medical care.", "Acute respiratory distress syndrome (ARDS) was identified according to the Berlin definition 12 and acute kidney injury (AKI) according to the Kidney Disease Improving Global Outcomes definition. 13", "Use of continuous renal replacement 4(66.67%) 0* 0* <0.001" ] },{ "paper_id": "11875dfda6cd04d5032611edf0e340582ceb620f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The copyright holder for this preprint (which was not peer-reviewed) is the .", "In the past of 18 years, many researchers have done lots of work on etiology mechanism related to SARS, and Spike glycoprotein (S-protein) was confirmed to be a key for entering human cell by binding with angiotensin converting enzyme 2 (ACE2) receptor 1 .", "The latest 2019-ncov sequences (Supplementary Table 1; in total 33 strains analyzed) from GISAID and MN908947.3 sequences published on NCBI were collected and analyzed. MEGA(Version 7.026) was used to align 33 nucleotide sequences. The aligned nucleotide sequences were constructed by NJ method.", "In addition, in the phylogenetic tree, the evolution of 33 virus samples was divided into three categories.Clade A is basically unchanged nucleotide sequence, Clade B is A sample with individual site variation (site<=3), and Clade C is A single sample (site=5).The distance scale of the tree is 0.0001. In the figure 1, we can see author/funder. All rights reserved. No reuse allowed without permission." ] },{ "paper_id": "11f96d05db6854ef95312aa3a4736724ce1f02d6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To determine the impact of interventions, we calculate the difference in time to outbreak occurrence with and without interventions: ", "Additional figures in the appendix show the complementary cumulative density functions, focusing on either variation with traveller sensitisation ( Figure S2 ) or arrival rate ( Figure S3 )." ] },{ "paper_id": "1218f278a4f8d83dac14b23c8f698062812ef9d5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We consider simple SIR models (Kermack and McKendrick, 1991) with an additional category E of exposed individuals of the form", "\u2022 R 0 was drawn from a normal distribution with mean 2.2 (see Supplementary Fig. 7 for R 0 = 1.5 and 3.0) and standard deviation 0.5.", "\u2022 Population sizes were drawn from a log-normal distribution with \u03c3 = 1 and a mean such that all populations sum to 7.6 billion.", "\u2022 Migration rates were sampled from a log-normal distribution with \u03c3 = 1 and a mean of 0.01." ] },{ "paper_id": "123db7cdec9fc63aa09782ea9f4267603be8f74d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "where fragile biomolecules need to be presented at a material interface.", "His-tag GFP were expressed by Escherichia coli BL21 (DE3) (Novagen) transduced with pRSET-EmGFP vector (ThermoFisher, #V35320) in E. coli expression medium (MagicMedia, Invitrogen #K6803), and extracted using cell lysis reagent (Sigma, #B7435) followed by the purification using nickel-nitrilotriacetic acid affinity chromatography (Invitrogen #R90115). The MAL-PEG4-NHS linker (Quanta Biodesign) was mixed with GFP at 30-fold molar excess, and incubated at 37\u00b0C for 1 hour followed by the size-exclusion chromatography to remove the excess. 3'Thiolmodified complementary DNA was decapped using the protocol described above, and reacted with modified GFP at 1:10 molar ratio at 37\u00b0C for 1 hour followed by 4\u00b0C overnight. The next day, GFP-DNA conjugates are purified using nickelnitrilotriacetic acid affinity chromatography to remove unconjugated DNA. Protein-DNA conjugates were analyzed through SDS-PAGE gel electrophoresis (Genscript #M42012L) with SYPRO Ruby dye staining (ThermoFisher #S21900).", "Human primary CD8+ T cells engineered with the above circuit were co-cultured for 24 hours with single antigen target cells (human melanoma cell line A375 with HER2 overexpressed) in the presence or absence of GFP+ AICE microparticles." ] },{ "paper_id": "12920263b2846c61d6f2b6105189367a8ff1bc39", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(1)", "Priors were chosen to be minimally informative. For fixed effects (\u00b5, a, and b inbred ) we used N 0, 1 \u21e5 10 3 . For variances of random effects (s 2 , t 2 a , t 2 m , t 2 b , t 2 v , t 2 w , t 2 order , t 2 batch ) we used an inverse gamma distribution with scale and shape both equal to 0.001. Posterior effect estimates are presented as posterior mean (and median), and the 95% highest posterior density (HPD) interval.", "All rights reserved. No reuse allowed without permission." ] },{ "paper_id": "12c8ef5614d9a35bed3ff95a3b1dc971842514fe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All Materials and Methods are described in Supplementary Information in detail." ] },{ "paper_id": "12fac9aedb1a09a3922a3c084ce4723708e463d6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Our study helps in choosing an appropriate duration for quarantine. Keeping infected persons in quarantine up to 14 days will ensure that they do not develop symptoms after release.", "We are immensely indebted to the work of Dr. Kaiyuan Sun, Ms. Jenny Chen, Dr. C\u00e9cile Viboud and the staff of MOBS Lab led by Prof. Alessandro Vespignani who traced and translated the information and generously made it available to the wider community.", "Here we present the distribution of incubation periods estimated for travellers from Wuhan with confirmed 2019-nCoV infection, using their reported travel histories and symptom onset dates.", "The travellers in this study represent a selective sample of the reported cases. We found travellers to be more often male and younger than the cases reported. The numbers are too small to detect systematic differences in incubation time with age or sex. Because we only have information on confirmed cases, there is likely a bias towards more severe cases in areas with a functioning health care system. As the epidemic continues, it remains important to collect more information on incubation periods of 2019-nCoV cases of older ages, of persons with underlying morbidity, of women, and of persons with mild symptoms." ] },{ "paper_id": "136ee862ad53b606c8f2bea917b9705f5079e88e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The technical details of the modeling and calculations can be found in Appendices A, B, and C.", "In this study we combine case estimates, epidemiological characteristics of the disease, international mobility patterns, control efforts, and secondary case distributions to assess the risks of major outbreaks from imported cases outside China.", "Our method has three main components:", "The authors declare no conflict of interest." ] },{ "paper_id": "138d4617f4f4984bec9cf2c7540fed533d9e4d6e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "T r e n d V a r i e t y :", "T r e n d V a l u e", "Medium (may be selfdisclosed in public)" ] },{ "paper_id": "13bf9fe0df944c0ee0debb0d445527ad4418cc19", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Fc and 1:500 of secondary antibody. Cells were stained with HE-Fc/anti-IgG complex 386 for 1 hr at room temperature. Coverslips were mounted using Prolong Antifade-Gold 387 with DAPI (Invitrogen). Cell were imaged using a Nikon TE300 fluorescent microscope. 388" ] },{ "paper_id": "14783283da3482bf2aab4e6100fe4ea5c29d8db7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "to Feb 21, 2020 (i.e., five weekdays). The Ethics Committee of the First Affiliated Hospital of Nanjing Medical University approved the study (approval number:", "The cumulative variance contribution rate reached 52.56%, which indicates positive reliability and validity." ] },{ "paper_id": "158e546658e42ab0a89d174bc9facb437a034df6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cases from the ongoing outbreak of atypical pneumonia caused by the 2019 novel coronavirus (2019-nCoV) exported from mainland China can lead to self-sustained outbreaks in other populations.", "The model was fitted in R (version 3.6.1) 5 to compute , the maximum likelihood estimate of \u03b2, and \u03b2 \ufe3f thus the expected case count given high surveillance (Figure 1, solid grey line) . We also computed the excluding Thailand from the model fit since it is a high-leverage point. In total, we thus did six additional regression analyses (see Supplementary Figure 1 ). All analyses are fully reproducible given code available online ( https://github.com/c2-d2/cov19flightimport ).", "where C i denotes the reported case count in the i -th location, \u03bb i denotes the expected case count in the i -th location, \u03b2 denotes the regression coefficient, x i denotes the daily air travel volume of the i -th location." ] },{ "paper_id": "15ad534bb2ec7bc4b0ee83ddac11a1b837d743c6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All statistical analyses were performed using SPSS 22.0 (SPSS Inc., Chicago, IL, USA). 102", "Hospital and informed consent was obtained from each patient. 109" ] },{ "paper_id": "15e5dd0eb126bfe384c25ba551317eb9ba2ad1ef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Background: COVID-19 outbreak is spreading globally. Although the risk of infection in", "Methods: Data were collected using an electronic questionnaire via Qualtrics\u00ae (Qualtrics, Provo, UT). Participants completed the questionnaire through the CloudResearch (4) online platform in early February 2020. We asked participants to rank who they felt should lead the US response to COVID-19. Options included the president, Congress, the Director of the Participants provided informed consent prior to data collection.", "Novel coronavirus is transmitted through coughing or sneezing. Novel coronavirus is not transmitted by close contact with people. Don't know.", "6. Which of the following is correct about \"close contact\" of novel coronavirus? \"Close contact\" involves a direct contact with persons' respiratory secretions. Relatives and healthcare workers are excluded from the category of close contact. Don't know. 7. Which one is correct about the treatment or vaccine for the novel coronavirus?", "Objective: In the first study of its kind on COVID-19, our objective was to survey the adult US population to better understand their risk perceptions about the COVID-19 outbreak." ] },{ "paper_id": "160ecaaa5a766c289fc2f6b5499f0dfe7aab971c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "where the random variables in (1) can be defined by binomial Bin(n, p) distributions as follows [10, 12] : ", "once infected or stay in compartment S otherwise. All definitions of variables and parameters have been listed in Table 1 .", ", before Jan 23nd ,2020", "where ( ) and ( ) are fitted values of and in the n-th iteration respectively. We stop the iteration when the error of fitting" ] },{ "paper_id": "164b0678afc42f1923aa100b624ca969a53fb3b2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In this work, we present the results of fitting a very simple (perhaps even simplistic) model to the available data and a forecast of new infections.", "Figure 5 Predictions of model using linearization in time (Eq. 6) together with those of Figure 4 .", "All data and materials used in this work were publicly available." ] },{ "paper_id": "180c88b68816bbb6eb57aa515a3aec4020178729", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "developed (72 hours), according to ATCC instructions. AF70 was thawed for 5 minutes, 113 directly plated onto Malt extract agar, and incubated at 25 \u00b0C in darkness until mycelium 114 was developed (72 hours), according to ATCC instructions. Agar plugs with actively 115 growing mycelia were re-plated in MEAbl agar and incubated at their optimal 116 temperatures in the dark until extensive conidial development (5 days) was observed. 117", "Cleveland 1997). 126", "Linux bash script and kept in a multi-fasta file for later e-probe design. 165" ] },{ "paper_id": "181b7b57851e6f58a601b68e613d10c10616f774", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Coronaviruses are positive-sense single-stranded RNA viruses belonging to the family Coronaviridae.", "All sequence and immunological data, and all scripts for reproducing the results are available at https://github.com/faraz107/2019-nCoV-T-Cell-Vaccine-Candidates. (Mirarab et al., 2015) and rooted with the outgroup Zaria Bat CoV strain (accession ID: HQ166910.1).", "Positive T cell assays T cell epitopes 115", "The ongoing outbreak of COVID-19 in the Chinese city of Wuhan (Hubei province) (C. Wang, Horby, Hayden, & Gao, 2020) and its alarmingly quick transmission to 25 other countries across the world (Centers-of-Disease-Control-and-Prevention, 2020) resulted in the World Health Organization (WHO) declaring a global health emergency on 30 January 2020 (World-Health-Organization, 2020b) . This came just one month after the first reported case on 31 December 2019 (https://www.who.int/emergencies/diseases/novel-coronavirus-2019). WHO, in its first emergency meeting (World-Health-Organization, 2020a), estimated the fatality rate of COVID-19 to be around 4%." ] },{ "paper_id": "18dc6a67045d2687d2b5c11c85797f42824ed243", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Coronaviruses (CoV) (order Nidovirales, family Coronaviridae) are enveloped, positive stranded RNA viruses, which includes 4 genera Alphacoronavirus (\u03b1-CoV),", "Betacoronavirus (\u03b2-CoV), Gammacoronavirus (\u03b3-CoV), and Deltacoronavirus (\u03b4-CoV) [1, 2] . Since 1960, six different CoVs have been identified and two epidemic CoVs have emerged in human during the last 2 decades [3] . Severe acute respiratory syndrome [4, 5] .", "All human CoVs may be of zoonotic origin, and may indeed originate from bats [9] ." ] },{ "paper_id": "1983cbc32412a9a7b1601b6778605f9e98ab69e0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Isolates containing PCR products of both sizes were inferred to be diploid. Meiosis was 522 induced by rapid passaging every day in CG medium. For both Seafoam and Soapsuds, 523", "Airyscan detector and a 63x/NA1.40 Plan-Apochromatic oil immersion objective. 729", "Confocal stacks were acquired in super-resolution mode using ILEX 730" ] },{ "paper_id": "1a12cc7d49d8521bec5d447ebb413cbcf5aca8f4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "the JX acquisition of data, project administration, manuscript revisions, and its final approval; the JX formal analysis, manuscript revision, and final approval; SLG conception, manuscript revision, and final approval; the YQL conception, design, funding acquisition, manuscript revision, and final approval; SN conception, design, project administration, manuscript revision, and final approval. All the authors read and approved the final manuscript.", "Not applicable.", "Permission to conduct the study and to obtain access for the purpose of gathering the data were obtained from by the Ethics Committee of Harbin Medical University(HRBYKD-A26). Written, informed consent was obtained from all the participants, or from their legal guardians, or caregivers prior to enrolment in the study." ] },{ "paper_id": "1a791c5c6543aca9391b77ae58b79d7ddf3c1f3c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Average relative Sia quantities as determined by HPLC analysis for each tissue tested in CMAH -/-C57BL/6 mice (n=3). Table shows ", "A549 conditioned media and collected mucus from NHBE cultures were analyzed for total sialic 600 acid content using HPLC analysis. Table shows " ] },{ "paper_id": "1a9c229f4f866db4f9c23a77b8c1275b52407c64", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Source of bacterial blight material used for the study 102 Ten Xanthomonas axonopodis pv. punicae (Xap) isolates collected from four different regions of 103 Karnataka, India were used in this study (Fig 1) . Additionally, we have also isolated 29 non-104 Xanthomonas bacteria from pomegranate Table 1 . The pure culture Xap isolates were maintained 105 in a Nutrient Broth for 72 hours and the DNA was extracted using crude method. The quality and 106 quantity of the DNA were determined using Nanodrop (Model -DS-11 FX +, DeNovix, USA).", "100", "MATERIALS AND METHODS" ] },{ "paper_id": "1ad1d4b84aea4ceaf05c62a1ad04e7150f7f4684", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Our data from the routine virological testing performed is in keeping with community based results", "Demographic, clinical, epidemiological and laboratory data were collected. We have compared clinical features and subsequent diagnosis between well patients not requiring admission for clinical reasons or antimicrobials with those assessed as needing either admission or antimicrobial treatment." ] },{ "paper_id": "1b4ab28a9391d516e1753874c73d2d244104f825", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Re-annotation of proteins from Betacoronavirus genomes using KAUST Metagenomic Analysis Platform (KMAP) annotation pipeline. To annotate uncharacterized genes in Betacoronavirus, we utilized all available protein sequences available from the clustering analysis as an input to our Automatic Annotation of Microbial Genomes (AAMG) pipeline 27 , available via KAUST Metagenomic Analysis Platform (http://www.cbrc.kaust.edu.sa/kmap). AAMG uses sequence-based BLAST to UniProtKB (www.uniprot.org), KEGG (www.kegg.jp) and also Protein Family (PFam) domain detection using InterPro (www.ebi.ac.uk/interpro).", ". CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.17.952895 doi: bioRxiv preprint", "Collection of Betacoronavirus strains. The NCBI genome assemblies page was searched, on January 26, for taxonid of genus Betacoronavirus, resulting in a list of 22 genomes, including four isolates of SARS-CoV-2. We downloaded in addition to this initial list two more assemblies one for a bat coronavirus (MG772933) and another for MERS (KF600630), see Table 1 . For easy identification of genes and annotations from GenBank, we included unique locus_tag identifiers containing locus id and an index number. Metadata was collected to define user friendly strain names and to understand phylogenetic trees in the context of virus host, country, taxon id and data release date.", "IA, TG and CMD conceived and designed the research, IA led the study and conducted the data analysis, A.K. helped developed the web-based resource and led computational components of the study, MK and SA contributed to the functional structural analysis, and AP contributed with inferences on virulence. IA and CMD developed the first draft of the manuscript and all authors contributed to writing and improving the manuscript, and approved the submission. " ] },{ "paper_id": "1b531d266b4933bf8040739ed199914655b075d6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The total reduced number of 2019-nCoV cases: 127", "The outbreak of pneumonia caused by a novel coronavirus (2019-nCoV) in Wuhan 17" ] },{ "paper_id": "1b9fed2824e97db8cb35912549dd2e9cde7b6c18", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Among these proteins non-structural protein NS4, with accession number A0A0A7UXD8, known as Beta coronavirus HKU24 (due to its Chinese origin) with length 136 is selected in FASTA format.", "Antigenicity of this protein is predicted by VaxiJen v 2.0, an online prediction server [10] .", "This work is not supported by any funding.", "The protein family information of Coronavirus nonstructural protein NS4 containing 78 protein is retrieved from InterPro database (https://www.ebi.ac.uk/interpro/entry/InterPro/IPR005603/). To find conserved region, retrieved sequences were aligned using Muscle tool 3.8.31 [8] where k-mer clustering is used. In the next step a phylogenetic tree is constructed by the method known as progressive alignment. The evolutionary divergence analysis for all 78 virus proteins are completed by forming a phylogenetic tree using Phy ML 3.1/3.0 aLRT software [9] . Here the phylogenetic tree was reconstructed using the maximum likelihood method. The default substitution model was selected assuming an estimated proportional of invariant sites (of 0.008) and 4 gammadistributed rate categorized to account for rate heterogenicity across sites. The gamma shape parameter was estimated directly from the data (gamma = 1.788). Reliability for internal branch was assessed using the aLRT test (SH-like)." ] },{ "paper_id": "1c06378f629bfa8870c89b3abfdecfc19db9b459", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "HEp-2 cells, a human laryngeal carcinoma cell line, were used for RSV culture and infectivity experiments.", "The authors declare no competing interests. " ] },{ "paper_id": "1c0b25c8e3c89243fd8797e2e964e12689bc8556", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As the predominant etiological agent of the common cold, human rhinovirus (HRV) is 19 the leading cause of human infectious disease. Early studies showed monovalent formalin-20 inactivated HRV vaccine can be protective, and virus-neutralizing antibodies (nAb) correlated 21 with protection. However, co-circulation of many HRV types discouraged further vaccine 22 efforts. We approached this problem straightforwardly. We tested the hypothesis that increasing 23 virus input titers in polyvalent inactivated HRV vaccine will result in broad nAb responses. Here, 24 we show that serum nAb against many rhinovirus types can be induced by polyvalent, 25 inactivated HRVs plus alhydrogel (alum) adjuvant. Using formulations up to 25-valent in mice 26 and 50-valent in rhesus macaques, HRV vaccine immunogenicity was related to sufficient 27 quantity of input antigens, and valency was not a major factor for potency or breadth of the 28 response. We for the first time generated a vaccine capable of inducing nAb responses to 29 numerous and diverse HRV types.", "The dashed line represents LOD. Undetectable nAb were assigned LOD/2, and some symbols 305 below LOD were nudged for visualization. Three independent experiments using low input titers 306 showed similar results. There was a statistically significant association between input TCID 50 307 virus titer and a detectable nAb response following prime (P = 0.01) and boost (P = 0.03) 308 vaccination (Fisher's exact test). The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/053967 doi: bioRxiv preprint ", "30 31 38" ] },{ "paper_id": "1c66ec8950cbd1e0f0d4bc4a43ba9c79411cc5fa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "So dium/po tassium-transpo rting A TP ase subunit alpha-1", "Co ato mer subunit beta 1", "Co ato mer subunit beta 2" ] },{ "paper_id": "1d2947d5c0addcbbcfa71d87ea074a8b6ff2a973", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We model disease incidence using the renewal equation, a simple, flexible framework that can cover a wide range of model structures (Heesterbeek and Dietz, 1996; Diekmann and Heesterbeek, 2000; Roberts, 2004; Aldis and Roberts, 2005; Wallinga and Lipsitch, 2007; Roberts and Heesterbeek, 2007; Champredon et al., 2018) . In our model, disease incidence at time t is given by:", "(3)", "The associated post-intervention epidemic speedr is given by:" ] },{ "paper_id": "1d882d90109fb4496088342cf2bcaa4fec40cf9f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "1dd898b5ca1ae70ec0e3cad89fc87a165002a99e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Such quantification for PED could also be considered a contribution to the general study of infectious diseases of livestock.", "This parameter is related to the variance by Var(", "We also verified that the flows term is significant in models lacking random effects, and after excluding any data points with dfbetas 38 above 0.2.", "To estimate how farm density and transport flows may affect transmission rates, we fit the parameters c i and \u03b7 in the following regression model" ] },{ "paper_id": "1df9ce60e358f6cef0be3f6e15fe2a9c6f93f39c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "11", "A novel coronavirus outbreak took place in Wuhan, Hubei province, China in December 31 2019 1 . This novel coronavirus (SARS-CoV-2) causes pneumonia in patients 2 and it has 32 rapidly spread to other provinces in China and other countries 3 . This novel coronavirus 33 outbreak had raised global concern but current knowledge on the origin and transmission 34 route of the pathogen is still limited. The SARS-CoV-2 belongs to the genus Betacoronavirus, 35 which also includes two highly virulent human coronaviruses, SARS-CoV and MERS-CoV. 36 Apart from human, many animal species, such as bat, rat, camel, swine and hedgehog, can be 37 infected by different types of coronaviruses. Further sequence analyses of this novel and 38 other betacoronaviruses might provide additional information to better understand the 39 evolution of SARS-CoV-2. 40 Preferential codon usage is commonly seen in different organisms, and it has been evident 41 that the uneven codon usage is not neutral but related to gene expression or other selection 42 pressures 4-6 . There are two levels of codon usage biases, one is at amino acid level and the 43 other is at synonymous codon level. The amino acid composition of proteins can be an 44 important factor that explaining certain sequence traits. For example integral membrane 45 proteins that are enriched in hydrophobic amino acids can create significant codon usage 46 bias 7 . Amino acid composition sometime can also introduce confounding effects when one 47 only focuses on studying the variations of synonymous codon usage. The use of global 48 correspondence analysis (CA) and its derivatives within-group correspondence analysis 49 (WCA) and between-group correspondence analysis (BCA) to analyze codon usages can 50 overcome the above problem. In fact, WCA becomes \"model of choice\" for analyzing 51 synonymous codon usage in recent years, as it is more robust than other traditional methods 52 (e.g. CA with relative codon frequency or CA with RSCU values) 7,8 . This analytic approach, 53 however, has not been used in studying viral sequences. As the natural history of the SARS- 54 CoV-2 remains largely unknown, an in-depth codon usage analysis of this newly emerging 55 virus might provide some novel insights. 56 In this study, we used both CA and WCA to analyses codon usage patterns of a vast number 57 of betacoronavirus sequences. We found SARS-CoV-2 and bat SARSr-CoV have similar 58 amino acid usage. However, our analyses suggested that the spike and member genes of 59 SARS-CoV-2 have rather distinct synonymous codon usage patterns. Table S1 . 86 The codon count for every gene sequence input for the correspondence analysis was All the correspondence analyses in this study were performed individually for each gene, to 103 achieve better resolution on gene specific codon usage pattern. Gravy score provides an easy way to estimate the hydropathy character of a protein 15 . It was 117 used in this study as a proxy to identify proteins that are likely to be membrane-bound 118 proteins. The GRAVY score was calculated in a linear form on codon frequencies as: The overall amino acid and codon usage of the dataset are plotted in an ascending order 140 ( Figure 1 ). We observed that leucine and valine were the two most frequently used amino 141 acids in the four studied genes, while tryptophan, histidine and methionine were the three 142 least used ones. We also found that codons ending with cytosine or guanine were generally 143 less frequent than the codons ending with adenine or thymine. This pattern of uneven usage 144 in synonymous codons is in accordance with the G + C content distribution results (codons 145 ending with guanine or cytosine were less frequently observed). 146 We found a substantial bias in amino acid usage among these four genes, and this bias is well 147 explained by the hydropathy of the encoded proteins (results from global correspondence 148 analysis on all the four genes, collectively, data not shown). The GRAVY scores for every 149 sequence were calculated to represent the degree of hydropathy. We discovered that the 150 . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.15.950568 doi: bioRxiv preprint nucleocapsid protein sequences had significantly lower GRAVY scores as compared to those 151 from other genes, while the membrane protein sequences had highest GRAVY scores (see 152 Supplementary Figure S3 ).", "Correspondence analysis 154 We first conducted a multivariate analysis of codon usage on the dataset by using global 155 correspondence analysis. We also conducted WCA and BCA to study these sequences at 156 synonymous codon usage and amino acid usage levels, respectively. Given that there were 157 different amino acid usage biases among different genes (Supplementary Figure S3) , we 158 performed correspondence analyses of these genes separately. 159 Of all the four correspondence analyses for the four genes, the extracted first factors 160 explained more than 50% of the total variance (see Supplementary Figure S4 The global codon usages of bat RatG13 virus were found most similar to SARS-CoV-2 in 196 orf1ab, spike and nucleocapsid genes, but not in membrane gene ( Figure. 2). In the analysis 197 of membrane protein, pangolin P1E virus had a more similar codon usage to SARS-CoV-2 198 than all the other viruses. We found the similarity in codon usage between pangolin P1E and 199 SARS-CoV-2 were also high in orf1ab, where P1E was the second closest data point to 200 SARS-CoV-2. But this is not the case for spike and nucleocapsid genes. 201 We also observed that the codon usage pattern in spike gene was more complex than in other (Table 217 1). 218 Results from the BCA suggested that the amino acid usage of SARS-CoV-2 is closely related 219 to bat and human SARSr-CoVs in all four genes ( Figure 3B and Figure 4B ). Specifically, we 220 discovered that the SARS-CoV-2 had amino acid usage pattern most similar to bat RaTG13 Figure S8A ). It is evident that the synonymous codon usage pattern of SARS-CoV-2 is 243 distinct from other bat origin coronaviruses. The difference in synonymous codon usage is 244 largely explained by the first factor (more than 50%), and our analysis on codon usages 245 suggest that the first factor maybe highly related to the preferential usage of codons ending 246 . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.15.950568 doi: bioRxiv preprint with cytosine (Supplementary Figure S9) . We also had similar observation for the membrane 247 gene. Our three-dimensional analysis revealed that the synonymous codon usage of SARS-248 CoV-2 in membrane was most similar to P1E and CoVZXC21 (Supplementary Figure S8B) . 249 It is worth noting that comparing to RaTG13, P1E and CoVZXC21 had lower synonymous 250 codon usage similarity to SARS-CoV-2 in the other three genes. 251 Overall, our WCA results support a more complex synonymous codon usage background on 252 spike and membrane genes, though we identified unique codon usage patterns of SARS-CoV-253 2 on these two genes. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10. 1101 /2020 In addition to global CA analysis, the application of WCA and BCA can eliminate the effects 279 caused by amino acid compositions and synonymous codon usage, respectively. These 280 alternative analytical tools were important to our study. It is because the amino acid 281 sequences are expected to be more conserved such that they can preserve biological functions 282 of the translated genes. By contrast, mutations at synonymous level tend to be more frequent, 283 as most of these codon alternatives do not affect the biological function of a protein. The S protein is responsible for receptor binding which is important for viral entry. The 302 genetic variability is extreme in spike gene 27 , and this highly mutable gene may possess 303 valuable information about recent evolution history. In our results, the synonymous codon 304 usage of SARS-CoV-2 in spike gene was distinct from those of RaTG13 and other 305 phylogenetic relatives ( Figure 3A) , which was not observed in orf1ab or nucleocapsid gene. 306 Although the codon usage in spike of SARS-CoV-2, RaTG13 and P1E were similar at amino 307 acid level, the difference at synonymous codon usage level indicates that they are unlikely to 308 share a very recent common ancestor. It is more likely that SARS-CoV-2, RaTG13 and P1E 309 might have undergone different evolution pathways for a certain period of time. The amino 310 . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.15.950568 doi: bioRxiv preprint acid usage of SARS-CoV-2 in membrane was clustered with bat SARSr-CoV, however the 311 synonymous codon usage of SARS-CoV-2 was still distinct to these bat coronaviruses. 312 Notably, in membrane gene, pangolin P1E had a more similar synonymous codon usage to 313 SARS-CoV-2 than RaTG13. These findings suggest that there may be different selection 314 forces between genes. Our result supports different evolutionary background or currently 315 unknown host adaption history in SARS-CoV-2. The codon usage of SARS-CoV-2 in 316 nucleocapsid gene was similar to bat SARSr-CoV both at amino acid level and synonymous 317 level, suggesting that no highly significant mutation happened in this gene. 318 Codon usage can be shaped by many different selection forces, including the influence from 319 host factors. Some researchers have hypothesised that the codon usage in SARS-CoV-2 320 maybe directly correlated to the codon usage of its host 28 . However our recent study on 321 influenza A viruses implied that these may not be the most influential factors shaping the 322 codon usage of a viral genome 19 . Our analysis took advantage of the existing genomes of 323 Betacoronavirus to study the complex host effect on codon usage, which warrants more 324 accurate but relatively conserved estimation. 325 " ] },{ "paper_id": "1dfcd4615a8763e053bd2fdb845f09fab68109f1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "E cology and evolutionary biology have provided a theoretical basis for understanding how interactions between pathogens and their environment shape epidemics. When combined with quantitative modeling methods, it offers a full systems perspective that has helped to characterize the actors, forces and interactions that create infectious diseases [1] - [9] . Classically, the pathogen-host interaction is the presumptive central determinant of infectious disease, and consequently, the focus of modeling efforts: understand it, model it carefully, and one gains a picture for how epidemics arise and persist.", "The S, I, and R compartments represent the usual susceptible, infected, and recovered populations of hosts. W u and W i represent uninfected and infected populations of environmental hosts, respectively.", "D. WAIT framework influences the basic reproductive number in a standard SIR model", "A concept that has been the object of recent inquiry includes infections transmitted indirectly between hosts via a surface or reservoir intermediate-often abiotic-where the pathogen lives freely and independently of a host [10] - [27] , sometimes described as \"sit and wait\" infections [28] . Much of this research has concentrated on fomite, aerosol and airborne-transmitted viruses [10] , [11] , [13] , [14] , [16] , [19] , [22] and waterborne infections [12] , [17] , [23] , [26] , [29] - [33] . Other studies have focused on systems where pathogens are growing in the environment [18] , or have explored indirectly-transmitted infections in theoretical terms [21] , [24] . One framework for studying indirect, environmental transmission-the environmental infection transmission systems (E.I.T.S)-is engineered with explicit constraints that render its application necessarily narrow [15] . We offer that these prior treatments are individual examples of a general phenomenon that would benefit from a mathematical treatment that is both more rigorous and more broadly applicable. This new formalism should accommodate a widerrange of pathogens than have been previously considered and should emphasize how the environment can comprise multiple discrete dynamic entities (not unlike how host populations are often modeled).", "The initial conditions across all simulations included a population of 400,000 susceptible individuals with an initial small amount of Vibrio cholerae present in each reservoir to prime the outbreak (5 cells in each reservoir). Additionally, the values of the symptomatic, asymptomatic, vaccinated, and recovered compartments were set to zero.", "These methods have been successful in balancing simplicity with generality, and have spawned different classes of models, summarized both in terms of the particular mathematical instruments applied (e.g. discrete-time, continuous models, network models, etc) and the particular biologies of host-pathogen systems (e.g. sexually-transmitted, vectorborne disease, food-borne pathogen, etc) [5] , [6] . These methods have been effective in many cases, supported by dozens of examples where they have captured the essential character or dynamics of an epidemic [6] , [8] . While these existing classifications have served an effective organizational and pedagogical purpose, there remains room for growth in how we translate certain epidemic phenomenon into theoretical formalism." ] },{ "paper_id": "1e45cd5feb7928bbc8bcd524d9c6b7adeae08a6b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "ZG and YL made substantial contributions to the study concept and design. LW was in charge of the manuscript draft. XL, CH, SY and DL took responsibility for obtaining written consent from patients, obtaining ethical approval, collecting samples, and confirming data accuracy. LW and ZG participated in drafting the manuscript, and revising it on the basis of reviewers' comments. LW made substantial contributions to data acquisition, analysis, and interpretation.", "With the permission of the corresponding authors, we can provide participant data without names and identifiers, but not the study protocol, statistical analysis plan, or informed consent form. Data can be provided after the Article is published. Once the data can be made public, the research team will provide an email address for communication. The corresponding authors have the right to decide whether to share the data or not based on the research objectives and plan provided.", "We declare no competing interests." ] },{ "paper_id": "1eaa329f608055620a57e6273e9d1c409de1e9ee", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Approximately 10mg of lyophilised cysteine mutant histone was resuspended in 800uL (me3) or 900uL (me0) degassed alkylation buffer (1M HEPES, 10mM D,L-methionine, 4M Guanidine HCl, pH7.8). Histones were reduced with fresh 30mM DTT for 30 minutes at room temperature.", "For trimethyl-lysine analogues, the reduced histone was added to approximately 125mg of (2-Bromoethyl) trimethylammonium bromide (Sigma", "The shift in molecular weight associated was confirmed via MALDI-TOF mass spectrometry." ] },{ "paper_id": "1f783a5e029f80516169b19fe6e0dacc1e171f87", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Synthesis of tagged, randomly primed cDNA and its subsequent amplification via SISPA [21] 106 required lengthy reverse transcription and PCR steps (1h and 3h 45min) respectively. 107", "Optimising these stages upgraded the reverse transcriptase from SuperScriptIII to 108 SuperScriptIV (ThermoFisher), reduced incubation time to 10min (processing time reduction of 109 50min) and reduced the PCR extension time within each cycle from 5min to 2min (1h 30min 110 processing time reduction). Comparing this final method with our original protocol, using 111 triplicate extractions from the pooled set of influenza A positive samples, demonstrated no 112 significant loss in performance in the more rapid protocol ( Fig S3) and we adopted this 113 approach as our routine protocol. 114 115", "To avoid these problems, we batched samples according to Ct value, and applied stringent 233 barcode demultiplexing criteria; however, this reduces the total data available for analysis [22] . in the clinical diagnostic laboratory to provide a large enough sample to assess 309 reproducibility ( Fig 1B) ; 310" ] },{ "paper_id": "1f9d3f9a1a0e8db6a086e0a2b5ba50cf9f235dae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Of the 12 types of changes from one nucleotide to another, 8 are \"transversions\" between a purine (A or G) and a pyrimidine (C or T) , and the other 4 are \"transitions\".", "The causes of the observed bias have not been resolved. The hypothesis of a mutational cause-a transition:transversion bias in mutation-was promoted early by Vogel (1972; see also Vogel and Kopun 1977) . This hypothesis was bolstered when DNA sequence comparisons revealed that a transition bias is observed in introns and other non-coding regions (Li, et al. 1985) , suggesting a cause that (like mutation) acts at the level of DNA, across the entire genome.", "Yet, natural selection has the ability to amplify small differences into major effects." ] },{ "paper_id": "1fb909712eea684a4fae4f0b419ca6bc7ba8e396", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All animal experiments were conducted in accordance to approved IACUC protocols at the Georgia Institute of Technology and Emory University (Shayakhmetov Lab). Female, [8] [9] [10] [11] [12] weeks old C57/Bl6 mice (Jackson Labs, Bar Harbor, ME) were used for all wild-type toxicity and mRNA transfection studies. Female, 8-12 weeks old TLR4 knockout mice (Jackson Labs, Bar Harbor, ME) were used in knockout studies. Euthanasia was performed with CO2 and confirmed by cervical dislocation.", "Mice were administered an 8 mg chitosan/kg body weight or 3 mg bPEI/kg body weight IV dose of nanoparticles. At specified endpoints, mice were sacrificed and blood or spleens were collected. Blood was stored at 4 C overnight and centrifuged at 12,000 g for 5 minutes to isolate serum. The IL-6, IL-1b, and TNFa ELISAs were performed on serum samples using supplemented with EGTA, proteinase inhibitors, and Triton X (1%). Lysates were frozen at -70 C and thawed. Cell debris was pelleted out by centrifugation at 10,000 g for 5 minutes. Blots of spleen lysates were prepared with a Proteome Profiler Mouse Cytokine Array Kit (Panel A, R&D Systems, Minneapolis, MN) using an established protocol. [23] After blot development, chemiluminescent imaging was performed using an Amersham Imager (GE Healthcare, UK).", "Benchtop Cytometer and median fluorescence intensity was reported." ] },{ "paper_id": "20154fa12ca525582cd1b42019927e8f7816fb51", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The use of metabolomics profiling to understand metabolism under different 20 physiological states has increased in recent years, which created the need for robust analytical 21 platforms. Here, we present a validated method for targeted and semi-quantitative analysis of 102 22 polar metabolites that covers major metabolic pathways from 24 classes in a single 17.5-min assay.", "after addition of an internal standards working solution, biofluid samples were extracted with 1% 96 formic acid in 99% acetonitrile. Tissue samples were extracted using homogenization in two steps.", "(ii) Process efficiency correction for the semi-quantification of metabolites without internal 266 standards." ] },{ "paper_id": "207dcb6e3cd43cdea91d29a15be1ee34068bd54e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Here, we describe the statistical model that was employed to estimate the asymptomatic proportion using the time-series dataset described above. Given an individual was exposed during the interval [a i, b i ] the probability for them being asymptomatic at time c is", "Word count:", "Main:", "In this paper, we conduct a statistical modeling analysis to estimate the asymptomatic proportion among infected individuals who have tested positive for COVID-19" ] },{ "paper_id": "20f2a638e2c9a1917b7c001c371335da3d288505", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Here, we examine the phylogenetic relationship from all identifiable public partial RdRp sequences 80 6 sequences. We compiled a database of our assigned classifications and developed the R package 87 \"MyCoV\" for assignment of user-generated sequences to these taxa. 88", "Outputs from this analysis are shown in Figure 5 . 159", "MyCoV is available at https://github.com/dw974/MyCoV. 160" ] },{ "paper_id": "21100aba41a4bfb48d7dc37f1bf5dbb38bf3867a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Selective estrogen receptor modulators (SERMs). An overexpression of estrogen receptor has been shown to play a crucial role in inhibiting viral replication [34] .", "SERMs have been reported to play a broader role in inhibiting viral replication through the non-classical pathways associated with estrogen receptor [34] . SERMs interfere at the post viral entry step and affect the triggering of fusion, as the SERMs' antiviral activity still can be observed in the absence of detectable estrogen receptor expression [17] .", "HCoVs. However, further preclinical experiments and clinical trials are required to verify the clinical benefits of these network-predicted candidates before clinical use." ] },{ "paper_id": "22264c65eb6c14ba96287ba4da536424dd083253", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "224a389bd5dbeab45b8a25965298016fbc44d669", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In the current study, we have demonstrated that we can modulate gene expression in transgenic ", "37" ] },{ "paper_id": "228edf7f7e53e88e246fc77b7b7664ac35d7278e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "22a4d26bde67d878869443ea26140f3d8239bed0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Calculating Between-Individual Variation in Transmission Potential, V 213" ] },{ "paper_id": "22f3be8bbf6d792549b7a6088df7440e425cb34f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We conducted cell-cell interaction analysis utilizing cellphonedb function curated by CellPhoneDB database [24] . The significant cell-cell interactions were selected with p-value < 0.01.", "Eyes also contain endothelial cells, melanocytes, pericytes, retinal pigment epithelium (RPEs) and Schwann cells.", "The viruses target host cells via binding host receptors before engaging the infection cycle." ] },{ "paper_id": "233978852b45429db49d2aabe1c9c9bfe73b1884", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As the data are announced daily, we adopt the following discrete version of the FUDAN-CCDC model proposed recently in (8):", "The data employed in this paper are the cumulative confirmed cases from Jan 16, 2020", "Wuhan also indicate independent self-sustaining human-to-human spread in multiple Chinese major cities (20) . Thus the risk of epidemic outbreak cannot be neglected outside Wuhan.", "Our findings suggest that effective isolation measures as early as possible are crucial for affected regions. Based on our model, the future trend of the epidemic highly depends on when and how the measures will be adopted. Effective interventions include limiting population mobility (e.g. cancellation of mass gathering, school closures and work-from-home arrangements) and public education (e.g. use of face masks and improved personal hygiene) (1)." ] },{ "paper_id": "23f1bab7d94bd0564e2319fddf75c1c7987ce75f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "24e17488d399c436305c819953beae2961214771", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Categorical variables were compared using the \u03c7 2 test or the Fisher exact test.", "Of the 5 remaining cases without an approved exposure history, 2 had unusual exposure. Patient A, who was long-term bed-ridden, was infected with SARS-CoV-2.", "Of the 55 patients, 52 received antiviral treatment, mostly with lopinavir/ritonavir and or arbidol. The mean duration from onset to admission was 5 (Table 3) .", "The members did not have direct or indirect exposure history. She was shortly carried into the Emergency Department of a nearby hospital to replace her gastric tube and highly suspected to be infected there. Patient B, she and her family members did not have any exposure history within past a month. Her sister and sister's husband from Wuhan visited her family and lived in the same building in a remote suburb of Beijing." ] },{ "paper_id": "24ff82a421f1a33db3ebaa22652bd62e0cb77c57", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The ethical approval or individual consent was not applicable." ] },{ "paper_id": "2536b83acf84368d7c13be81fe07aa0575115da7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "If we look at the ith row of this set of equations, we have", "The age-specific susceptibility z i can thus be estimated as", "and the eigenvalue of this matrix gives us the estimated basic reproductive ratioR 0 for the new population." ] },{ "paper_id": "264a816e7099246c13a5dad3a581a474d85d50bd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Only a small proportion of cases were used to evaluate the treatment outcomes.", "RESULTS", "Since this life-threatening disease is still ongoing in China and is developing in several countries, we expect our findings can provide timely information about better understanding and treatment of COVID-19." ] },{ "paper_id": "267729947ca478946d5a4bffb8e13d50c3545120", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "26cb6703ca72bf97887abbc29a40b1bd9d7890f4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Here, we perform ChRO-seq in primary FLC and matched nonmalignant liver (NML) samples. As FLC is a rare adolescent cancer, we", "Further information and requests for resources and reagents should be directed to and will be fulfilled by the Lead Contact, Praveen Sethupathy (pr46@cornell.edu).", "Relative quantification values (RQVs) were calculated by normalizing the effect of drug treatment against DMSO controls following CellTiterGlo cell viability experiments. RQVs were generated from 4-12 replicates and were entered as effect values at appropriate drug dosages in single and combination drug treatments in CompuSyn Software using non-constant ratio design parameters. Individual Combination Index values are reported for each dose combination.", "AML12 cells were reverse transfected using Lipofectamine RNAiMAX (Thermo Fisher Scientific) per manufacturer's instructions. Briefly, transfection mixes were assembled in wells by adding 1 pmol of the appropriate siRNA and 0.3 \u00b5L RNAiMAX (96-well plates) or 5 pmol siRNA and 1.5 \u00b5L RNAiMAX (6-well plates) according to manufacturer's protocols. OptiMEM was added to each well and the plates were incubated for 15 minutes at room temperature. 1,500 cells (96well plates) or 5,000 cells (6-well plates) were plated on top of transfection mixes. Cells were incubated for 24 hours prior to further treatment." ] },{ "paper_id": "26e75d3c815aae7fd9b094c3e5c74d3f7132ca13", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The initial draft of review was drafted with representatives of the RCPCH and RCOG who also provided expert consensus on areas where data were lacking. This is presented as an appendix to this review. Registration on PROSPERO and contact with study authors was not undertaken due to time constraints. Quality of study was assessed subjectively as anecdotal, low, medium or high.", ". CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.", "Delivery occurred in all women within 13 days of onset of illness, fetal growth is unlikely to be affected in this time period. No placental pathology is available to date.", "BACKGROUND The common human coronaviruses; 1. 229E (alpha coronavirus), 2. NL63 (alpha coronavirus), 3. OC43 (beta coronavirus) and 4. HKU1 (beta coronavirus) cause the common cold. Three human coronaviruses cause more severe, acute illnesses; MERS-CoV causes Middle East Respiratory Syndrome, MERS, SARS-CoV causes severe acute respiratory syndrome, or SARS and SARS-CoV-2 coronavirus that causes COVID-19." ] },{ "paper_id": "26f1c42474966b8daede2912e06175bd8b864f8e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Infectious diseases represent a major public health problem in the world. In the poorest 68 countries, they continue to deeply impact economies and paralyze health systems. Progress 69 remains uneven, and millions of people do not benefit from prevention and treatment. In ", "Several diagnostic methods could be used for the identification of suspected respiratory 84 pathogens. For a long time, it mainly relied on culture but during the last decades, the 85 development of qPCR has revolutionized diagnostic strategies and largely contributed to 86 expand the knowledge on the epidemiology of respiratory diseases, especially for viruses (6).", "The prevalence of this pathogen was higher during the winter season but the difference 263 observed in our results was not significant. We noticed seasonal differences in the apparition 264 of this pathogen, as described by previous studies (16). As expected, RSV was essentially 265 identified in the 0-5 years group, suggesting that this group is more susceptible to infection. Health personnel were able to receive considerable support for the diagnosis of respiratory 282 tract infections. Before the installation of BioFire, it was impossible to identify the respiratory 283 pathogens circulating in this area, with the exception of influenza viruses diagnosed by RDTs." ] },{ "paper_id": "278e2c52630f1dbbda6a79db15a2260510586150", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "!\"#\"$%#\"#$#$%%#%\"$%$#\"#%$ ", ".", "Positive predictive value, sensitivity, and false positive rate are calculated from the numbers of true and false positives and negatives:" ] },{ "paper_id": "2858f25f5364b0ef37ceeaa370471ee6b3fac29d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "28b107243576723248ad4053261000311a22f134", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2913d91f13fd59c698f68ba63008d8e0550c0607", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Author Contributions: XZ designed the experiments. PJ, ZQ, and JY collected and processed data. AZ and SX analyzed data. All authors interpreted the results and wrote the manuscript.", "The authors declare no conflict of interest.", "All rights reserved. No reuse allowed without permission." ] },{ "paper_id": "295036c0448244642eb6533de571def6cd8437e5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Failure to consider evolutionary trade-offs can lead to teleological errors, in which the 272 consequences of a process (e.g. increased genetic diversity) are misinterpreted as a cause (e.g.", "Single replication cycle growth curve", "3D K359H RdRp has similar characteristics (see Table S4 ). HeLa cells were transfected by 453 electroporation with viral RNA transcript, added to HeLa cell monolayers and incubated at 37\u00b0C." ] },{ "paper_id": "2989bf36068372cfedef82f58f4777e60ccbcfaa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "After aerosol sample collection, all samples were handled immediately in the BSL-2 laboratory of Wuhan University. The 25, 37mm and 80 mm filter samples were dissolved in deionized water, then TRIzol LS Reagent (Invitrogen) was added to inactivate SARS-CoV-2 viruses and extract RNA according to the manufacturer's instruction. First strand cDNA was synthesized using PrimeScript RT kit (TakaRa). Optimized ddPCR was used to detect the presence of SARS-CoV-2 viruses following our previous study. 10 Analysis of the ddPCR data was performed with QuantaSoft software (Bio-Rad). The concentration reported by the procedure equals copies of template per microliter of the final 1x ddPCR reaction, which was normalized to copies m -3 in all the results, and hence the virus or viral RNA concentration in aerosol is expressed in copies m -3 hereafter. A detailed protocol is provided in Supplementary Appendix.", "The ongoing outbreak of COVID-19 has spread rapidly and sparked global concern. While the transmission of SARS-CoV-2 through human respiratory droplets and contact with infected persons is clear, the aerosol transmission of SARS-CoV-2 has been little studied." ] },{ "paper_id": "29b3eaeacecf2bfc95b9a493dbb1ba4b2323dd46", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(which was not peer-reviewed) The copyright holder for this preprint ", "In this work, we propose a comprehensive solution to the estimation of CFR from surveillance data during outbreaks [3] , and apply it to data from the COVID-19 epidemic in Hubei, China. Our work has three important strengths.", "(4) Our findings regarding the CFR are specific to the context, and should be interpreted in that light. The findings describe the situation in Hubei from 1 January to 11 February, 2020. It was demonstrated there, that mortality rates have changed over time as a result of an improvement of the standard of care [10] . The standard of care and, as a result, the CFR is setting-dependent and cannot be directly applied to other contexts.", "(2) In a related matter, our results depend on the assumption that older individuals have more severe symptoms and are more likely to be identified. In the absence of an outside reference point, the reporting rate cannot be estimated from surveillance data only. We chose to fix to 100% the reporting rate of infected individuals that have symptoms and are aged 80 and more, and estimate the reporting rates in other age groups relatively to that of older individuals. If further data, coming from a study in the general population, shows that this assumption is violated, this would lead to an overestimation of the CFR in our study." ] },{ "paper_id": "29bc34aad802ab6b35074f23c631540a84b16d0d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "where '\"' means 'distributed as'.", "Finally, we notice that", "Taken (1), (2), (3) and (5) together, the loglikelihood function was" ] },{ "paper_id": "2af91bbb625d983d5ad3aadb9e5f1d82268a0f1f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "However, in the causes of pancreatitis, virus infection factors such as mumps, herpes simplex virus should not be ignored [18] . Our study provides a new idea and a possible mechanism.", "For comparison, we compared ACE2 expression in lung and pancreatic tissues, since the lung is known to be the first target organ to be attacked by SARS-CoV-2. The mRNA level of ACE2 in pancreas was higher than that in lung ( Fig. 1A , P < 0.001, Wilcoxon signed rank test).", "Therefore, increased attention should be paid to the pancreas in patients with SARS-CoV-2 infection, especially in severe cases." ] },{ "paper_id": "2afff5fe89a3e3ec270a41c2b929dfeec68d7d50", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "where and are the times at which the first exportation event and the first death are observed. The total log-likelihood is given by the sum of two log-likelihoods:", "that is maximized to find the mean values of the parameters \u0303= {\u0303,\u0303}, used in the following step. Second, we fitted the observed counts of exported cases and deaths by considering two other likelihoods respectively to each process: ", "( | \u0394 , ) = \u2211 log(gamma(\u0394 , | shape = , scale = )", "where p describes the probability of finding a traveler from Wuhan among all travelers from China subject to the detection time window of the virus T = 12.5 days [8] . Given that the total volume of inbound passengers from China is M = 5.56 million passengers per year, the fraction of Wuhan travelers is = 0.021%, and the population of Wuhan is n = 11 million, the probability p is given by", "Since 8 December, 2019, clusters of pneumonia cases of unknown etiology have emerged in Wuhan City, Hubei Province, China [1, 2] . Virological investigation suggests that the causative agent of this pneumonia is a novel coronavirus (COVID-19) [3] . As of 27 January, 2020, a total of 4515 cases including 106 deaths were confirmed [4] . Forty-one cases of COVID-19 infections were also reported outside China, in other Asian countries, the United States, France, Australia, and Canada.", "From the technical side, it should be emphasized that our proposed approach can be especially useful during the early stage of an epidemic when local surveillance is affected by substantial ascertainment bias and export and death data are available and better ascertained. Nonetheless, caution must be used when implementing similar estimations for the COVID-19 epidemic, as all flights from Wuhan airport were grounded as of 23 January, 2020 [13] and this intervention abruptly changed the human migration network. Despite the decrease in the outbound flow of travelers from Wuhan, there is a substantial risk that the next epidemic wave will originate from other cities." ] },{ "paper_id": "2c18d80cfc792faa3d6e35c72d4b6b58ee93fdad", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All chemicals were of analytical grade and were purchased from Sigma-Aldrich (St. Louis, MO, U.S.A.) unless otherwise indicated. All enzymes and related buffers were purchased from New England Biolabs (NEB, Ipswich, MA, USA) unless otherwise indicated. All oligonucleotides and gene blocks (summarized in Supplementary Tables T1, T2 Table T4 ) were obtained from BEI Resources (Manassas, VA, USA)." ] },{ "paper_id": "2cc809ed4d5c3640ee2351fdb1876e8ff6c01b51", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All code is available as an R package (https://github.com/epiforecasts/ringbp).", "The authors have no interests to declare." ] },{ "paper_id": "2cfe7a4cc1fceed0ad7ffbd6244a61e0b2c3ac8b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2d02192c3d251c2b561d37274350660277658a74", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "One Sentence Summary: Base editing with reduced DNA nicking allows for the simultaneous 10", "Figures S1 to S16 Tables S1 to S5 35 Supplementary results" ] },{ "paper_id": "2d0285c90976dfa43d58eca6b7d1d7ef29994fc2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "119 34 The calculations were carried out in Gromacs 2019, and the thermodynamic cycle and procedure 120 was similar to that used by Matteo et al. 35 In the calculation, the ligand electrostatic and van der 121 Waals interactions were decoupled using a linear alchemical pathway with \u0394\u03bb = 0.10 for the van der 122 Waals and \u0394\u03bb = 0.20 for electrostatic interactions. To add the restraints, 12 \u03bb values were used.", "61 62" ] },{ "paper_id": "2da0a7ba851e53d21dba05042a397eafcdab093d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Given the risk associated with NSP16 mutation as a single target attenuation platform,", "we evaluated ways to increase safety without sacrificing vaccine efficacy. We first considered " ] },{ "paper_id": "2dc6766fe253b1b832d8a3074404fb5daae4762f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "with TbpA leads to a conformational change that increases the affinity of TbpA for transferrin. 247", "H. somni strain H191 was grown overnight at 37\u00baC and 5% CO2 on chocolate agar plates 376 containing 1% IsoVitalex. Cells were harvested from plates, washed once in PBS, and 377 resuspended at an OD 600 of 0.05 in BHI broth containing 0.5% yeast extract, 0.05% thiamine 378 pyrophosphate and 50 uM deferoxamine, and left to grow for 16 hours overnight at 37\u00baC with 379", "Dunnett's post test. Normalized readings were compared to a value of 1, the normalized signal 397 for the \"no competitor\" column, and the value that is expected when no binding occurs. 398", "There were some discrepancies between the results obtained in the assays used in our study. 279" ] },{ "paper_id": "2e41aee6651cf4cab4edf5aa67cc401c2bef9d67", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To compare the sex differences in the clinical findings among patients with severe coronavirus disease 2019 .", "We obtained demographic, illness history, physical examination, laboratory test, management, and outcome data from patients' medical records. Blood oxygen saturation was measured after oxygen therapy. Clinical outcomes were followed up by February 22, 2020.", "Laboratory tests were conducted within 24 hours after admission, including a complete blood count, procalcitonin, interleukin-6, Ferritin, hypersensitive troponin I (hsTnI) and N-terminal-pro brain natriuretic peptide (NTproBNP)." ] },{ "paper_id": "2e5d79e1e6ebeed6cffdad2b474ca7675da969e7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2e7c17caecfe67b64f9b59df404f0761df96987f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The level of interaction between spatial regions is determined by the mobility matrix 120 and its interaction kernel, \u03ba(r ij ):", "In this study, we have described our participation in a prospective forecasting challenge. 491", "It is estimated that there are between 3 and 5 million worldwide annual seasonal cases 1 of severe influenza illness, and between 290 000 and 650 000 respiratory deaths [1]." ] },{ "paper_id": "2ea102f58147dab02e4dea90eb90dbc67149f678", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Therefore, our studies not only emphasize the critical role of the RBM in determining the specificity of entry receptors but also raise the question on how homologous strains of betacoronavirus switch tropism through mutations such as indel or recombination in the RBM." ] },{ "paper_id": "2eac7de1c407d9eab13a6d538142cd21a814ee7b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Overall, agnostic or unbiased metagenomic sequencing capabilities in-country provide the ability to detect and respond to a variety of pathogens, even those that are unanticipated or unknown. Bridging of existing local and global resources for sequencing and analysis allows for better realtime surveillance locally, while also enabling better health pursuits overall, not just during outbreaks. The example described here serves as a call for continued training and infrastructure to support mNGS capacity in developing countries as bioinformatic tools proliferate and the cost of sequencing decreases.", "All human SARS-CoV-2 genomes are very similar, including the SARS-CoV-2 genome from the Cambodian case as we would expect given that he transited directly from Wuhan. One SNP was noted at position 25,654 in ORF3a resulting in a valine-to-leucine substitution when compared to NCBI accession MN908947.1.", "Rapid production and publication of pathogen genome sequences during emerging disease outbreaks provide crucial public health information. In resource-limited settings, especially near an outbreak epicenter, conventional deep sequencing or bioinformatics are often challenging. Here we successfully used metagenomic next generation sequencing on an iSeq100 Illumina platform paired with an open-source bioinformatics pipeline to quickly characterize Cambodia's first case of COVID-" ] },{ "paper_id": "2fe18190f7b54e589dccf1d3bbfd73e87bfd2ab9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "ecologies, poultry plus pig production and ruminant plus equine husbandry, as well as to 23 create a distinction among the RNA, DNA and retroviruses, also ranked in an outer-to inner-24 body fashion. Spearman correlation reveals the matches among these various virus traits, as 25 pertaining to the two host-ecologies, four infection-shedding-transmission related variables, 26 and the three virus genomes. The collective results reveal the outer-to inner-body shifts in 27 the interplay of host environment, virus-host interactions, and nature of the virus. Two 28 opposing virus evolution pathways emerge, respectively for generalist type, outer-body and 29 for specialist type, inner-body viruses. The ecological virus classification here presented is 30 broadly consistent with the current virus classification system and offers the advantage of 31 bringing substance and cohesion to the interrelationships among viruses and virus families.", "12 The current classification of animal viruses primarily relates to the virus molecular world, the 13 genomic architecture and the corresponding host-cell infection cycle. This virus centered 14 perspective does not make allowance for the precept that virus fitness hinges on the virus 15 transmission success. Virus transmission reflects the infection-shedding-transmission 16 dynamics and, with it, the organ system involvement and other, macroscopic dimensions of 17 the host environment. This study examines the transmission ecology of the world main 18 livestock viruses, 36 in total, belonging to eleven different families, and a mix of RNA, DNA 19 and retroviruses. Viruses are virtually ranked in an outer-to inner-body fashion, based on 20 the shifting organ system involvement and associated infection-shedding-transmission 21 dynamics. As a next step, this ranking is disentangled with the aim to contrast two main host 22 45 the virus. Two opposing virus evolution pathways emerge, respectively for generalist type, 46 outer-body and for specialist, inner-body viruses.", ". CC-BY 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/492603 doi: bioRxiv preprint 3 32 Author Summary 33 It remains unknown how exactly viruses fit in the tree of life. Still, there is growing 34 awareness that viruses as biological replicators are subjected to ecological sorting and so 35 require a viable propagation strategy. In the current analysis I depart from the precept that 36 virus fitness hinges on the virus transmission success. I examine the transmission ecologies 37 of the world main livestock viruses, 36 in total, a collection of pathogens well described in 38 terms of the organ system involvement, infection course, the extent of host damage, virus 39 shedding profile, and virus transmission modes. The viruses are on this basis ranked in an 40 outer-to inner-body fashion, virtually. As a next step, this ranking is disentangled with a 41 view to contrast two main host ecologies, poultry plus pig production and ruminant plus 42 equine husbandry, as well as to create a distinction among the RNA, DNA and retrovirus in 43 the study. The matches among these various virus traits serve to establish the outer-to 44 inner-body shifts in the interplay of host environment, virus-host interactions, and nature of Introduction 48 Increasingly, viruses are viewed in an ecological context, as living entities [1, 2, 3, 4, 5] . Viruses, 49 like all biological replicators, form a continuum along the selfishness-cooperativity axis, from 50 the completely selfish to fully cooperative forms [6] . In a deeper sense, the history of life is a 51 story of parasite-host coevolution that includes both the incessant arms race and various 52 forms of cooperation [7] . 53 Organ systems and virus transmission success 54 The current paper approaches the evolution of viral replication and propagation strategies [11] . 80 The study 81 The study explores the transmission ecology of the world main livestock viruses, 36 in total, 82 a collection of well described pathogens. Viruses are ranked in an outer-to inner-body 83 fashion, virtually, on the basis of the shifting organ system involvement, transmission 84 modes, and infection-shedding-transmission related variables. Next, this virus infiltration 85 ranking is disentangled to contrast the poultry plus pig to the ruminant plus equine viruses, 86 as well as to separately consider the RNA, DNA and retroviruses in the study, also ranked in 87 an outer-to inner-body fashion. 94 As a first step, the one-to-three scores allocated to the 36 livestock viruses for the four 95 ecological variables were matched on the basis of Spearman correlation, see also S2 Fig reflects, respectively, acute, acute and persistent, and persistent infections. Likewise, the 589 score for the infection severity level concerns a case fatality of less than one, one to ten, and 590 above ten percent. The score for the virus environmental survival rate refers to the number 591 of days that the virus remains infective outside the host body, ranging from up to three, 592 three to ten, to over ten days. Also shown are the virus host range and references to the The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/492603 doi: bioRxiv preprint" ] },{ "paper_id": "2fe6b550f737baa47a5f2c8ab64cc3d9271c308a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Acknowledgments YM acknowledges partial support from the Government of Aragon, Spain through grant E36-17R (FENOL), and by MINECO and FEDER funds (FIS2017-87519-P). AA and YM acknowledge support from Intesa Sanpaolo Innovation Center. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript." ] },{ "paper_id": "2ff168d83528e6dd46e8c5358fb84fd63f7a8f2c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "2ffc83b88bc84615273e97d8109e5439ce4dce60", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "N p ] and then log-transforming, with \u2207 N := { \u2202 /\u2202Nj} as the vector derivative operator [17] . The result is Eq. (5) [28] .", "QK p :", "parameter space knowledge.", "The maximum likelihood estimate (MLE), and Fisher information (FI) are important measures for describing how estimates of N (or log N ) depend on T T 0 . We compute the MLE, logN j , and FI, I(log N j ), of the skyline model by solving \u2207 N p = 0 and E[\u2212\u2207 2" ] },{ "paper_id": "3028628066ec2401f3981f4e70c5b1acd4cef573", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All datasets and R code are available on GitHub (github.com/carolinecolijn/ClustersCOVID19).", "Singapore data was obtained from the Ministry of Health Singapore [14] online press releases.", "These are integral parameters for disease forecasting and for informing public health interventions." ] },{ "paper_id": "30457ee3ce0001f33938fbc246b4ce4eacd74f5d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Data Availability. The mass spectrometry data were deposited on MassIVE (MSV000079949).", "We will refer to this candidate list as the top 50.", "Next, we dene the prior probability of an assignment as the product of priors for pairs of compounds:" ] },{ "paper_id": "30814fcc87b8f3e5d4f7431d75b9505b049021e0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The 2015-2016 emergence of Zika virus (ZIKV) in the Americas, and recognition that ZIKV 15 infection during pregnancy can result in birth defects, revealed a need for small animal models to 16 study ZIKV pathogenic mechanisms and evaluate candidate vaccines and antivirals. Mice would 17 be an attractive system for such studies, but ZIKV replicates poorly in laboratory mice because it 18 fails to antagonize murine STAT2 and STING. To address this, most ZIKV pathogenesis studies 19 have used mice with impaired interferon signaling (e.g. Ifnar1 -/or treatment with IFNAR1-blocking 20 antibodies). However, using mice with severe defects in innate antiviral signaling confounds 21 studies of viral pathogenic mechanisms. Collaborative Cross (CC) mice have proven to be a 22", "to H/PF/2013 (2, 17). Dakar-MA was generated by passaging a ZIKV strain isolated from 161 mosquitos in Senegal in the 1980s (Dakar 41525) serially in Rag1 -/mice, resulting in a virus with 162 enhanced pathogenesis in mice (4). Mice were weighed daily after infection, as weight loss is a 163 sign of ZIKV disease in immunocompromised mouse models and typically precedes lethality (2). 164" ] },{ "paper_id": "30b5c7b8faf95265f67ae59f4686eaf9b2772893", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "311a15d92b87b2bc41f00afed881b95e93c22fcc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "SLFNTLFFNPCCLGFVAFAYSVKSRDRKMVGDVIGAQSYASTAKCLNIWAVVLGLLVIVA 120 E.serotinus_IFITM3 SLFNTLFFNTCCLGFVAFAYSVKSRDRRMVGDVIGAQSYASTAKCLNIWAVVLGLLMTIG 120 P.hastatus_IFITM3 SLFNTLFFNVCCLGFVAFAYSVKSRDRKMVGDVIGAQSYASTAKCLNICALVLGLLGTIG 120 C.brevicauda_IFITM3 SLFNTLFFNVCCLGFVAFAYSVKSRDRKMVGDVIGAQSYASTAKCLNICALFLGLLGTIG 120 ********* *****************:******************** *:.**** :. ", "These properties correlated with the reduced viral restriction observed for mbIFITM3 P70W (Fig. 3) . The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/737841 doi: bioRxiv preprint S-palmitoylation of IFITMs has only previously been studied for human and mouse proteins. To 280 investigate S-palmitoylation in mbIFITM3, cysteine-to-alanine substitutions were made at 281 conserved cysteine residues (C71, C72 and C105). A549 cells stably expressing single mutants C71A, 282 C72A and C105A, the double C71A-C72A mutant and the triple C71A-C72A-C105A mutant were 283 generated. Two methods were used to assess S-palmitoylation: (i) the acyl exchange gel shift 284 method described above ( Fig. 5 and 6A ), and (ii) visualisation of palmitoylated proteins by in-gel 285 fluorescence (Fig. 6B ). For this, cells were metabolically labelled with a 'clickable' alkyne palmitate 286 analogue followed by further modification of the palmitoylated proteins via copper-catalyzed 287 azide-alkyne cycloaddition reaction (i.e. 'click chemistry') using a TAMRA-labelled capture reagent.", "Host interferon-induced transmembrane proteins (IFITMs) are broad-spectrum antiviral restriction 28 factors. Of these, IFITM3 potently inhibits viruses that enter cells through acidic endosomes, many 29 of which are zoonotic and emerging viruses with bats (order Chiroptera) as natural hosts. We (Fig. 2B) . The amino acids at codon 70 for the 31 functional mammalian IFITMs, as well the 176 likely ancestral codons at this site at key nodes in the phylogeny inferred using a parsimony 7 distinct amino acid at codon 70 (P, T and W, respectively). A further three amino acids occur in 179 IFITM proteins with confirmed antiviral activity: F (in mouse IFITM3 and IFITM1), A (in mouse 180 IFITM2) and G (in mouse IFITM6; not used in the phylogenetic analysis). Assessing novel IFITM3 181 sequences we obtained using RACE and RT-PCR for 4 species of microbat also highlighted codon 70 182 as the only non-conserved residue within the CD225 domain of microbat IFITM3, and it was notable 183 that two microbat species encode valine (V) at this position (Fig. 2C )." ] },{ "paper_id": "313dd0869f169624e78d770963eacb0d1641cafa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(residues 201-303) contains five \u03b1-helices arranged into a largely antiparallel globular 104 cluster, and is connected to domain \u2161 by means of a long loop region (residues 185-200). strand155-168 on one side, and with residues 189-191 of the loop linking domains \u2161 and \u2162", "kinetic analysis (Extended Data Fig. 1e ). The catalytic efficiency (kcat/Km) for COVID-19 72 virus M pro was measured to be 28,500 M \u22121 s \u22121 which is slightly higher than that for SARS- 73 CoV M pro (kcat/Km=26,500 M \u22121 s \u22121 ) 10 , but over 30-fold higher than that of human rhinovirus 74 3C protease (kcat/Km=920 M \u22121 s \u22121 ) 11 .", "The MS/MS data shows that ebselen, PX-12 and carmofur are all able to covalently bind Fig. 7) . Since ebselen has even stronger inhibition than the others, 173 there is a possibility that ebselen could also inhibit M pro through non-covalent binding. compound has been investigated for the treatment of multiple diseases, such as bipolar 186 author/funder. All rights reserved. No reuse allowed without permission." ] },{ "paper_id": "315197247b230bab03786c197dc1fc795164c371", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/623132 doi: bioRxiv preprint Quantitative real-time PCR 504 Total RNA was extracted from cultured cells using TRIzol reagent (Invitrogen). cDNA was 505 generated by reverse transcription with commercial PrimeScript RT Master Mix (Takara). 506 Primer pairs (Table S12) For northern blotting, total RNA was isolated from A549 cells using TRIzol reagent. Probes 523 (Custom LNA mRNA Detection) were designed and synthesized by Exiqon and were also 524 All rights reserved. No reuse allowed without permission.", "The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/623132 doi: bioRxiv preprint used for FISH. Northern blotting was performed as described previously (46). Technologies. Cells were observed on a FV1000 confocal laser microscope (Olympus). 546 All rights reserved. No reuse allowed without permission.", "The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/623132 doi: bioRxiv preprint 548 RIP assays were performed as described (51) with minor modification. Briefly, after 549 incubation, the magnetic beads were washed with high salt lysis buffer (containing 500mM 550 NaCl) 5 times. RIP products were analyzed by qRT-PCR using the primer pairs listed in Table 551 S12. ChIP was performed as described (67). The ChIP-enriched FOXO3a promoter was 552 quantified by qPCR using the primer pairs listed in Table S12 . LacZ as control. Next, C-1 magnetic beads were added to the probe-chromatin mixture. After 565 five total washes with washing buffer (2\u00d7SSC, 0.5% SDS, add DTT and PMSF before use), 566 the beads were separated into two parts, 1/10 for RNA elution and 9/10 for DNA elution or 567 protein elution. For elution of the RNA, the beads were treated with Protease K Buffer and 568 All rights reserved. No reuse allowed without permission." ] },{ "paper_id": "317215c463463ddb39fa7564f67239dc484b86a9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The models developed here and data are available at https://github.com/kath-o-reilly/ Zika-LAC-Outbreaks.", "The authors declare that they have no competing interests. " ] },{ "paper_id": "317943dec06b88c1c62ef0ecd832f0d644b1d417", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "where \u02c6m h is the estimator from candidate model m. The major advantage of using the ensemble estimator is its ability to account for model uncertainty and obtain better predictive performance than any single constituent candidate model.", "The ordinary differential equations were solved using the LSODA algorithm (Petzold & Hindmarsh, 1997) with both the absolute and relative tolerance set to 10 -3 .", "Multiple chains with a Metropolis-Hastings sequential sampler were used to draw samples from the posterior of the model parameters. Python packages numpy and pymc3" ] },{ "paper_id": "31e67053158e68f513214a7a33046b5cc5f26249", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "7 147 parasites, such as the microsporidia Nosema ceranae, are associated with high JH and low vg 148 levels and precocious foraging [25] . However, little is known about the molecular mechanism by 149 which colony nutritional conditions lead to changes in behavioral development, susceptibility to 150 pathogens and ultimately, colony survival." ] },{ "paper_id": "329dfdd2fbe4b3c510c5329219bfd33764ab1710", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "When the nutrient status switches back to favourable, cells re-activate translation, rebuild growth-required cell functions, revert to single, vegetative cell status and re-initiate the asexual cell cycle 34 .", "We recovered known causes of domestication effects, e.g. SUC2 gain (sucrose use, d),", "Besides domestication, two events stand out in S. cerevisiae evolution since the S. paradoxus split. First, the out-of-China dispersal separated East Asian wild isolates from other yeast clades, driving the earliest and most profound genetic differentiations 20, 78, 79 ." ] },{ "paper_id": "32c2e402c3c88c3024a4dec3d78ba67c24f89ca6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Step one of this process necessitated constructing two transition matrices: the F matrix, which describes how new infections are created and the V matrix which represents host transitions between exposed and infected states.", "And, by extension, our susceptible population can be represented as:", "For cells with either absent or fully induced immunity, for which 6 = 0, this contracts to:", "All experiments were carried out on three immortalized mammalian kidney cell lines: run in duplicate on 6-well plates, such that a typical plate for any of the three viruses had two 512 control (mock) wells, two MOI=0.0001 wells and two MOI=0.001 wells, excepting PaKiT01 513 plates, which had two control and four MOI=0.0001 wells at a given time. We justify this 514 PaKiT01 exemption through the expectation that IFN-expression is constitutive for these cells, 515" ] },{ "paper_id": "3319392ca8bd2b8f2e2d00bccdb80deaa8a77c2e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.13.945485 doi: bioRxiv preprint", "). We were also 72 able to successfully isolate the virus using the Vero E6 cell line (Extended Data Figure S1 ). 73 author/funder. All rights reserved. No reuse allowed without permission.", "The copyright holder for this preprint (which was not peer-reviewed) is the . https: //doi.org/10.1101 //doi.org/10. /2020 author/funder. All rights reserved. No reuse allowed without permission." ] },{ "paper_id": "331a7033bb8e6d4618e4e83b74aff1aec42764a6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "33565294e6bc67fb7ee14dcae6cfdb08148f4ea5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Abstract: 25 26", "* Author for correspondence: moritz.kraemer@zoo.ox.ac.uk or rcreiner@indiana.edu" ] },{ "paper_id": "33bd85ea9ca61c4d0674c43ae5b901b271b46f1e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ ": Deaths in China vs. Time (days since 1/21) on a log-log plot), and (inset) on a log-linear plot.", "(1)", "The authors thank Greg Huber, Ginestra Bianconi, and Youjin Deng for discussions and communications related to this work.", "[2020], Hu et al. [2020] , Maier and Brockmann [2020] , , , Xu et al. [2020] , . These tend to predict an S-shaped curve with a tapering off in the near future as is being seen. These models depend upon assumptions of the reproduction rate, incubation period, etc." ] },{ "paper_id": "341fe593ea84b66223d50924bddbba252c37bc4e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3461d71f6890f7e5ba53bf168be3945cdb16d901", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Other, more complicated tests, such as composite likelihood methods, are also available but in our experience were incompatible with temporal sampling and rate heterogeneity.", "Recombination leaves several characteristic clues in genomes:" ] },{ "paper_id": "35604e3a5d38d6794543372e4dd9ccf1d8d9cd2a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Comprehensiveness and-to some extent-specificity of the designs can be verified in silico .", "Ongoing SARS-CoV-2 sequencing is key to developing and monitoring diagnostics and similar surveillance tools. In the case of the SARS-CoV-2 outbreak, genomes have been generated and shared at a remarkable pace, and we thank those who have contributed their data through GISAID [13]. We and others, relying on this data [14] , have shown that it is possible to rapidly design CRISPR-based tools for detection and surveillance during an outbreak.", "List of equipment and materials " ] },{ "paper_id": "3579a2b0053bef55f93716e444173727a6c94c6d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "35ac99bfeb665ce0a2ae361dba1161e69eb8b7d5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "However, much concern remains about the potential for attenuated viruses to recover virulence.", "\u03a6X174 genomes.", "A phage assembly platform for \u03a6X174 was devised following (120 Unsuccessful attempts to create live virus using synthesized fragments were repeated at least three times, then passaged in liquid culture for 24 hours to allow for recovery mutants to arise." ] },{ "paper_id": "36521caf90f471c9da1a4e84f8562440d73ead9a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The copyright holder for this preprint (which was not peer-reviewed) is . https://doi.org/10.1101/2020.02. 18.20024315 doi: medRxiv preprint ", "The funders had no involvement in study design, data collection, analysis or interpretation of the data, had no influence on the writing of the report or the decision to submit for publication.", "The authors have no conflict of interests to declare. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity." ] },{ "paper_id": "368fb114dfd565dedb635f62b9062956b49cd475", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Biofilm ECM Isolation. Biofilm ECM was harvested by disrupting biofilms using vortex and sonication as previously described. 32 Briefly fibers were collected after 5-day static growth by scraping biofilms into 3 mL of potassium phosphate buffer (50 mM, pH 7.4). The biofilm suspensions were homogenized using a tissue homogenizer (Power 4, 3 minutes) to shear fibers free from the cell walls. Supernatants were clarified by repeated (\u00d72) centrifugation at 4,000 g for 15 minutes to remove cells. The cell-free supernatant was incubated in 200 mM NaCl for 24 hours at room temperature. The fibers were isolated using Millipore Amicon Ultra Centrifugal Filter Units with a pore size of 30 kDa.", "Biofilms were cultured on sample holders as the standard procedure. GQDs (500 \u00b5g/mL) were added incubated for 24 hours at 37 \u00b0C. Similarly, isolated ECM was placed on sample holders and treated with GQDs. All samples were fixed in glutaraldehyde, serially dehydrated in ethanol, air dried at room temp, sputter-coated with gold and visualized using AMRAY 1910 Field Emission Scanning Electron Microscope.", "The sample was stained with 1% (w/v) uranyl acetate for 40 s. Grids were then blotted and airdried before imaging. For imaging cells with amyloid containing ECM, biofilms were scrapped directly on to copper TEM grids, stained with uranyl acetate, dried and imaged.", "The structural changes of amyloid-rich biofilms before and after GQD (500 \u00b5g/mL) treatment was further verified by scanning electron microscopy (SEM) (Figure 1i, j) . Here the change in porosity of the PNG biofilm is even more distinct than that in confocal microscopy, which increased to 71.2 \u00b1 6.6 % (Figure 1k) . This is likely a result of dehydration process required for SEM sample preparation, which washed off weakly attached bacterial cells and loose ECM content. The phenomenon not only confirmed the increase of biofilm porosity after GQD treatment but also indicated reduced integrity of remaining biomass." ] },{ "paper_id": "36a5f6d55d7c5f67d4344e36da0a72856ad3dda0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "real-time domestic travel data in China. Third, to address the issue of potential data collection and methodological bias or incomplete control of confounding variables, we implemented two distinct modeling approaches using different sets of data. These analyses produced estimates of the exponential growth rates that are consistent with one another and higher than previous estimates.", "A unique feature of our case report dataset (Table S1) is that it includes case reports of many of the first or the first few individuals who were confirmed with the virus infection in each province, where dates of departure from Wuhan were reported. All together, we collected 140 individual case reports (Table S1 ). These reports include demographic information including age, sex and location of hospitalization, as well as epidemiological information including potential time periods of infection, dates of symptom onset, hospitalization and case confirmation." ] },{ "paper_id": "36e602b7081e7bb8a1cfeaa2fb92b0c43abd4fef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In this work, we demonstrated the potential of longread data as produced by nanopore sequencing. We were able to directly sequence the RNA molecules of two different samples of one of the largest RNA virus genomes known to date. We showed how very large RNA genomes and a diverse set of sg RNAs with complex structures can be investigated at high resolution without the need for a prior assembly step and without the bias introduced by cDNA synthesis that is typically required for transcriptome studies.", "to handle special read data sets such as those originating from a small RNA virus genome. In addition, we assembled WT and SL2 consensus sequences using Nanopore and Illumina data with HG-CoLoR 48 in an approach that uses long nanopore reads to traverse an assembly graph constructed from short Illumina reads. We thereby recovered 99.57 % of the reference genome in a single contiguous sequence at 99.90 % sequence identity to reference using this approach with the single longest read from the SL2 sample. This hybrid approach illustrates how short-and long-read technologies can be combined to reconstruct long transcripts accurately, which will greatly facilitate studies of haplotypes.", "author/funder. All rights reserved. No reuse allowed without permission.", "Both the short-read cDNA (Illumina) and the basecalled long-read RNA (ONT) data are available from the European Nucleotide Archive (ENA) under accession PRJEB33797, as well as from the Open Science Framework repository UP7B4. Raw long-read data in fast5 format are also available from this OSF repository. All analysis code has been deposited in the same OSF repository and is also available in Supplemen-tal_Code.zip from the supplemental material." ] },{ "paper_id": "374a5295716649a80dca87097ad9ac902d344db6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Databases of ICMJE-accepted clinical trial registry platform were searched on February 14, 2020.", "2. All the database of ICMJE-accepted clinical trial registry platform were searched, and randomized controlled trials and observational studies were considered.", "shown in Figure 1 . Figure 6 ." ] },{ "paper_id": "37afeaa38d66b8097cc7637bf62ac7d142e6b362", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In addition, we applied parsimony reconstruction models to trace trait evolution, using 121 Mesquite V 3.5.1 (http://www.mesquiteproject.org), with the input phylogenies being generated 122 with the protein sequences of each virus genus via maximum likelihood method, using RaxML 123 V 8 (WAG+G, bootstraps n=1000) 12 . We obtained excellent agreement between mean 124 estimates of numbers of forward transitions using parsimony analysis and counts estimated 125 from our discrete traits analysis (Table S1, Fig. S12b) , noting that the parsimony approach does We calculated the depth of the node of each transition on the genus-level phylogenetic tree 151 relative to the ancestral node ( Fig. S4 and Data Files 2 and 3) . We used a beta distributed 152 GLMM (using the R package 'glmmTMB' 13 ) to compare node depth (response variable) across level transition types (explanatory variable) with genus as a random factor. We used a linear 154 mixed model (LMM) with a normal distribution to compare loge-transformed transition rates 155 (response variable) by level transition groups (explanatory variable) with genus as a random 156 factor. We also included genome type/enveloped and vector-borne in the model as potential 157 confounding variables.", "The absence of a clear association between human infectivity and human transmissibility may 208 reflect the key role that cell receptors play in determining a virus's capacity to infect and be 209 transmitted by humans 16, 18 . Cell receptor usage varies between virus genera and sometimes Our study supports a recent proposal for a large-scale survey of viral diversity in non-human 217 reservoirs, the Global Virome Project (GVP) 11 . Though this idea is controversial and would be 218 costly to implement 19 , its relevance is underlined by our finding that most species of human-219 transmissible viruses (L3/4) evolve from mammal/bird RNA virus lineages not known to be 220 infective to humans (L1), coupled with the expectation that the great majority of mammal and 221 bird viruses are still unrecognised 12 . We note recent progress in using machine learning to 222 predict host range from sequence data 20 and the potential of this kind of approach to help 223 identify human-infective and human-transmissible viruses even in the absence of human cases." ] },{ "paper_id": "380a4d07d22910246c6f189fd2da93b270b96981", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In conclusion, the results presented in this study show that many protein regions rely on metal binding disulfide bonds for stability, which are potentially redox-regulated, and involve structural transitions from an ordered state to a disordered state, or vice versa. The abundance of these types of regions dramatically increases from yeast to human, and involves a wide range of processes related to multicellularity, signaling and regulation of transcription and translation.", "The set of human proteins containing predicted redox-sensitive conditionally disordered protein regions (RSCDP) was determined as described for all proteomes. The list of 5,644 proteins together with the 10,109 identified regions is listed in the Supplementary material.", "At the organism level, the cellular functions involving redox-regulated conditionally disordered protein regions are typically embedded in a wide variety of developmental processes. Several of these processes are focused on either reproduction, such as the formation of a labyrinthine layer, or the very early developmental stages of life, such as somitogenesis, gastrulation, or endoderm formation. As these high level organismal processes typically rely on a large number of proteins, they do not show exclusivity towards either structural element. ", "Judging by sheer numbers of occurrence, the most abundant domain of interest in humans is the C2H2 zinc finger. This structural unit is present in all three studied proteomes in high numbers. Furthermore, the ratio of conditionally disordered C2H2 domains compared to the total number of such domains is surprisingly stable across the three organisms, with values of 59.5%, 66.6%, and 53.9%, for yeast, drosophila and human. This indicates that the study of the redox-sensitivity of simple model organisms, such as yeast can have implications in human physiology as well. The identification and functional characterization of redox-sensing structural switches can therefore serve as a guide to the understanding of the more complex roles these protein regions play in human regulation." ] },{ "paper_id": "38bab3f17b186bd8ee289e5d135bb7d500ef500b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As measles is highly infectious, under-immunized communities (also called pockets of susceptibles) 58 resulting from local heterogeneity in vaccine coverage can lead to large, long-lasting outbreaks [30] [31] [32] [33] [34] . 59" ] },{ "paper_id": "38e796bbec2f90b1b802c14dc922102e96f6361e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We use the following ordinary differential equation model to simulate the coronavirus within-lung growth:", "By the definition of generation matrix of basic reproduction number R 0 [3] , the R 0 of model (1) can be written as,", "We believe this study could give some help to the diagnosis and treatment of the COVID-19. For other disease that infect the lung, this method we believe also could be used to do analysis.", "At the end of 2019, a new type of coronavirus, SARS-CoV-2, began to threaten the people in China, especially in Hubei province. As of March.3, 2020, 80302 individuals have been confirmed to be infected by this virus in China, including 2946 deaths. To mitigate the spread of the virus, the Chinese Government has progressively implemented metropolitan-wide quarantine in Wuhan and several nearby cities from Jan 23-24, 2020 [18] . The virus has also spread to several other countries, such as the Republic of Korea, Japan, Italy, and USA. Around the world, many new deaths are reported every day." ] },{ "paper_id": "395e8569a0e6fc129029cb0b8cda1f7381954976", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Models of host-microbe dynamics typically assume a single-host population infected by a single 21 pathogen. In reality, many hosts form multi-species aggregations and may be infected with an 22 assemblage of pathogens. We used a meta-transcriptomic approach to characterize the viromes of 23 nine avian species in the Anseriformes (ducks) and Charadriiformes (shorebirds). This revealed the 24 presence of 27 viral species, of which 24 were novel, including double-stranded RNA viruses 25 (Picobirnaviridae and Reoviridae), single-stranded RNA viruses (Astroviridae, Caliciviridae, 26 ", "Abstract 20 Models of host-microbe dynamics typically assume a single-host population infected by a single 21 pathogen. In reality, many hosts form multi-species aggregations and may be infected with an 22 assemblage of pathogens. We used a meta-transcriptomic approach to characterize the viromes of 23 nine avian species in the Anseriformes (ducks) and Charadriiformes (shorebirds). This revealed the 24 presence of 27 viral species, of which 24 were novel, including double-stranded RNA viruses 25 (Picobirnaviridae and Reoviridae), single-stranded RNA viruses (Astroviridae, Caliciviridae, 26 Picornaviridae), a retro-transcribing DNA virus (Hepadnaviridae), and a single-stranded DNA virus 27 (Parvoviridae). These viruses comprise multi-host generalist viruses and those that are host-specific, 28 indicative of both virome connectivity and heterogeneity. Virome connectivity was apparent in two 29 well described multi-host virus species (avian coronavirus and influenza A virus) and a novel 30 Rotavirus species that were shared among some Anseriform species, while heterogeneity was 31 reflected in the absence of viruses shared between Anseriformes and Charadriiformes. Notably, 32 within avian host families there was no significant relationship between either host taxonomy or 33 foraging ecology and virome composition, although Anseriform species positive for influenza A 34 virus harboured more additional viruses than those negative for influenza virus. Overall, we 35 demonstrate complex virome structures across host species that co-exist in multi-species 36 aggregations.", "Many hosts are members of multi-species aggregations and may be infected by an assemblage of 43 specialist and/or multi-host generalist infectious agents. Host community diversity is central to 44 pathogen dynamics (1, 2), and pathogen species richness, relative abundance, specificity and intra- 45 and inter-species interactions within assemblages likely have complex roles in modulating pathogen 46 levels within populations (1, (3) (4) (5) (6) (7) (8) . A significant limitation in studying viral communities in hosts is 47 that most viral species remained undescribed (9), such that viral ecology across multi-host systems 48 has been limited to \"single-virus\" dynamics, particularly in vertebrate systems (for example, 49 Influenza A virus [IAV] in avian populations). With the advent of unbiased, bulk 'meta-50 transcriptomic' RNA sequencing we can now explore, in more detail, how viral community structure 51 may be shaped by host-species interactions. 52 Birds of the orders Anseriformes and Charadriiformes, the central reservoirs for avian viruses such 53 as IAV, avian avulavirus and avian coronavirus (10, 11), form multi-host flocks, in which many 54 species may migrate, forage, or roost together (e.g. (12) . These flocks may comprise species along a 55 taxonomically related gradient and may utilize similar or different ecological niches in the same 56 environment. For example, in Australia, taxonomically related dabbling Grey Teals (Anas gracilis) 57 and Pacific Black Ducks (Anas superciliosa) may share the environment with the distantly related 58 filter feeding Pink-eared Duck (Malacorhynchus membranaceus). These multi-host flocks form 59 multi-host maintenance communities (6), with consequences for virus ecology, transmission, and 60 virulence (1, 13, 14) . 61 Studies of the ecology of IAV, the best studied multi-host virus in wild birds, have shown that not all 62 hosts are equal (15, 16 The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/528174 doi: bioRxiv preprint A combination or oropharyngeal and cloacal samples were collected using a sterile-tipped swab and 103 were placed in viral transport media (VTM, Brain-heart infusion broth containing 2x106 122 U/l 104 penicillin, 0.2 mg/ml streptomycin, 0.5 mg/ml gentamicin, 500 U/ml amphotericin B, Sigma). 106 RNA was extracted and libraries constructed as per (25) " ] },{ "paper_id": "3a6544f6f247366d4c12167f7fba743e9d981c63", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "However, replacement of Arg426 to Asn439 appears to weaken the interaction by losing one important salt bridge with Asp329 on ACE2 (Fig. 4B) .", "Our structure provides the molecular basis for computational and mutational analysis for the understanding of the affinity difference. It should be noted that additional approaches, such as isothermal titration calorimetry (ITC) and microscal thermophoresis (MST), should be applied to validate SPR-measured affinities." ] },{ "paper_id": "3a73b880acd8983f87b210ff7fee434fd6ecc8c8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "At first clinical assessment, data were recorded on 21 signs and symptoms (see supplement), and disease severity was assessed. Cases with fever, respiratory symptoms, and radiographic evidence of pneumonia were classified as having moderate symptoms. Cases were classified as having severe symptoms if they had any of: breathing rate \u226530/min; oxygen saturation level \u226493% at rest; oxygen concentration level PaO 2 /FiO 2 \u2264 300mmHg (1mmHg=0.133kPa); lung infiltrates >50% within 24-48 hours; respiratory failure requiring mechanical ventilation; septic shock; or multiple organ dysfunction/failure. All other symptomatic cases were classified as mild .", "Relationships between demographics, mode of detection and symptom severity were assessed and characterized using 2 -tests, and logistic regression.", "Attack rates were similar across infectee age categories (Table 3) , though there is some indication of elevated attack rates in older age groups ( Figure 1) . Notably, the rate of infection in children under 10 (7.4%) was similar to the population average (7.9%). There was no significant association between probability of infection and age of the index case. Surprisingly, in univariate analysis a longer time in the community prior to isolation was associated with a reduced risk of causing infections. However, this association was no longer significant after adjusting for contact frequency and type." ] },{ "paper_id": "3a81dbb6350d25798f401c332abcf1b49616ffef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "respectively. Based on this observation alone, the conclusion would be that this combination of 224 antiviral agents is not even additive. Analysis of the entire single-cell dataset is presented in 225", "Single-cell occupancy of the device was sensitive to the width of the channels used for loading 77 ( Fig. S3a ) and cell density ( Fig. S3b) with maximum occupancy near 90% (Figs. 1d and S3) . 78", "All rights reserved. No reuse allowed without permission." ] },{ "paper_id": "3afd5fba7dc182ddfa769c0d766134b525581005", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Standard questionnaire and form were used for contact investigation and data collection. The data were independently reviewed by two trained physicians (Ye Deng and Xin Liao) and checked by another two physicians (Hongqiang Wang and Da Long) respectively. Every one signed Data Authenticity Commitment and stamp official seal.", "Considering the infectious of NCP, we conducted an oral informed consent with every patient instead of written informed consent (www.chictr.org.cn Chi CTR2000029734).", "Normally distributed continuous variables were described as mean and standard deviation (SD). For non-normally distributed continuous variables, we used median and interquartile range (IQR) or range. Categorical variables were expressed as ratio and percentages (%).", "Province geographically adjacent to Wuhan, Hubei Province, high-efficiency transport between the two provinces may lead to a rapid spread of COVID-19", "in Hunan Province. This report included the hospitalized patients with COVID-19 to assess the transmission and clinical characteristic of two hospitals, which designated as the treatment center for the NCP in Huaihua and Shaoyang cities, Hunan Province, China. These findings could provide value information to better understand such new illness." ] },{ "paper_id": "3b181a741d4beafda3ba3a8fc68239493d49f6aa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In Equation (3),", "In addition, we analyze the correlation between the two data sources. We found that Pearson ", "All data and materials used in this work were publicly available.", "Similarly, we used exported cases from Wuhan to predict numbers of local imported COVID-19" ] },{ "paper_id": "3b22eecad8a582436c52284a4db2198a98a94e18", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The human DUSP1-pCMV6XL5 plasmid was obtained from Origene. The pcdna3 Flag JIP1b (Addgene plasmid # 52123) and pcdna3 Flag JIP3b (Addgene plasmid # 53458) plasmids were a gift from Roger Davis 50, 94 . All constructs were verified using Sanger sequencing at the McGill University and G\u00e9nome Qu\u00e9bec Innovation Centre, Montr\u00e9al, Canada." ] },{ "paper_id": "3b73c8abb7528c958cec0bae1890828af007b599", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3c12e50b9da4b1fde21d68040610b73b8c216bf3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "34", "Importance", "74" ] },{ "paper_id": "3c14c4c3a176c86833794029e787ce460c9d89dd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Genome assemblies and annotations are essential starting points for many moleculardriven and comparative studies. 20 . Especially, studies of non-model organisms play important roles in many investigations 21 . In most cases, however, these organisms lack well-annotated genomes 22 , which severely limit our ability to gain a deeper understanding of these species and may further impede biomedical research 23 .", "Contig ID in assembly NCBI accession", "We want to further automate our ncRNA annotation workflow, to easily include these and any new bat (or other mammalian) genomes that will be sequenced and assembled in the future. Our current identification of ncRNAs in bat species will be usable as a resource (Electronic Supplement) for deeper studying of bat evolution, ncRNAs repertoire, gene expression and regulation, ecology, and important host-virus interactions." ] },{ "paper_id": "3c476baf5542bef88b8aad92bcca6786d1afa282", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 Understanding DENV transmission in populations where the infection is endemic through the use of metagenomics is a most promising strategy to get insight into the dissemination of the virus and to support measures to prevent or decrease further spread." ] },{ "paper_id": "3c70c99afc7a38df3c4807857856ea258d378429", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Introduction encompasses residues 347-726 and has the characteristic (\u03b2/\u03b1) 8 topology found in the catalytic 109 domain of family 31 glycoside hydrolases. C-terminal to the catalytic (\u03b2/\u03b1) 8 domain, the GAA 110 structure contains two additional \u03b2-sandwich domains. Domain C1 spans residues 727-820 and 111 is composed of seven antiparallel \u03b2-strands in 5-and 2-stranded \u03b2-sheets. The C2 domain has 112 a \u03b2-sandwich topology and is composed of 10 \u03b2-strands in two 5-stranded \u03b2-sheets, with two 113 small \u03b1-helices inserted ( Fig. 1 and Fig. 1 supplement B) . and the surface-exposed C938 and C952 in the C2 domain (Fig. 1) .", "Pompe disease results from a defect in human acid \u03b1-glucosidase (GAA), a lysosomal enzyme 17 that cleaves terminal \u03b11-4 and \u03b11-6 glucose from glycogen. In Pompe disease (also known as 18 Glycogen Storage Disorder type II), the accumulation of undegraded glycogen in lysosomes 19 leads to cellular dysfunction, primarily in muscle and heart tissues. Pompe disease is an active 20 candidate of clinical research, with pharmacological chaperone therapy tested and enzyme 21 replacement therapy approved. Despite production of large amounts of recombinant GAA 22 annually, the structure of GAA has not been reported until now. Here, we describe the first 23 structure of GAA, at 1.7\u00c5 resolution. Three structures of GAA complexes reveal the molecular 24 basis for the hundreds of mutations that lead to Pompe disease and for pharmacological 25 chaperoning in the protein. The GAA structure reveals a surprising second sugar-binding site 26", "Proteolytic treatment prior to crystallization mimics proteolytic maturation in the late endosome 124 and lysosome. Electron density is missing for loops 116-122, 199-205, and 782-792. 125 Presumably, the flexible loops in the intact protein limited the resolution of the intact GAA 126 crystals. After cleavage of the three loops, the remaining fragments remain associated by non- Active site and ligand binding 136 The active site of GAA is an acidic pocket at the base of a conical funnel lined by hydrophobic 137 residues in the (\u03b2/\u03b1) 8 barrel catalytic domain (Fig. 1, Fig. 2, and Fig. 2 supplement A) . The To better understand substrate recognition in GAA, we determined complexes of the enzyme 155 with isomaltose and maltotriose (di-and tri-saccharide fragments of glycogen) at 2.0 and 1.9\u00c5 156 resolution, respectively. The structures show glucose present in the active site with no clear proximity of active site residues D282, M519, and R600, \u03b2-linked substituents beyond a 161 hydroxyl are sterically blocked, and thus we conclude that the \u03b2-glucose appears in the active 162 site after cleavage of \u03b1-linked substrate and subsequent ring opening of the \u03b1-glucose product. 163 Residues D404, D616, and H674 confer glucose substrate specificity by hydrogen bonding to 164 hydroxyls on the ligand (Fig. 2) . Hydrophobic residues W376, L405, I441, W481, W516, M519, 165 W613 and F649 contribute to active site architecture and substrate binding. We also determined the complex of GAA bound to 1-deoxynojirimycin (DNJ) (Fig. 2) shallow cleft in the N1 domain 34\u00c5 away from the active site ( Fig. 3 and Fig. 3 supplement A) . 176 In the second site, the non-reducing ends of isomaltose and maltotriose bind identically, with 177 hydrogen bonds between the glucose hydroxyls and the side chain of D91 and the main chain per side chain atom possessing less than 2 \u00c5 2 , between 2-9 \u00c5 2 , and above 9 were considered 249 buried, partially buried or exposed respectively. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/212837 doi: bioRxiv preprint . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/212837 doi: bioRxiv preprint The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/212837 doi: bioRxiv preprint" ] },{ "paper_id": "3c94f582610453b6c1389c3a5d6ad57bcf0ba033", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis was done with SPSS, version 20.0. Continuous variables were directly expressed as mean \u00b1 SD. Categorical variables were expressed as number (%).", "( Table. 2)", "ZG and BS made substantial contributions to the study concept and design. XL was in charge of the manuscript draft. LW took responsibility for obtaining ethical approval and collecting samples.", "We declare no competing interests." ] },{ "paper_id": "3d3d536de77577af8dbf3067883990ff6d17faa8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "AQUA-DUCT defines the pockets as areas of the overall distribution of tracked water molecules; the outer pocket represents the maximal possible space that could be explored by tracked molecules.", "The AQUA-DUCT 1.0 (AQ) software was used to track water and cosolvent molecules. Molecules of interests, which have entered the so-called Object, defined as 5\u00c5 sphere around the centre of geometry of active site residues, namely H41, C145, H164, and D187, were traced within the Scope region, defined as the interior of a convex hull of both COVID-19 Mpro and SARS Mpro C\u03b1 atoms. All visualizations were made in PyMol 47 .", "In early December 2019, the first atypical pneumonia outbreak associated with the novel coronavirus of zoonotic origin (COVID-19) appeared in Wuhan City, Hubei Province, China 1,2 . As of 23 February 2020, COVID-19 has been reported in 26 countries and nearly 79,000 infection cases (both laboratory-confirmed and reported as clinically diagnosed), including more than 2400 fatal ones, have been confirmed 3 . According to the World Health Organization, a precise estimate of the infection fatality rate is therefore impossible at present. However, the National Health Commission of China, at the press conference on February 4 evaluated that the virus mortality rate stood at 2.1% nationwide (4.9% in Wuhan).", "Six different cosolvents: acetonitrile (ACN), benzene (BNZ), dimethylsulfoxide (DMSO), methanol (MEO), phenol (PHN), and urea (URE) were selected to perform the mixed-solvent MD simulations. The chemical structures of cosolvents molecules were downloaded from the ChemSpider database 42 and a dedicated set of parameters was prepared. Parameters for ACN were adopted from the work by Nikitin and Lyubartsev 43 , and parameters for URE were modified using the 8Mureabox force field to obtain parameters for a single molecule. For the rest of the co-solvent molecules, parameters were prepared using Antechamber 44 with Gasteiger charges 45 ." ] },{ "paper_id": "3d498994d143a4ed7cc381700a19f2790d46bb36", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3d5093a8e079fb17262111e5ef94bf01a3007971", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Strongyloidiasis is a prevailing helminth infection ubiquitous in tropical and subtropical areas.", "There was only one case (1/14 (7.14%) from an individual from East European countries. The patient was from Montenegro and he had not travelled outside Europe." ] },{ "paper_id": "3d690de86ca6e200f4f9cac61b004e47ad753aae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Altogether, the possibility of a common innate immune antagonism function for nsp14 across 342", "Alpha-and Beta-CoVs is apparent but clearly differing requirements exist that may be dependent 343 on the CoV genus and cell types used. 344" ] },{ "paper_id": "3da1a03cb675f463b0d8e30744aa33512241dd29", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.16.20023655 doi: medRxiv preprint", "The newly established 2019-nCoV modified SEIR propagation dynamics system model is as follows 3 / 5 " ] },{ "paper_id": "3ddc987158400d3867939d3594da56dd546d6ddd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3deb6393bd43f440a69c84da9ed61986b1781d36", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "An ongoing novel coronavirus pneumonia ", "Accordingly, we determined a scoring rule by referring to previous judgment rules 14-16 . Firstly, 126", "December 2019 has subsequently spread across China and worldwide, resulting in numerous cases 40 of infection and death 1 . Usually, COVID-19 has an incubation period of 2-7 days 2 with no obvious 41 symptoms, during which time the virus can spread from infected to uninfected individuals. 42 Therefore, early accurate diagnosis and isolation of patients is key to controlling the epidemic. 43" ] },{ "paper_id": "3e5633a9a76a8c03e4ec57e4659872a63f045117", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Designating 2019-nCoV as SARS-CoV-2 and providing guidance for naming its variants", "Is the outbreak of an infectious disease caused by a new or a previously known virus (Box 1)? This is among the first and principal questions because the answer informs measures to detect the causative agent, control its transmission and limit potential consequences of the epidemic. It also has implications for the virus name. On a different time scale, the answer also helps to define research priorities in virology and public health.", "To facilitate good practice and scientific exchange, the CSG recommends that researchers describing new isolates of this virus and other viruses in this species adopt a standardized format for public databases and publications. The proposed naming convention includes a reference to the host organism that the virus was isolated from, the time of isolation, and the place of isolation (geographic location): Virus/Isolate/Host/Date/Location, e.g. SARS-CoV-2/X1/Human/2019/Wuhan. This complete designation along with additional and important characteristics, such as association with pathogenicity in humans or other hosts, should be included in the submission of each isolate genome sequence to public databases, e.g. GenBank.", "Even without knowing anything on the species concept of classifying different forms of life, every human recognizes another human as being a member of the (same) species Homo sapiens. However, for assigning individual living organisms to most other species, specialized knowledge and tools for assessing inter-individual differences are required. The CSG uses a computational framework of comparative genomics 22 that is shared by several Study Groups concerned with the classification and nomenclature of the order Nidovirales and coordinated by the Nidovirales Study Group 23 (Box 3). The Study Groups quantify and partition the variation in the most conserved replicative proteins encoded in open reading frames 1a and 1b (ORF1a/1b) of the coronavirus genome ( Fig. 2A) to identify thresholds on pair-wise patristic distances (PPD) that demarcate virus clusters at different ranks." ] },{ "paper_id": "3e9ae5329eecab16d7c39f1f6dc778cf4a53ee0d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "3ebbcdddb122f405061bb5e1ddcf94abe9258d58", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In December 2019, a severe respiratory disease of unknown origin emerged in Wuhan,", "Substrate hydrolysis was measured for 30 min using the following wavelengths: ", "Information provided here can be used for the design of inhibitors and activity-based probes against the SARS-CoV-2." ] },{ "paper_id": "3fac0b7a9917984764a77f7fcb327e820e770d1b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "and their abundance and composition changes according to identifiable spatial and temporal scales 49", "[5-7]. Archaea is represented in 26 phyla [8] , most of which are novel and some lineages include 50 only one species of uncultivated strains that have been assembled through metagenomics [9, 10] . 51", "Herein we describe the Archaea diversity in a shallow pond in the Cuatro Ci\u00e9negas Basin (CCB), 24" ] },{ "paper_id": "3fe2552d3d8e6c9ead2c41e30fbb69e917277f53", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "402041df2d9812dbcdae08153d0350eee170eea9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We have used multi-pronged chemogenetic approaches to investigate the translational control of long- ", "Lateral amygdala is the central sensory gateway for the amygdaloid complex and is crucially engaged both in 95 the processing and storage of the associative aversive memories 4, 5, 6 ." ] },{ "paper_id": "403d885a33958731c4607ea632453e25a89e2b57", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "compounds and identify novel antivirals is one means to accelerate drug discovery for viruses 47 with no approved treatments. We used this approach to screen hundreds of compounds against 48 La Crosse virus, an emerging bunyavirus that causes significant disease, including encephalitis. 49", "Ionophores are selectively antiviral. Given that valinomycin is a potassium ionophore, we 206 wished to investigate whether other ionophores, for potassium or otherwise, were antiviral. 207" ] },{ "paper_id": "409c431edf54d022463f40f2d31a0dfab42f5324", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The copyright holder for this preprint . https://doi.org/10.1101/2020.02.12.20022400 doi: medRxiv preprint", "The copyright holder for this preprint .", "The prediction capacity of the current's prediction model is limited for the 2019-nCov, an emergent infectious disease. This paper just brings forth a prediction idea and the prediction precision needs further improvement, which also implies the arduous task for epidemic forecast.", "National Health Commission of PRC released a report on Unexplained Viral Pneumonia in Wuhan on Jan. 11 th ,2020. NHC shared the Gene sequence of the novel coronavirus with WHO. This virus was named as 2019-nCov officially by WHO [1] . This coronavirus has not wild spread at first. The mobility of the population has greatly increased before Lunar New Year at the end of January, and the coronavirus is contagious, the infected cases rapid growth. Up to Feb. 9 th , the cumulative diagnosis cases is 42368 in China and 386 abroad 1 ." ] },{ "paper_id": "4144f646c2005c781d7834d5950dc3490cd082d0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To control the spread of Corona Virus Disease , screening large numbers of suspected cases for appropriate quarantine and treatment is a priority.", "Conservative estimates of the detection rate of nucleic acid are low (between 30-50%) [6, 7, 8] , and tests need to be repeated several times in many cases before they can be confirmed.", "Retrospective collection of datasets.", "The hallmarks of COVID-19 are bilateral distribution of patchy shadows and ground glass opacity [2] . Based on this, we believed that CNN might help us identify unique features that might be difficult for visual recognition." ] },{ "paper_id": "4151e9b4ea5395d73bf33309dbca26551cc7c657", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ants were fed with crickets and honey three times a week. We randomly marked either all 128 young (upon eclosion in the lab) or all old (field collected) workers with thin metal wires 129 (0.02mm, Elektrisola) in each colony, allowing us to differentiate between the two age cohorts.", "In our laboratory in Mainz, Germany, the ant colonies were transferred to slide glass nests and 125 kept in plastered 3-chambered nest-boxes ( Figure S1 ). We maintained them at a 14h:10h 126 light:dark photoperiod and a +22\u00b0C:+18\u00b0C temperature regime to facilitate brood development." ] },{ "paper_id": "41d412415c46baf70ca91ebf049c0352ead19f18", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A spinning disc confocal microscope (Zeiss Axio Observer Z1 with Yokagawa CSU-X1M) was used to image GUVs and tethered vesicles. Laser wavelengths of 488 and 561 nm were used for excitation. Emission filters were centered at 525 nm with a 50 nm width, and 629 nm with a 62 nm width. A triple-pass dichroic mirror was used: 405/488/561 nm. The microscope objective was a Plan-Apochromat 100x, 1.4 numerical aperture oil immersion objective. Images were collected on a cooled (-70 \u00b0C) EMCCD iXon3 897 camera (Andor Technology; Belfast, UK).", "SUPER template experiments: Plots in Fig. 1F , 3H, and 5C display n = 3 independent measurements of SUPER template membrane release at each protein concentration. The indicated p values were calculated using unpaired, one-tailed Student's t-tests. Fig. 4E ,F indicate means. The indicated p-values were calculated using unpaired, two-tailed Student's t-tests." ] },{ "paper_id": "41fc7191573c2f01fdef9c8ebb072e5f54cbb598", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "MAD2 O-C conversion is a key signal amplification step for the mitotic checkpoint.", "Next a mCherry-Mis12-MAD1 CTD4E phosphomimic mutant was prepared and surprisingly found to be also defective in maintaining the mitotic arrest (Fig. S4b) . We reasoned that for a functional mitotic checkpoint in cells one or more of the four residues identified through in vitro kinase assays could not tolerate mutations.", "All rights reserved. No reuse allowed without permission." ] },{ "paper_id": "4380f0251c595d6cb551e643198d2dacd3c6746c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Coronaviruses (CoVs) are enveloped single-stranded positive-sense RNA viruses, which are widely distributed in humans and other mammals. Coronaviruses usually cause respiratory, digestive and nervous system diseases in humans and animals (1) .", "Z test was used to compare AUC between two groups. All tests were two sided and P values < 0.05 were considered statistically significant.", "Of the 3 cases of confirmed case, 2 were male and 1 was female. The age ranged from 39 to 57 years. 2 patients had diabetes and hypertension respectively. 1 was a common case, 2 were severe cases. 1 case had history of Wuhan contact and the other 2 cases had no clear epidemiological history (Table 1 ).", "In this study, we used automated chemiluminescent immunoassay to detect serum IgM and IgG antibodies to 2019-nCoV, to understand the process of antibody production in disease progression, and to evaluate the value of antibody detection in the laboratory diagnosis of COVID-19." ] },{ "paper_id": "43f760b5cb9c3b430c6d0b31fa90d42e71a6429c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "imported and local cases, we assumed that they were infected locally, as it is likely that transmission has 75 been ongoing in Iran for some time (4). 76", "Poisson error structure. See Technical Appendix for detailed description of data and Method 1. 50", ". 29" ] },{ "paper_id": "4485b9462ebf52c0062692d7ab7e423c2ae05d9e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "2 Abstract:", "IgG subclass distribution and binding to membrane-associated gB.", "Assay correlation matrix." ] },{ "paper_id": "44a440cc1c135c938d2216ea672f8ef4f9c01296", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "MicroRNAs (miRNAs) are small regulatory non-coding RNAs, ranging from 19 to 24 nucleotides in length, that post-transcriptionally regulate target gene expression by inhibiting the translation of mRNA transcripts or leading to their cleavage [15] . While encoded not only by cellular genomes but also by viral genomes [ ", "Computational prediction represents a widely used and effective strategy to identify novel miRNAs that can be further examined and validated by experimental approaches.", "Flavivirus conserved 5'-ACAG-3' sequence in the top loop of the 3'SL is indicated by a red bracket. Mature miRNA-MD21 sequences are indicated by a black line next to the sequences." ] },{ "paper_id": "44b6eea3629b4e13595dc49813ee39a0d20dc5f2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Tetherin through its transmembrane domain [32] . In group O the virus adapted its Nef protein 140 to counteract the human Tetherin, albeit with less efficiency than in group M [33, 34] . Notably, a 141 single O strain that uses its Vpu protein to encounter human Tetherin has been described [35] . 142", "Finally, for each such site, the method lists the lineages where the rate shift occurred with the 293 highest probability, and further categorizes each sites as undergoing either a rate-deceleration 294 or a rate-acceleration. 295", "Implications. The compiled list of the positions suggested as rate decelerating can now serve as 254 a guide for future functional studies that aim to understand the differences among HIV-1 and 255 SIV proteins. Furthermore, the ability to track adaptation events by utilizing sequence data 256 highlights the power of the method when studying emerging pandemics, strengthening the 257 need to sequence full genomes of pathogens broadly. 258" ] },{ "paper_id": "45f184e736c4a857bc0e3df0d55962f743c1493a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The sum of the regions therefore contains more exon than case A above.", "Contig2 Contig3", "Ab initio gene", ". CC-BY-NC-ND 4.0 International license is made available under a" ] },{ "paper_id": "4602afcb8d95ebd9da583124384fd74299d20f5b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Influenza A virus has caused four pandemics since the early 20 th century and infects millions of 11", "Cells, plasmids, viruses, and proteins 17", "replicate. Experiment was conducted three times. 10" ] },{ "paper_id": "46030e9b8451bf3b0c90833dbeacce286a263a09", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Participants were not included in the study if they reported previous methamphetamine abuse or dependence.", "All results reported below withstood FDR correction. " ] },{ "paper_id": "4609a2dd3568a7241548b7303e0d836e33d4d5ca", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "462cbb326ccd8587cae7a3538c8c6712d9013698", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Lei, MD have contributed equally to this work.", "(2) shock; (3) other organs failure need intensive care unit (ICU) monitoring and treatment.", "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request." ] },{ "paper_id": "46634d03aa169aab9c372746ebaf3aaa65d7c7d9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "were increase trends at later stage which meant they were smaller than the true T value. 167", "Background: A pandemic of coronavirus disease 2019 which have caused more 24 than 80 thousand persons infected globally is still ongoing. This study aims to calculate its 25 case fatality rate (CFR). 26" ] },{ "paper_id": "47b07518dc0f608e53198bb5f8a95caa1c164fe5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "47f65bff75b7752a38ccbb540fbd74955b3addea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In 1984, a cluster of true appendicitis occurred in a town of 8,000 people in the United States. 31 Thirteen patients of appendicitis occurred during a 3-month period.", "The study was approved by ethic board at participating hospital and Wuhan University School of Medicine, written informed consent was obtained from each patients and the subjects were interviewed since 2005.", "All histologic slides from appendectomy were re-examined in Department of Pathology, Zhongnan Hospital of Wuhan University." ] },{ "paper_id": "48656efc59191537073975938f25f201524971af", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper." ] },{ "paper_id": "48df5b06710467cbe5b41dd851e946fc936ecf15", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "49ac69f362c27acbc6de0c5cbb640267e7a1e797", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nucleic acid tests for SARS-CoV-2 were repeated twice and shown virus clearance before patients discharge or discontinuation of quarantine.", "Pan and ZY Peng are cocorresponding authors.", "The funder of the study had no role in study design, data collection, data analysis and interpretation or writing of the manuscript. The corresponding authors had full access to all the data in this study and had final responsibility for the decision to submit for publication.", "Rationale: In late December 2019, an outbreak of acute respiratory illness, now officially named as COVID-19, or coronavirus disease 2019, emerged in Wuhan, China, now spreading across the whole country and world. More data were needed to understand the clinical characteristics of the disease.", "Abstract: 247 words" ] },{ "paper_id": "4a24fcf8d2a7c69aef247ea12a740145daf68407", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The Singapore Neurologic Infections Program (SNIP) is a prospective cohort approved by the Singhealth Centralised Instituitional Review Board (CIRB Ref: 2013/374/E). The SNIP study aims to describe the epidemiology of CNS infections in Singapore; improve the diagnosis of etiologies of CNS infections through a systematic clinical, laboratory and neuroradiological evaluation and extensive diagnostic testing; evaluate the prognosis, long-term outcomes and socio-economic costs of CNS infections; and establish an archive of biological tissues from patients with encephalitis and CNS infections that can be utilized for future testing for emerging pathogens or non-infectious etiologies.", "The diagnostic and epidemiologic utility of antibody analyses has been limited in large part due to the difficulty in accounting for antibody cross reactivities among closely related organisms 10 . The development of an analytical framework that accounts for potential cross reactivity in pan-viral serological data, and which provides probabilistic assessments of infections, is therefore an important advance. Our current study has demonstrated that AVARDA, when applied to VirScan analysis of longitudinally collected serum samples, can reliably identify evolving IgG responses against specific viruses.", "Subjects were enrolled from 6 hospitals in Singapore (Singapore General Hospital, Tan Tock Seng Hospital, National University Health System, Changi General Hospital, Khoo Teck Puat Hospital, Kandang Kerbau Hospital). Individuals, both male and female, more than one month of age, were enrolled upon admission to the hospital with clinical suspicion for CNS infections, or one or more of the following: Fever or history of fever (\u2265 38\u00b0C) during the presenting illness; seizures; focal neurological deficits; CSF white cell count pleocytosis (> 4 WBC/uL); abnormal neuroimaging suggestive of CNS infection; abnormal electroencephalogram suggestive of CNS infection; depressed or altered level of consciousness, or no alternative etiology for acute paralysis identified. Patients with indwelling ventricular devices such as EVD and ventriculo-peritoneal shunts were excluded from the study. Blood samples were be obtained on enrollment into the study and then at 2 weeks after enrollment or at time of discharge.", "Comprehensive profiling of virome-wide antibody binding specificities has broad utility for epidemiological investigations, surveillance of emerging viruses, and the unbiased diagnosis of infections 1, 2, 3, 4 . Phage ImmunoPrecipitation Sequencing (\"PhIP-seq\") 5 with a peptide library spanning the human virome (\"VirScan\") 6 provides a platform for unbiased, high-throughput, low cost analysis of anti-viral antibodies. While other multiplexed serological techniques exist 7 , each is limited in its representation of viral antigens 8 , the size and quality of the epitopes presented 9 , the per-sample assay cost and/or sample throughput. VirScan provides favorable performance characteristics, but until now interpretation of assay results has been limited by a rudimentary analytical framework." ] },{ "paper_id": "4b1a08339bb5508f830e09f1a2c3a8022526cce0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4b56993a4d0f091e70ef5dec2e5a61c3043f752e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "There are two main approaches to predict protein structures: homology modeling and de novo structure prediction. They differ in such that homology modeling requires structural knowledge about a homologous protein for its prediction while de novo methods do not. This limits the", "As a consequence, knowledge about the structure of a protein helps to gain a deeper understanding about its behavior. This can be particularly useful, e.g., in the development of new vaccines and drugs for new viruses such as Novel Coronavirus (2019-nCoV) [3] - [5] , as the surface proteins of a virus determine how it will interact with a person [6] , [7] . Therefore, it is fundamentally important to be able to accurately predict the 3D structure of a protein.", "For an \u03b1-helix which centers around the z-axis, we can use Equation 2 to model its shape where the variables s and r represent the initial shift and rotation of the helix. The values 2.11 and 1.149 are constants that define the radius and pitch of the helix to best match those of an \u03b1-helix.", "The functionality of our new DeepTracer is explained in the Methods section. In the Results section, the DeepTracer is applied on a test set of 30 density maps in order to assess and compare its accuracy with other methods. The implications of the project and possible future work is examined in Discussion. Finally, we recapture our findings in the Conclusion section." ] },{ "paper_id": "4b57ff228e46255a0ba7114af86ff26af4152d9b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Casd1 knock-in mice were generated at the BWH Transgenic Core facility. The resulting chimeric mice were crossed into C57BL/6NTac (Taconic) and interbred to homozygosity.", "The Casd1-deficient mice were viable and fertile. The Casd1 knockout colony was maintained by homozygous mating. Each experiment was performed at least twice on three mice each.", "RESULTS", "They were then crossed into (B6.C-Tg(CMV-cre)1Cgn/J mice, (stock # 006054, Jackson Laboratory) to obtain the Casd1 tm1b null allele, which lacks exon 2 of Casd1. Excision of the neomycin expression cassette (Fig 1A) was confirmed by PCR. The following primers were used for genotyping. The wild-type allele was specifically amplified using TCCTCCCTCACTGTTCCTTC and AGGTGGGGAGGAAAGACAGT (291bp) and the Casd1 tm1b allele could be selectively amplified using TCCTCCCTCACTGTTCCTTC and GACAGCCAGTCACACAGCTT (5540bp). This allele was interbred to homozygosity to yield Casd1 tm1b/tm1b mice (referred to as Casd1-KO mice in the accompanying figures)." ] },{ "paper_id": "4b5ba0d8c476c899a79cec7872f7d2287937a59d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4b8bdaf9670d7c24f952ca38bfe6c699152421b7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Here, we analyse pairwise viral sharing using a novel, conservative modelling approach 61 designed to partition the contribution of species-level traits from pairwise phylogeographic 62 traits. This method of analysis stands in contrast to previous studies of mammalian viral 63 sharing which have mainly focussed on host-level traits, and importantly buffers against 64 certain inherent biases in the observed viral sharing network, including host sampling bias, 65 when making predictions. 66 ", "orders, but not between orders. The trend line and 95% confidence intervals are derived from a linear 702 model fitted to the data. The trend lines and 95% confidence intervals were derived from a linear mixed model fitted to the 723 data. 724 725 . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/732255 doi: bioRxiv preprint", "Previous investigations into pairwise determinants of viral sharing have been limited to one 47 or two host orders (e.g., bats 17,18 , primates 19 , ungulates 16 , and carnivores 14,16 ), while 48 sometimes lumping together different types of pathogen (e.g., helminths, viruses, and 49 bacteria). Viruses are sometimes shared across large host phylogenetic distances (e.g., Nipah 50 virus in bats and pigs, among many others 20,21 ), requiring a broader understanding of viral 51 sharing across mammals to predict patterns at different taxonomic and geographic scales. In 52 addition, many mammalian orders have yet to be investigated in these analysesmost 53 notably rodents, which are highly diverse and host important zoonotic viruses 5, 8 . In addition, 54 although phylogenetic and geographic viral sharing effects have been empirically 55 demonstrated, the models have not yet been applied to validate viral sharing predictions using 56 external datasets or make inferences about mammals with no known viral associations. If 57 geographic and phylogenetic effects on viral sharing are as ubiquitous as they seem, these 58 variables alone could provide a useful baseline model of viral sharing applicable across the 59 mammal class." ] },{ "paper_id": "4bc43084ccdb8d3bb704ca577473169cd1a64f9c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(1)" ] },{ "paper_id": "4bd697fdded7ee65154e28def586a7e9b60e7078", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "control strategies. The outbreak patterns in these provinces thus may provide crucial information for the control of COVID-19 outbreaks in other countries.", "where -. is the probability that an individual who infected others was infected by a patient who infected individuals. The basic reproduction number \u211b \" is the dominant eigenvalue of . The average number of secondary infections is calculated from data is 1.53. The next generation method gives \u211b \" = 1.54. Thus, the correlation of secondary infections has negligible effect on \u211b \" .", "is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.02.26.20028431 doi: medRxiv preprint" ] },{ "paper_id": "4c24ee4a86de1d5207d93ce39132f7b660cf82e0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Microbial metagenomics studies overcome enrichment biases common to traditional culturing approaches 6 ; however, they usually depend on expensive and stationary equipment, highly specialised operational training and substantial time lags between sample preparation, raw data generation and access.", "We show that nanopore sequencing can identify human pathogen community shifts along rural-to-urban transitions within a river reach, as illustrated by downstream increases in the abundance of pathogen candidates.", "R9.4 MinION flow cells (Oxford Nanopore Technologies) were loaded with 75 \u00b5l of ligation library. The MinION instrument was run for approximately 48 hours, until no further sequencing reads were collected. Fast5 files were basecalled using Guppy (version 3.15) and output DNA sequence reads with Q>7 were saved in fastq files." ] },{ "paper_id": "4c35605124dd8011395240fac71e80b52ddbbe7e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "With both likelihood and prior from iteration t, the expected probability that c j belongs to haplotype H i at iteration t + 1 can be calculated as likelihood * prior, that is", "Step 1: estimate the number of haplotypes via contig alignment", "This work is supported partially by Michigan State University and City University of Hong Kong.", "3.1.1 Data simulation HIV haplotype construction There are many sequenced HIV strains in the HIV Sequence Database (Foley, Brian and Leitner, Thomas and Apetrei, Cristian, 2018) . However, many of the strains do not possess sufficiently high similarity to be included in simulated quasispecies. Thus, we use both real and simulated strain sequences to simulate haplotypes of high similarity. Simulated strains were produced by mutating, deleting, or inserting bases at random positions from a real strain in the HIV database." ] },{ "paper_id": "4c84d1153daa335f5ff6d61db665024b32ac8195", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(1,023) death cases, and 80.9% mild cases among 44,672 confirmed cases. 51.4%", "All antibodies were obtained from BD Biosciences (San Jose, CA, USA). Two 100-\u03bcL samples of blood were placed in two tubes for staining according to mmanufacturer's manual.", "After this procedure, 1 mL of red-cell lyses buffer was added to each tube and incubated for 10 minutes and then washed with Sorvall cell washer (Thermo Fisher Scientific, Waltham, MA, USA). Cells were then resuspended in 350 \u03bcL of phosphate-buffered saline and acquired with the use of FACSCanto\u2122 flow cytometry; daily quality control and assurance were carried out with the use of seven-color setup beads (BD Bioscience, San Jose, CA, USA)." ] },{ "paper_id": "4ce668fe6eee9f59ed5ad0dfc0e9787777acd3be", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4d1090e239baa1ea54af521f4b8bd8b5ab51fd35", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "r(t) = u n t n + u n-1 t n-1 + \u2026 + u 1 t + q (polynomial function)" ] },{ "paper_id": "4da8a87e614373d56070ed272487451266dce919", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Protein reference database For the analysis of human clinical samples, we use a custom reference database that combineds viral, bacterial, human and mouse RefSeq proteins. All viruses are used (ftp://ftp.ncbi.nlm.nih.gov/refseq/release/ viral/viral.1.protein.faa.gz) as well as all the bacteria of the human microbiome, according to ftp: //ftp.ncbi.nih.gov/genomes/HUMAN_MICROBIOM/Bacteria/all.faa.tar.gz.", "The posterior probability of the model M k is:", "P (X) = w P (X|w)\u03c0(w)dw", "Alphaproteobacteria --10 28037", "Streptococcus mitis --8 562" ] },{ "paper_id": "4e2bc97a6164191ba3d53abfa49ccd973aa80326", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Logistic regression analysis showed that baseline NLR (odds ratio [ ", "Heatmap depicting the correlations between inflammatory markers and CT characteristics (within the red dotted box). It shows the correlation coefficients r with P < 0.05 of all pairs. It can be observed that C-reactive protein and CT severity score had the strongest correlation. CT, computed tomography.", "There were 87 (61.7%) patients with 4 to 5 lobes involved, with a median of 9 segments involved. Most lesions were bilateral (87.2%) and peripheral or mixed distributed (98.6%). The main CT characteristics of patients with NCP included GGO, GGO with crazy-paving, consolidation, and GGO with consolidation, ranging from 29.8%~95.7% (Table 1 ; Figure 2 a-f). Other infrequent features included discrete nodules, lymphadenopathy, and small pleural effusion. Compared with stable group, patients in progressive group had more lobes and segments involved, higher proportion of crazy-paving sign, and higher CT severity score (all P < 0.05; Figure 3 a).", "There were some limitations in our study. First, our study retrospectively included 141 patients with moderate NCP on admission from one single city outside Wuhan. Data from multiple cities are needed to further validate our findings. Second, dynamic inflammatory indexes and treatment during hospitalization were not included in the analysis. More comprehensive investigation of the relationship between CT characteristics and cytokine storm induced by COVID-2019 needs to be performed." ] },{ "paper_id": "4e3f4e31c370281c2d721d6113265c25d9c566c5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sequence ( " ] },{ "paper_id": "4e7cd4e923777d6caaa76bb2b93f6121bcd5b6a3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sequencing was carried out in both directions directly from PCR-amplified DNA on the ABI PRISM 3730 (Applied Biosystems) sequencer using ABI PRISM\u00ae BigDye\u2122 Terminator v. 3.1.", "Genomic sequences were assembled using SeqMan software (DNAstar, USA).", "Overall, the ALSV nuORF encoded 132 amino acids. According to the prediction, this protein may have an N-terminal signal sequence and three transmembrane regions with a Cterminal tail, thus making the nuORF product a small membrane protein ( Figure 5A ).", "The specimens after ultracentrifugation were adsorbed onto Formvar film attached to 200-mesh nickel EM grids and contrasted with 2% uranyl acetate (Nikitin et al., 2015) . The grids were exposed to UV light for one hour to inactivate the virus, air-dried and examined in a JEOL JEM-1400 transmission electron microscope (JEOL, Tokyo, Japan) operated at 80 kV. Images were acquired with an Olympus Quemesa digital camera using iTEM software (Olympus Soft Imaging Solutions GmbH, Munster, Germany).", "The pellet obtained following ultracentrifugation of culture supernate was dissolved overnight in borate saline buffer (0.05M H 3 BO 4 , 0.12M NaCl, 0.24M NaOH), pH 9.0 (BSB), at 4 \u00b0C. A portion of the dissolved pellet was applied to a sucrose density gradient (15-60%) and centrifuged at 30,000 rpm for 4 h at 4\u00b0C using an SW-40 rotor in the Optima L-90K Ultracentrifuge (Beckman Coulter, USA). To identify resultant density gradient fractions containing virus particles, aliquots of each fraction were subjected to RT-PCR and sequencing of amplified products as described below." ] },{ "paper_id": "4eb8b7fd0032816e4a29d65b06939266d6446624", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The Adeno-associated viruses (AAVs) were generated at Penn Vector Core, University of Pennsylvania (serotype 8, 10 13 genome copies/mL, 1:2 dilution with sterile PBS on the day of injection).", "Sniffing behavior was monitored in freely moving mice using a plethysmograph (Emka Technologies). Electrical signals were amplified using RHD 2132 amplifier boards (Intan Technologies) and band-pass filtered (1-30 Hz).", "Odors were delivered using an 8 channels olfactometer (Automate Scientific)." ] },{ "paper_id": "4ed084719f40fac25989dbc99d08c2c609b33289", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "G4 formation may be largely affected by G/C content, which greatly varies in viral genomes (from 76% of Cercopithecine 2 herpes virus to 27% of Yaba like disease virus).", "Overall, we generated 10,000 independent sequences for three different simulated datasets, one for each island length.", "Orange and blue box plots refer to positive and negative strand respectively.", "The evidence provided here, the previous studies on G4s in viruses, and the possibility to correctly classify the majority of viruses based on their G4 features (Table 3) suggest that most of the virus classes adopted G4-mediated mechanisms to control their viral cycles." ] },{ "paper_id": "4f1c22de2d2e0b3f2a12bf2a557d429d3ae31a5b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "4f392ef1aa2234dda52ab8e6540f275322a20697", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The density of three IBV S bands, corresponding to S0, S2 and S2', was measured and the percent for each band was calculated from the total S for each treatment condition.", "Bands were visualized using the Licor Odyssey CLx and quantified using Image Studio software." ] },{ "paper_id": "4f5901d41427c10d4dafdc6d3cef2dd20bba871a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "6 . CC-BY 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/742122 doi: bioRxiv preprint", "8 . CC-BY 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/742122 doi: bioRxiv preprint Table S3 for model details.", "14 . CC-BY 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It ", "Wrightian fitness (Eqn. S3). We let a strain's absolute Wrightian fitness be w = n /n, which measures the fold increase in absolute abundance of the strain over the course of an experiment. A genotype becomes more abundant if w > 1 and less abundant if w < 1. When convenient, we also analyzed Malthusian fitness m = ln w." ] },{ "paper_id": "4f8d24c531d2c334969e09e4b5aed66dcc925c4b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The technical parameters included 64-section scanner with 1 mm collimation at 5 mm intervals. All CT examinations were performed with the patient in the supine position and with breath-holding following inspiration, without administration of contrast material. Images were obtained with both mediastinal (width 350 HU; level 40 HU) and parenchymal (width 1500HU; level -600 HU) window settings.", "Points from all zones were added for a final total cumulative score, with value ranging from 0 to72 ( Figure 1 ).", "Continuous variables were expressed as median (interquartile range, IQR) and compared with the Mann-Whitney U test or Wilcoxon test; categorical variables were expressed as number (%) and compared by \u03c7 2 test or Fisher's exact test if appropriate." ] },{ "paper_id": "500c5ea0961b573ba5355d364ca94c00a0a26e4a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "11 12 Keywords: 13 dengue virus; zika virus; yellow fever virus; flavivirus; NS1; caveolin-1; chaperone caveolin 14 complex; viral protein trafficking; unconventional secretion; mosquito cells 15 16 17 ABSTRACT 18 Dengue virus (DENV) is a mosquito-borne virus of the family Flaviviridae. The RNA viral genome 19 encodes for a polyprotein that is co-translationally processed into three structural proteins and . CC-BY 4.0 International license is made available under a", "172 Thus, the effect of the HSP90 inhibitor geldanamycin (GA) in NS1 release from DENV infected 173 C6/36 cells was tested. As shown in Figure 3E , NS1 secretion was not affected after GA 174 treatment. The expected reduction in virus yield observed in GA treated cell (Fig 3F) show that 175 effective GA doses were used. These results indicate that the effect in NS1 secretion observed 176 after FKBP52 silencing is not related with HSP90 activity and was rather associated with the", "164 The expression of FKBP52 in C6/36 cells was knock down by siRNA transfection. Optimal gene 165 knock down was achieved after 48h post transfection (Fig 3A) . The effect of FKPB52 reduced 166 expression in cholesterol and lipid metabolism was evaluated measuring the lipid droplet 167 counting per cell and a reduction of about 50% in the number of lipid droplets was observed after 168 the treatment (Fig 3B) . In cells treated with siRNA FKBP52, a significant reduction in NS1 of 169 about 20% secretion was observed ( Fig 3C) . Viral release was not affected by FKBP52-knock 170 down (Fig 3D) . Given that FKBP52 is a co-chaperone of HSP90 [17,23], we wanted to discard if 171 the observed inhibitory effect on NS1 secretion might be related to a reduction in HSP90 activity." ] },{ "paper_id": "50688ca74af7fb4395c03e3cf7ec3bddc84e6165", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This discrepancy is partly due to the difficulties posed to tracking ccfRNAs from transcriptional 42 source to potential sites of action in-vivo. Indeed the tools available to study ccfRNAs in 43 physiological settings are limited and very few studies attempt to tackle this problem directly.", "90 91", "Results" ] },{ "paper_id": "50aa3305f87a409bd1601bdec5d3cd404fe825a3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The nucleotide sequences were compared with those of the reference strains available in the NCBI GenBank using BLAST tool available at http://www.ncbi.nlm.nih.gov/blast then analyzed for their respective genotypes.", "The authors declare no conflict of interest." ] },{ "paper_id": "50ed5cabf8d74c2a700184f876ad15de2239adfa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "333 In order to produce histidine tagged SFTSV Gn glycoprotein, a ligand for surface plasmon 334 resonance analysis, a Gn-C\u03ba with six carboxy-terminal poly-histidine residues was designed 335 and produced as described above. ", "330 Subsequently, influenza hemagglutinin (HA) tag sequence (YPYDVPDYA) was introduced 331 to the C-terminus of the Fc region of human immunoglobulin heavy gamma1 and the whole 332 protein, designated as Gn-Fc-HA, was produced as described above.", "In the stem region, replacing the cystine residues (C349, C356, C376, and C381) 211 reduced the relative reactivity by more than 80%. This observation was consistent with a 212 previous report that the structural stability of Gn was disrupted by a C356A mutation [29] ." ] },{ "paper_id": "510ecab01c66bc2a911abcf67451ec482ed18a05", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The disease has rapidly spread from Wuhan to worldwide 1 . On January 30, the World Health Organization has declared the COVID-19 outbreak as a public health emergency due to this rapid infection spreads. However, as one of the major cities imported passengers from Wuhan in China 9 , the regional characteristics of COVID-19", "Coronavirus; Novel coronavirus (2019-nCoV); COVID-19; Chongqing; Clinical characteristics Introduction:", "Background" ] },{ "paper_id": "5129bb31949c66ebd544658c531004046d4102da", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Continuous variables were expressed as medians with interquartile ranges (IQR).", "Categorical variables were expressed as numbers and percentages in each category.", "Data are presented as medians (interquartile ranges, IQR) or N (%)." ] },{ "paper_id": "518b635f78bdc65dc6666380eafc3b7a283b3af7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "526c800695643e303ad5671d00693dd0f9b84eb0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "52a8089242fbe484e537cd8ea5c0c9ec3bf32150", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Many viruses including alpha-and gammaherpesviruses, influenza A virus, and SARS 28 coronavirus induce widespread mRNA decay through the use of virally encoded endonucleases 29", "To identify transcripts that escape degradation from all 4 endonucleases, we performed 112 hierarchical clustering on the transcript expression data. Figure 1E shows a heatmap of the 113 correlation matrix across all transcripts. A cluster encompassing 75 transcripts (Table S2 ) 114", "and reactivated for 72h. Supernatants containing GFP expressing KSHV virions were collected 198 and used to spinfect 293T cells (Fig. 5B) . 24h later, we observed a higher number of GFP KSHV life cycle, we next assessed whether C19ORF66 also affects viral gene expression. 202" ] },{ "paper_id": "530f3ba1a2c044305d73123fd8d2246f63120bc3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This is a descriptive study.", "In terms of parental education level, 345 (46.9%) had a junior high school or lower education, 276 (37.6%) had a senior high school or vocational college education, and 114 (15.5%) had an undergraduate or postgraduate education. In terms of family income, 300 (40.8%) had an annual income of less than $5000, 241 (32.8%)", "Eighty-one percent of those hoping the medicines could be delivered were from rural areas or were patients from other provinces (Fig. 2) ." ] },{ "paper_id": "532dc582abd41e833303742ca40976db63fe6fc1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "KSHV SOX was codon optimized for Sf9 expression and synthesized from GENEWIZ.", "3'", "SOX was then subcloned using restriction sites BamHI and SalI (New England BioLabs) into pFastBac HTD. This vector was modified to carry a GST affinity tag and PreScission protease cut site as described (31). All SOX mutants were generated using single primer site-directed mutagenesis (32). Sequences were validated using standard pGEX forward and reverse primers. Generation of viral bacmids and transfections were prepared as described in the Bac-to-Bac\u00d2 Baculovirus Expression System (Thermo Fisher Scientific) manual. After transfection, Sf9 cells (Thermo Fisher Scientific) were grown for 96 hr at 22 \u00b0C using SF-900 SMF media (Gibco) substituted with 5% fetal bovine serum (FBS) and 1% antibiotic antimycotic (AA). Supernatant was transferred to a 6-well tissue culture plate containing 1 ml of 2x10^6 cells/well. Cells were incubated for 96hr to generate Cleaved protein was concentrated to ~ 1 mL using Amicon filter concentrator membrane cut off 30 kDa (EMD Millipore), then loaded onto a HiLoad Superdex S200 pg gel filtration column (GE Healthcare Life Sciences). Protein elutions were concentrated using an Amicon concentrator described above to 5 mg/mL and aliquots were snap frozen in liquid N 2 and stored at -80 \u00b0C." ] },{ "paper_id": "53326420d7eb607538a248c0da27d3b092f651e2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "( A ), date of first flight cancellations 18 . No change was considered for the other countries ( = constant over time), as no restrictions of travel were established towards these countries. The scale parameters of the exponential functions ( @ '() , @ '45$ , A '() , A '45$ , = ) were assumed to be different among the three sources, to account for different traveling volumes and dates of beginning of importations.", "(2), cJP05 (2), cJP07 (2), cSG03 (2), cSG05 (2), cSG06 (2), cSG07 (2), cSG08 (2), cSG10 (2), cSG12 (2), cTH01 (2), cTH02", "(2), cTH03 (2), cAE01(****) \u00a7 Cluster associated to two traveling cases *The index case was identified independently from secondary transmissions **The index case was either:" ] },{ "paper_id": "53442eacc3f233078507fa37b78267399e8c1e3b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The Vero cell line (ATCC, USA) (kidney cells from an African green monkey) was cultured using complete Dulbecco's modified Eagle's medium (DMEM) (Fisher Scientific, USA). DMEM was supplemented with 10% fetal bovine serum (FBS), penicillin (100 units/ml), streptomycin (100 mg/ml), 10 mM Hepes, and 2 mM L-glutamine (Fisher Scientific, USA). The cells were cultured at 37 o C with 5% CO 2 conditions and passaged every second or third day for experimental assays or when the cells reached over 80% confluency.", "Significantly expressed genes were assessed for pathway enrichment using DAVID release 6.7", "(https://david.ncifcrf.gov/) and Ingenuity Pathway Analysis (http://www.ingenuity.com/products/ipa) (QIAGEN, Redwood City). The significantly enriched canonical pathways were defined as having a q-value of <.01.", "Benjamini and Hochberg procedure [24] was applied to adjust for multiple hypothesis testing and differential expressed gene candidates were selected with a false discovery rate of less than 0.10. For visualization of coordinated gene expression in the samples, a hierarchical clustering with the Pearson correlation distance matrix was performed with differential expressed gene candidates using the Bioconductor gplots package (version 2.14.2) in R." ] },{ "paper_id": "536dc3fc3226429da5bf028cc5563bf9ac5b6311", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ ", -and its median aggregates were calculated (Fig.1) . It was observed that ,manifests a random fluctuation around a constant center. It is reasonable to assume that is a constant. The estimation of currently (Feb 10) is 0.904. A future diagnosis number formula is obtained based on this estimation: ", "In December of 2019, the increasing number of patients with pneumonia of unknown cause emerged in Wuhan, the capital of Hubei province, Central China. Most of the early patients had directly or indirectly related to wild animal source in the seafood and wet animal wholesale market through epidemiological survey [1] [2] [3] [4] [5] . Then laboratory tests found that the infection was caused by a novel coronavirus (now named as NCP 6-7 ).", "We obtain this elegant formula with both curve plot visualization and mathematical intuition. We plot ln (Ni/Ni-1) against time (Fig.3 ). First few observations showed a linear decay of spread rate. However, later data points realized us at Feb 4 that it is an exponential decay. Later data points further confirm our model. " ] },{ "paper_id": "537009c0181c3269f40753f75ddca4d17ae8abae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The average CR is shown in Table 1 .", "The authors declare no conflict of interest." ] },{ "paper_id": "54122e9771f67d234bdcc67172a788bc96eec34e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Two previous studies have suggested that reovirus limits the innate immune 287 response. Reovirus can inhibit IFN production by sequestering IRF3 into viral factories 288 (39). Additionally, reovirus can inhibit IFN signaling by nuclear sequestration of IRF9, 289 which functions with STAT1 and 2 to promote expression of IFN stimulated genes (40). 290", "Pathogens therefore have evolved mechanisms to limit its activity. Infection with human 258 coronavirus causes a loss of both IKK\u03b2 and NEMO through an unknown mechanism 259 (30). The MCMV protein M45 targets NEMO for autophagolysosomal degradation (31). 260", " 18 " ] },{ "paper_id": "541777e512aa3907a9db91cde5207a07eabde5ef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Blood samples were collected from gilts at 48 h postnatal. A 22 g x 1.5-inch needle and a 3 ml 125 serum Vacutainer \u00ae (BD Life Sciences) tube was used to collect blood by jugular venipuncture.", "2 postnatal diet. 3 4 Running Title. Effect of diet on lipidome of perinatal vagina 5 6 Summary sentence. Vaginal swab lipidome profiles at 48 h reflect the fat composition of 7 neonatal diet during first two days postnatal.", "While our previous studies supported the potential of using biological material obtained from 85 vaginal swabs to distinguish between gilts exposed to different nutritional environments the first The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. Three to four gilts were selected per litter from eight different sows which were monitored 102 during parturition (Supplemental Figure S1 ). Immediately after delivery, all gilts were towel-103 dried, weighed, and placed in a holding cart until at least three gilts above 1.3 kg were delivered." ] },{ "paper_id": "541e7d329fa466fe7b961263666386dddec75894", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "However, outbreaks with high overdispersion are often shorter with a smaller final epidemic size, but by chance, can also be long with a very large number of cases (Web Figure 2) .", "Recrudescence of EVD cases has been problematic in the field, as for example, there were three EO declarations in Liberia before the outbreak was actually over (16) .", "as expected, assuming perfect isolation of past cases leads to shorter waiting times.", "where is the typical infectivity profile of a case at time , which can be described by the probability distribution of the serial interval." ] },{ "paper_id": "54ae20515fcef8417e255b19df1a5bf6f2ab40bb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The 95% confidence intervals (95%CI) of R0 and k are calculated by using the profile likelihood estimation framework with a cutoff threshold determined using a Chi-square quantile [10] .", "Furthermore, we consider four 'what-if' scenarios and they were \u2022 scenario (0): the best-fit model, i.e., baseline scenario;", "\u2022 scenario (1): 1000 susceptibles were removed on February 11, 2020;" ] },{ "paper_id": "54cfc3c68e1e4832fee5b3294e5673e37978ebdf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The laboratory data of 85 patients at admission were collected. Laboratory assessments consisted of complete blood count, blood chemistry, coagulation test, liver and renal function, C-reactive protein, procalcitonin, lactic acid, cardiac markers.", "large-sample cohort studies are still needed to verify this in the future." ] },{ "paper_id": "54d2fd5689ac3255e8041c36b5fb333a3bd3f9b2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "These functions could be better described this way. The average K value as of day t,", "The graphs below show the computed values of / *** (t) and 0 *** (t), respectively, plotted over time. For the complete data generated, see the Appendix." ] },{ "paper_id": "5502de277b6ee34f29d813cc49d7cda1168c202d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5507325ad63261970f22c625abcfa59f99e24efd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Magnetic protein A beads were incubated with 2 \uf06dg anti-FLAG (Sigma) or anti-eIF2\u03b1 (Santa Cruz) antibodies in IP buffer (10 mM HEPES (pH 7.5), 150 mM NaCl, 0.1% Nonidet P-40 (NP-40), 1x complete protease inhibitor cocktail, RNase inhibitor) at 4\u00b0C for two hours. Excess unbound antibody was removed by washing the beads twice in IP buffer for 5 minutes. Cells transfected with or without 2-5A for three hours were lysed in 10 mM HEPES (pH 7.5), 10 mM NaCl, 2 mM EDTA, 0.5% Triton X-100, 1x complete protease inhibitor cocktail and RNase inhibitor for 7 minutes while rotating, at 4 \u00b0C.", "Lysates were clarified at by spinning at 10,000 x g for 10 minutes and incubated with antibody-bound beads for two hours at 4 \u00b0C. After two hours, beads were subject to 5 x 2 min washes with IP buffer. RNA and protein from inputs, supernatants (unbound) and", "IPs were analyzed using qPCR, western blot and mass spectrometry, respectively." ] },{ "paper_id": "552548a4e9a576953acad9fa549ec4d796fe52c9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Seeds of hybrid sweet corn variety Hawaiian supersweet #10 were provided by UH seed lab, HI (Agricultural Diagnosis Service Center); seeds were sown in Sunshine#4 soil mix in 20 cm pots (1 seed/pot) -experiment was conducted in 2017 at Pope Greenhouse, College of Tropical Agriculture and Human Resources, University of Hawaii at Manoa. Fourteen strains of C. m. subsp. nebraskensis (S1 Table) were grown on YSC medium (yeast extract 10 g/L, sucrose 20 g/L, calcium carbonate 20 g/L and agar 17 g/L) and incubated at 26\u00b0C (\u00b12\u00b0C) for 3 days; bacterial cells were harvested by flooding each plate with 5 ml of PBS buffer (pH 7.0). Corn plants (V-3 developmental stage) were inoculated using the dropped-wounded protocol described by Ahmad and collaborators [24] with a minor modification -the third leaf of each plant was wounded half way between the sheath and the tip by making a cut across 3 veins on one side of the midrib; immediately after wounding, 10 \u03bc l of inoculum was dropped on to the wound using a plastic dropper. Negative control plants were inoculated with 10 \u03bc l PBS (mock inoculated). Inoculated plants were covered with a plastic bag for 24 hours to increase the humidity to facilitate infection. Leaf samples from inoculated plants were collected 30 days post inoculation (dpi); DNA was isolated from each sample using the Wizard \u00ae Genomic DNA Purification Kit according to the manufacturer's instructions.", "Real-Time qPCR is a powerful and robust technique and offers greater sensitivity and speed compared with conventional PCR; however, qPCR sensitivity can be compromised as a result of poor primer thermodynamics. Primer thermodynamics can be improved by adding 5' AT-rich sequences often called overhang, flap, or tail [16, 17, 18] ). In addition, primer Tm and length can also be fine-tuned to harmonize the amplification reaction conditions [16, 17] . The tailed primers have been reported to provide higher PCR yields and sensitivity [16, 17, 18] . Unfortunately, the underlying mechanism behind the action of flap primers is still unknown." ] },{ "paper_id": "5570cb9ff2905fda60cfd6e94f3c32774b765265", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5585d267f9b505b068f9f72bff5f12c248472f0a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "China need to respond based on current actual infections and predictions based on the estimates. Joint efforts need to be done by whole society in order to control the epidemic.", "Comprehensive Meta Analysis Software V2.0 was used. Based on the number of current people stay in Wuhan, we quickly estimated the outbreak size.", "This estimate is consistent with 21,022 (11,090-33,490) total infections from Jan 1 to 22, 2020 estimated by Read and colleagues [7] and 75,815 individuals (95% CI 37,304-130,330) as of Jan 25, 2020 by Joseph's team if progression of the epidemic was accounted for [8] , but it is much higher than the number that Chinese authority reported." ] },{ "paper_id": "558d318e1655da9f5e9507ccf24fc773a0d377ff", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ ".", "For pioglitazone studies (in a different cohort of mice, Table S6 ), we assessed caloric intake and body weight to ensure pioglitazone treatment did not have adverse effects.", "In the puzzle box assay, we found that one week of pioglitazone treatment decreased (improved) time to perform task in GluN1 mice in Trial 1 (training, p=0.011) and Trial 4 (longterm memory, p=0.017) ( Figure 6 , Panels C and D)." ] },{ "paper_id": "55e0d20b6cc56c2cdc131e1dcc51f752575cf532", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "the transcription machinery. These results mechanistically uncovered how the steps of pause-30! release and termination maintain transcriptional memory over mitosis.", "Subsequently, the number of reads in a given region was counted as fraction of total uniquely 634! mapping reads in the PRO-seq data. ", "! ! 2! Summary 18!" ] },{ "paper_id": "564f8823050b52b5f5c36638ac1ae07557963f36", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "56a81431a148344381a1da80c877885f3f3d6d59", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We correlated the ONT sequencing data with the Illumina datasets as previously described [104] using the wub package (v.0.2) [105] . The genome coverage of sequencing datasets were generated using bedtools genome coverage (v2.27) [106] and visualised via J-Circos (v1) [107] . Log2-fold ratios were calculated using DeepTools bamCompare (v.2.5.1) [108] .", "zoonoses that primarily impacts immunocompromised, young, and pregnant individuals [2] , and is thought to infect a third of the world's population [3] . The pathogenesis of apicomplexan infections is intimately linked to the parasites' life cycles. The life cycle of most parasitic apicomplexans is complex, involving multiple differentiated forms and hosts, and this requires reprograming of the parasite transcriptome.", "Gene set enrichment analyses were carried out by ranking the genes based on their alternative splicing levels and using the first and third quartile of the ranked list as input for GO enrichment analysis via ToxoDB/PlasmoDB based on curated and computed assigned associations. We required the adjusted p-value to be smaller than 0.05 and FDR q-value of less than 0.25. This approach was validated using GSEA via WebGestalt [112] ." ] },{ "paper_id": "5796fdc80a85b6e634a279c57711356055b65880", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "First considers the kindergarten and school closure time. The assembly of youngsters in a compact environment increases the risks of virus exposure. Evaluation of children and adolescents' transmission risks is of particular interest in determining school closure duration and children's wellbeing and education [2] . Public disclosure information indicates that children with 10 years of age or younger have higher risks of infection than slightly older adolescents. Therefore, local kindergarten and primary schools should postpone their admission and regular operation, to at least not earlier than local secondary schools.", "+ These first authors contributed equally to this article BACKGROUND As of February 29, 2020, nearly 80 thousand confirmed novel coronavirus (SARS-CoV-2) infection cases had been reported in China. Risk factors for transmission remain largely uncharacterized. The reproduction of infection can be characterized in two major scenarios, i.e., within-households and between-households [1]. Within-household transmission provides important information of infections cross age groups and genders. Estimation of the within-household transmission for SARS-CoV-2 is particularly important for disease control to characterize whether household contact might be driving the outbreak. If it transpires that virus is prone to transmit to a particular age group or gender, then special measures can be taken to control the transmission [2]. This study describes the transmission of the virus within households and close contacts.", "Our results suggest that male family members are the primary sources of infections in the family. As shown in Table 2 , the proportion of male to female transmission in household is 44.0% (253 in 574 cases with disclosed information, with 98 husband-to-wife cases, 89 son to parents cases, 61 father to children cases and 24 brother to brother/sister cases), higher than cases of transmission from female to male cases (19.0%, with only 28 wife-to-husband cases) and between the same genders (36.9%). " ] },{ "paper_id": "57e01ad2a4961cd5cc6a3733f5f8c013a8946f3c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "57eb12d93057a4bc1a043420327251b2327c9b39", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We used this ensemble to derive a distribution of outbreak sizes and durations.", "and T.C.P. contributed to concept and design, analysis, interpretation, revising, and final approval. a." ] },{ "paper_id": "58bc0f2712ea1ced1f886c9fdd17b8cf014e66cb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(2)", "We apply the restrictions i \u2208 [0, 1] and \u03c9 i \u2265 0.", "Baseline parameter values are summarized in Table 1 " ] },{ "paper_id": "594d23a412649df7dbfef5347a2a0c208ed4417d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The methods for these procedures are conducted as described in the Supplemental Appendix.", "Background The outbreak of COVID-2019 is becoming a global public health", "As of Feb 29, 2020, more than 80000 cases have been confirmed in China and other countries, including South Korea, Japan, Italy, and Iran. This global public health emergency is attracting most concern throughout the world." ] },{ "paper_id": "598b8f280571ace476ad56a469e7959918fa7958", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "22", "Tilorone is a 50-year-old synthetic small-molecule compound with antiviral activity that is 23", "In recent years we have witnessed major Ebola virus outbreaks in Africa, the Zika 33 outbreak in Brazil and now the novel coronavirus (2019-nCoV) in China. These viruses 34 are rarely confined to their original locations and thus create challenges in containment. 35" ] },{ "paper_id": "59eab95c43fdea01481fdbf9bae45dfe28ffc693", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Counts of single cells were downloaded, and subsequent data analyses were performed using the Seurat 3.0 package 15 , including data normalization, high variable feature selection, data scaling, dimension reduction and cluster identification. We also used SCANNER 16 to assist the data visualization and cell type identification.", "There is no direct involvement of human subjects in this study. All the data use existing deidentified biological samples and data from prior studies. Therefore, ethical oversight and patient consent were not handled in this project. Figure Figure 1 . ACE2 gene expression profiles in groups." ] },{ "paper_id": "5a425d474d13cbcfc448f36de539d4a679f7b618", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5a5a7b6d40c4b752aabf69f69bbd7c71e2658e8e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We introduced a new framework for analysing individual level surveillance data and found that in 208", "which is attributable to a seasonal or holiday effect. 491 " ] },{ "paper_id": "5a843f4299b04090ff76451decfe9f0b025cfe48", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "{(p, {(s, {bases in s covered by p}) for all s in d}) for all candidate probes p}.", "We represent a set of taxa and its target sequences with a dataset d, with its own set of parameters \u03b8 d . Let {\u03b8 d } be the collection of \u03b8 d across all d. We wish to find S({\u03b8 d }), the union of s(d, \u03b8 d ) across all datasets d. CATCH finds this by solving a constrained nonlinear optimization problem:", "where \u03b8 di is the value of the ith parameter for d and \u03b2 i is a specified coefficient for that parameter.", "Sequencing of patient samples has revolutionized the detection and characterization of important human viral pathogens 1 and has enabled crucial insights into their evolution and epidemiology [2] [3] [4] [5] [6] . Unbiased metagenomic sequencing is particularly useful for identifying and obtaining genome sequences of emerging or diverse species because it allows accurate detection of species and variants whether they are known or novel 1 . However, in practice its utility is often limited because of extremely low viral titers, e.g., as seen in the recent Zika virus outbreak [7] [8] [9] , or high levels of host material 10 . The low ratio of viral to host material results in few viral-derived sequencing reads, which can make genome assembly, if even attainable, prohibitively expensive. To fully realize the potential of metagenomic sequencing, we need new tools that improve its sensitivity while preserving its comprehensive, unbiased scope." ] },{ "paper_id": "5a9164999237a46d3d6aed53bd59b17d91a9e6d0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5b1a2b3207e3f674b94f6f271b92c29f3a8a6754", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Among the 41 patients, 10 patients have underlying complications, as shown in patients.", "Objective: To investigate the correlation between clinical characteristics and cardiac injury of COVID-2019 pneumonia.", "The authors declare no competing financial interests.", "Recently, a pathological study of COVID-19 showed that few monocyte cells were found in myocardial interstitial, however, no inflammation cells were observed in myocardial tissue [8] ." ] },{ "paper_id": "5b27a16123f46b5aaeda3171d22e075dcbd36ee6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "On the other hand, Quercetin is a flavonoid extensively found in many fruits, vegetables, leaves and grains, which have been used as an ingredient in supplements, beverages, or foods.", "Currently we are focused on optimizing various conditions which would allow atomic resolution studies on the structures, dynamics and inhibitor design for Zika NS2B-NS3pro by NMR spectroscopy [27] [28] [29] [30] . ", "Zika virus was originally isolated from a sentinel rhesus monkey in the Zika Forest of Uganda in 1947 (1) , which is transmitted to humans by Aedes species mosquitoes. Since 2007, large epidemics of Asian genotype Zika virus have been reported around the world (2) (3) (4) ." ] },{ "paper_id": "5b9a15ad62b0e85fcb5012e7e08e5183b4da786b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "137 Screening and eligibility determination:", "60 pandemic. We conducted a comprehensive review of such ZIKV prediction studies and 61 evaluated their aims, the data sources they used, which methods were used, how timely they 62 were published, and whether they provided sufficient information to be used or reproduced by 63 others. Of the 73 studies evaluated, we found that the accessibility, reproducibility, timeliness, 64 and incorporation of uncertainty in these published predictions varied and indicates that there 65 is substantial room for improvement. We identified that the release of study findings before 66 formal journal publication ('pre-prints') increased the timeliness of Zika prediction studies, but" ] },{ "paper_id": "5ba386b58c8d194e8cbe581eed95f7c64d05cd53", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To characterize the relative strengths of these promoters, we assembled a panel of 14", "Since sgRNA targeting has variable efficiency 18 This is in accordance with the inefficiency of the mScarlet sgRNA targeting (Fig. 5f ).", "EBOV is encoded by ~19 kbp negative sense single stranded RNA genome that contains 3' non-coding regulatory leader (ldr) and 5' non-coding regulatory trailer (trl) sequences. These sequences flank a large central region that encodes seven distinct proteins (nucleoprotein, NP; 35 kDa phosphoprotein/polymerase co-factor, VP35; 40 kDa matrix protein, VP40; surface glycoprotein, GP; 30 kDa phosphoprotein/polymerase co-factor, VP35; 24 kDa regulatory protein, VP24; and a large RNA dependent RNA polymerase protein, Lpol) (Fig. 7a ).", "In light of these limitations, several strategies have been developed to streamline the assembly of different parts in the construction of DNA vectors for mammalian biology [1] [2] [3] [4] [5] [6] [7] . Notable among those is the Gibson modular assembly platform (GMAP) 7 , a framework for DNA vector" ] },{ "paper_id": "5bb89950ec5a06e2b7f69b2a9c4213dda19b1ab0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Since January 23, 2020, all provinces across the country have adopted strict isolation and precautionary measures, and Wuhan has closed all public transportation facilities. China's response to the epidemic is mainly divided into three stages: the first stage is to control the source of infection and block transmission around key areas in Hubei Province such as Wuhan; the second stage is to actively treat confirmed patients, reduce mortality, and prevent Export; the third stage is to reduce the epidemic situation, thoroughly control the disease epidemic, and significantly reduce the contact rate between people. In this paper, the trajectory of the curve is Therefore, local governments and public health departments should focus their efforts on controlling the source of infection and cutting off the transmission channels, such as early detection, early isolation, and early treatment, to reduce the gathering of large groups of people, and to regularly and completely kill public toilets and public spaces." ] },{ "paper_id": "5bbc428de7fc2f10c24d8439edda26d84b319687", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The reproduction number .", "is 10 times the average number of confirmed cases from Day 0 to Day 7 and \u07db \u0d4c 1 0 . 9 1 obtained from the collected data described ahead.", "The maximum likelihood method is used to estimate model parameters where the likelihood is obtained by sequential Monte Carlo method, and parameters are estimated using the Iterated Filtering algorithm (IF2) 9 implemented as mif in the R package pomp 10 with \u0735 \u123a 0 \u123b equals the population of the region," ] },{ "paper_id": "5c31897d01f3edc7f58a0f03fceec2373fcfdc3d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "is the (which was not peer-reviewed) The copyright holder for this preprint .", "is the (which was not peer-reviewed) The copyright holder for this preprint . " ] },{ "paper_id": "5c525cc04075b7c82e52b1e80d96bb394b1a0907", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We define the vaccination reproduction number (Rv) for a given effective vaccination coverage level (v) as follows:", "In January, the mean R was estimated at 2.2 (3.9, upper bound of 95% confidence interval), with each infection on average resulting in two or more infections [1]. Although cases of asymptomatic transmission have been documented [2,3], the World Health Organization advises that transmission is still primarily driven by symptomatic patients [4] .", "Where b is the transmission rate and q is a parameter ranging from 0 to 1 that models the relative infectiousness of individuals during the incubation period of the disease." ] },{ "paper_id": "5cf2bec1530cef38cd0eea173fb90ba1a788e11f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "[2012] did not benefit fully from the potential SNR advantages of the 7T scanner.", "All subjects were scanned at the National Magnetic Resonance Research Center (UMRAM) in Bilkent University, using a 3T MRI system (Siemens Magnetom Trio, Germany). A 32-channel head coil was used for data acquisition. The MRI protocol was composed of a T1-weighted sequence, a high-resolution susceptibility-weighed imaging (SWI) sequence and a high-resolution DWI sequence, described next.", "Hz/pixel; parallel imaging, GRAPPA with an acceleration factor of 2 along the phase-encoding direction. It is important to note that only the subcortical region was covered during the SWI acquisition, not the whole brain. The total acquisition time was approximately 5 min." ] },{ "paper_id": "5cfb44ecdfb61b2898b6cf7315b1e810874a9560", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Importantly, this approach assumes that none of the observed cases remains infectious and that there are no patients who are already infected but are pre-symptomatic. This may be a reasonable assumption if transmission primarily occurs when patients are symptomatic and if symptomatic patients are quickly quarantined. However, until there has been a substantial gap in time (at least one serial interval) since a patient is quarantined this assumption cannot be validated. This approach also does not account for the possibility of symptomatic cases that remain unobserved. Further, subcriticality in one subpopulation does not imply subcriticality in other populations. In addition, if the capacity for isolation is exceeded due to an excess of imported cases, subcriticality now does not imply subcriticality in the future.", "Here we present a simple analysis for monitoring the upper bound of estimates for R in settings where there are very few cases of disease. This has immediate relevance to the 2019-nCoV virus, but can also be applied to other infectious diseases in the early stage of an epidemic. We focus particular attention on the threshold at which epidemic transition appears possible." ] },{ "paper_id": "5d3612cd95331a2f0c43ef9d03ce583b5ff8c995", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Six independent studies (GSE37758, GSE73395, GSE89809, GSE63127, GSE97010, and GSE14700), covering healthy volunteers, COPD patients, asthma patients, smoking individuals were collected from GEO data repository (https://www.ncbi.nlm.nih.gov/geo/). The samples consist of lung tissues, bronchoalveolar lavage, bronchial epithelial cells, small airway epithelial cells, and SARS infected cells.", "In conclusion, 2019-nCoV infection is a serious public health problem, endangers human health seriously. Due to the strong human to human infectivity, it needs to be further studied. Our current study found that there was no significant difference in Note all results are based on data mining, thus, further experiments are needed." ] },{ "paper_id": "5d768aca47f1452fd3e3d2c246926b8532ca1c87", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nevertheless, as only two droplets are needed to confirm a sample as positive with ddPCR, this 397 method could confirm the status of samples found to be negative by real-time PCR due to high 398", "The data acquisitions and data analyses were performed using Bio-Rad CFX Manager, v 3.0. 170" ] },{ "paper_id": "5d9e490190986584d799e2828c6fd9679e5ae159", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Genes in this list include HERC5, IFI6, IFIH1, MX1, NLRC5, OAS2, OASL, and PARP12.", "This study aimed to identify IFN-stimulated transcripts in the viral reservoir P. alecto.", "Heatmaps. Heatmaps were constructed using GENE-E and Morpheus, both available at https://software.broadinstitute.org. Nanostring analysis. Total RNA was isolated from IFN-treated samples as described above.", "Transcriptional analysis revealed over 100 genes induced in response to IFN\u03b1. Most of these genes have been previously described as ISGs, suggesting strong evolutionary conservation of the ISG pool, as would be predicted by previous genomic studies of immune genes in P. alecto (11, 16) ." ] },{ "paper_id": "5daceb492bad28a61fc43c4be83a164042d8c430", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Immunofluorescence experiments were performed using \u00b5-Slide 8 Well Chamber 294", "Rotavirus (RV) replicates in round-shaped cytoplasmic viral factories although 37 how they assemble remains unknown. 38" ] },{ "paper_id": "5f06ba54c9208857d92abfd16488c44217f8d726", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For expression in HEK293 cells, all plasmids encoding opsins and fluorescent proteins were constructed by subcloning into an empty pCMV vector unless otherwise noted. pCMV-PsChR-Venus and pCMV-C1V1-Venus were obtained from H. Yawo (Tohoku University). bReaChES-TS-eYFP was isolated from pAAV-CaMKIIa-DIO-bReaChes-TS-eYFP gifted by K. Deisseroth (Stanford University). A full-length gene encoding BeGC1 (accession number KF309499) was synthesized after human codon optimization and inserted into the peGFP-N1 vector. For expression in primary cultured neurons, the bReaChES-TS-eYFP fragment was subcloned into an empty pCAG vector. For AAV production, pAAV-Ef1a-DIO-bReaChes-TS-eYFP was obtained from K. Deisseroth (Stanford University) and pAAV-hSyn1-SIO-stGtACR1-FusionRed was obtained from Addgene (#105678).", "All values are expressed as mean \u00b1 SEM. Statistical analyses were performed using one-or two-way ANOVA followed by Bonferroni's multiple comparison tests or Dunn's multiple comparison tests vs. the control with GraphPad Prism or Igor Pro, unless otherwise noted.", "For immunostaining of cultured neurons, fixed neurons were washed three times with 1% bovine serum albumin (BSA) and 0.25% Triton-X in PBS (blocking buffer), and then incubated with primary antibodies (anti-GFP, mouse monoclonal, 1:1000, Wako; anti-c-Fos, rabbit polyclonal, 1:1000, Santa Cruz Biotechnology) in blocking buffer for 24\u221248 h at 4\u00b0C. The fixed neurons were washed three times with blocking buffer and then incubated with secondary antibodies (CF594 donkey anti-rabbit IgG, 1:1000, Biotium; CF488A donkey anti-mouse IgG, 1:1000, Biotium) overnight at 4\u00b0C.", "We have here demonstrated the feasibility of a novel, scintillation-mediated optogenetic technology that allows fully wireless control of neuronal activity in behaving animals. The scintillator crystal was biocompatible and safely implantable for long periods. Thermal effects on neuronal activity were negligible using this technology, a significant advantage over conventional (22, 23) and NIR-mediated (9, 10) optogenetics. Given the deep tissue penetration of X-rays ( Fig. 1A) , scintillation-mediated optogenetics can be readily applied to larger animals including monkeys. Future innovations and technical advances, such as minimizing the size of the implanted scintillator crystals, or reducing the dose of X-rays through the use of pulsed and targeted X-ray irradiation, should further enable manipulation of neuronal functions with less invasiveness.", "Thus, scintillation-mediated remote optogenetics can be used for bi-directional neuronal actuation deep in the brain of mice, resulting in behavioral changes." ] },{ "paper_id": "5f6a410a4ba086b296100a8a5a10df59eb337c90", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "5f72fd41d7ba8d4d7de7aa1f83fc5c90ffa50b03", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The estimators as in (3) can also be viewed as a penalized version of local constant kernel smoothing estimator [41] . We utilize a modified version of the fast iterative soft thresholding algorithm (FISTA) [42] to solve the optimization problem (3).", "To capture both dynamic and sparse structure of the Granger causality coefficients, we solve the following optimization problem:", "where", "Coronaviruses have lead to three major outbreaks ever since the SARS occurred in 2003." ] },{ "paper_id": "5fb2cce255dd56b944ae52cec664bd7f4f222c66", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We display the epidemiological data categorized by the date of confirmation in Table 2 .", "2. There is a = 1 + 2 -day window between infection to detection, including a 1day incubation period and a 2 -day delay from symptom onset to detection.", "The numbers , , and are the observed data used in our model, , , and are the parameters that determine how changes over time.", "A parameter that determines the growth rate of" ] },{ "paper_id": "610549c879c62efc42f2ad32f63c65b25d8931c7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Background The outbreak of the recently emerged novel corona virus disease 2019", "is the (which was not peer-reviewed) The copyright holder for this preprint ", "is the (which was not peer-reviewed) The copyright holder for this preprint CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity." ] },{ "paper_id": "6186828135d9e5e7e50f66567505d02e910b3ee2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "618cd102ec5051a05ca5131e21961c964152f15c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Adenoviruses in bats, which are known to be natural reservoir of many viruses, using the results 33 of recent screenings for prevalence of these viruses in 33 European bat species. Our aim is to 34 find association between Adenoviruses prevalence and biological and behavioral host traits, 35 considering the heterogeneity both between and within species in order to have a deeper 36 understanding of mechanisms of viral transmission.", "species Pipistrellus pygmaeus, P. kuhlii and Nyctalus lasiopterus and we found that in the latter, 20 males were more likely to be infected by Adenoviruses than females, due to the 21 immunosuppressing consequence of testosterone during the mating season. As a general trend 22 4 29 Author Summary 30 Adenoviruses are DNA viruses with a wide range of vertebrate hosts, including humans, 31 causing ocular, respiratory and gastrointestinal diseases. Here, we focus on the prevalence of 32", "Our results highlight the importance of mating strategy: bats species using swarming as mating 38 strategy are less likely to be infected by Adenoviruses. Moreover, we found that locality of 39 capture can explain a higher prevalence of Adenovirus within species. However, no general 40 pattern has been found in the analysis at individual level, suggesting a strong species specificity 41 and complex viral transmission dynamics. 42 43" ] },{ "paper_id": "620d69e419e3c8756de8bf96d86f6bf0de7ed919", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Terminally anesthetized mice (isoflurane overdose) were perfused with 50 mL of 4% paraformaldehyde (PFA) via intracardiac puncture and tissues were postfixed in 4% PFA for 24 hours. Brain tissue was macrosectioned using a brain matrix, making cuts through the optic chiasm and infundibulum. The resulting tissue block containing the dorsal hippocampus was embedded in 4% agarose gel and sectioned at 70 \u00b5m thickness by vibratome. Free floating sections were blocked in PBS containing 1% BSA, 10% normal donkey serum, 1% FBS, and 0.1% Triton-X 100 for 1 hour, incubated overnight at 4\u00b0C with primary antibody (anti-MCP-1/CCL2: Cell Sciences, CPM001, 1:400 in block), incubated with secondary antibody for 1 hour (donkey anti-rabbit Cy3: Jackson ImmunoResearch, 711-166-152, 1:1000 in block), washed, and mounted in DAPI-containing mountant on charged slides. CCL2 immunoreactivity was imaged with the Zeiss AxioObserver.Z1 and ApoTome.2 structured illumination system (Carl Zeiss Microscopy GmbH, Jena, Germany) using a 20x objective (LD Plan-Neofluar 20x/0.4 Korr Ph 2 M27, 0.55 NA), 538-562 nm bandpass excitation, 570-640 nm bandpass emission, 7 \u00b5m optical thickness, and 300 msec exposure time. For detection of the mCherry fluorophore in CCL2:RFP animals, free floating 70 \u00b5m sections were mounted on charged slides in DAPIcontaining mountant. Fluorescence images were captured with a laser scanning confocal microscope (LSM780, Carl Zeiss Microscopy GmbH, Jena, Germany) using a 40x objective (C-Apochromat 40x/1.20 W Korr FCS M27, 1.2 NA) with water as the refractive medium. Validation of mCherry-specific emission and exclusion of autofluorescence was obtained with spectral imaging using a lambda scan at 488 nm, 561 nm, and 594 nm excitation and 8 nm-stepped emission spectra. 40 \u00b5m z-stacks were acquired with a step thickness of 2 \u00b5m, pixel dwell time of 0.39 \u00b5s, and pinhole equivalent to 1 airy unit across all samples. Uncompressed TIFF-images were exported from Zen software (Zen Black 2012 64-bit, Carl Zeiss Microscopy GmbH, Jena, Germany) and post-processed in ImageJ (ImageJ v1.50b, Wayne Rasband, National Institutes of Health, USA) and Photoshop (Adobe Photoshop CC, 2014 Release, 64-bit). Levels were normalized, when appropriate, equally across images and groups; gamma values were not changed.", ". CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. CCL2 CCL3 CCL4 CCL5 CCL7 CCL9 CCL11 CCL17 CCL19 CCL21A CCL21C CCL24 CCL25 CCL27 CXCL1 CXCL2 CXCL4 CXCL9 CXCL10 CXCL12 CXCL13 CXCL14 CXCL16 CXCL17 CX3CL1 IL1a IL1b IL6 IL11 IL12a IL13 IL15 IL16 IL17d IL18 IL19 IL27 IL33 IFNa1 IFNa2 IFNa4 IFNa5 IFNa6 IFNa11 IFNa14 IFNaB IFNb1 IFNe1 TNFa TRAIL M-CSF OSM LIF ICAM1 ICAM2 ICAM4 ICAM5 VCAM1 PECAM1 CD62L CD62P The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/208587 doi: bioRxiv preprint", "RNA was isolated from the whole brain of mice following perfusion with ice cold PBS using the RNeasy Lipid Tissue Midi Kit (Qiagen, Valencia, CA). RNA integrity, purity, and concentration was assessed using an RNA Analysis kit (Agilent Technologies, Santa Clara, CA). Samples passing quality control were analyzed on Illumina mouse WG-6 v 2.0 expression BeadChips in the Mayo Clinic Medical Genome Facility Gene Expression Core. Expression data were analyzed using Excel and MATLAB, where fold change was calculated and converted to log 2 . Heatmaps and hierarchical clusters were derived using Gitools v2.2.2." ] },{ "paper_id": "62298f90df017016d34e978befc29acbec201ccd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For optimal exploitation of nanoparticles (NPs) in biomedicine, and to predict nanotoxicity, detailed knowledge on the cellular responses to cell-bound or internalized NPs is imperative.", "The fact that many normally 'inert' materials become substantially more reactive when downsized to NPs can be beneficial in nanomedicine, but also give rise to nanotoxicity [1] .", "Finally, the proteins were dissolved in 0.1 M KOH and radioactively labeled leucineincorporation was quantified by \u03b2-counting with a Tri-Carb 2100TR \u00ae Liquid Scintillation Analyzer (Packard Bioscience)." ] },{ "paper_id": "63781701d3aac3b1640caae24b2c8c2a06c8e6ab", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "December 16, 2019 7/15 a CC0 license.", "Stouffer's original model was framed in the context of continuous distribution of 159 population across a landscape. In the present metapopulation context, we therefore 164" ] },{ "paper_id": "63b645b7d8cd2502bedca374d0418486838bf4a0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Due to parameter identifiability, we treated the product 0 TL as one parameter. Moreover, since ( ) yields unphysical results for < 0 , we used the more robust function \u0302( ) for fitting, which contains an additive time-independent fluorescence background parameter :", "We conducted the non-linear least-squares fits using Python with Numpy and Scipy. The analysis scripts are published together with the data (see Data Availability).", "The data and the code for conducting the analysis are available at https://doi.org/10.5281/zenodo.2626006." ] },{ "paper_id": "6445688d3f59cb7e02f2a8b28450cdf118a8a373", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We also analysed the relationship between the density locations participants typically visited and their social contacts. We focused on a subset of the data with participants that had at least 10 recorded GPS locations (n=26,153). We used data from 2011 Lower Layer Super Output Areas for England and Wales, Small Areas for Northern Ireland, Data Zones for Scotland to estimate the population density per square km for each recorded GPS location in our dataset, with density layers matched to GPS location based on whichever had the nearest centroid. We then calculated the mean density across all GPS locations recorded for each participants.", "Finally, we compared reported household size with social contacts for participants that had at least one reported physical or conversational contact (n=40,575). To explore the relationship between household size, average density of GPS tracks and social contacts, we used a generalized additive model [30] . The model was defined as g(E(y)) = b + f (x) + a, where y was the binary outcome variable (i.e. reported contacts made), x was the predictor (i.e. household size or average density of GPS tracks on log 10 scale), g was the link function, b was the intercept, a was age (to adjust for possible confounding), and f was a smooth function represented by a penalized regression spline. Results for fitted GAMs are shown for a = 30.", "Out of all reported contacts in the POLYMOD dataset, 46.3% were physical (involved touch),", "Overall, over 86,000 participants started the survey and filled out their profile. Participants with no encounter or location data were excluded, as were users whose location recordings were all outside the UK. This leaves a rich dataset of around 55,000 participants. Of those, 40,177 completed the study and reported their social contacts at the end of the survey -this is the focus for this paper.", "The data collection process had some limitations. In particular, the initial version of the app had the default age of a contact as 50-years-old. Participants were free to change the value on slider, but if they just clicked through, it would record that contact's age as 50. As a result, the early data had more contacts of this age than was plausible. In our analysis, we therefore remove users with 3 or more contacts of the age exactly 50 (4,007 users dropped). These users together reported 101,880 contacts out of which 24,171 were aged exactly 50-years-old. Second, the initial version did not allow users to record precisely zero contacts: these users may thus be missing from our denominators, we do not expect this effect to be large and for simplicity have not attempted to correct for it here.", "The BBC Pandemic study has the potential to provide extremely detailed insights into patterns of movements and social mixing in the UK, which will be valuable for understanding the dynamics of circulating infectious diseases as well as informing the prevention and control of new outbreaks.", "Information was provided and consent obtained from all participants in the study before the app recorded any data. The study was approved by London School of Hygiene & Tropical Medicine Observational Research Ethics Committee (ref 14400)." ] },{ "paper_id": "64478db449af8e4a5645c17f548649a0159da0c6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Tasmanian devil populations. This is because strong population declines of devils after 45 disease emergence do not necessarily translate into long-term population declines at 46 equilibria. Our modelling approach is widely applicable to other host-pathogen systems to 47 predict disease impact beyond transient dynamics.", "Emerging infectious diseases increasingly threaten wildlife populations. Most studies focus 27 on managing short-term epidemic properties, such as controlling early outbreaks. Predicting 28 long-term endemic characteristics with limited retrospective data is more challenging. We 29 used individual-based modelling informed by individual variation in pathogen load and 30 transmissibility to predict long-term impacts of a lethal, transmissible cancer on Tasmanian 31 devil (Sarcophilus harrisii) populations. For this, we employed Approximate Bayesian 32 Computation to identify model scenarios that best matched known epidemiological and 33 demographic system properties derived from ten years of data after disease emergence, 34 enabling us to forecast future system dynamics. We show that the dramatic devil population 35 declines observed thus far are likely attributable to transient dynamics. Only 21% of 36 matching scenarios led to devil extinction within 100 years following devil facial tumour 37 disease (DFTD) introduction, whereas DFTD faded out in 57% of simulations. In the 38 remaining 22% of simulations, disease and host coexisted for at least 100 years, usually with 39 long-period oscillations. Our findings show that pathogen extirpation or host-pathogen 40 coexistence are much more likely than the DFTD-induced devil extinction, with crucial 41 management ramifications. Accounting for individual-level disease progression and the long-42 term outcome of devil-DFTD interactions at the population-level, our findings suggest that 43 immediate management interventions are unlikely to be necessary to ensure the persistence of 44", "Here we develop an individual-based model to explore the long-term impact of devil The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/392324 doi: bioRxiv preprint 6 (~3 generations) after initial local disease emergence and that the time until death after initial 125 infection may be as long as two years (Wells et al. 2017 ). Therefore, despite high lethality, 126 the rate of epidemic increase appears to be relatively slow, prompting predictive modelling of 127 population level impacts over time spans well beyond those covered by field observations." ] },{ "paper_id": "6499f5c865c3db3bdfc1e969ea940a80d547a5bb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "It is known that the genetic code shows redundancy and most of the amino acids can be translated by more than one codon. This redundancy represents a key step in modulating the efficiency and accuracy of protein production while maintaining the same amino acid sequence of the protein.", "Codon usage patterns of viruses reflect a series of evolutionary changes that enable viruses to shape their survival rates and fitness toward the external environment and, most importantly, their hosts. In the present study, we employed multiple codon usage analysis indices to determine genotype specific codon usage patterns of Zika virus (ZIKV) strains from the current outbreak and those reported previously. Several genotype specific and common codon usage traits were noted in ZIKV coding sequences, indicative of independent evolutionary origins from a common ancestor.", "Zika virus (ZIKV), a member of the genus Flavivirus in the family Flaviviridae, is an enveloped, single-stranded positive-sense RNA virus. Like the closely related Dengue virus (DENV), ZIKA is also mosquito borne, spread by multiple Aedes species. Since its discovery in 1947, previous reports of ZIKV detection have been largely sporadic until the recent and ongoing outbreak of ZIKV in the Americas (Campos et al., 2015) , with a few notable exceptions, including the ZIKV outbreaks in the Yap Islands (2007) (Duffy et al., 2009 ) and French Polynesia (2013 (Cao-Lormeau and Musso, 2014) . The close similarity between the clinical manifestations of ZIKV and those of DENV and Chikungunya virus (CHIKV) remains a potential obstacle to the efficient surveillance and management of ZIKV." ] },{ "paper_id": "64b327001f8fa95b83dc23259a2ad617be12498c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "One unexplored aspect of HIV-1 genetic architecture is how codon choice influences 27 population diversity and evolvability. Here we compared the development of HIV-1 28 resistance to protease inhibitors (PIs) between wild-type (WT) virus and a synthetic 29 virus (MAX) carrying a codon-pair re-engineered protease sequence including 38 (13%) 30 synonymous mutations. WT and MAX viruses showed indistinguishable replication in 31 MT-4 cells or PBMCs. Both viruses were subjected to serial passages in MT-4 cells 32 with selective pressure from the PIs atazanavir (ATV) and darunavir (DRV). After 32 33 successive passages, both the WT and MAX viruses developed phenotypic resistance to 34", "PIs (IC 50 14.6 \u00b1 5.3 and 21.2 \u00b1 9 nM for ATV, and 5. 9 \u00b1 1.0 and 9.3 \u00b1 1.9 for DRV, 35 respectively). Ultra-deep sequence clonal analysis revealed that both viruses harbored 36 previously described resistance mutations to ATV and DRV. However, the WT and 37 MAX virus proteases showed different resistance variant repertoires, with the G16E and 38 V77I substitutions observed only in WT, and the L33F, S37P, G48L, Q58E/K, and L89I 39 substitutions detected only in MAX. Remarkably, G48L and L89I are rarely found in 40 vivo in PI-treated patients. The MAX virus showed significantly higher nucleotide and 41 amino acid diversity of the propagated viruses with and without PIs (P < 0.0001), 42 suggesting higher selective pressure for change in this recoded virus. Our results 43 indicate that HIV-1 protease position in sequence space delineates the evolution of its 44 mutant spectra. Nevertheless, the investigated synonymously recoded variant showed 45 mutational robustness and evolvability similar to the WT virus.", "46 47 IMPORTANCE 48 Large-scale synonymous recoding of virus genomes is a new tool for exploring various 49 aspects of virus biology. Synonymous virus genome recoding can be used to investigate 50 . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/315366 doi: bioRxiv preprint 3 how a virus's position in sequence space defines its mutant spectrum, evolutionary 51 trajectory, and pathogenesis. In this study, we evaluated how synonymous recoding of 52 the human immunodeficiency virus type 1 (HIV-1) protease impacts the development of 53 protease inhibitor (PI) resistance. HIV-1 protease is a main target of current 54 antiretroviral therapies. Our present results demonstrate that the wild-type (WT) virus 55 and the virus with the recoded protease exhibited different patterns of resistance 56 mutations after PI treatment. Nevertheless, the developed PI resistance phenotype was 57 indistinguishable between the recoded virus and the WT virus, suggesting that the 58 synonymously recoded protease HIV-1 and the WT protease virus were equally robust 59 and evolvable." ] },{ "paper_id": "656ef218f7dcea5555a59cdc29d0f9ec8d5c2a82", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CAACCTCAATACAAGCAGAC. The two resulting products were digested with SapI" ] },{ "paper_id": "661003bddb5c847237ff4a1f34a823f7971e2090", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Consequently, we focus on broad generalities that arise from many simulations and illustrate these for a 211 few specific cases, reserving the supplement for further details. The presentation below briefly discusses 212 the individual dynamics of individual trials for illustration but then moves to plots that reveal differences ", "initial resource 2 \u00d7 10 5 , 10 20 * *The higher value of R(0) is used to eliminate it as a basis for viral clearance." ] },{ "paper_id": "671b44ae9bec89cacf7ae9e7b2a79649a9b66773", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Accessed: 2020-01-23.", "[12] Tianmu Chen, Jia Rui, Qiupeng Wang, Zeyu Zhao, Jing-An Cui, and Ling Yin. A mathematical model for simulating the transmission of wuhan novel coronavirus. bioRxiv, 2020. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.01.23.917351 doi: bioRxiv preprint", "We performed stochastic simulations of the first few generations of human-to-human transmission of 2019-nCoV." ] },{ "paper_id": "6726b273f345838661eaa39e8adb5df4e1815a9a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "key words: COVID-19, ACE2, viral spike Receptor Binding Domain, 1 homology-based protein-protein docking, variants.", "Sequences and data retrieval 21 Full genome sequences of 10 Coronaviruses isolates were retrieved from NCBI 22 GeneBank corresponding to the following accessions: AY485277. 1 " ] },{ "paper_id": "672ca9b6e50e26c49fc7be2ef3b4f685badf9db1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 M records migration from one city to another. Movement within a city is not counted, i.e., m ii (t) = 0 for all i.", "\u2022 M is non-symmetric as traffic from one city to another is not necessarily reciprocal at any given time, i.e., m i j (t) m ji (t).", "In the above derivation, we should note that" ] },{ "paper_id": "681c5099b2afb08fe5cb2f58d92e9c6e4873bec2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The main assumptions underlying the model are:", "Using the identities \u2207A(\u03c3) = A(\u03c3) \u03c3 \u2207\u03c3 and \u2207 C(\u03c3) 2 = 2C(\u03c3)C(\u03c3) \u03c3 \u2207\u03c3 and integrating, we get \u03bb as a function of A(\u03c3) and C(\u03c3) up to a constant \u03bb 0 , such that", "Finally, introducing Eqs. S9 and S10 into Eqs. S3 and S4, we can rewrite the normal and tangential force balances (Eqs. S6) as" ] },{ "paper_id": "683416e300a4f4075835852558855b07c342bd72", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "448 MS data were acquired on a Bruker UltraFlex II MALDI-TOF Mass Spectrometer instrument.", "65" ] },{ "paper_id": "685cdc49b5db13ec22f0eda615b026bf59cd23f4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "27", "Both trees and alignments are available from https://github.com/sarisbro." ] },{ "paper_id": "68e509d42a7d3349550512d80eca4e2b2123613f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Firstly, we used Seurat (version 2.3.4) to read a combined gene-barcode matrix of all samples. We removed the low-quality cells with less than 200 or more than 6,000 detected genes, or if their mitochondrial gene content was > 10%.", "This study provides a biological background for the epidemic investigation of the 2019-nCov infection disease, and could be informative for future anti-ACE2 therapeutic strategy development.", "Public datasets (GEO: GSE122960) were used for bioinformatics analysis.", "The expression level of highly variable genes in the cells was scaled and centered along each gene, and was conducted to principal component analysis." ] },{ "paper_id": "68ed7bb581b0cf32116ee46767c08e3180b05c34", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "69008e4d4e158ae9484c3821e4384aa5948c3209", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In less than two months since initially reported in mid-December 2019, the recent coronavirus outbreak in Wuhan has caused more than 900 fatalities associated with severe respiratory disease. The causative agent was identified as a previously unknown RNA coronavirus virus, dubbed 2019-nCoV (for 2019 novel Coronavirus), of the betacoronavirus genus 1 , with 80% similarity at nucleotide level to SARS coronavirus 2 .", "The evolutionary relationships between 2019-nCoV and other SARS/SARS-like viruses was inferred from genome alignment using PhyML (GTR + GAMMA 4CAT) 26 . The same program and model were used to reconstruct the phylogenetic tree of the (potentially recombinant) RBD, using only 3 rd codon positions.", "The recent outbreak of a new coronavirus (2019-nCoV) in Wuhan, China, underscores the need for understanding the evolutionary processes that drive the emergence and adaptation of zoonotic viruses in humans. Here, we show that recombination in betacoronaviruses, including human-infecting viruses like SARS and MERS, frequently encompasses the Receptor Binding Domain (RBD) in the Spike gene." ] },{ "paper_id": "691da9d5576aa959e22114a1ebb35548efd276a0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Infectious diseases occur frequently within last twenty years.", "where A and p are constant, \u03b2 is stretched exponential parameter of values between 0 and 1, E a is the energy barrier for a human to move around, and w is the basic energy that a person may need during a normal circumstance.", "Both equations above are first-order differential equations of standard form:" ] },{ "paper_id": "691f54c001708f6684ae7837adc749fe09404e61", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "160 For Figure 5 (G.L.) The vector was digested with PspXI and Bgl-II. Using forward and 161 reverse PCR primers (Supplementary Table 1), the CCR5 WT, SSM and IFC were all 162 amplified from genomic DNA with enzyme overhangs. These PCR products were 163 subsequently digested and ligated into pSGDlucV3.0. 164 165 Transfections and Dual Luciferase Assays 166 For Figures 4 and 6 (Y.A.K.) HeLa and HEK293T cells were reverse transfected with 167 100 ng of plasmid using 0.2 \uf06dL Lipofectamine 2000 in a 96-well format. Transfection mix 168 was added to 30,000 cells and incubated for 1-2 minutes at room temperature, before 169 adding Fetal Calf Serum. The next day, media was removed from cells and 100 \uf06dL of 170 fresh 1X passive lysis buffer (Promega) was added to each well. Samples were frozen For Figure 5 (G.L. ) HeLa and HEK293T cells were reverse transfected with 25 ng of 174 plasmid using 0.2 \uf06dL Lipofectamine 2000 in a half-area 96-well format. Transfection mix 175 was added to 40,000 cells. The next day, transfected cells were lysed in 12.6 \uf06dL of 1X 176 passive lysis buffer (Promega) and luciferase activity was measured by injection of 20 177 \uf06dL of each reagent. 178 179", "Using BLAST, we first identified orthologues of human CCR5 in the NCBI RefSeq 37 database. Sequences were aligned and, on examining the frameshift region, we 38 observed substitutions in the slippery site sequence which would likely decrease or 39 eliminate frameshifting in related organisms. Indeed, none of the nucleotides in the 40 slippery site are conserved across vertebrates (Figure 1). The predicted frameshift site 41 in CCR5 was previously reported as most highly conserved in primates, except for 42 Lemur catta 3 . Primate CCR5 CDS sequences were aligned and nucleotide conservation 43 was measured at single nucleotide resolution (Figure 2A) and smoothed in a 10 44 . CC-BY-NC-ND 4.0 International license is made available under a", "Background level readings (measured from water transfected cells) were subtracted" ] },{ "paper_id": "69f473aee22a4ac8df15a54a6109b70b1ae9b7e7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Autocorrelation curves from in vitro measurements were fit to a 3D diffusion equation (Equation 1):", "Where N A is Avogardro's number (6.0221413 x 10 23 mol -1 ). Autocorrelation curves from in cellulo measurements were fit to an anomalous diffusion model:", "Where \u03c1 is mean density, which is 1.2 g/cm 3 for proteins." ] },{ "paper_id": "6a8d26d75bd44c7666c9b7ed782c13a57f409122", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The RNA was isolated and assessed for quality and quantity (average yield 275 ng per sample). 1 ng of total RNA was amplified using the SMARter Ultra Low amplification kit (Clontech, Mountain, CA) with PCR amplification to generate sufficient cDNA for library construction. Amplified cDNA quantification was determined with the Qubit Flourometer (Life Technologies, Grand Island, NY) and quality was assessed using the Agilent Bioanalyzer 2100 (Santa Clara, CA). Library construction was performed using NexteraXT library kit (Illumina, San Diego, CA) with 1 ng of input amplified cDNA per manufacturer's recommendations. Nextera libraries were quantified with the Qubit Flourometer (Life Technologies, Grand Island, NY) and quality was assessed using the Agilent Tape Station (Santa Clara, CA). Libraries were sequenced on the Illumina HiSeq2500 (Illumina, San Diego, CA) to generate 20 million 1X100-bp single end reads per sample 35 .", "Sequences were aligned by STAR against human genome version of GRCh38 and normalized to FPKM. We used the following non-specific filtering strategy to remove genes with low expression values indistinguishable from background signal. First, we compute , the 95% sample quantile of the expression level of the th gene, for all genes. Next, we defined trimmed maximum log-expressions as = log 2 ( + 1), and removed those genes with < 0 (or equivalently, < 7.0). After this filtering step, a total of 13,819 genes were selected for further analyses. After removing fifteen samples with total number of mapped reads less than 5 million and ten samples with low average correlation with other samples, 175 samples were selected for further analyses.", "Long established major risk factors for severe illness include prematurity, bronchopulmonary dysplasia, cyanotic heart disease, neuromuscular disease, and immune compromise 4, 10 . However, approximately 70% of hospitalized infants in the US have no overt risk factors for severe illness. Although young age at infection, environmental influences such as tobacco smoke exposure, viral load and strain, low levels of maternally derived RSV-neutralizing antibody, as well as a multitude of genetic host factors have been associated with severe disease in some but not all studies 4,11-22 . likely to play pivotal roles in both eliminating virus replication as well as enhancing or moderating the inflammatory response 31, 32 .", "Objective metrics for data from these samples suggested a high degree of quality (Supplemental Figure 1) , similar to what we have previously published 35 ." ] },{ "paper_id": "6aa2716c00d89f4b760a9167b15d6203303ae6b9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To assess the versatility of this approach, we implemented this multiple blotting scheme for a range of protein complexes, several of which had proven reluctant to the standard vitrification procedure.", "Yeast glucokinase 1 and human inosine-5'-monophosphate dehydrogenase are two key metabolic enzymes involved in carbohydrate and nucleotide metabolism, respectively. These two enzymes self-assemble as elongated homomeric filaments, which can only be structurally characterized by cryoEM due to their repetitive and flexible nature. Although sample availability was not a limiting factor for these two specimens, both proved reluctant to spread over the holes of cryoEM grids. We successfully enhanced particle distribution, following up to three consecutive applications of sample onto the grids, to achieve a particle density that was useful for high-resolution imaging (Figures 3 and 4) .", "Adenoviruses are ~1000 \u00c5-wide non-enveloped icosahedral pathogens involved in respiratory, ocular and gastro-intestinal infections (Veesler et al 2014) . Samples of adenovirus serotype 26 virions showed a low propensity to evenly spread in thin films of suspended vitreous ice, which was problematic because a limited amount and concentration of sample was available for our cryoEM study. Using a double blotting strategy, we were able to overcome this issue, as attested by the densely packed virions in the micrograph presented in Figure 2 , and to collect a large dataset which led to the determination of a structure at 3.7 \u00c5 resolution (manuscript in preparation)." ] },{ "paper_id": "6ad14ceec74dc9b3d3dc6db7fc319b9dc22dc546", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6ae20454d1a9f228864de24660c2460becbc8151", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Essentially nCoV-2019 protease and inhibit its function.", ". CC-BY-NC 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.01.30.927889 doi: bioRxiv preprint ", "SupplementaryMaterial-1.csv: A list of SMILES strings, predicted binding affinities, logP, logS and synthesizability of 319 potential inhibitors of 2019-nCoV 3CL protease, including two anti-HIV protease drugs." ] },{ "paper_id": "6b039b72ca7301c604c743ce7ca3e2c4f5659068", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Tamoxifen free base (Sigma T5648) was dissolved in 100% ethanol (200mg/ml) at 55\u00baC and added to pre-warmed sterile corn oil (ThermoFisher S25271) to make 20mg/ml frozen stocks.", "Freshly dissected muscles were kept moist, coated with O.C.T. compound, snap-frozen in liquid nitrogen-cooled isopentane, and stored at -80\u00baC until sectioning. 12\u03bcm cryosections were mounted on slides and air-dried before staining or storage. Sections were used for H&E staining [41] or picrosirius red staining.", "EDL muscles were excised from deeply anesthetized mice with 3% isoflurane, hung from a computer-controlled servomotor (300B, Aurora Scientific, Inc), and mounted in a heated (30\u00baC) oxygenated tissue bath containing a physiologic salt solution as described [52] . Experiments were performed and data were analyzed using DMA software (Aurora Scientific, Inc) and Prism 7 (Graphpad), as previously described (Treat-NMD SOP, DMD_M.1.2.002 and [53] )." ] },{ "paper_id": "6bdd6867205d9b09f833f01c65f1bbfdae469164", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6c3e940e2848827af17dd23005a9dee8ac0cd349", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Prime/MM-GBSA approach was used to calculate the free energy of binding for XP docked complex. This method was utilized as described previously by Sharma et al., (2017) (17) . MM/GBSA is an empirical scoring that approximates the ligand binding affinities with the receptor. Following equation is used for calculating the free energy of binding-\u0394G (bind) = E_complex(minimized) -(E_ligand(minimized)+E_receptor(minimi zed)" ] },{ "paper_id": "6c91b00faa16142426820016ad3a7847fc77c8e4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "MacrovascularEndo.", "OtherEndo." ] },{ "paper_id": "6cb02c7565f6f74a3d165e14196de5e9e87d2d04", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6cbefcf4c0fbb8466db7d00b8f53e1f37a6bf8b5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\"At first, we are going to each and every household\u2026but this time it's not often.\" HSA,", "For instance, there were 31 Viral Hemorrhagic Fever cases recorded in DHIS2 in 2015, but none confirmed by the department." ] },{ "paper_id": "6cf87a546884756094da0d300e85a061c2cc43ea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The study was approved by the instututional of research ehtics committee of the Third People's Hospital of Shenzhen ([2020-063]).", "All patients were treated in isolation. Medicines for treating COVID-19 include oseltamivir, ribavirin, interferon, kaletra and traditional Chinese medicine.4 patients (15%) were treated with interferon alone and 1 patient (4%) was treated with kaletra alone.26 patients discharge (13.6\u00b11.03 days on average) or improvement after treatment.", "Program(6th edition) issued by the National Health and Health Committee of China [5] .", "All data used during the study appear in the submitted article.", "We reviewed 26 cases of children(>1 year old and <14 years old) in the Third People's Hospital of Shenzhen from January 16 to February 8, 2020 . Diagnosis of" ] },{ "paper_id": "6d0127f985edbe088bc279865bef25a31f54a066", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Chi-squared test was used to compare any two data sets, and data were considered significantly different if the two-tailed p value was less than 0.05.", "The SARS-CoV-2 reference genome Wuhan-Hu-1 (NC_045512) and WIV04 (MN996528) was downloaded from the GenBank database. Other newly sequenced 2019-nCoV genomes were downloaded from the Global Initiative on Sharing Avian Influenza Data (GISAID) database (https://www.gisaid.org/). Twenty-one closely related coronavirus complete genome sequences and their coding sequences (CDS) were downloaded from GenBank database (Supplementary Table S1 ).", "Statistical analyses were performed using the R statistical package (version 3.", "Different organisms, even different protein coding genes of the same species, have different frequency of codon usage (16) . The RSCU bias will reveal the difference of the host source. We calculated the distance of RSCU between spike genes of 20 representative coronaviruses and" ] },{ "paper_id": "6d1b40bcdde63e22931509db389c6bf1949901dd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Our findings motivate future studies to screen phage-displayed peptide libraries against individual CF patients for personalized medicine strategies.", "To measure transport of our peptide conjugated nanoparticles in individual representative patients, we selected two patients that presented similar porosities (Fig. 7E ).", "Unless otherwise indicated, data are presented as mean \u00b1 standard deviation. All statistical analyses were performed using GraphPad Prism 8 (GraphPad Software, La Jolla, CA), at a significance level of p \u2264 0.05, and are indicated in each figure legend.", "(TUP) motifs [97, 98] ; peptide sequences that appeared in the search were excluded from subsequent analysis. These databases have identified a large set of sequences with undesired proliferation advantages and false positive target-unrelated peptides." ] },{ "paper_id": "6d3b3f4ab80a61c45f82c61c6c756cfc6ddf4bf2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "6efe01046ce81279412ea440a4b246f942f29124", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The common characteristics of the exclusion criteria are: severe and critical patients with COVID-19; pregnant and lactating women; allergic patients; patients with serious heart, brain, kidney, tumor, hemoglobin disease and other diseases; patients with mental disorders, drug abuse or dependence history; those who do not get informed consent; the researchers think the subject is not suitable.", "In terms of trial stages, 20 trials are exploratory studies or in the preliminary experiment " ] },{ "paper_id": "6f53b9dff58818839c45410d11b58f0f3e327d8a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We have also assumed independence between risk factors but the logistic regression assumes the same. Therefore, the impact is not expected to be significant.", "Since late December 2019 a new epidemic outbreak has emerged from Whuhan, China. Rapidly the new coronavirus has spread worldwide. China", "Since this is an in-progress situation, CFR value is naturally uncertain, which undermines all parameters computed from this value, and naturally, the results obtained herein suffer from this fact.", "Thus, our main goal is to establish the odds ratio for COVID-19 mortality, adjusted to age and gender-specific prevalence of the morbidities reported in the CDC paper 11 , namely hypertension, diabetes, cardiovascular disease, chronic respiratory disease and cancer." ] },{ "paper_id": "6f8a531b4b84d4daaadcff9d7e03ee24274baf0b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Clinical data: 374", "To address these challenges, we developed IDseq, a cloud-based open-source 90 bioinformatics platform and service for detection of microbial pathogens from metagenomic 91 next-generation sequencing (mNGS) data. IDseq requires minimal computational hardware and 92 is designed to enhance accessibility and build informatics capacity in resource limited regions. 93" ] },{ "paper_id": "70c7260fc0702bd4a554421ac68972c991313e56", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Muc4 drives sex-based difference in weight loss 81", "Muc4 has been detected in synovial sarcomas in humans, thus presenting a novel tissue Screening genetically diverse mouse models provides an opportunity to identify natural 163 variation in novel factors which drive viral disease responses. These studies can also provide 164 therapeutic, prophylactic and molecular insights into emerging pathogens, which are difficult to 165 study during the context of an outbreak. Here, prior phenotypic QTL analysis, bioinformatics, 166", "we built a framework to integrate knowledge about the preCC genome sequences and a partner 185 microarray dataset to narrow a QTL region down to a likely candidate based on expression 186" ] },{ "paper_id": "70cc2e5152d3dc4d44494124ff556c9bbe9e6f41", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this 190 manuscript.", "\uf0d8 The SD of the D-dimer is 3.25." ] },{ "paper_id": "7116ddab89281e7641fb659019c90ee3715f5039", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The bacteria present in the lungs of patients with persistent bacterial bronchitis were less 39 diverse in terms of richness and evenness. The results validate the clinical diagnosis, and 40", "suggest that more attention to bacterial communities in children with chronic cough may lead 41 to more rapid recognition of this condition with earlier treatment and reduction in disease 42 burden. 43", "Adonis showed significant differences in community composition (R 2 = 0.082, P = 0.001). 189", "Persistent bacterial bronchitis is a leading cause of chronic wet cough in young children. This 20 study aimed to characterise the respiratory bacterial microbiota of healthy children and to 21 assess the impact of the changes associated with the development of persistent bacterial 22 bronchitis. 23" ] },{ "paper_id": "712f1a74a5083d690832eed5fd9ff16a04434d8d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "COVID-19 is difficult to diagnose early in infection as patients can remain asymptomatic or present with non-specific flu-like clinical symptoms including fever, cough, or shortness of breath." ] },{ "paper_id": "7207df5b61e93fa5a2b6e720c91aed05270e81be", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7325363d061f0f4699e29bfa544438e14e7c207d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7344c6de7ce2258e74ce131bed72e6ad465f0ce8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As R 0 increases from 1, p (\u221e) increases from zero and saturates at a large R 0. When R 0 is larger than 2.5, more than 90 % of people in the group are ", "By using R 0 , Eq. (7) is rewritten as", "Thus, Eq. (8) is derived.", "The above information helps greatly to understand the to-be-planned analysis of COVID-19." ] },{ "paper_id": "734779fad93249a2f6fede6afd10eeff7b37919b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We thank Marie Killerby and Amber Haynes for their helpful comments on early versions of this manuscript.", "Author contributions. SMK conceived of the study, conducted the analysis, and wrote the manuscript. CT conceived of the study, conducted the analysis, and wrote the manuscript." ] },{ "paper_id": "736b4793b11d01f4b55ea53eaf59f7325493b27b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The majority of responders (62%) would be likely or very likely to shun someone with the disease; while 21% were neutral in response. When asked about a family member with EVD, 24% were neutral, and 35% likely or very likely to shun their family member.", "Responders obtained their information from various media sources. Media coverage can have a great impact. Governments may therefore use this route for dissemination of clear, accurate information during outbreaks (19) .", "Design and Methods: A cross sectional study whereby respondents (n = 920) were sampled from public places. Data were collected via interviewer administered questionnaires. Data were analysed using SPSS version 23.", "Objective: Health system resilience and resilience of a country include the capacity of health personnel, institutions, and populations to prepare for and effectively respond to crises. This study investigates the knowledge and attitudes of the public concerning Ebola Virus Disease in Trinidad and Tobago.", "The University of the West Indies, St. Augustine, Trinidad and Tobago Ethics Committee granted ethical approval for this study (Reference: CEC063/11/15)." ] },{ "paper_id": "7395de48b2402e5e1561a93b99e8aae8728c6ff1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This confirmed the specificity of the in vitro ubiquitination assay. Finally, to see if TRIM25", "Step qRT-PCR Kit (Life Technologies) following the manufacturer's instructions on a Roche 480 LightCycler.", "Immunoprecipitation was performed as described above. Following the final wash proteins bound to beads were incubated with Ube1, His-Ube2D3 and ubiquitin (UBPBio). 1 mg/ml Ube1, 2 mg/ml His-Ube2D3 and 50 mg/ml ubiquitin was used for TRIM25 autoubiquitination. 5 mg/ml Ube1, 10 mg/ml His-Ube2D3 and 250 mg/ml ubiquitin was used for ZAP ubiquitination. The reactions were carried out at 37C for 1 hour or as indicated and were stopped by addition of loading buffer and reducing agent. The protein ubiquitination was analysed by Western blot with anti-TRIM25 or anti-ZAP antibodies." ] },{ "paper_id": "73998a3f565b661816d48aa7c20fa5ae617864d5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As an angiotensin-converting enzyme (ACE) homologue (19, 20) , ACE2 is a zinc metallopeptidase that catalyzes the conversion of angiotensin I (Ang I) and", "External data sources: GSE97693 and GSE81861 were used for bioinformatics analysis. The reads or fragments per kilobase per million mapped reads (RPKM or FPKM) or transcripts per million mapped reads (TPM) were retrieved from GEO database(https://www.ncbi.nlm.nih.gov/geo/). In GSE97693 dataset, only TPM data were used for analysis." ] },{ "paper_id": "73a954bbd21a08cf0a662b37f1f97989285969c4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "transistor. These results demonstrated that antimicrobial drugs could be modeled with similar input and output characteristics compared to N-type and P-type transistors. heat-triggered, drug-loaded liposomes allow the input bacteria (Bin) to survive (Bout = 1) when the gate signal (G) is low (i.e., G = 0 when temperature < Tcrit). All truth tables depict binary inputoutput combinations.", "To construct bacteria-activated prodrugs, we synthesized cationic (polyarginine) AMPs in charge complexation with anionic peptide locks (polyglutamic acid) by a linker peptide (RRS|RRV) specific for the ubiquitous bacterial protease OmpT 26 . Upon proteolytic cleavage of the linker, the hairpin prodrug is unlocked to release free AMP, creating a mechanism for auto-titration (Fig. 1B) . 10", "While AMP prodrugs eliminate the majority of bacteria, we observe bacteria populations exhibiting a phenotype we named \"defiant\", proliferating in the presence of active drug by consistently outpacing prodrug activation at all stages of growth (i.e., log phase, stationary phase)." ] },{ "paper_id": "73c8af41cfdbf52c0dfba37727e3b94cb56b495e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Wuhan Novel Coronavirus disease outbreak has become a global outbreak which has raised the concern of scientific community to design and discover a definitive cure against this deadly virus which has caused deaths of numerous infected people upon infection and spreading.", "Two proteins: nucleocapsid phosphoprotein and surface glycoprotein, were identified as potent antigens and hence used in the next phases of the experiment ( Table 02 ). The physicochemical property analysis was conducted for these two selected proteins. Nucleocapsid phosphoprotein had the highest predicted theoretical pI of 10.07, however, surface glycoprotein had the highest predicted extinction co-efficient of 148960 M -1 cm -1 . Both of them were found to have similar predicted half-life of 30 hours. However, surface glycoprotein had the highest predicted aliphatic index and grand average of hydropathicity (GRAVY) values among the two proteins (Table 03) .", "Authors received no specific funding from any external sources." ] },{ "paper_id": "73d80c8f5780d70bd8d343188c56e898e91557b6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "One possible explanation is that these mutations impacts the integrity of the FP domain in a manner that hinders virion incorporation.", "Recombinant L-1-Tosylamide-2-phenylethyl chloromethyl ketone (TPCK)-treated trypsin was purchased from Sigma. The protease inhibitor dec-RVKR-CMK was obtained from Tocris. Calcium chelators BAPTA-AM and EGTA were purchased from Tocris and VWR, respectively.", "Image was created using Adobe Illustrator CC 22.1." ] },{ "paper_id": "74b00f19c3af87d1081644f02490ba250f57b7ca", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In silico Molecular Docking:", "Target structure was further optimized and energy minimized using Swiss PDB viewer V.4.1.0 software [53] .", "The four proteins were then analyzed by Vaxigen software to test the probability of antigenic proteins. Protein E was found to be the most antigenic gene with the highest probability as shown in Table 1 . Literature survey confirmed this result in which protein E was investigated in severe acute respiratory syndrome (SARS) in 2003 and, more recently, Middle-East respiratory 1 8 syndrome (MERS) [72] . Furthermore, the conservation of this protein against the seven strains was tested and confirmed through the use of BioEdit package tool (Fig. 3) .", "However, COVID-19 differs from other previous strains in having several critical residues at 2019-nCoV receptor-binding motif (particularly Gln493) which provide advantageous interactions with human ACE2 [15] . This difference in affinity possibly explains why the novel coronavirus is more contagious than those other viruses.", "At present, there is no vaccine or approved treatment for humans, but Chinese traditional medicine, such ShuFengJieDu Capsules and Lianhuaqingwen Capsule, could be possible treatments for COVID-19. However, there are no clinical trials approving the safety and efficacy for these drugs [22] .", "All water molecules and heteroatoms in the retrieved target file 4UQ3 were then removed." ] },{ "paper_id": "74bee8bf3229f4c28991a7231c02d911d24770e9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All volunteers agreed to participate, signed informed consent and the internal use of these samples for diagnostic workflow optimization was according to the medical ethical rules of our institution." ] },{ "paper_id": "75216c0238ddc17dec8ef66adcc84bd48922cae4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Precise estimation of genetic substitution patterns is critical for accurate reconstruction of 18 pathogen phylogenies. Few studies of viral evolution account for variations of mutation rate 19 across a single gene. This is especially true when considering evolution of segmented viruses 20 where individual segments are short, encoding for few proteins. However, the structural and 21 functional partitions of these proteins could provide valuable information for more accurate 22 38 All rights reserved. No reuse allowed without permission.", "The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. Victoria, the dataset finally retained 214 isolates after randomly sampling down to 50% of the 316 All rights reserved. No reuse allowed without permission.", "The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/228692 doi: bioRxiv preprint" ] },{ "paper_id": "754315299d847600d6c5d414665c728d40bf731d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Chinese new year and panic about the lockdown) [14] , which may compromise the antispread effect of such city lockdown measure as to spreads to other cities. To date, information on transmission modes and severity of this novel coronavirus is still limited [15] .", "Operational issues associated with wearing disposable facemasks to maximise their preventive effectiveness should be also publicised and educated to the general public including correct ways of wearing facemask, hygiene practices across the procedure of mask wearing, disposal of used masks.", "However, the mayor of Wuhan later announced approximately five million of residents had left the city ahead of the implementation of lockdown (due to scheduled travel during" ] },{ "paper_id": "75e68869f9b65bca661e768402395d9dede6de2c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The two parameters can be solved from fitting the observed confirmed cases over time.", "Besides the aforementioned variables, we have a composite variable" ] },{ "paper_id": "760481ce5a46e6efa12a80202bbd240dcbefa8fd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7607a4ad84452e29998a80f44bfd6bb2f5f68a7f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Phylogenetic analyses showed that the viruses possessed high homology with the other isolates, and two closest isolates are BetaCoV/Wuhan/IPBCAMS-WH-04/2019 from Wuhan and SARS-CoV-2/NTU01/2020/TWN from Taiwan ( Figure 1F ).", "The BALF was collected from the patient at 1 day after admission. Vero, LLC-MK2 and Huh-7 cells were used for the virus isolation in the biosafety level 3 (BSL-3)", "We observed that the virion particles are roughly spherical or moderately pleiomorphic." ] },{ "paper_id": "77a04c5091c0457ad305691d4d4f24354d6bae79", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Reconstructed density maps and refined coordinates have been deposited in the Electron Microscopy Database (EMDB-0520 and EMDB-0521) and the Protein Databank (6NUR and 6NUS) and will be released upon manuscript acceptance.", "The initial coordinates of rhinovirus serotype 16 polymerase 47 (1XR5.pdb) and SARS-CoV NSP7 and NSP8 15 (2AHM.pdb) were rigid body docked into the map and used as starting models for coordinate modeling. Rebuilding and sequence assignment was performed using Coot 48 . The coordinate models were refined using RosettaRelax 49 and phenix.real_space_refine 50 . Final models were assessed using Molprobity 51 and EMRinger 52 .", "Fractions containing NSP12 were concentrated with an Amicon Ultra concentrator (Millipore Sigma).", "Codon optimized SARS-CoV NSP12 with a C-terminal strep-tag was cloned into pFastBac-HT excluding the vector encoded N-terminal tags. This vector was used to create recombinant bacmids by transformation into E. coli DH10B (Life Technologies). The NSP12 bacmid was transfected into Sf9 cells (Expression Systems) using Cellfectin II (Life Technologies). The recombinant baculovirus was amplified twice in Sf9 cells. 13 mL of the second amplification was used to infect 1 L of Sf21 cells (Expression Systems) at 2.8 \u00b4 10 6 cells/mL and incubated at 27\u02daC for 48 hours. Cells were harvested by centrifugation at 1,000 \u00b4 g and resuspended in 70 mL of 25 mM HEPES pH 7.4, 300 mM sodium chloride, 1 mM magnesium chloride and 5 mM betamercaptoethanol. The resuspended cells were then mixed with an equal volume of the same buffer containing 0.2% (v/v) Igepal CA-630 (Anatrace) and incubated with agitation for 10 minutes at 4\u02daC. The cell lystate was then sonicated before clarification by centrifugation at 35,000 \u00b4 g for 30 minutes and passing through a 0.45 \u00b5m filter. Cleared lysates were loaded onto Streptactin Agarose (Qiagen), washed with same buffer and eluted with same buffer containing 2 mM desthiobiotin. Eluted protein was concentrated and further purified by size exclusion chromatography using a Superdex200 column (GE Life Sciences) in 25 mM HEPES pH 7.5, 300 mM NaCl, 0.1 mM magnesium chloride and 2 mM tris(2carboxyethyl)phosphine." ] },{ "paper_id": "7808e4cd470a379b12470833f4a6fc7e1b567c96", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/460832 doi: bioRxiv preprint", "Recent outbreaks of African swine fever virus (ASFV) in China severely 17 influenced the swine industry of the country. Currently, there is no", "The suids include domestic pigs and wild boars, and were reported as the 48 natural hosts of the virus 4,5 . ASFV was firstly discovered in Kenya in 49 1921 6 . It remained restricted in Africa till 1957, when it was reported in 50 Spain and Portugal. Up to now, the virus has caused ASF outbreaks in 51 more than fifty countries in Africa, Europe, Asia, and South America 4 . 52 The latest reports showed that the virus has caused outbreaks in more 53 than fifteen provinces in China 7,8 . Because of the high lethality of ASFV 54 in domestic pigs, the most commonly used strategies to control the virus 55 were the massive culling campaigns and the restriction of pig movement 5 . 56 Both strategies have resulted in a huge economic loss for pig industry and 57 affected people's livelihoods. Unfortunately, currently there is no 58 available effective vaccine against ASFVs. 59 60 Many efforts have been devoted to developing the vaccine for the ASFV 61 1,5,9-11 , however, most of these attempts failed. One of the most important 62 reasons was the complex composition of the antigenic proteins 5,12 . 63 Previous reports showed that p72, p30, and p54 were the three important 64 antigenic proteins during the infection of ASFVs, but the immunity 65 against them could only provide a partial protection 12, 13 . Many other 66 . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/460832 doi: bioRxiv preprint proteins or other factors such as phospholipid composition may also 67 influence the antigen of the virus 12 . Therefore, it is necessary to 68 understand the mechanisms of the antigen diversity of the ASFV virus 1 . 69 " ] },{ "paper_id": "780fc85ab807f33f706a38c86480e284da800cb8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Notwithstanding the significance of the S protein in viral entry and host 110 immunity, high-resolution structural details of this large macromolecular 111 machine have been hard to acquire. In this study, a cryo-EM structure of 112 SADS-CoV S glycoprotein at 3.55 \u00c5 resolution is determined.", "by the interplay of the viral particle with specific cell surface S trimmer [12] . 78 CoVs from various genera display evident serotypes, for the most part, 79 because of the dissimilarity of their envelope-anchored diversified S proteins. with the assistance of S1 retains a \"lying down\" inactive state, which transits ", "The current outbreak of Coronavirus Disease 2019 (COVID-19) by a novel 28 betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-29 CoV-2) has aroused great public health concern. Coronavirus has a history of 30 causing epidemics in human and animals. In 2017 an outbreak in piglets by a 31 novel coronavirus was emerged designated as swine acute diarrhea 32 syndrome coronavirus (SADS-CoV) which is originated from the same genus 33 of horseshoe bats (Rhinolophus) as Severe Acute Respiratory Syndrome CoV 34 (SARS-CoV) having a broad species tropism. In addition to human cells, it 35 can also infect cell lines from diverse species. Coronavirus host range is 36 determined by its spike glycoprotein (S). Given the importance of S protein in 37 viral entry to cells and host immune responses, here we report the cryo-EM 38 structure of the SADS-CoV S in the prefusion conformation at a resolution of 39 3.55 \u00c5. Our study reveals that SADS-CoV S structure takes an intra-subunit 40 quaternary packing mode where the NTD and CTD from the same subunit 41 pack together by facing each other. The comparison of NTD and CTD with 42 that of the other four genera suggests the evolutionary process of the SADS-43 CoV S. Moreover, SADS-CoV S has several characteristic structural features, 44 such as more compact architecture of S trimer, and masking of epitopes by 45 glycan shielding, which may facilitate viral immune evasion. These data 46 provide new insights into the evolutionary relationships of SADS-CoV S and 47 would extend our understanding of structural and functional diversity, which 48 ." ] },{ "paper_id": "7837a1b529936ac78b802e41daa73ddab8bfc41a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Additional investigations are needed to determine how nascent chain-and RNA-mediated -1PRF mechanisms are balanced against one another, and how this mechanistic diversity ultimately influences viral evolution.", "During this window, pulling forces were measured at a rate of 333 frames per second. In order to sample a wide range of topologies and conformations, each mutant was independently simulated 560 times. This protocol is analogous to force measurements performed in previous work, with exception of a shortened pausing duration. 47", "-1PRF occurs during synthesis and processing of the nascent alphavirus structural polyprotein at the endoplasmic reticulum (ER) membrane. Following autoproteolytic cleavage of CP in the cytosol, a signal peptide at the N-terminus of the E3 protein directs the nascent polyprotein to the endoplasmic reticulum (ER) lumen where processing of the downstream proteins occurs." ] },{ "paper_id": "7852aafdfb9e59e6af78a47af796325434f8922a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Serum samples or throat-swabs were collected from all patients and RNAs were Inflammatory cytokine IL-6 levels were detected with kit from Roche Ltd (Mannheim, Germany, Cat# 05109442190)." ] },{ "paper_id": "78ab74f8133c0dfe8fb414c216350dd37f69b0bf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "October 1, 2019 10/28 ", "One thread of the quantitative narrative that emerges from simulations of our model 354 is that competition causes the period of prey-predator oscillations to increase and be 355 dampened more rapidly, with this increase and dampening accentuated as colony 356 mixing increases. A second thread is that a \"grass is greener syndrome\" (i.e., movement 357 decisions are based purely on resource considerations) leads to increased stress in " ] },{ "paper_id": "78e49fdb6f0aa9924a5b510341d52b618fff0ca6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The recent outbreak of COVID-19 has drawn substantial attention especially after 5 it spread to more than thirty countries and became a Public Health Emergency of 6 International Concern (PHEIC) [2, 36, 37 ]. The disease is caused by a new type of ", "Considering that the function of a bio-system is often under kinetic, rather than 11 thermodynamic, control [28, 29] , we suggest that this time-dependent behavior is 12 biologically more relevant. In reality, not all the viruses have the opportunity to find their 13 target receptors on host cells. Many of them will be recognized and removed by our 14 innate immune system. Therefore, the capability of how fast a specific type of 15 coronavirus can target its receptors is especially critical to the process of its invasion, as 16 well as the follow-up stages in its life cycle.", "15" ] },{ "paper_id": "7a51b191fd6575831585eee67a0ac67f209d8fcb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "15", "The second strategy to monitor host endonuclease activity was to express the nsp1 179 protein from SARS coronavirus. Nsp1 is not itself a nuclease, but it binds the 40S ribosome 180 and causes it to stall on the mRNA, thus activating cleavage of the mRNA by an as yet 181 unknown cellular endonuclease via a mechanism reminiscent of no-go decay [47, 48] . 182", "deciphering conditions under which such elements impact RNA fate in uninfected cells. 337", "ChIRP-MS runs with probes were filtered out together with common contaminants. 861 862 Table S2 : List of proteins identified by ChIRP-MS that are in common with previously 863" ] },{ "paper_id": "7aa49aa2b76ea92b9265ad9d5a9d9ef0ea585b24", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In.; 2019. 332", "Countries/areas with reported cases of novel coronavirus infection (Last updated on February 21, 333 2020, 6 pm). In.: Center for Health Protection; 2020. 334" ] },{ "paper_id": "7ab9f9fcea519ebce527c3ede8091beedbb26ad9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Amino acid alignments and phylogenetic trees:", "Sequences:" ] },{ "paper_id": "7b40dfdf9a60cfe4a199cb967ee458b7dfaabe0c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The analyses were conducted using the coarseDataTools and activemonitr packages in the R statistical programming language, version 3.5.3. All code and data are available at https://github.com/HopkinsIDD/ncov_incubation (release at time of submission at 10.5281/zenodo.3634050) [13] .", "All estimates are based on those who developed symptoms, and this work makes no inference about asymptomatic cases.", "that further symptomatic infections would be undetected among high-risk individuals (mean: 0.6, 99th percentile: 4.5 undetected infections per 10,000 individuals). However, we note that there remains substantial uncertainty in the classification of individuals as being at 'high', 'some' or 'low' risk of being symptomatic, and that this method does not consider the role of asymptomatic infection." ] },{ "paper_id": "7b5be48b7769ccad2f44a8c54efcea5281a6c633", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(which was not peer-reviewed) The copyright holder for this preprint .", "The copyright holder for this preprint . https://doi.org/10. 1101 and started to decline from Feb 3 rd , 2020 (Fig. 1C ).", "40 41 .", "20 BACKGROUND The COVID-19 epidemic, first emerged in Wuhan during December 2019, has 21 spread globally. While the mass population movement for Chinese New Year has significantly 22 influenced spreading the disease, little direct evidence exists about the relevance to epidemic and its 23 control of population movement from Wuhan, local emergency response, and medical resources in 24 China. fatality rate was 2.84%, much higher in Hubei than in other regions (3.27% vs 0.73%). The index of 29 population inflow from Hubei was positively correlated with total (Provincial r=0.9159, p<0.001; 30 City r=0.6311, p<0.001) and primary cases (Provincial r=0.8702, p<0.001; City r=0.6358, p<0.001). 31 The local health emergency measures (eg, city lockdown and traffic control) were associated with 32 reduced infections nationwide. Moreover, the number of public health employees per capita was 33 inversely correlated with total cases (r=-0.6295, p <0.001) and infection rates (r =-0.4912, p <0.01). 34 Similarly, cities with less medical resources had higher fatality (r =-0.4791, p<0.01) and lower cure 35 rates (r = 0.5286, p<0.01) among the confirmed cases. 36 CONCLUSIONS The spread of the COVID-19 in China in its early phase was attributed primarily 37 to population movement from Hubei, and effective governmental health emergency measures and 38 adequate medical resources played important roles in subsequent control of epidemic and improved 39 prognosis of affected individuals." ] },{ "paper_id": "7b89a657dde3e5888c31d1d5ef3b90ceb0f66a62", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7bc87a77a7aba144248cfa3bc514541f09047edf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To the memory of Rossiter H. Crozier , an evolutionary biologist, who with his generosity and inquisitiveness inspired many students and scientists, in Australia and abroad. doi: bioRxiv preprint", "How phylogenetically informative are phylogenetic data (143-145)?", "CONFIRMATION BIAS IN PHYLOGENETICS", "Having obtained a sub-MSA, the next step in the protocol is to select a phylogenetic method." ] },{ "paper_id": "7bdceb3b947ec934199d0c97fb9ec5a0e2bac776", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Parameter estimates 2\u2206L df p-value Positive selection sites", "We reconstructed an maximum likelihood (ML) tree and neighbor-joining (NJ) tree using MEGA X 40 . For ML analyses, the WAG+ G model was selected as the best amino acid substitution model according to the Bayesian information criterion. All amino acid sites with an alignment gap were included for analyses. For NJ analyses, JTT+G was selected as the best model. For the ML and NJ analyses, the bootstrap value was set to 1, 000. Other parameters were used as defaults in the program.", "Previous studies show that spike protein interacts tightly with a related protein ORF3a and they likely coevolved [28] [29] [30] . If their coevolution does occur, we may expect that the evolutionary convergence of the spike protein found may have led to the occurrence of the evolutionary convergence of ORF3a as well." ] },{ "paper_id": "7c17c6f5e434f1d8227c9d8c5f9da26200364491", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7cdd50888f639629380fa9906d73f97010158127", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Background. T cell immunoglobulin mucin domain-1 (TIM-1) is a phosphatidylserine (PS) 28 receptor, mediating filovirus entry into cells through interactions with PS on virions. TIM-1 29 expression has been implicated in Ebola virus (EBOV) pathogenesis; however, it remains 30 unclear whether this is due to TIM-1 serving as a filovirus receptor in vivo or, as others have 31 suggested, TIM-1 induces a cytokine storm elicited by T cell/virion interactions. Here, we use a 32 BSL2 model virus that expresses EBOV glycoprotein and demonstrate the importance of TIM-1 33 as a virus receptor late during in vivo infection. 34", "suggesting that virus entry via this receptor contributes to virus load. Consistent with higher 43 virus loads, proinflammatory chemokines trended higher in organs from infected TIM-1-44 sufficient mice compared to the TIM-1-deficient mice, but proinflammatory cytokines were more 45 modestly affected. To assess the role of T cells in EBOV GP/rVSV pathogenesis, T cells were 46 depleted in TIM-1-sufficient and -deficient mice and the mice were challenged with virus. 47", "53 Author summary 54 T cell immunoglobulin mucin domain-1 (TIM-1) is one of a number of phosphatidylserine (PS) 55 receptors that mediate clearance of apoptotic bodies by binding PS on the surface of dead or 56 dying cells. Enveloped viruses mimic apoptotic bodies by exposing PS on the outer leaflet of the 57 viral membrane. While TIM-1 has been shown to serve as an adherence factor/receptor for 58 filoviruses in tissue culture, limited studies have investigated the role of TIM-1 as a receptor in 59 vivo. Here, we sought to determine if TIM-1 was critical for Ebola virus glycoprotein-mediated 60 infection using a BSL2 model virus. We demonstrate that loss of TIM-1 expression results in 61 decreased virus load late during infection and significantly reduced virus-elicited mortality. 62 These findings provide evidence that TIM-1 serves as an important receptor for Ebola virus in 63 vivo. Blocking TIM-1/EBOV interactions may be effective antiviral strategy to reduce viral load 64 and pathogenicity at late times of EBOV infection. 65 66 . CC-BY 4.0 International license is made available under a" ] },{ "paper_id": "7d3dcbbc2b0741fc544693d7b3fc185f0bd50eac", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7d91bba210d98289dac830135c56c13e206837ec", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "benthamiana appeared as early as 5 dpi (Fig. S1B ) and remained visible during the experimental time frame (14 dpi) (Fig. 2C) .", "N. benthamiana plants were grown in a growth chamber set at 25\u00b0C with a 16 h photoperiod, and used at 4-5 weeks old. Arabidopsis thaliana seeds were surface sterilized using 50% bleach solution for 5 minutes, rinsed five times with sterile distilled water and plated on \u00bd MS plates containing 1% agar. Ten-day old seedlings were transferred to soil, grown in a growth chamber at 22 \u00b0C, 60% relative humidity, and at a light intensity of 120 \u00b5mol/m 2 s 1 at a 10 h photoperiod, and used when 4-5 weeks old.", "OuMV-MP_D 0/6 0/6 0/6 0/12 0/11 1*/12 OuMV-MP_Y/G 0/6 0/6 0/6 0/12 0/12 0/12 OuMV-MP_D/G 6/6 5/5 6/6 6/12 8/12 6/12" ] },{ "paper_id": "7d98a73314cd9f923aaa367f3f4de056b8cedec5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "word count: 197", "All spectra were acquired using an Orbitrap Fusion Tribrid mass spectrometer controlled by Xcalibur 2.1 software (Thermo Scientific) and operated in data-dependent acquisition mode. FTMS1 spectra were collected at a resolution of 120 000 over a scan range (m/z) of 350-1550, with an automatic gain control (AGC) target of 300 000 and a max injection time of 100 ms. Precursors were filtered using an Intensity Range of 1E4 to 1E20 and according to charge state (to include charge states 2-6) and with monoisotopic precursor selection. Previously interrogated precursors were excluded using a dynamic window (40 s +/-10 ppm). The MS2 precursors were isolated with a quadrupole mass filter set to a width of 1.4 m/z. ITMS2 spectra were collected with an AGC target of 20 000, max injection time of 40 ms and CID collision energy of 35 %." ] },{ "paper_id": "7e6bd4f9d794f87445f67c9ed9d5699706040fa4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "IBV is a major avian pathogen and presents a substantial economic burden to the poultry industry. ", "[MYH15], encoding myosin heavy chain 15) had a significantly higher translation efficiency in M41-infected samples compared with Beaudette-infected samples.", "RiboSeq analysis, in conjunction with RNASeq, revealed that the N protein is not more efficiently translated than other structural proteins, despite being a structural component of IBV virions.", "In contrast, RiboSeq coverage of the ORF1a and ORF1b coding sequences was relatively low; reflecting the fact that a substantial proportion of newly synthesised gRNA (but not sgmRNA) transcripts are likely to be destined for packaging rather than translation (Kuo and Masters, 2013) ." ] },{ "paper_id": "7e80848c7b22e870b0e0a458dce96f6955576f04", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "7e9cd4bbf0fba1cc0bcded40041fd01b9dfb683f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The horizontal axis represents the onset date of confirmed cases or suspected cases.", "162 laboratory-confirmed cases related to COVID-19. We described the demographic 15 characteristics of the cases and estimated the incubation period, serial interval and 16 basic reproduction number. With an estimation of 8 days incubation period and 6 days 17 serial interval, our results indicate that there may exist infectiousness during the 18 incubation period for 2019-nCoV. This increases the difficulty of screening or", "The copyright holder for this preprint (which was not peer-reviewed) is . https://doi.org/10.1101/2020.03.01.20028944 doi: medRxiv preprint " ] },{ "paper_id": "7ea2f1ca7b3c2370d413ae990eb71b2b990c91fe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Furthermore, isolates recovered from immunocompetent patients with persistent candidemia 40 displayed significantly higher tolerance than isolates that were readily cleared by fluconazole. 41 Thus, tolerance correlates with the response to fluconazole therapy in patients and may help 42 predict whether infections will respond to fluconazole alone. Similarly, measuring tolerance may 43 provide a useful clinical parameter for choosing appropriate therapeutic strategies to overcome 44 persistent clinical candidemia.", "Only four classes of antifungals are currently in clinical use, and resistance to azoles, 63 including fluconazole (FLC), the most commonly administered antifungal against Candida 64 species, is an increasing problem. Altered drug uptake/drug efflux and changes in ergosterol 65 biosynthesis (the target for azole drugs) 13 are the major known mechanisms of azole resistance.", "Stress responses have been proposed as a third mechanism of antifungal resistance 14 . A 67 broad range of small molecules enhance antifungal activity in vitro and in vivo, with inhibitors of 68 Hsp90, calcineurin and TOR the most prominent among them 15-18 . Combination therapy using 69 antifungals together with such inhibitors has been proposed as a promising strategy to extend 70 the efficacy of current drugs [19][20][21][22][23][24]25,26,27 . In addition, several psychotherapeutic agents such as 71 fluoxetine, fluphenazine or sertraline can enhance FLC activity against fungal species 21,28-30 ." ] },{ "paper_id": "7ed2c0786eef3d39fa0435b461aa34ab454a4753", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The present status of COVID-19 is analyzed and the end of the disease is forecasted. The", "The convergence of fluctuation is necessary to forecast the end of the epidemic in Wuhan.", "All rights reserved. No reuse allowed without permission.", "The data on the epidemic of COVID-19 was obtained from ref. 2." ] },{ "paper_id": "7f8c673d136b9bc0aeda55e49cc72aacaa5688de", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "During its first month, the recently emerged 2019 Wuhan novel coronavirus (2019-nCoV) has already infected many thousands of people in mainland China and worldwide and took hundreds of lives.", "Here, using an integrated bioinformatics approach, we provide a comprehensive structural genomics and ", "NSP8 is the other major hub and interacts with other replicase proteins, including two other hubs, i.e. NSP7 and NSP 12, which together play a crucial role in replication [63] ." ] },{ "paper_id": "7fb7c0c48b30e66dfaea5fdec16d999ed52d1ee0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The transmission process was simulated stochastically.", "(1)" ] },{ "paper_id": "7fd337f16780aba8f1e599ce7516dc9b1d80a546", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All statistical analyses were performed using R (version 3.3.0) software. The significance threshold was set at a P<0.05.", "the cerebrospinal fluid of those patients and also in their brain tissue on autopsy [12] [13] .", "Abbreviations: CNS, central nervous symptoms; PNS, peripheral nerves symptoms.", "Three designated COVID-19 care hospitals", "Here, we would like to report the characteristic neurological manifestation of SARS-CoV-2 infection in 78 of 214 patients with laboratory-confirmed diagnosis of COVID-19 and treated at our hospitals, which are located in the epicenter of Wuhan." ] },{ "paper_id": "815745bf1b522d33fd7371cc9a6561a2a93ef87e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Exposed", "Huili Yan designed the experiments and collected data. Hao Xiong analysed data, interpreted the results and wrote the manuscript.", "We declare no competing interests." ] },{ "paper_id": "815f653470c57a95b92e3857d8f5d038b4000d99", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "82468c289eb562a3e63d084238c08f62e617eb64", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "It is of special significance to find a safe and effective vaccine against coronavirus disease 2019 (COVID-11", "Authors declare no conflict of interest.", "197 Acknowledgment" ] },{ "paper_id": "82c1bf108f88d4ec2b4e68106d9531f1c8b45a5c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "83323659de2f2d5ed3ca6ada7cf137a8a17bb014", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "ESI-MS (m/z): 187 (M + H) + .", "RESULTS" ] },{ "paper_id": "8349823092836fe397a59e38615d1491423dbe70", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The detail information of 45 defined chemical reaction rules is presented in Table S2 .", "(4):", ". To make our RL agent more robust to be more stable learning and to handle the problem of the overestimation of Q-values, double Qnetwork 43 and fixed Q-targets 44 are also incorporated: ", "Although compound #46 has the best covalent docking score, it has the alerting group aldehyde. Considering there is still much space for compound #46 to fill in the S1'" ] },{ "paper_id": "836190d366ba8e34c3a5df8a24d17a36fd503505", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Note that, when N approaches the number of all thermodynamically probable conformations, \u2329\u2206 \u232a becomes the exact value.", "In contrast, a few other human CoVs of zoonotic origin only cause mild infections of the respiratory tract, such as HCoV-OC43 and HCoV-HKU1 (Gaunt et al., 2010) ." ] },{ "paper_id": "8367c21d603a58c206ae740debdb10099f84f198", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "VADR is written in Perl and is available at https:// github.com/nawrockie/vadr. The new software uses the existing software packages and libraries listed in Table 2 .", "v-build.pl is designed to allow input alignments instead of single RefSeq accessions. Although models built from alignments have not yet been tested, we plan to use alignment-derived models in the future.", "Alignment and feature mapping stage Each complete sequence S is aligned to the covariance model for model M (S) using Infernal's cmalign program generating a Stockholm formatted alignment file. The alignment is then parsed to determine a mapping between sequence positions and model positions, from which per-feature coordinates for S are derived. The cmalign output Stockholm alignment file includes posterior probability values that indicate a level of confidence in each aligned nucleotide. These posterior probability values are used to identify features for which the endpoints are not confidently assigned by the model, which are reported as fatal alerts (indf5loc and indf3loc). Different fatal alerts are reported if an input sequence has a gap at a feature endpoint (indf5gap or indf3loc). Additional alerts are potentially reported at this stage as well (Table 3) .", "For bacterial genomes, these limitations were addressed by the release of NCBI's Prokaryotic Genome Annotation Pipeline (PGAP) [21] , which is now available for download as a standalone package (https://github.com/ncbi/pgap/releases). For influenza virus, the limitations were addressed first by FLAN [2] and then by the influenza virus submission tools provided by GenBank [3] . Tools for checking submissions of non-influenza viruses have lagged but VADR begins to close the gap. Importantly, VADR can already be used for many viruses (currently excluding circular genome and segmented viruses) breaking from the paradigm of developing code for one virus at a time that has limited the breadth of the Virus Variation Resource." ] },{ "paper_id": "837c77d566651f559ed3f78c2e490213f99212e6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "No-choice phase 251 Dietary P:C ratio had a strong effect on the total amount of P eaten (linear model using The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/397802 doi: bioRxiv preprint showed a good fit. Note that no non-linear effects were observed, that is, we did not identify an 272 optimal amount of protein or carbohydrate that maximised cocoon weight.", "The fact that larvae consumed very different amounts of protein, despite its importance to 433 larval insects, suggests that bee larvae may be vulnerable to environmental variations in the 434 protein:carbohydrate ratio of pollen -in a similar but opposite manner to humans, who will 435 consume excesses of carbohydrate in order to eat enough protein, rendering them vulnerable to 436 variation in protein:carbohydrate ratio of food (Simpson and Raubenheimer, 2005) . Since bee 437 larvae appear to be able to regulate carbohydrate, they may therefore rely on parents to regulate The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/397802 doi: bioRxiv preprint", "In the choice experiment, mean final consumption of each nutrient was investigated using 239 linear models with diet combination, dilution and their interaction as predictors. The minimal 240 model was determined using reverse stepwise model selection and pairwise differences among 241 groups were examined using Tukey's Post Hoc tests. We additionally tested whether larvae were 242 exercising a choice at all, i.e. whether they were consuming the available diets non-randomly. 243 We calculated the expected protein and carbohydrate that would be consumed under random 244 consumption of each diet by assigning exactly half the total amount of food consumed by each 245 larva to each of the two choices offered to that larva. We then re-ran our models, using \"random 246 vs. observed consumption\" as a predictor variable. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/397802 doi: bioRxiv preprint" ] },{ "paper_id": "83cca3779f8aeea47c5426e1d0fa65f1e9567e0c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Henceforth, targeting these genes will make S. enterica unable to grow inside the gastrointestinal tract.", "For our prediction, we used G-tracts -3 or 4 and loop length 1-20 nucleotide [63] . The results were further cross verified by using QGRS Mapper [64] and PGSFinder [65] tools.", "Consensus sequences representing the whole G4 sequence with -5 and +5 flanking regions were constructed using the Glam2 tool of MEME Suite [66] .", "Salmonella enterica belongs to Enterobacteriaceae family and known to cause typhoid fever and food poisoning in the human. Salmonella enterica consists of six subspecies namely 1) enterica 2) salamae 3) arizonae 4) diarizonae 5) houtenae 6) indica (Fig 1a) . Among these subspecies, subspecies S. enterica is known to infect human and possess ~2463 serovars that can be further divided into two subclasses [1, 2] ." ] },{ "paper_id": "84c3cb4cff4551bf95b6f79bd6c52525faee0a44", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The network was visualized with the help of Cytoscape (version 3.7.1) 17 .", "All the swine PPIs were downloaded from STRING database 15 on January 8, 2019.", "Only the PPIs with a median confidence (score greater than 0.4) were kept. Besides, the redundant PPIs were removed. Finally, a PPI network which consisted of 731,174 non-redundant PPIs between 18,683 swine proteins was obtained for further analysis." ] },{ "paper_id": "854a29cd858f64982c799eb27c0a45cb762adfa8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cloning, expression and purification 95", "To obtain more specific information, we first mapped the conserved residues between SARS-172", "The authors declare no conflict of interest 268" ] },{ "paper_id": "86b6b0c1b2777541feb83116bcb7a5cb12a52310", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "874eaaeda2e803101ab952b3d9bc73426111b3d4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "875b7c463f00772fa0dc18ada678bc1ff16a4274", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8762adc9311e5803d1de438493772269acfe7fa3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Both SPAR and IDVI indicators range from 0 to 100, with increasing levels of capacity and decreasing vulnerability.", "Background. The novel coronavirus (2019-nCoV) epidemic has spread to 23 countries from China. Local cycles of transmission already occurred in 7 countries following case importation.", "Three clusters were identified among the countries with non-negligible risk (Figure 4) . Each of the clusters corresponds to different Chinese airports as main source of entry risk (pie charts of Figure 4 ). The red cluster is highly exposed to Beijing province, moderately exposed to Guangdong and Shanghai provinces. The green cluster (including Botswana and Lesotho only)" ] },{ "paper_id": "87b89b038b28d2ba0bcfd2203845bf15f922c1b5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We also validated our individual records against the official line lists obtained from the websites of Shandong Provincial Health Commission, Shenzhen Municipal Health Commission, and Hunan Provincial Health Commission for the key variables used in this study (see Tab. S3 in Appendix).", "The presence of at least one known exposure was reported by 77% of cases. In A similar decreasing trend over time was observed for the interval from symptom onset to first healthcare consultation as well (Tab. 2).", "The COVID-19 epidemic originated in Wuhan City of Hubei Province in December 2019 and has spread throughout China. Understanding the fast evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy." ] },{ "paper_id": "87bfa13221ccf5a02d4a888ef1320b57f2c2d5e2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Bats are unique among mammals due to the ability of powered flight and exceptional longevity. They 2 are also asymptomatic hosts for numerous viruses, including recently emerged zoonotic 3 Henipaviruses Nipah and Hendra, which are highly pathogenic for humans and other mammals. 4 Better understanding of how bats control viral infection requires development of relevant permissive 5 cellular experimental models. By applying a somatic reprogramming protocol to Pteropus bat primary 6 cells, using a novel combination of ESRRB, CDX2, and c-MYC transcription factors, we generated 7 bat reprogrammed cells exhibiting stem cell-like characteristics and a neural stem cell-like molecular 8 signature. These cells present a unique interferon-stimulated transcriptomic signature and both 9 produce and respond to interferon type-I, highlighting differences between stem cells from bats and 10 other mammals. In contrast to primary bat cells, these reprogrammed cells are highly susceptible to 11 infection by Henipavirus, thereby enabling isolation of new bat viruses, study of virus-bat 12 interactions, and better understanding of bat biology.", "The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/846410 doi: bioRxiv preprint", "13 14" ] },{ "paper_id": "88e3b43319399c339186c02c44d369228c35eef4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "technologies. Cancer therapy is approached by four main directions: i. Radiation therapy (XRT);", "All the experiments were at least repeated tri times.", "To construct DTA carried plasmids we used the less toxic DTA-176 mutant (G128D). (37) ." ] },{ "paper_id": "896cb03362facd2a670bee13dc5368b81768b2ba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Paran\u00e1. We thank Elizabeth Droppa, C\u00e9lia Cruz, Carla S. Felippe and the LACEN-PR group for their support in clinical sample collection and shipping. We express our gratitude to Wagner Nagib for graphical design and to Associa\u00e7\u00e3o Amigos do HC for logistic support. ", "The authors declare that the research was carried out in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.", "All rights reserved. No reuse allowed without permission." ] },{ "paper_id": "898880683d9a962428033fd7500f74647c4a36f0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "become publicly available in the first weeks of an outbreak, when the information is most needed.", "Building on prior experience collating news reports to monitor Ebola transmission 7 , here we present an effort to compile individual patient information and subnational epidemic curves on 2019-nCoV from a variety of online resources. Data were made publicly available in real-time and were used by the infectious disease modeling community to generate and compare epidemiological estimates relevant for interventions.", "The database was made available as a Google sheet disseminated via Twitter on Jan 21, 2020 and posted on a university website on Jan 24, 2020 10 . Statistical Analysis.", "In conclusion, crowdsourced epidemiological data can be useful to monitor emerging outbreaks, such as 2019-nCoV (see also 7 for a related study in the context of Ebola). These efforts can help generate and disseminate detailed information to the scientific community, particularly in the early stages of an outbreak when little else is available, enabling independent estimation of key parameter estimates that affect interventions." ] },{ "paper_id": "8a1fde8c65e439496ac5810504de23ef77312f28", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We use C-I-TASSER 5 to create structural models of the full-length spike protein. Here, C-I-TASSER is an extended pipeline of I-TASSER 19 and utilizes the deep convolutional neuralnetwork based contact-maps 20 to guide the Monte Carlo fragment assembly simulations. Since the RBD domain of spike exhibits different conformations relative to the remaining portion of . CC-BY 4.0", "As per the previous study 4 , the RSCU for codon j in a species is calculated as where k j is the number of codons synonymous to codon j (including j itself), p j is the probability of the respective amino acid being encoded by codon j among all k j synonymous codons in the CDSs of the whole genome. The difference of codon usage in two different species (a virus versus a vertebrate in our case) is defined by squared Euclidean distance of RSCU, i.e.," ] },{ "paper_id": "8aa021696a6accab9053f1d779eef6710439bfa5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8b2e50eb3ea84225580fbdbccccb4fcd3f062feb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Background 33", "Analytical solution of Eq. (1) could be written in the form of Eq. (2) 116", "(4) and Eq. (6). 120" ] },{ "paper_id": "8b71ce92ec03e066eca7792bfd17e2f210d50ce3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The epidemiological characteristics (including recent exposure history), clinical symptoms and signs, laboratory assessments and CT scans were obtained with data collection forms from electronic medical records. Laboratory assessments consisted of complete blood count, liver function, C-reactive protein and direct antigen Flu A+B test." ] },{ "paper_id": "8b88901d0bb033af3a18ebcdf7f2aa7110b21504", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8b88d01563538e4abd29c3ba493c534af30664cc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "On 31 December 2019, the World Health Organization (WHO) China Country Office was informed of cases of pneumonia of unknown etiology (unknown cause) detected in Wuhan City, Hubei Province of China, and WHO reported that a novel coronavirus (2019-nCoV) was identified as the causative virus by Chinese authorities on 7 January(1). Potential for international spread via commercial air travel had been assessed (2) . Public health concerns have been paid globally on how many people had been infected actually.", "a) The transmission network of Bats-Host was ignored. b) Based on our previous studies on simulating importation (3, 4) , we set the initial value of W as following impulse function:", "Based on the equations of RP model, we can get the disease free equilibrium point as: Interest of Conflicts: None." ] },{ "paper_id": "8bd8158e4a47c65b12a462b49b4b8b4af1488dc3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(3) we obtain the total population size, N.", "The initial conditions are \uf028 \uf029 0", "Eliminating I from (1) and (3) yields" ] },{ "paper_id": "8c223fd63ba6a924ecd3df8d32bcf0556758cb95", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8c900409a679dc1f16ef13c73500cbb53605b683", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "[24] as well as the annotate package in R. ", "47 MHV-1 is a strain of mouse hepatitis virus that preferentially replicates and causes disease in the 48 respiratory tract of specific mouse strains and thus serves as a model for respiratory coronaviral infections [6, 49 7]. MHV-1 causes severe disease in A/J-strain mice and milder pathology in other mouse strains [6, 8]. Mouse" ] },{ "paper_id": "8cfb8dfc2f8b2c6e1d60ff48da02de6670694869", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ ". All rights reserved. No reuse allowed without permission.", "All rights reserved. No reuse allowed without permission." ] },{ "paper_id": "8d6d3be5f9353eb3358b44e646c83f1a90861b4d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Two investigators (Z.H.X and J.M.Z) independently reviewed and abstracted data from each retrieved article and supplement. Discrepancies were resolved by discussion and consensus.", "We assessed the quality of all included trials based on review of the details in the method section and supplements of included trials. We appraised trial quality using the Cochrane collaboration tool for assessing risk of bias (RoB) (16) including assessment of random sequence generation, allocation concealment, blinding (of interventions and outcome measurement or assessment), incomplete outcome data, selective reporting bias and other potential sources of bias (e.g., industry funding). For each criterion, we appraised the RoB to be either of low, high, or unclear risk (e.g., insufficient details). Two authors (Z.H.X, J.Z.M) independently assessed study quality and disagreements were resolved by consensus.", "We used the I 2 statistic to evaluate the impact of heterogeneity on pooled results." ] },{ "paper_id": "8e0481979dcd13b668686cbf3e2c8b51e5b8cf64", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Not applicable", "The authors declare no conflicts of interest.", "Funding G.C. is supported by NSF grants 1610429 and 1633381.", "We obtained the daily series of confirmed cases of COVID-19 in Singapore as of March 5, 2020.", "Beyond Singapore, COVID-19 clusters are being reported in an increasing number of countries including Germany, Iran, Italy, South Korea and on the Diamond Cruise ship in Japan (2, (68) (69) (70) (71) ." ] },{ "paper_id": "8e830dc6cb2de091920ff5b3b14f806a61a8aef4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "8eb99586e9103599ab2f58cc33ca94cd0b60ae53", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Deviations from neutral expectation were detected with p < 0.05 in a X 2 goodness-of-fit test." ] },{ "paper_id": "8eef6fec694446e150e95dfbef3a3579ae8806d3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All rights reserved. No reuse allowed without permission." ] },{ "paper_id": "8f4b98da50277e6c9516aef0227f5cca9af6b5e8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The recombinant proteins were expressed in BL 21 cells and then purified by Ni 2+ -affinity chromatography, followed by further purification with FPLC gel-filtration chromatography.", "Recombinant protease samples were checked by SDS-PAGE, molecular weights verification with ESI-MS and protein sequencing with time-of-flight-mass spectrometer (Applied Biosystems). Protein concentration was determined by the UV spectroscopic method with 8 M urea (19) ." ] },{ "paper_id": "901572f1595cb6ea733858d3fc15b8ea46054061", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(1,023) death cases, and 80.9% mild cases among 44,672 confirmed cases. 51.4%", "All antibodies were obtained from BD Biosciences (San Jose, CA, USA). Two 100-\u03bcL samples of blood were placed in two tubes for staining according to mmanufacturer's manual.", "After this procedure, 1 mL of red-cell lyses buffer was added to each tube and incubated for " ] },{ "paper_id": "905603e9db862f9b4b42a95f51e9c8d0015d1dff", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Since the first identified individual of 2019 novel coronavirus (COVID-19) infection on Jan 20, 2020", "Under the empirical reporting delay distribution from Korean cases with available dates of onset, the intrinsic growth rate (r) was estimated at 0.6 (95% CI: 0.5, 0.7) and the scaling of growth parameter (p)", "A novel coronavirus (SARS-CoV-2) that emerged out of the city of Wuhan, China in December 2019 has already demonstrated its potential to generate explosive outbreaks in confined settings and cross borders following human mobility patterns (1) . While COVID-19 frequently induces mild symptoms common to other respiratory infections, it has also exhibited an ability to generate severe disease among certain groups including older populations and individuals with underlying health issues such as cardiovascular disease and diabetes (2) . Nevertheless, a clear picture of the epidemiology of this novel coronavirus is still being elucidated.", "Next, to estimate the most recent estimate of Rt, we simulate the progression of incident cases from GGM, and apply the discretized probability distribution ( ) of the generation interval using the renewal equation (17-19) given by", "The reconstructed daily incidence curve of COVID-19 after the imputing the onset dates for the Korean cases is shown in Figure 1 . Between January 20 and February 18, 2020 an average of 2 new cases were reported each day, whereas between February 19-26, 2020, 153 new cases were reported each day on average." ] },{ "paper_id": "906b616191eea5e5e724d47546f7d2d9d096ed7a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "MicroRNAs (miRNAs) are non-coding RNA molecules that regulate gene expression. In the last years, the under and over expression of miRNAs has been related to the diagnosis and prognosis of specific cancer types. While machine learning techniques can efficiently exploit the information contained in thousands of miRNAs to detect the", "Assign weight w f nk to each f of the 1,046 features; 6 for each feature f of F do if f is among the top 100 features in l kn then" ] },{ "paper_id": "907da65e13cde5d7ad71f304967a7ab9dcb5efa1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "These observations that PARP2 is tightly regulated by distinct pathways highlights the 27 critical roles PARP2 plays under different physiological conditions. 28 29", ", these studies confirm that PARP2 is not 68 entirely functionally redundant with PARP1. Furthermore, they underscore the importance 69 of PARP2 in maintaining a number of key cellular physiological processes. For these 70 reasons, we sought to investigate the mechanism by which PARP2 is regulated under 71 normal and stress-induced conditions. 72", "PARP2 belongs to a family of proteins involved in cell differentiation, DNA 15 damage repair, cellular energy expenditure, chromatin modeling and cell differentiation. 16", "Given the shortcomings on being unable to find a sequestration mechanism noted 519 above, our data does indicate that PARP2 is degraded through the UPS in cells when serum 520 is present (Fig. 5B) (Fig. 5A) , where cells should have retained some of the PARP2 protein when they 543 were transferred to serum-free medium. 544" ] },{ "paper_id": "90b5ecf991032f3918ad43b252e17d1171b4ea63", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "90e28ff462882ca7a9329beb879f73c2e99430e4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "91098f6fe46a21565bf0cb06fe960cdb2c3f5e38", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The copyright holder for this preprint ", "The study also found that uptake of prevention practices was poorer among older 247 members of the public, which warrants serious attention. It has been found that older 248 adults affected by 2019-nCoV are likely to have a higher risk of complications and 249 mortality (4). There is a need to find out whether a lack of appropriate prevention 250 practices among people of older age is due to knowledge deficiency or to their being 251 out-of-reach of current public health intervention." ] },{ "paper_id": "91233a0c35364955d1fdbf2f980f7220f9bafc70", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Respanel is a convenient and inexpensive assay that is more sensitive than Resplex and 42 comparable to FTDRP21 for the detection of common respiratory pathogens. 43 44 45 46 . CC-BY-NC-ND 4.0 International license is made available under a", "PPMs from strip-tubes were then added to the wells using a multichannel pipette for real-time 34 PCR. Individual PCR assays were optimized using previously known specimens (n=397) with 35 91%-100% concordance with culture, DFA or PCR results. Respanel was then tested in a routine 36 manner at two different sites using specimens (n=147) previously tested by Qiagen Resplex I&II 37 or Fast-Track Diagnostics Respiratory Pathogens 21 assays. The sensitivity, specificity and 38 accuracy of Respanel were 94%, 95% and 95%, respectively, against Resplex and 88%, 100% 39 and 99%, respectively, against FTDRP21. Respanel detected 48% more pathogens (p<0.05) than 40 Resplex but the rate of pathogen detection was not significantly different from FTDRP21.", "Commercial multiplex assays, built on different chemistries and platforms are widely 25 available for simultaneous detection of pathogens that cause respiratory infections. However, 26 these tests are often difficult to implement in a resource limited setting because of high cost. In 27 this study, we developed and validated a method for simultaneous testing of common respiratory 28 pathogens (Respanel) by real-time PCR in a convenient, strip-tube array format. Primers and 29 probes for sixteen PCR assays were selected from the literature or newly designed. Following 30 optimization of individual PCR assays, strip-tube arrays were prepared by dispensing primer-31 probe mixes (PPM) into two sets of 8-tube strips. Nucleic acid extracts from specimens were 32 mixed with PCR master mix, and dispensed column-wise into 2X8-wells of a 96-well plate." ] },{ "paper_id": "9211b1703c76e20afdee8fcb9f7996edadef0e9e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\uf020\uf020\uf020Constipation \uf020\uf020\uf020Diarrhea \uf020\uf020\uf020Fainting spells \uf020\uf020\uf020Nose bleed", "The proper way to wear an N---95 mask is: \uf020\uf020\uf020Make sure it covers your nose and mouth, and check for air leakage during exhalation. \uf020\uf020\uf020Make sure it covers your nose, and check for air leakage during exhalation. \uf020\uf020\uf020Make sure it covers your mouth, and check for air leakage during exhalation. \uf020\uf020\uf020Make sure it covers your nose, mouth, and chin and check for air leakage during exhalation.", "The first step to remove an N---95 mask properly is: \uf020\uf020\uf020Lift off the top elastic. \uf020\uf020\uf020Lift away from face while holding the elastic. \uf020\uf020\uf020Lift the bottom elastic over your head. \uf020\uf020\uf020Clean hands." ] },{ "paper_id": "924500c41931aa9192ccc820467818297c1679d8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "9261e7a9a4d3febda29d574074a79f02376249a3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To make the RPE1 line containing PCNA-mTurq2, Cdc6-mVenus, and DHB-mCherry, the plasmids were transfected into 293T with pCI-GPZ or \u0394NRF and VSVG virus packaging plasmids with 50 ug/mL Polyethylenimine (Aldrich Chemistry). Viral supernatants were transduced onto RPE1 cells with 8 ug/mL Polybrene (Millipore). A clonal cell line was picked based on fluorescence of all 3 biosensors. siRNA transfections and drug treatment siRNA concentration and sequences: siControl, (siLuciferase) 100 nM (synthesized by Life Technologies) 5\u2032-CUUACGCUGAGUACUUCGA-3\u2032 siCdt1 A, mixture of 4 sequences, 25 nM each. (siGENOME CDT1 siRNA, Dharmacon) 5'-CCAAGGAGGCACAGAAGCA-3' 5'-GCUUCAACGUGGAUGAAGU-3' 5'-UCUCCGGGCCAGAAGAUAA-3' 5'-GGACAUGAUGCGUAGGCGU-3' siCdt1 B, 50 nM (synthesized by Life Technologies)", "To prepare total protein lysate for immunoblot, cells were harvested with trypsin and frozen in dry ice, then lysed in cold cytoskeletal buffer (CSK) (10 mM Pipes pH 7.0, 300 mM sucrose, 100 mM NaCl, 3 mM MgCl2 hexahydrate) with 0.5% triton x-100 (Sigma Aldrich) and protease and phosphatase inhibitors (0.1 mM Pefabloc, 1 \u00b5g/mL pepstatin A, 1 \u00b5g/mL leupeptin, 1 \u00b5g/mL aprotinin, 10 \u00b5g/mL phosvitin, 1 mM \u03b2-glycerol phosphate, 1 mM sodium orthovanadate) on ice for 15 minutes. Lysate was centrifuged at 13,000 x g at 4\u00b0C for 10 minutes, and a Bradford Assay (Biorad) was done on the supernatant to load equal amounts of protein per sample." ] },{ "paper_id": "92860a0f4425d12aafb8e096d8e65d38eb67dff5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "92c020779e68e82d9a5f5898435e618caa63a099", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The sudden outbreak of the new coronavirus (SARS-CoV-2) at the end of December 2019 poses a huge threat to human health worldwide. The SARS-CoV-2 virus causes severe respiratory disease that can quickly spread from person to person and in some cases lead to death.", "Although TWIRLS only identified 623 CSSEs after collation, for human researchers, the information is scattered in words, which is limited for reconstructing understandable mechanistic models. Therefore, TWIRLS clusters CSSEs according to the rules defined by CSHG distribution, as genetic level research can accurately answer and solve physiological and pathological problems.", "The Renin-Angiotensin system consists of an enzymatic cascade beginning with liver-mediated production of AGT [21] . Angiotensin-converting enzyme (ACE), part of RAS, regulates many physiological processes including inflammation and brain functions [22] . Angiotensin II (Ang II) is the main effector of this system and is formed by successive enzymatic actions of renin and ACE.", "Part of the algorithm was developed using the MatLab programming environment and Python language. Algorithm efficiency improvements and the targeted parallel acceleration module were developed in C/C++ language. The automated text analysis took about 4 hours to complete on a workstation with an Intel Xeon CPU E5-2690 v4 X2 (28 cores) and 128 GB of memory." ] },{ "paper_id": "93d8f1552a81587e2f88e38580cbe4753b9934f1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Determining the background microbiome in near real time can inform potential treatment strategies in the event specific co-infections are identified. Future efforts will quantify the limits of detection using genome sequencing by these approaches.", "To identify and sequence SARS-CoV-2 two complementary techniques were used.", "Three samples were used -Patient 1 -Days 1 and 3 and Patient 2 -Day 1. Amplicons were generated and sequenced using the MinION with reads mapping to SARS-CoV-2 (Fig. 1C) . The data indicated that potentially some amplicons were potentially more abundant than others, but nevertheless resulted in identification and sequencing of the viral genome." ] },{ "paper_id": "93f67ffe7803061de9b19c4dfa346b3aa97aa4eb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "With one regularization parameter at each voxel, i.e., \u03b8(x), this reduces to a large set of decoupled optimization problems, one for each voxel. That is, for voxel x one obtains", "Require: Particle image dataset D with pose estimates z 1: Randomly partition D into halves, D 1 and D 2 with corresponding poses z 1 and z 2 2: Reconstructm 1 andm 2 , the raw (noisy) 3D maps from each half-set 3: Estimate regulization parameters \u03b8 * by solving Eqn. 6 4: Reconstruct a single map from D, z, and apply the optimal regularizer r \u03b8 * \u03b8(x). A window function can be used to gives more weight to points close to x. We thereby obtain the following least-squares objective:", "Such methods presume a Fourier basis and shift-invariance. Although well-suited to stationary processes, they are less well suited to protein structures, which are spatially compact and exhibit non-uniform disorder, motion, or variations in signal resolution. FSC, for instance, provides an aggregate measure of resolution. To the extent that FSC under-or over-estimates resolution in different regions, FSC-based shift-invariant filtering will over-smooth some regions, attenuating useful signal, and under smooth others, leaving unwanted noise. To address these issues we introduce a family of adaptive regularizers that can, in many cases, find better 3D structures with improved estimates of the latent poses during refinement." ] },{ "paper_id": "94284e14b36025dc9c7072dc90dfd8c72dc429ad", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In more severe cases, infection can cause pneumonia, severe acute respiratory syndrome, kidney failure, and even death. There is currently no specific treatment for diseases caused by COVID-19 [3] .", "However, many symptoms can be managed, so they need to be shown that cases can be traced to close contact with confirmed cases [4, 5] ." ] },{ "paper_id": "949feecec7c10e71532e860f7f1230bd696e8234", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The authors declare no potential conflicts of interest. ", "Methods" ] },{ "paper_id": "94df380f8a3bab7e30d39cc9d7e95d1f302f5f9f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Most infections result in pyrexia [2, 3] , therefore body temperature-based surveillance systems are unspecific but sensitive to virtually any pyrexia causing disease.", "All data were processed using MATLAB R2017a (The MathWorks, MA, USA)." ] },{ "paper_id": "95688a7f321e4fc9cce4af03c8e3eb8e7ad8f935", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Estimating the basic reproduction number ( R 0 ) Given an epidemic growth rate r and normally distributed generation times with mean ( ) and standard deviation ( ), the basic reproduction number is given by (6) .", "The data include only confirmed cases that were compiled from online reports from 18 provincial centers for disease control and prevention (Table S3) ." ] },{ "paper_id": "95754ec84bdee0637765a5ee34983a5f6cc86eed", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/111567 doi: bioRxiv preprint", "The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/111567 doi: bioRxiv preprint 2 prolonged starvation and involved in mitochondrial metabolism, we hypothesized that 29 PGC-1\u03b1 might be related with the cell cycle function of Bcl-2. Here, we showed that 30 PGC-1\u03b1 was upregulated upon Bcl-2 overexpression and downregulated following 31 Bcl-2 knockdown during serum starvation. Knockdown of PGC-1\u03b1 activated Bcl-2 32 expression. Taken together, our results suggest that after serum depletion, PGC-1\u03b1 33 might coordinate with Bcl-2 to reduce ROS, which in turn delay cell cycle 34 progression. 35 36" ] },{ "paper_id": "957e71389292e0881dff2bbe0e87fe6bf8b2d381", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We considered a simple hierarchical model to describe the dynamics of 2019 novel coronavirus (COVID-19) infections, detections, and spread.", "The prevalence of infectious cases is given by the following:", "in which N = 11.08 million, the population of Wuhan. \u03c9", "where t 0 denotes the beginning of the study period, December 1, 2019." ] },{ "paper_id": "960732b8d97d746a065188436b88f8b26af9ab4b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "At the end of 2019, a cluster of patients in Hubei Province, China was diagnosed with a 17 viral pneumonia of unknown origins. With community links to the Hunnan seafood market in 18", "Wuhan, the disease cluster had echoes of the severe acute respiratory syndrome coronavirus 19" ] },{ "paper_id": "96ef1767754a53f792951ba1752440ae94e90c60", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Viral escape from CD8 + cytotoxic T lymphocyte responses correlates with disease progression and 6 represents a significant challenge for vaccination. Here, we demonstrate that CD8 + T cell 7 recognition of the naturally occurring MHC-I-restricted LCMV-associated immune escape variant 8 T cell epitope associated with impaired peptide processing TEIPP 40 41 .", "Y4F is restored following vaccination with a proline-altered peptide ligand (APL). The APL 9 increases MHC/peptide (pMHC) complex stability, rigidifies the peptide and facilitates T cell 10 receptor (TCR) recognition through reduced entropy costs. Structural analyses of pMHC 11 complexes before and after TCR binding, combined with biophysical analyses, revealed that 12 although the TCR binds similarly to all complexes, the p3P modification alters the conformations 13 of a very limited amount of specific MHC and peptide residues, facilitating efficient TCR 14 recognition. This approach can be easily introduced in peptides restricted to other MHC alleles, 15 and can be combined with currently available and future vaccination protocols in order to prevent 16 viral immune escape. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/862144 doi: bioRxiv preprint 3 understanding of the molecular mechanisms underlying this reestablished recognition. We 24 believe that this approach can be implemented to currently available or novel vaccination 25 approaches to efficiently restore T cell recognition of virus escape variants to control disease 26 progression. pMHC stability and immunogenicity has been to optimize interactions between peptide anchor 62 residues and MHC binding pockets [17] [18] [19] . However, escape variants that target TCR recognition 63 often exhibit optimal MHC anchor residues, reducing possibilities for such modifications. 64 . CC-BY 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. Next, P14 TCR down-regulation was assessed upon exposure to gp33, V3P, Y4F or PF-loaded H-120 2D b+ RMA cells (Fig. 1C) . While H-2D b /gp33 induced significant TCR down-regulation, none 121 was detected with Y4F, even at high peptide concentrations. Exposure of P14 T cells to V3P 122 equaled or increased TCR internalization compared to gp33. Importantly, exposure to PF 123 significantly increased P14 TCR down-regulation compared to Y4F (Fig. 1C) . The crystal 124 structures of H-2D b /V3P and H-2D b /PF were determined to 2.5 and 2.6 \u00c5 resolution, respectively 125 . CC-BY 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/862144 doi: bioRxiv preprint 8 (Table S1) , and compared with H-2D b /gp33 [3] and H-2D b /Y4F [2] (Fig. 1D, Fig. S2, Fig. S9 ). 126 The overall structures of all pMHCs are nearly identical, and the amount of hydrogen bond and 127 van der Waals interactions formed between H-2D b and each p3P-APL was equivalent to each wild-128 type epitope counterpart. The backbone of the p3P-APL corresponds exactly to the wild-type 129 peptides, indicating strict molecular mimicry (Fig. 1D) The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/862144 doi: bioRxiv preprint 10 and TNF towards gp33. This is well in line with previous studies in which the Y4F-specific T cell 174 clone YF.F3 killed efficiently targets presenting gp33 but did not produce IFNg [32] . Similar 175 results were obtained using bronchoalveolar lavage (BAL)-derived T cells (Fig. S4 ). In conclusion, The p3P modification facilitates TCR recognition 209 The three ternary TCR/MHC/peptide structures were compared with each corresponding TCR-210 unbound pMHC (Fig. 4, Fig. S8 ). The side chain of p4Y, essential for recognition by P14 [4, 33, 211 34], rotates down following P14 binding to both H-2D b /gp33 and H-2D b /V3P (Fig. 4A-B) . A 212 similar rotation was also observed for residue p4F in H-2D b /PF upon binding to P14 (Fig. 4C) . 213 The side chain of p6F in gp33 is also affected upon binding to P14 (Fig. 4A) . Interestingly, the 214 p3P modification resulted in a similar conformation for p6F in both H-2D b /V3P and H-2D b /PF 215 prior to binding to P14 ( Fig. 1D and Fig. 4) . Furthermore, the side chain of residue p1K in H-216 2D b /gp33 also moves towards the N-terminal of the peptide binding cleft following P14 binding 217 (Fig. 4A) , taking an identical conformation as in both p3P-substituted peptides (Fig. 4D) . The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/862144 doi: bioRxiv preprint 12 P14 docking, p3V in gp33 extends 1.2 \u00c5 deeper into the D-pocket of H-2D b , combined with a 180\u00b0 222 rotation (Fig. 4A) . In contrast to gp33, the p2-p4 section is more constrained in both V3P and PF, 223 following TCR binding (Fig. 4B, 4C ). However, it should be noted that the final conformations of 224 all three peptides in the ternary complexes is nearly identical (Fig. 4D ). In conclusion, residues 1 225 and 6 in p3P-APLs take the same conformations prior to TCR binding as found in the ternary 226 complexes, potentially enabling a more favorable surface for P14 TCR binding. Furthermore, p1K in gp33 also takes a different conformation upon binding to P14, bending 239 backwards towards the H-2D b residues R62 and E163, which conformations are affected (Fig. 4A , 240 5A). Here again, the side chain of p1K takes exactly this conformation in both V3P and PF already 241 before TCR binding (Fig. 4, 5) . Altogether, p1K, P6F and heavy chain residues R62, H155 and 242 E163 have already adopted in the unbound V3P and PF complexes similar conformations to those 243 observed in all three ternary structures (Fig. 4, 5) . Thus, the p3P substitution potentially facilitates 244 TCR recognition by positioning specific key peptide and MHC residues prior to the formation of 245 . CC-BY 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/862144 doi: bioRxiv preprint 13 the ternary complexes. This is well in line with our SPR and ITC results, which indicate that the 246 energy required for P14 recognition of V3P is reduced compared to gp33 (Table 1, Fig. S1 ). The results presented within this study indicate in our opinion that i) docking of P14 to p3P-331 modified peptides is facilitated since the conformations of key residues in both peptide and heavy 332 chain are already optimal prior to TCR binding (ready-to-go conformation); ii) consequently, the 333 energetic costs for TCR recognition should be reduced since there is no need for any major 334 movement in the rigidified epitope besides the conformational change for residue p4Y. As The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/862144 doi: bioRxiv preprint" ] },{ "paper_id": "9701a8c529cd8c18124da4cd61c1165a64b50281", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The ethics approval was considered exempt because all date collection and analyses belong to a part of continuing public health outbreak investigation determined by the National Health Commission of China.", "The details of the model assumptions and dynamics of these six compartments across time are described in the Supplementary Methods." ] },{ "paper_id": "97027e08cb413795cf19064338efd049fe5d491b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Introduction 36", "AdV DNA polymerase (AdPol) [25][26][27]. The E3 region encoded on the top strand also has two 68" ] },{ "paper_id": "970a28c4a3c1fbcb5322772956955b8c4a3bb257", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Additionally, we suppose that the varied tropism as well as virulence of these three coronaviruses may in part account for the discrepancies, which warrants further All rights reserved. No reuse allowed without permission.", "RESULTS" ] },{ "paper_id": "97339c9d365437d54ea33be1a1b634d35f460208", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "975349ac1c79fc64525ee17e7d088c88c2c2071b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Assumptions/Notes References Delta approximation", "We write:", "All calculations, numerical analyses and figures were made with the software platform R [34] . Code is freely available at https://github.com/dushoff/ link calculations." ] },{ "paper_id": "97a34a062a7ad09f7633d4a0e76d013b28b9b582", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To determine the key evolutionary changes in major tRNA modification pathways across bacteria, 27", "The cmo5U modification exists in tRNA molecules for four box codons (Leucine, Valine, Serine, 1", "although the modification may exist in several species, we could not reliably identify homologs of 5 the proteobacterial CmoA and CmoB in other bacteria. 6", "Chlorobi-Bacteroidetes. 7", "QueG, TadA and TilS -were predicted to already occur at the root of the phylogenetic tree, i.e. 31", "Tenericutes and the endosymbiotic species from Enterobacterales (Figs. 3G, 3I and 3M), we also 6 observed a significant reduction in the total number of tRNA genes (Fig. S3G , S3I, S3M), 7" ] },{ "paper_id": "97e0830fe6c8bf6facb896320dd1b8d31ab49a54", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All authors declare no competing interests." ] },{ "paper_id": "982a6fe2fdba30430b547741811ff4411f1485f1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Metals are a limiting resource for pathogenic bacteria and must be scavenged from host proteins. 22" ] },{ "paper_id": "9896bc65559e6406d0d3cb35e9b01b953d61959d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "99a46ba28f5811c112876ec77f570d6c10778db6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The main limitation of the study lies on its retrospective nature. The outbreak is a solitary case.", "Using WeChat data to early detect outbreaks like this should be valued in the future. In addition, history data of WeChat Index 90 days ago is unavailable and how the index is calculated is not open.", "Better early warning and response systems should be established to avoid such disasters." ] },{ "paper_id": "99dab788e984601ee4efcd1138926caf10c00dcf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The three-interaction-site (TIS) model", "Note that if a is zero, then Eq. " ] },{ "paper_id": "9a077c5ff1dcbb9104feeaa832e73ccdcf5fdcc9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Therefore, all cases in this study that had been classified as \"suspicious\" were in fact positive cases. In addition, they all met the criterial for clinical diagnosis. In the following analysis, we keep the label of \"suspicious\" but also analyzed the initially confirmed cases in a separate group, side-by-side.", "Categorical variables were described as frequency rates and percentages.", "Proportions for categorical variables were compared using the " ] },{ "paper_id": "9a3de625119a83aa1401eeb297937d9605f0d1f1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "+ + + + + + + + + + + + + + + + + ++ + + + ++ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + 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Briefly, 500 \u00b5L samples preserved in R503 was first added into a 1.5 ml EP tube containing 200 \u00b5L of absolute ethanol and 200 \u00b5L samples preserved in Hank's solution was added into a 1.5 ml EP tube containing 500 \u00b5L lysis buffer.", "author/funder. All rights reserved. No reuse allowed without permission.", "The reaction was carried out on ABI StepOnePlusTM using following conditions: " ] },{ "paper_id": "9af0b8e13e1e5ac714135dca8ba6d5216966066b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Detailed molecular and structural evidence for such a high affinity state remains elusive. In this context, it is worth noting that most models for FtsZ assembly have been motivated primarily by the structure and dynamics of the conserved and well-folded GTPase domain.", "CTT \u03ba-values span a narrow range even though CTL sequences are hypervariable:", "Instead, it appears that variants that have low cellular levels are actively degraded as opposed to being under expressed.", "were performed using the ABSINTH implicit solvent model and forcefield paradigm as made available in the CAMPARI simulation package (http://campari.sourceforge.net) (Radhakrishnan et al., 2012; Vitalis and Pappu, 2009a; Vitalis and Pappu, 2009b) . Simulations utilized the abs_3.2_opls.prm parameter set in conjunction with optimized parameters for neutralizing and excess Na + and Clions . Simulations were performed using a spherical droplet with a diameter of 285 \u00c5 with explicit ions to mimic a concentration of 10 mM NaCl." ] },{ "paper_id": "9b17a9fa6be11d8b3dbed9f3dea2516020083bd3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "FastViromeExplorer is freely available at https://code.vt.edu/saima5/FastViromeExplorer.", "C o is the observed extent of genome coverage by the mapped reads, computed as", "It is worth noting that the three criteria are introduced to alleviate annotation artifacts caused by factors such as repeat sequences and low genome coverage, the actual cutoff values for R, C o , and N are based on our empirical experience and literature observation, and depending on the specific studies and the need of users, the cutoff values used here might not be suitable. To allow for flexibility and customization, FastViromeExplorer incorporates these three filters as parameters so that users can easily adjust the values to adapt to their own studies. For example, users can deploy more stringent criteria by setting higher values for R, C o , and N than the default, to get a \"high confidence\" set of viruses." ] },{ "paper_id": "9b5f5119bbfbded3245acc37859cefde967458e7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Infectiousness after the peak is scaled by , which is the slope of the post-peak infectiousness line:", "If individual i generates infections (i.e., ! > 0), then each infection generated is assigned to a particular time drawn from a random sample 0,1, \u2026 , !\"# ! that is weighted by ! ! ! ! so that hours of high infectiousness are more likely to have larger values of ! ! . Therefore, each individual i has a vector of ! ! , ! ! , \u2026 , ! !\"# ! of onward infections that occur during each hour of their infectiousness.", ") also varies widely, with quarantine reducing RS by over 65% for influenza A and hepatitis A and by less than 10% for pertussis (Fig S1) . The reader can explore results from landscapes with different intervention performance settings and disease transmissibility in the interactive supplement (https://coreypeak.shinyapps.io/InteractiveQuarantine).", "The steps are as follows:" ] },{ "paper_id": "9bbfd3d34ee18ea1b9f4669331a6cee9c5992893", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "emerged in late 2019 1,2 . Initial outbreaks in China involved 13.8% cases with severe-, and 6.1% with critical courses 3 . This severe presentation corresponds to the usage of a virus receptor that is expressed predominantly in the lung 2,4 . By causing an early onset of severe symptoms, this same receptor tropism is thought to have determined pathogenicity but also aided the control of severe acute respiratory syndrome (SARS) in 2003 5 . However, there are reports of COVID-19 cases with mild upper respiratory tract symptoms, suggesting a potential for pre-or oligosymptomatic transmission 6-8 .", "None of 27 urine samples and none of 31 serum samples were tested positive for SARS-CoV2 RNA." ] },{ "paper_id": "9bf1677e5f822110e736076a4ba6960a80f2f348", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "2.2.2 Exclusive criteria: articles were published repeatedly; studies did not include the research indicators needed for Meta-analysis; research data were missing.", "is the", "Therefore, very likely it can be confirmed that 2019-nCoV comes from bats.", "A total of 284 articles were retrieved, among which 39 papers were removed due to repeated retrieval, 212 papers were removed after reading abstracts, 23 were eliminated after reading the full text. At the end, a total of 10 articles [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] were included in this Meta-analysis, including data from 50466 patients. The specific operation flow is shown in Figure 1 . The characteristics of the literature are shown in Table 1 .", "The results of Egger test in Table 3 . There was publication bias in the Meta-analysis of the ARDS group(P=0.008).." ] },{ "paper_id": "9c32d461dc9d4737756a990cf13bae1a03e078a9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Given that ELISA-based quantification of sputum mucins may be influenced by proteases present in this sample type 14 , we further confirmed our observations using quantitative PCR to measure mucin expression in RNA extracted from sputum cells from the same subjects.", "Data from human COPD studies were analysed using the Wilcoxon matched-pairs signed rank test or Mann-Witney U test. Correlations between datasets were examined using Spearman's rank correlation coefficient. For mouse experiments, animals were studied in group sizes of 5 mice with data shown representative of at least 2 independent experiments.", "Previous studies revealed that the properties of commercially available mucins differ from key properties of native mucin systems as they, e.g. the lack of the ability to reduce friction [1] [2] [3] or lead to cytotoxic effects 4 . These differences are attributed to the harsh conditions during the commercial purification process 5 . As a consequence, here, the purification of porcine gastric MUC5AC is performed manually from fresh pig stomachs. An optimization of the original purification protocol from Celli et.al 6 was described in detail previously 3 . In brief, crude mucus was obtained by gently scraping pig stomachs after rinsing them with tap water. The mucus was diluted 5-fold in 10 mM sodium phosphate buffer (pH 7.0, supplemented with 170 mM NaCl) and homogenized by stirring at 4 \u00b0C overnight. Cellular debris was removed via several centrifugation steps (8.300 x g for 30 min at 4 \u00b0C and 15.000 x g for 45 min at 4 \u00b0C) and a final ultracentrifugation step (150.000 x g for 1 h at 4 \u00b0C). Afterwards, the supernatant was separated chromatographically by size-exclusion chromatography (\u00c4KTA purifier system, GE Healthcare, equipped with a XK50/100 column packed with Sepharose 6FF), and the fractions containing the mucin glycoproteins were identified via PAS (periodic acid/Schiff's base) staining and pooled. After a subsequent dialysis step against ultra-pure water via cross-flow filtration, the mucin-solution was concentrated, lyophilized and stored at -80 \u00b0C.", "Lyophilized bovine salivary mucin MUC5B powder was purchased from Merck (499643, Darmstadt, Germany) and dissolved in 10 mM sodium phosphate buffer (pH 7.0, supplemented with 1 M NaCl) at a concentration of 1 mg mL -1 and the solution was rotated on a rotating incubator for 1 h at 4 \u00b0C. Further purification of salivary mucin MUC5B was conducted according to the protocol used for purifying gastric mucin MUC5AC as described above." ] },{ "paper_id": "9c33486a49de4aea64ce61c0a2c21a88c316b6a8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "with N i the population size in age class i [13] . This reciprocal behavior might not be valid for specific contact types, e.g. contacts at work for retail workers are most likely not contacts at work for their customers. Therefore, reciprocity should not always be imposed.", "To estimate the relative change in R 0 , we used the R 0 ratio:", "All data and material is open source." ] },{ "paper_id": "9ca81dfa68fcbff13166d810aca929027bb3763b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Broca's, 19; conduction, 6; global, 1 and Wernicke's, 2. Four participants scored above the cut-off for demonstrating aphasia (>93.8 out of 100), as specified by the WAB AQ. Average AQ was 68.78\u00b123.91 and lesion volume was 111.27\u00b194.44 cm 3 .", "A flowchart of the groupings described above is available in Supplementary Figure 1 .", "These groups are described and statistically compared in Table 1A ." ] },{ "paper_id": "9cfdce851951c817101b36f7b292e744906474c4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The n-of-1 trial involves measuring a single patient repeatedly over time, while introducing different therapies (these could be multiple active therapies [178] or comparing therapy to placebo [179] ). In addition to individual-level analyses to understand therapeutic effectiveness for a particular patient, several N-of-1 trials can be statistically aggregated to outcome, should also be explored. Furthermore, the strongest form of n-of-1 trials not only requires a baseline phase (without treatment) and treatment phase (where you introduce the drug) but also requires treatment withdrawal and washout periods to observe the effect before reintroducing the treatment. If a positive effect of the drug is observed, withdrawal may not be possible on ethical grounds, and washout periods without any treatments may also harm patient safety. Given these scenarios, other forms of singlesubject designs that do not require treatment withdrawal (such as multiple baseline designs), or a baseline phase (such as alternating treatment designs) could be considered.", "In the absence of an effective antiviral agent or prophylactic vaccine for NiV in human, it is imperative to develop better therapeutic agents to address such infectious disease threats.", "Depending on the query signature and reference databases, many candidate compounds will often be extracted -such lists can be trimmed and prioritized for most likely candidates using annotations from reference databases (for example RepurposeDB, KEGG drugs, DrugBank, etc.) and also using specific characteristics including mechanism of action, side effects, chemical properties or biological targets. " ] },{ "paper_id": "9daed5e675ac113d1939056dcebbb1f32ec0d7ec", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Current methods for studying novel \u03b2-CoVs are technically demanding. Viral isolation from field samples is rarely successful and reverse genetics recovery of recombinant virus is labor-intensive, and expensive as synthesis of a single genome can cost upwards of $15,000. These limitations are prohibitive to studying novel CoVs at the scale in which they are discovered.", "293T, A549, BHK, Caco-2, Huh-7.5, PK-15, and Vero cells were maintained in DMEM (Sigma) supplemented with 10% FBS, penicillin/streptomycin, and L-glutamine.", "RhiNi/40.1, AJ-primary, AJi, HypNi, RaKSM-2.5i, RhiLu, and RhiNi cells were maintained in DMEM/F12 (Gibco) supplemented with 12% FBS, penicillin/streptomycin, nonessential amino acids, sodium pyruvate and L-glutamine. AJ-primary cells were immortalized with a lentiviral vector expressing SV40 T-antigen following the manufacturer's instructions to generate AJi cells (abm; #G203). RaKSM-2.5 primary cells have been previously described and were immortalized in this study similar to AJi cells 17 ." ] },{ "paper_id": "9e780780dbaf35c0d537ddb290dfd484148a3c55", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "( \u2192 ) = P(L ij = 1|Z 1ij = z 1 , \u2026 , Z pij = z p ) = P(Z 1 = z 1 , \u2026 , Z p = z p |L = 1)P(L = 1) P(Z 1 = z 1 , \u2026 , Z p = z p )", "We calculate the conditional probability of all covariate values given link status P(Z 1 = z 1 , \u2026 , Z p = z p |L = 1), as the product of the conditional probabilities of each covariate, P(Z k =", "All methods except random probabilities show spikes in at the second peak in case counts, but to different degrees (Figure 7) Figure 8 ).", "Finally, as with other infectious disease analytical approaches, our method assumes that cases were infected in the same order that they were observed (39, 59) . Although not a strong assumption for diseases with clear symptoms and a short latent period, this may not be appropriate for diseases such as TB, with a highly variable and potentially long latent period, and often substantial delays in care-seeking care and diagnosis (60, 61) . Although this assumption is a known problem in infectious disease research, it is frequently made (43, 44) because relaxing it complicates models substantially." ] },{ "paper_id": "9e94f9379fd74fcacc4f3a57e03cbe9035efee8e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To analyze the structure changes of proteases caused by induced-fit effect after binding the drugs, Steepest Descent and Conjugate Gradient Algorithms were used to minimize the energy of the protease-drug complexes successively through Minimization module of Discovery Studio software. During calculation, fixed constraint of the backbone of proteins was used first and removed later.", "Since the catalytic mechanisms of CEP_C30 and PLVP domains are both unknown, it is unable to determine whether ritonavir, lopinavir and darunavir are competitive or non-competitive inhibitors, although these drugs are all peptide analogues and seem to be competitive.", "Since there was no gene of protease identified in the ten SARS-CoV-2 genes directly, the protease-like conserved domains in the orf1ab polyprotein (GenBank: QHO60603.1) of the virus were analyzed through NCBI Conserved Domain Search Service (https://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi) [14] [15] [16] [17] . The sequences of the found protease-like domains were then used to build molecular models by homology modeling through SWISS-MODEL (https://swissmodel.expasy.org/) [18] [19] [20] [21] [22] . To evaluate qualities, Verify score, Errat score, Prove score and Ramachandran plots of the built models were automatically created by Structure Analysis and Verification server (version 5.0, https://servicesn.mbi.ucla.edu/SAVES/)." ] },{ "paper_id": "9fb5ca87ca47d35d87161158ae37fc0ca642c51e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ctrl brains (Fig 2H) . Iba1 was used as a microglial marker. The fluorescence intensity of P2ry12 119 and Tmem119 per Iba1+ cell was significantly decreased in D0 microglia compared with Ctrl 120 microglia (Fig 2I, J) . 121 122", "In order to analyze the cell populations from each cluster in more detail, we manually compared 129 the most prominently expressed markers from each cluster with the tabula-muris dataset, a single-130 cell atlas that contains annotation data for 100,000 cells from 20 different organs and tissues 131 (Tabula Muris et al., 2018) ( Fig 3C) . Cluster-1 and Cluster-2 resembled homeostatic microglia, 132 with Cluster-1 expressing high-levels of homoeostatic genes including P2ry12, Tmem119 and 133", "10" ] },{ "paper_id": "a01672035e0b9d21f9a934b9c9071610513325f2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Note: this report is a pre-print and has not yet been peer-reviewed.", "As of 29 Jan 2019, 5,997 confirmed and 9,239 suspected cases of 2019-nCoV have been reported from China with 132 deaths confirmed so far 1 . There were cases in at least 15 other countries, identified due to symptoms plus recent travel history to Hubei province, China, which strongly suggests that the reported cases constitute only a small fraction of the actual number of infected individuals in China 2 . While the most affected region, Hubei province, has now ceased air travel and closed major public transport routes 3 it is unlikely that these measures will fully contain the outbreak.", "In many international airports, information is provided to travellers from affected regions advising recommended action if they develop symptoms on or after arrival [11] [12] [13] [14] . While this is likely to be an effective strategy, we find that airport screening for initial symptoms, via thermal scanners or similar, on either exit or entry is unlikely to detect a sufficient proportion of 2019-nCoV infected travellers in order to avoid entry of infected travellers and therefore the potential for seeding of local transmission.", "It is important to note that our estimates are based on a number of key assumptions that cannot yet be informed directly by evidence from the ongoing 2019-nCoV outbreak. The current outbreak has spread rapidly and early evidence suggests that the average severity is lower than SARS. This may also suggest a substantial proportion of asymptomatic cases. A recent analysis of a family transmission cluster is based on a small sample size but 1 in 6 infections was asymptomatic 9 ; a major impediment for the effectiveness of syndromic screening. However, if asymptomatic cases were not infectious they would not pose a risk for seeding infection chains on arrival. To allow easy adaptation of our results as new insight becomes available in the coming weeks we developed an online app." ] },{ "paper_id": "a05179c57d5e1cdddc839ff3c0b70a614efbb6cb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "coronaviruses have strong potential to infect human. This method will be helpful in future viral analysis and early prevention and control of viral pathogens.", "The recently outbreak of pneumonia in Wuhan, China has brought the 2019 Novel Coronavirus Currently there is urgent need to identify the hosts potentially infected by the 2019-nCoV viruses.", "The similar probabilities of 2019-nCoV and other human Coronaviruses illustrates the high risk of 2019-nCoV. Part of the p-value results is shown in Table 1 , which is ranked by the decreasing order of the p-value for a virus to infect human." ] },{ "paper_id": "a09c1ad0f05bbcc256cd667ad7411e6690134370", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(1)" ] },{ "paper_id": "a0ecc9b46addbc1faab491434b5331702f7883b8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The flowchart of the model was shown in Figure 1 ", "Since the different dimension of people and the virus, we adopt the following sets to perform the 133 normalization:", "According the official report by National Health Commission of the People's Republic of China, we 163 collected the data of daily fatality from January 24 th to 30 th , 2020 [16] . Therefore, we set f as 0.02348", "There were several studies focusing on mathematical modelling on 3] , calculating the 78 R 0 by using the serial intervals and intrinsic growth rate [2, 5, 6] , or using ordinary differential equations 79 and Markov Chain Monte Carlo methods [3] . We also developed a Bats-Hosts-Reservoir-People (BHRP) " ] },{ "paper_id": "a1bff76ce360e8990b0a4ee2a5228a6e6e63d9c1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The epidemic of novel coronavirus infections that began in 12", "We scanned publicly available information published in research articles 5 and quoted from official reports of outbreak investigations to obtain our dataset. 6", "Here, g(.) is the probability density function (p.d.f.) of exposure following a 20" ] },{ "paper_id": "a22ceac8d5e1cfaf2e79557d3c794458d0e1cdbe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "of \"no substitution\" at any position if one read matches the 2019-nCoV genome. This will provide a 306 lower bound of variation, although regions covered by a single read are still subject to amplification 307 and sequencing error. Near-perfect overlaps between reads from SRR10168377 argue that such error 308" ] },{ "paper_id": "a2a6e262098539eb875a26800d9f6d3d0d5d1875", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We used a previously described biodegradable dry powder, PLGA microsphere, synthetic vaccine platform adjuvanted with TLR-4 and TLR-9 ligands", "Animals having unwitnessed demise did not have serum samples collected. A", "We observed low levels of IL-6 in surviving mice. NHPs infected with EBOV have been determined by other researchers to have elevated levels of IL-6 in plasma and serum [23] [14] . EBOV infected humans have also shown elevated 145 IL-6 levels and these elevated levels have been associated with increased morality [58] .", "mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within COVID-19 contain multiple class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus. (IPVYQVNNLEEICQLIIQAF). They also suggested that a CTL vaccine for could be designed using epitopes targeted by CD8+ T-cells identified in these EBOV controllers." ] },{ "paper_id": "a2ab0a998912ed2ec93187333dca03aa22e39a71", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ ". CC-BY-NC 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.08.939553 doi: bioRxiv preprint", "Overall, our work provides a window into the immunological features of 2019-nCoV, and we hope our work could aid therapeutic development against this virus to stop this pandemic earlier and to aid the vaccine development to prevent future breakouts.", "The 2019-nCoV complete genome sequences and meta data were downloaded from the https://bigd.big.ac.cn/ncov database, before the data lock of Feb 5 th , 2020. The reference genome annotation was acquired from NCBI: https://www.ncbi.nlm.nih.gov/nuccore/MN908947. The complete genome SARS and MERS sequences are also downloaded from NCBI: https://www.ncbi.nlm.nih.gov/nuccore/?term=txid694009%5BOrganism%3Anoexp%5D+and+c omplete+genome and https://www.ncbi.nlm.nih.gov/nuccore/?term=txid1335626%5BOrganism%3Anoexp%5D+and+ complete+genome" ] },{ "paper_id": "a2ba0a34df31fd8059ed22787331a75b65eafa74", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "When the tolerance of the filter on case counts is small, quenching of transmission ", "This analysis was conducted using R 3.4.2 (R Foundation for Statistical Computing, 225 Vienna, Austria). ", "This analysis was conducted using R 3.4.2 (R Foundation for Statistical Computing, 245 Vienna, Austria).", "These additional results can be found in the Supplemental Material." ] },{ "paper_id": "a3116a1ea2e157c8855023d968cc0f0bd6c9846f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "These data along with data from our study, enforcing bat origin of infection, could clarify the transmission dynamic of the 2019-nCoV supporting infection control policy during the ongoing epidemic.", "Recently, Ji et al. described homologous recombination within the spike glycoprotein of 2019nCoV favoring cross-species transmission and suggested snake as probable virus reservoir for human infection because its Resampling Similarity Codon Usage (RSCU) bias is more similar to Bungarus multicinctus snake compared to other animals and humans [3] . In a previous article has been proven that compositional properties, mutation pressure, natural selection, gene expression and dinucleotides affect the codon usage bias of Bungarus species [14] .", "The family Coronaviridae comprises large, single, plus-stranded RNA viruses isolated from several species and previously known to cause common colds and diarrheal illnesses in humans [1] . A previously unknown severe acute respiratory syndrome (SARS) [4] and manually edited using Bioedit program v7.0.5 [5] ." ] },{ "paper_id": "a33f451d8e2caff57c1133f14198454a64993c47", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Thermo Scientific) supplemented with 10% foetal bovine serum (FBS; HyClone) and 6 8 penicillin-streptomycin solution (Thermo Fisher Scientific). Cells were maintained at 6 9 37 \u00b0C with 5% CO 2 .", "1", "1 4 3" ] },{ "paper_id": "a34d2c1876ffedc4f95f3af13ac06039cd38a5b0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "is the proportion of cases with delay between onset or hospitalisation and death.", "All ages combined 0.91% (0.11% -4.3%)", "1.9% (0.60% -4.3%)" ] },{ "paper_id": "a36bfdd1c9a1666401269fb0c08a3c2922bd6812", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The demographic characteristics of the 24 asymptomatic cases are shown in Table S1 .", "History of smoking and coexisting disorders was also collected.", "Pharyngeal swab specimens, as described above, were tested for COVID-19 by using qRT-PCR kits (BGI Genomics, Beijing, China) recommended by the Chinese Center for Disease Control and Prevention (CDC) following WHO guidelines 11 " ] },{ "paper_id": "a388cca261e8af7936cf3b79c35f43442f65706b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Protein sequence alignments were performed using Clustal Omega 36 .", "SB: salt-bridge. HB: hydrogen bond. PI:\u03c0-stack or \u03c0-anion interaction. NP: non-polar interaction." ] },{ "paper_id": "a3dcd6b3f0551e607d0235616109ab8d506f81a2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Because this latter approach leads to bias in estimating VES (see Figure 1 and Results), we consider five additional approaches.", "Approach 4 corrects this bias by converting the risk-based analysis into a rate-based analysis (18, 23 )." ] },{ "paper_id": "a42ff48d50aa3a0ebfe840d46ed2204c49955442", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "SPSS 21 software was used for data statistics. Independent sample t analysis, analysis of variance, correlation analysis and regression analysis were mainly used.", "* p\uff1c0.05\uff0c** p\uff1c0.01\uff0c*** p\uff1c0.001", "The authors declare that they have no conflict of interest." ] },{ "paper_id": "a44334e676e43c1889d282b0f0a8365f0f1e0c52", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The sponsor of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication" ] },{ "paper_id": "a4d1861ceb0adf8dbdb8aed9465a3487fded5568", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "using ImageJ, and each lane was normalized to its respective densitometry value for beta actin. 206", "We analyzed food consumption in R (https://www.r-project.org/) using mixed model 212", "novelty-induced hypophagia due to a depressive-like effect (Dulawa & Hen, 2005) . 343" ] },{ "paper_id": "a5039336577ac0fed15b784adb912df2a6a143f3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This paper is the first reported clinical study in a non-Hubei study in China." ] },{ "paper_id": "a555fbeeffc44dfdb5087c83395f0f743654cbba", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In addition to transcriptome analysis, we directly investigated whether the virus influences 398 the cellular morphology of M. restricta and the structures of its intracellular organelles by 399", "Cryptococcus neoformans, E. coli, and Staphylococcus aureus. Unexpectedly, the purified 220 protein displayed no growth inhibitory effect on the microbial cells tested (data not shown).", "397", "Sucrose gradient ultracentrifugation was conducted to purify virus particles to confirm that 146 the dsRNA segments in the Malassezia strains were indeed viral elements. The separated 147 nucleic acids and proteins in each fraction were analyzed. Two dsRNA fragments (~5.0 and 148 ~1.7 kb) were clearly visible in fractions 1-6 following agarose gel electrophoresis ( Fig. 2A) ." ] },{ "paper_id": "a5944e859b017fd4504ea042daaec613f3fba167", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "However, these studies will be useful to further evaluate the general entry mechanism of 530 tibroviruses, including, for instance, the identification of (the) tibrovirus cell surface receptor(s), 531 which appear to be rather ubiquitously expressed. To evaluate the pathogenic potential of alleged 532 human tibroviruses such as BASV, EKV-1, and EKV-2, replicating isolates will have to be 533 obtained either by means of isolation from a natural host reservoir or vector or by means of 534 reverse genetics. ", "Tibrovirus cell entry 12 some tibroviruses could infect humans. Because BASV was discovered in the serum of a severely ill individual, tibroviruses should be considered potential human pathogens for 459 surveillance purposes until this hypothesis is ruled out.", "32" ] },{ "paper_id": "a59906b732bf4a489e282c3e4f499d4166c622e7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a625e5d6fc8956c231c500a40e887e248a69de61", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "is urgently needed to improve the outcome of infected patients.", "Radiological analyses comprised of X-ray and computed tomography.", "Inflammation markers were calculated using specific parameters of blood tests." ] },{ "paper_id": "a6af28a7f0a0d8d1e4d5b06f5ae38412298bbcb4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nasopharyngeal samples were collected by study coordinators once a week irrespective of participant symptoms. Samples were screened using the GenMark eSensor RVP system for 18 different respiratory viruses, including coronavirus 229E, NL63, OC43, and HKU1. Sample collection and extraction followed the same protocol as in Shaman et al. (5) ." ] },{ "paper_id": "a6b05fa393f9404c906099e179ca476294068394", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sequence-diverse Omps are also commonly used as receptors by phages that infect Gramnegative hosts; examples include OmpA, OmpC, OmpF, LamB, FhuA, as well as others [15] [16] [17] [18] [19] [20] [21] .", "Previously published kinetic analyses performed with BLI for animal viruses and their respective host receptors have shown that binding affinities are in the \u03bcM -pM range [30] [31] [32] ." ] },{ "paper_id": "a6d2875c8b70a41ea815511417546a0689816964", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We used the monthly number of air ticket bookings during 2017 from the Official Airline Guide 14 to approximate the volumes of air passengers for each origin-destination route.", "(which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.02.17.20024075 doi: medRxiv preprint", "Background" ] },{ "paper_id": "a6e5c7919fa1f35244c27ef7e31f6b5817211b66", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a726e1844e86c7c17b8b4461dd4c29ad3094c792", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a7804d77d1a75810af0148d8fea8acbe2941f1b9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a7a4a5568e5b7c921bc616eedf532a393229decb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We also considered overlap type (internal vs. terminal) as a fixed effect, but removed it because it did not significantly enhance our model (p = 0.86). To determine the statistical significance of each effect, we used the anova function in R to compare nested models.", "For each viral species, codon usage data [29] , [55] were used to calculate a relative synonymous codon usage (RSCU) value for each codon [17] :", "Scripts and data tables used in this work may be accessed at: https://github.com/ MaselLab/Willis_Masel_Overlapping_ Genes_Structural_Disorder_Explained", "Frameshifting these control sequences was performed in two ways. First, removing one or two nucleotides immediately after the start codon and two or one nucleotides immediately before the stop codon generated +1 and +2 frameshifted non-ORF controls, respectively ( Figure 4A ). Any stop codons that appeared in the new reading frames were removed." ] },{ "paper_id": "a7ac40c0f2083c733cc714e563b21c2d606818c0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "a83b9f98ccbd6dd76d47c49cfe5785f9c2ecc09e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Our estimated Rs for 2017-18 (1.33 with 95% CI: [1.29, 1.37]) and 2018-19 (1.29 with 95% CI: [1.27, 1.32]) are significantly higher than those for 2016-17 (1.23 with 95% CI: [1.22, 1.24])", "We present the modeling analysis procedures in a flow diagram in Figure 2 . All analyses are conducted by using R (version 3.4.3 [32]), and the R function \"nls\" is employed for the NLS estimation of model parameters." ] },{ "paper_id": "a891d059692c951d1fb0fb36914fe451f973684a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Plasmid constructs 358 KLK13 and TMPRSS2 genes were amplified by PCR using cDNA obtained from HAE 359 cells. Each PCR product was cloned into pWPI plasmid for lentivirus production and sequence Table 2 . (Table 3 ; 500 nM each). \u03b2-actin was used as a household gene reference.", "important factor pre-determining the cell and tissue specificity of the virus, but also regulating 121 the interspecies transfers.", "113" ] },{ "paper_id": "a8be6ba53508e988c2c8c153478ff615b0d77687", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As an RNA-targeting CRISPR effector, CasRx is especially appealing for ", "Hydrodynamic tail-vein injection, a simple yet effective method, can be used to deliver naked DNA into hepatocytes of mouse liver in vivo (Kim and Ahituv, 2013) . After 96 hours of plasmid injection, individual hepatocytes were dissociated through liver perfusion. Hepatocytes expressing both GFP and mCherry implied successful vector delivery and were purified through cell sorting. Though not mathematically significant, results suggested that the Pten mRNA level in GFP+/mCherry+ hepatocytes had decreased in comparison with that in GFP-/mCherry-hepatocytes (Fig. S3B) .", "CasRx-mediated lncLstr knockdown was sufficient to result in reduced expression of Cyp8b1 (Fig. S3F ). Thus, efficient knockdown of lncRNA was successfully obtained in hepatocytes using the CasRx system." ] },{ "paper_id": "a8e53c77bc72f467723a7d5b8020875c0e96f8aa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We used BALB/c mice to determine the pharmacokinetic profile of the fusion protein.", "Y.L., and M.D. declare they are employees of Pharchoice Therapeutics Inc. " ] },{ "paper_id": "a9a978c056422f979395ce56c96738d33b104a3e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "protective RFs that dually served as a barrier against host sensors in addition to providing 122 sites of replication. 123 124", "In this study, we present findings supporting a proviral role of the host RNase L protein, 378 which has otherwise been considered strictly antiviral. RNase L nucleolytic activity is 379 highly effective at restricting replication of a diverse range of DNA and RNA viruses 380 (Silverman, 2007) . However, catalytic activation of RNase L by ZIKV does not limit 381 infection, and instead ZIKV titers are paradoxically increased with RNase L expression. 382" ] },{ "paper_id": "a9c58042555c0d56b8e94bc5558db0c3dd697dcc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Retrospective case series.", "We present the summary statistics of continuous variables using the means and standard deviations (SD) or median (IQR), comparison across groups were performed using the Mann-Whitney U test. Categorical variables were expressed as the counts and percentages in each category. Chi-square tests was used for categorical variables as appropriate. All analyses were analyzed by IBM SPSS statistics version 26.0.", "Methods", "This was a retrospective case series study, no patients and public were involved in the design, or conduct, or reporting, or dissemination plans of our research." ] },{ "paper_id": "aa507fcd3876f8c422993c8dd13847b1b8e77471", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "aa5a99e67d3e887b3fa88575fb0d4a662d0a60ce", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In a recent comprehensive review of epidemiological models, Smith et al. [1] trace the development of systems of differential equations used over the past 100 years to study disease processes. Once the purview of mathematicians, physicist and engineers, dynamical system formulations of epidemic processes are increasingly being used by epidemiologists, ecologists and social scientists to study the potential for disease pandemics to threaten the lives of humans, domesticated animals and plants, and all organisms across the globe.", "Finally, given the centrality of dynamic epidemic models to containment of outbreaks, policy formulation and response logistics, modeling tools are needed that can be used by healthcare professionals not trained in computational methods to carry out containment policy, and response analyses. Thus, our strong focus is on how to use the Numerus Model Builder and demonstrate its use to address these issues in the context of epidemics that are spatially structured, such as the recent outbreak of Ebola in West Africa [16, 17] .", "To complete the description, we need to include the relationship" ] },{ "paper_id": "aacc3acdd6a928fd820d51a2d1ea98c164b6abd4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "B. C.", "B.", "D." ] },{ "paper_id": "aad76905ce54679c80b75e4ee35717c30e7e1099", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "ACCGCTGCCA|cacctcagaa. Using 5' and 3' sRNAs, the 3' cleavage site of TRL-TAG3-1 was determined as 179", "Among these full-length mature tRNAs, 8,539 TRD-GTC2-1 tRNAs (for Asp) and 16,900 TRE-CTC1-1 174 tRNAs (for Glu) were obtained. These results suggested that 3' sRNAs were produced by tRNA degradation 175 during its synthesis, when CCAs were post-transcriptionally added to 3' ends of tRNAs one nucleotide by 176 one nucleotide. Another example was the correction of TRL-TAG3-1's annotation. The mature TRL-TAG3-177 1 was annotated as a 82-nt sequence from the human genome with its 3' cleavage site 178", "RNA sequencing (RNA-seq) , usually based on the Next Generation Sequencing (NGS) technologies 54 is widely used to simultaneously measure the expression levels of genes with higher accuracy than Serial 55" ] },{ "paper_id": "ab1692d56f32fdb0922e5f323f6ca385fb1e0808", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A. castellanii cells, the cellular support of the system, were resuspended three times in PAS.", "in the absence of cell lysis.", "The obtained sequences were assembled with ChromasPro 1.7.7 software (Technelysium Pty Ltd, Australia)." ] },{ "paper_id": "abcfffafab399149d4adadd6bb458c4994e2025d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "were considered statistically significant for all statistical tests.", "The Table 1 ).", "Therefore, more efforts are needed to prevent the transmission in communities and other public places." ] },{ "paper_id": "abe590b95aa51e7309844156acdae4085870ea33", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The area under curves (AUC) of receiver operating characteristic (ROC) were calculated for predictive analysis. Spearman rank correlation coefficient was used to analyze the linear correlation between two sets of continuous variables. It was considered statistically significant when the P value was less than 0.05. All statistical analyses were processed using SPSS 25.0 statistical software.", "Patients were not directly involved in the design, planning and conducting of this study.", "The study was an observational, descriptive study." ] },{ "paper_id": "ac35eeb6eaaf382fe0e123719f7dc409046e5d87", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Additional information about these confirmed cases was retrieved from the websites of the official provincial and municipal health commissions throughout mainland China. A listing of these websites is provided by the National Health Commission of People's Republic of China at http://www.nhc.gov.cn/xcs/yqfkdt/gzbd_index.shtml." ] },{ "paper_id": "ac4a3bbe27272cd6780e7168906b0bf1413fc749", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ac81102667b0d56edeb8ab0044765dc49a19f374", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Positive-strand RNA viruses replicate at membranous structures that accommodate the viral 37 replication complex and facilitate RNA synthesis in the cytosol of infected host cells (1-5). 38", "Collectively, we establish a spatial link between viral RNA synthesis and diverse host factors 32 of unprecedented breadth. Our data may serve as a paradigm for other positive-strand RNA 33 viruses and provide a starting point for a comprehensive analysis of critical virus-host 34 interactions that represent targets for therapeutic intervention.", "To confirm the accommodation of BirAR118G within the viral RTC, MHV-A59-, MHV-103" ] },{ "paper_id": "acb0e11e5763dbf7588ec435751a2ab705a783f1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Coronaviruses are single positive-stranded RNA viruses belonging to Coronaviridae family 1 , which are divided into four genera: Alpha-, Beta-, Delta-and Gammacoronavirus. CoVs are commonly found in many species of animals, including bats, camels and humans. Occasionally, the animal CoVs can acquire genetic mutations by errors during genome replication or recombination mechanism, which can further expand their tropism to humans. The first human CoVs were discovered in the mid-1960s. A total of six human CoV types were identified to be responsible for causing human respiratory ailments, which include two alpha CoVs (229E; NL63), and four beta CoVs (OC43; HKU1; SARS-CoV; MERS-CoV) 2 . Typically, these CoVs cause asymptomatic infection or severe acute respiratory illness, including fever, cough, and shortness of breath. However, other symptoms such as gastroenteritis and neurological diseases of varying severity have also been reported [3] [4] [5] .", "Here, we report a detailed genetic analysis of 2019-nCoV evolution based on 47 genome sequences available in Global Initiative on Sharing All Influenza Database (GISAID) (https://www.gisaid.org/) (Supplemental Table 1 ) and one genome sequence from GenBank. We further defined potential epitope targets in the structural proteins (SPs) for vaccine design.", "Envelope protein shares 100% identity." ] },{ "paper_id": "acd5cb2ba08da5c0f6bc310d74d497d38aa86be2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "have not tested this directly. 413", "Kit, Thermo Scientific #23227), were acetone precipitated by incubating with 4x volume ice cold 469 acetone overnight at -20\u02daC. Precipitated proteins were pelleted at 4\u02daC at 13,000 x g for 10 470 minutes and the pellets were dried for 30 minutes at room temperature. Pellets were resuspended 471 in 10 \u00b5L Pierce TM RIPA lysis buffer (Thermo Scientific #89900), 3.25 \u00b5L NuPAGE 4x LDS 472", "Photometrics, Tucson, AZ), and a temperature-controlled stage, set at 37\u02daC. To image the DQ-564 BSA, we used an excitation filter centered at 572 nm and an emission filter centered at 635 nm. 565" ] },{ "paper_id": "acd8d28ae75dc1ec5fea2d767e3158545011c1f7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/502609 doi: bioRxiv preprint", "85 Previous data suggested a crucial role of adaptive immunity in host resistance to 86 causative agents and the disease progression. The recently identified IL -35 and IL-37 87 cytokines revealed an important role in immune suppression. Nevertheless, the 88 expression of these interleukins in patients with mycetoma has not yet been 89 investigated. Therefore, the present case-control study aimed to determine the levels of 90 IL-1 family (IL-1\u03b2, IL-37) and IL-12 family (IL-12, IL-35) in these patients and the 91 association between these cytokines levels and the patients' demographic 92 characteristics. . CC-BY 4.0 International license is made available under a", "The results of this study showed that the levels of IL-37 and IL-35 were consistently 94 positively correlated with different diameters of mycetoma lesions as well as its duration. 95 However, the levels of IL-1\u03b2 and IL-12 were consistently negatively correlated with 96 different diameters of lesions and the duration of mycetoma infection. The analysis of 97 the risk factors of higher circulatory levels of IL-37 in patients of mycetoma showed a 98 significant negative association with IL-1\u03b2 cytokine. Furthermore, the risk factors of 99 higher levels of IL-35 in patients of mycetoma revealed a significant negative 100 association with IL-12. These findings uncover a possible the role of IL-35 and IL-37 in 101" ] },{ "paper_id": "adb09e4e5c7331b2aa661b3d3bb0a643e00d11bc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Using VirMAP 5 , we aimed to reconstruct coronavirus genomes to compare recovered RBM sequences to that of nCoV-2019.", "The two genomes were merged using the easymerge.pl subcommand from VirMAP to create the final pangolin-associated coronavirus (Pangolin-CoV) genome.", "Of the three viral metagenomic datasets inspected, only the pangolin dataset contained coronavirus genomes sharing significant homology with the outbreak strain. Two samples in this dataset yielded two partial coronavirus genomes that overlapped >8.4kb at >99% nucleotide identity with each other." ] },{ "paper_id": "adb3a6501ad731eda95d0a1a182a793a0dcd58b0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "2 may be underestimated by several fold, and severity correspondingly overestimated by several fold." ] },{ "paper_id": "ae4f1ac93bb55da1231f08eb1654f19352ab1a3f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ae61300f4e7a12a68baf114f199eb51940c7aad3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "epidemic can be completetly controlled in May,2020.", "epidemic can be completetly controlled in May,2020 (Figure 5,Figure 7) . It can be probably avoided the pandemic of global" ] },{ "paper_id": "ae66f22f886d3b019934ae237c11a5fb53dbefb2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Then, the node degree was calculated with the functions of degree in the R package igraph (version 1.2.4.2) (Csardi and Nepusz, 2006) .", "The frequencies of k-mers with one or two amino acids were calculated for each human protein with a Python script.", "Combination of the random-forest model with protein-protein interactions between human and viruses predicted in previous studies further predicted" ] },{ "paper_id": "ae6fc64042b050df93ebb8f8045892952f18510f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For MSTI to be beneficial, one needs to minimize and maximize [9] . An approach to reduce 94 could be the use of dedicated testing sites separate from the usual healthcare facilities [10] . 95", "A symptom-based mass screening and testing intervention (MSTI) can identify a large fraction", "part of containing infectious disease outbreaks [1, 2] . A symptom-based mass screening and 23 testing intervention (MSTI), is an approach that can identify a significant fraction of infected 24" ] },{ "paper_id": "aef0734eb2538d3624d650a4ae20c3f66cace5f2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "af266fac8970a7960e96630a67d91bec5dda0335", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ ". The density function h(.) is given by [11] ,", "To account for uncertainty in the transmission links we resort to a Bayesian framework in which missing links are imputed [10] (see Subsection 2.3). The likelihood function is then given by L \u0398, v(i) missing |z i , v(i) .", "We use the Bayesian method described in te Beest et al. [10] for parameter estimation." ] },{ "paper_id": "b0746b57a6c8f3cd9e52a27b0d708d069134b502", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b0899a264af548a89d649154aec569889717b295", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 How well can deterministic models match the predictions made using stochastic simulations?", "\u2022 Do the concepts such as 'breakpoints' in transmission still apply when stochasticity is introduced?", "\u2022 How are transmission and control affected by infected human migration in a world of stochasticity?" ] },{ "paper_id": "b117016a887f05386acc4387dab5bf8c769cf90e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CoV-2 post the critical date is below 70.", "Ethical approval or individual consent was not applicable. 256", "All data and materials used in this work were publicly available, and also available based on request. 258" ] },{ "paper_id": "b1a5096c2bfbb4ab9826c36e3961929a744134ca", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "102", "The dilution term, \u03b4(a), models how contacts are distributed among susceptible acquain-147 tances.", "dI n dt = n I \u03b3(I n\u22121 I n ) for n = 2, 3, . . . , n I" ] },{ "paper_id": "b1b9d81726e56c2781ce6b63ae5015cf2f314c6f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A2: The flows in domestic provinces are concluded, the abroad flow-in is not considered. A3: Only the susceptible with no clinical symptoms can flow in and out, the exposed and infections will be quarantined.", "A6: The recovery rate is time-dependent and will linearly increase.", "A1: The outbreak of COVID-19 started on the beginning of Dec., 2019." ] },{ "paper_id": "b1ce6ca5960cb799403188ca303a364428f812d8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "However, most current screening methods rely on PCR, which is expensive and relies on 81 laboratory facilities. In addition to screening for Wolbachia infection, it would also be desirable to 82 identify the host mosquito species using these assays since different mosquito species differ in 83 their ability to transmit pathogens [20] . Knowledge of vector species, and prevalence and stability 84 of Wolbachia is essential for effective vector control and pre-emption of disease outbreaks with 85 public health measures [21] . 86", "Unfortunately, mosquitoes are most commonly identified using morphological taxonomic keys. 87", "This process can be tedious, and requires highly trained personnel and undamaged mosquitoes. 88" ] },{ "paper_id": "b1e7752cbf528db99723a3a67b49b9b5c6e449af", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As a measure of genetic differentiation we estimated F ST between all the virus lineages based on the (1). H w was calculated separately for the two lineages being compared, and 302 the unweighted mean used in equation (1).", "Mutations ordered by position in DCV genome 214 352 363 454 794 849 1206 1281 1290 1299 1331 1445 1529 1576 1589 1811 1829 1850 1901 1976 2018 2318 2509 2610 2804 2891 2930 3023 3111 3154 3291 3349 3491 3721 3761 3807 3824 3864 3884 3966 3989 3998 4118 4832 4934 5219 5453 5510 5552 5573 5696 5936 6008 6227 6235 6312 6495 6551 6719 6722 6787 6927 6990 7014 7016 7039 7084 7087 7388 7703 7711 7922 7923 7936 7939 7981 7992 7997 8000 8012 8041 8069 8070 8072 8073 8075 8076 8079 8084 8142 8144 8153 8154 8282 8285 8294 8392 8677 8761 8845 8869 8961 Mutations ordered by position in DCV genome ", "This processes was then repeated using the DCV samples from the first dilution series. One clone,", "To generate a reference ancestral Drosophila C Virus sequence we amplified the ancestral starting 262 virus by PCR as above. PCR products were treated with exonuclease 1 and Antarctic phosphatase to " ] },{ "paper_id": "b38ed62b303eaa444d188deb2ab0b23bbdb79211", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Coronaviruses (CoV) first became widely known after the emergence of severe acute respiratory syndrome (SARS) in 2002. They are are positive, single-strand RNA viruses that often infect birds and a variety of mammals and sometimes migrate to humans [1] . While coronaviruses that infect humans usually present mild symptoms (e.g. 15% of cases involving the common cold are caused by a coronavirus), several previous outbreaks, such as SARS and Middle East respiratory syndrome (MERS) [2] , have caused significant fatalities in infected populations [3] .", "From an economic perspective, the development of coronavirus vaccines faces significant financial hurdles as most such viruses do not cause endemic infections. After an epidemic episode (e.g. SARS) there is little financial incentive for private companies to develop vaccines against a specific strain of virus [10, 2, 8] . To address these incentive issues, governments might provide greater funding support to create vaccines against past and future outbreaks.", "Supplementary " ] },{ "paper_id": "b38f3c83aaa3fa7c8f5c87af266793afcbd11c86", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Histological examination of COVID-19 showed bilateral diffuse alveolar damage with cellular fibro-myxoid Exudates, evident desquamation of pneumocytes and hyaline membrane formation [7] and then interstitial fibrosis." ] },{ "paper_id": "b3cb1d91dcd7f78dd9bbc88b93d2403eb6869746", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Conforming to the recently identified role of APOC3 in insulin resistance, HOMA-IR plasma insulin levels, body weight and adiposity correlated positively with HDL associated APOC3 levels (r=0.50, P=0.00017; r=0.44 P=0.0015; r=0.23, P=0.048; r=0.26, P=0.021, respectively).", "Supplementary Figure 2 . A representative QTLs for HDL proteins normalized to total PSMs. Loci associated with A) APOA2, B), NAPSA, C) SAA2, D) SAA4.", "HDL-C was negatively associated with ABCA1 mediated sterol efflux from both BHK and J774 cells (r=-0.58, P=0.00036 and -0.49, P=0.03 respectively) and was positively associated with the diffusional (unstimulated) efflux from both cell types (r=0.62 P=6.14e-06 for BHK and r=0.64 P=2.04e-05 for J774)." ] },{ "paper_id": "b4d9a00412c65725de441654454803bb20ecb931", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Publicly available experiments on other coronavirus experiments were found by searching the ProteomeXchange Consortium web interface (http://www.proteomexchange.org/). 45, 46 Clarification of the identity of unpublished data from Pacific Northwest National Laboratory (PNNL) was provided by Dr. Michael Monroe.", "Our work demonstrates not only the feasibility of this approach, but also its ability to rapidly develop methods even in the face of limitation of access to sample experimental data. We use the example of SARS-CoV-2 viral protein detection to underscore the utility of this approach in responding to an urgent public health crisis.", "PRM methods monitor multiple transitions simultaneously but at a time cost. The highest scan speed currently available in Orbitrap instruments is 48 scans per second and is only available on the Exploris 480 system (data not shown). In order to achieve maximum sensitivity, higher fill times are often required for these instruments. We chose to utilize three peptides/protein for these methods. Alternative peptides can be selected from the Skyline files provided (Supplemental Information) or by selecting peptide mass targets from the other transition lists. " ] },{ "paper_id": "b4edd81e0d2770b0d6e0e3c93c7fffc43e3caa80", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Two different periods of time of 12 and 15 days were tested, along with 3 and 5 different starting points.", "These results are in agreement with other studies that suggested that the aerosol spread of the influenza virus is both dependent upon relative humidity and temperature, although performed in animal models 14 , and that the virus survival in droplets is higher at high humidity levels with a significant decrease on its infectivity rate at mid-levels of humidity 15 . Additionally, other authors suggest that some diseases spread faster in high humidity levels 16 , reporting an odds ratio for a community-acquired pneumonia case, diagnosed with leggionaire's disease a , 3.1 times higher in high humidity level (above 80%) than when submitted to humidity levels below 50%, at temperatures of 16-27 \u00baC (60\u00ba-80\u00baF).", "Wei Lo et al 17 However, their predictions were performed using SARS data and meteorological a Caused by bacteria, not virus, but symptoms are similar to flu, with pneumonia as an expected outcome.", "To compute the rate of spread a simple exponential model was assumed, described by:", "Funded by National Funds via FCT (Foundation for Science and Technology) through the Strategic Project UIDB/04539/2020 and UIDP/04539/2020 (CIBB)." ] },{ "paper_id": "b4fc44eabb1f640124fff98990c85dc5c9984aee", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The subset of genomic sequences which included 5\u2032 UTRs was identified, and these sequences were 182 aligned against one another using Kalign (24). The synonymous site variability analysis was 183 performed as described in (25) ", "We utilized sequencing of ribosome protected fragments (RPFs), known as ribosome profiling 66 (Ribo-Seq), in combination with whole transcriptome sequencing (RNA-Seq), to investigate 67 translation of the ZIKV genome at sub-codon resolution. African green monkey (Vero E6) cells 68", "West Nile virus; 13) except near the 5\u2032 end (Fig. 1D) . Note, however, that these comparative 82 analyses are restricted by the low sequence diversity available in the ZIKV clade. 83 84 Strikingly, we found significant ribosome occupancy within the ZIKV 5\u2032 UTR ( Fig. 2A) . The 85 length distribution of Ribo-Seq reads mapping to this region mirrored that of polyprotein-mapping 86" ] },{ "paper_id": "b5161b031c7f720562e94735a018d1c3c8be3ae5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "During outbreaks of deadly emerging pathogens (e.g., Ebola, MERS-CoV) and bioterror threats (e.g., smallpox), actively monitoring potentially infected individuals aims to limit disease transmission and morbidity.", "When estimating incubation periods in real-time, care must be taken to adjust for possible truncation of longer incubation periods (26,27) or selection biases that could favor reporting of shorter incubation periods (9) ." ] },{ "paper_id": "b51d1c7287ac75790a52752489577d33d522898b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analyses were performed using the R software, version 3.5.3.", "of exported infection cases have been identified in Japan, Korea, the United States, Canada, France, etc. On January 30, 2020, the WHO has confirmed 7,818 cases worldwide, and 7,736 cases were reported in China.", "Journal of virology 2020." ] },{ "paper_id": "b53dd68cad40cbcd698a848f53853e5f03d44a1f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b579c3547bba2a33057373d57b7c05f37dd4cfc3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "greatly relieved.", "Overall, there are significant differences in the three detection methods (P<0.001)." ] },{ "paper_id": "b5b029e65b963ae092dd88b21911e74b0cf557cc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Antibiotics comprise a large and complex group of compounds typically secreted by 44 bacteria targeting other prokaryotes. Antibiotics have revolutionized medicine since its 45 discovery. However, overuse and misuse of antibiotics have led to the emergence of 46 resistant bacteria in humans and in livestock. Current medicine faces a dire threat of 47 antibiotic resistant bacteria, which is rampant in many hospitals around the world. In 48 addition to its microbicidal activities, antibiotics can also directly affect mammalian cells in 49 a variety of ways. Antibiotics have been reported to directly inhibit eukaryotic translation 1 , 50 inhibit mitochondrial function 2,3 and induce changes in mammalian metabolic pathways 4 . 51", "We previously showed that oral neomycin treatment renders Mx1 deficient mice 181 susceptible to influenza disease because it depletes gut commensal bacteria that normally 182 support the function of dendritic cells that prime CD8 T cells 18 with an otherwise lethal dose of hvPR8, with 50% of mice protected (Fig. 3b) . These 191 results demonstrate that mucosal application of a single dose of neomycin can result in 192 substantial protection against a highly virulent influenza A virus infection. 193", "To extend our findings to human cells, we treated primary peripheral blood monocytes 203 knockout hosts showed relatively lower levels of ISG induction ( Supplementary Fig. 5a,d) . 220", "The specific RNA bound by the aminoglycoside that triggers TLR3 remains unknown. The 391 interaction of aminoglycosides with mitochondrial ribosomal RNA, which is closely related 392 to bacterial ribosomal RNA, is well characterized and aminoglycosides have also been 393 found to bind mitochondrial ribosomal RNA at multiple sites 38,55 . It is possible that 394 mitochondrial rRNA-bound aminoglycosides might activate TLR3 in XCR1+ DCs in the 395 endosome. Our results show that aminoglycoside and Poly I:C can synergize to induce 396 increased ISG expression (Supplementary Fig. 13 ). Future studies are needed to identify 397 the manner in which aminoglycoside-bound RNA stimulate TLR3. 398" ] },{ "paper_id": "b5e1d36298a78690140d5ccb9673dbd48a0ddcd3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The genus Torovirus (subfamily Torovirinae, family Coronaviridae, order Nidovirales) 12 encompasses a range of species that infect domestic ungulates including cattle, 13", "sequences and the inferred amino acid sequences are subject to purifying selection, 27", "The order Nidovirales currently contains four families of positive-sense, single-44 stranded RNA viruses: the Coronaviridae, Arteriviridae, Roniviridae and 45" ] },{ "paper_id": "b696d208705fcb1925693c5f0d118733bb557ea6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "higher than the binding affinity to the previous SARS-CoV spike glycoprotein 12 . This provides strong evidence that ACE2 is a target of the novel coronavirus.", "MR results are presented in Tables 1 and 2 (full results shown in Tables S2 and S3 ). Traits were shown if any of the three methods (MR-IVW, MR-Egger, Wald ratio) showed nominally significant (p<0.05) results. For traits that do not show evidence for directional pleiotropy (p-value of Egger Intercept>0.05), we shall primarily report the results from MR-IVW, as generally the SE of causal estimates is larger with MR-Egger 30 (hence power is weaker). Results from MR-Egger will be presented if there is significant directional pleiotropy.", "However, to our knowledge, GTEx is probably the largest database with both genotype and expression data for lung tissues." ] },{ "paper_id": "b6d2052bb9aef4f3b1d21e86ca164cd43d020857", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b6e92eda6c26b456165422d4e5552b81754c4a82", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "12", "been observed for outbreaks of other diseases (e.g. the ongoing outbreak of Ebola virus 199 disease in the Democratic Republic of the Congo). ", "This can then be combined into a single estimate for the probability that an imported case 98 leads to sustained transmission, , given by 99" ] },{ "paper_id": "b705170c7527f5bc6842d90bf443fa9f9ee00bf9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Although ACE2 is known to the public because it is hijacked by coronaviruses, the primary physiological role of ACE2, as its name indicates, is to facilitate maturation of angiotensin, a peptide hormone that controls vasoconstriction and blood pressure.", "In addition to kidney and intestine, where B 0 AT1 is primarily expressed, ACE2 is expressed in lung and heart (26) . It remains to be tested whether B 0 AT1 can suppress SARS-CoV infection by blocking ACE2 cleavage." ] },{ "paper_id": "b7f94d0b929301cc7a5d8f68a74d4f0270c74649", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "to homogeneity ( Figure S2) . 211", "The modification of biological macromolecules through the introduction of new 356 functionalities has progressed at a tremendous pace in recent years, enriching the palette of 357 tools for biological investigation with a wide spectrum of functionalities. For instance, 358 genetic code expansion, an approach that allows to introduce old and new chemical 359 functionalities into proteins, from synthetic, photostable fluorescent dyes with high quantum 360 yields to highly reactive activatable groups (e.g. UV-activated cross-linkers and click 361 chemistry tools), is undergoing an explosive development (3, 59). With rapid growth of 362 chemical and synthetic biology, the demand for robust methods to deliver modified 363 synthetic or semi-synthetic macromolecules into cells is growing (60). 364", "Only a small fraction of the tested recombinant proteins proved unsuitable for EP delivery. 422", "The experiments discussed in the previous section described delivery of single polypeptides. 201" ] },{ "paper_id": "b801b7f92cff2155d98f0e3404229c67b60e2f9f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The V6 and V6-Y312A reporters were subcloned into pCDNA4.TO using primers " ] },{ "paper_id": "b80d9de7750d627a0189fcd2dfd82c7efcb1c079", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ovaries from well-fed flies were dissected in PBS and stored at -80 \u00baC. For immunoprecipitation, frozen ovaries were thawed on ice in lysis buffer (50 mM Tris-HCl pH 7.5 at 4 \u00baC, 100 mM NaCl, 250 mM Sucrose, 0.1% NP-40 and 1 mM DTT) and pooled together in required numbers (see Table S2 ). Ovaries were mechanically homogenized in lysis buffer (320 \u00b5l/ 40 flies), supplemented with protease inhibitors (cOmplete\u2122, EDTA-free Protease inhibitor cocktail, Roche), using tissue homogenizer with a glass pestle.", "Eluates were separated on 10% polyacrylamide gels and transferred to a nitrocellulose membrane.", "Membranes were blocked in PBS containing 5% milk powder and 0.1% Tween-20. HA-tagged, HA-Flagtagged and GFP-tagged proteins were detected using HRP-conjugated monoclonal anti-HA (1:5000, BioLegend #901501) or polyclonal anti-GFP antibodies (1:2000, Thermo Fisher Scientific #A11122) respectively. Blots were developed with ECL (GE healthcare) reagents, as recommended by the manufacturer, and imaged using an Amersham Imager 600 (GE healthcare)." ] },{ "paper_id": "b8bb4db131a25b1bbb30d4205b16dc9ef988d22f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "b9548530d954b407b35fb266e2b4192402c982a1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "An outbreak of clusters of viral pneumonia due to a novel coronavirus (2019-nCoV / SARS-", "We employed an infectious disease dynamics model (Susceptible, Exposed, Infectious and Removed model; SEIR model) for the purpose of modeling and predicting the number of COVID-19 cases in Wuhan, China. The model is a classic epidemic method to analyze the infectious disease which has a definite latent period, and has proved to be predictive for a variety of acute infectious diseases in the past such as Ebola and SARS. 22, [26] [27] [28] [29] [30] [31] Application of the mathematical model is of great guiding significance to assess the impact of isolation of symptomatic cases as well as observation of asymptomatic contact cases and to promote evidence-based decisions and policy.", "An average of 2,279-3,318 deaths were also estimated ( Table 1) .", "In this article, we intended to make phase-adjusted estimation of the epidemic trend for the 2019-nCoV / SARS-CoV-2 infection transmission in Wuhan, China under two assumptions of Rt (maintaining high >1 or gradually decreasing to <1). We hope to depict two types of epidemic dynamics to provide potential evaluation standard for the effects of current prevention and control measures, and to provide theoretical basis for future prevention decisions of the current epidemic in China.", "In response to the outbreak of COVID-19, a series of prompt public health measures have been taken. On 1 January, the Huanan Seafood Wholesale Market was closed in the hope of eliminating zoonotic source of the virus. 5 On 11 January, upon isolation of the viral strain for COVID-19 and establishment of its whole genome sequences, 17 RT-PCR reagents were developed and provided to Wuhan, which ensured the fast ascertainment of infection. 15 On 21 January, Emergency Response System was activated to better provide ongoing support to the COVID-19 response. 18 Ever since the outbreak, the work of intensive surveillance, epidemiological investigations and isolation of suspect cases gradually improved. Those having had close contacts with infections were asked to receive medical observation and quarantine for 14 days. 19 Travel from and to Wuhan City as well as other medium-sized cities in Hubei Province has been restricted since 23 January 2020. 20" ] },{ "paper_id": "b970b7a807f37678f91d4b989ffdb7d7606d754d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Since December 2019, a novel coronavirus named 2019 coronavirus (2019-nCoV) has emerged in Wuhan of China and spread to several countries worldwide within just one month.", "To validate this result, we further analyzed normal kidney samples from 2 healthy donors." ] },{ "paper_id": "b9b0cad2db02479624a3d087626811e4d2fbcdb9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Our main model therefore assumes a Brownian motion model of evolution [62] . 292", "All data were analysed using phylogenetic mixed models to look at the effects of 275 host relatedness on viral load across temperature. We fitted all models using a 276", "Bayesian approach in the R package MCMCglmm [59,60]. We ran trivariate models 277 with viral load at each of the three temperatures as the response variable similar to 278 that outlined in Longdon et al. (2011) [34] . The models took the form: 279" ] },{ "paper_id": "ba1c4c0de19352d0b9ed7db6199803b621f0a8f2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A population-based telephone interview was carried out between 1 and 10 February, 2020.", "The survey was conducted by well-trained interviewers with 1,011 residents of Wuhan (n=510) and Shanghai (n=501) using a computerized random digital dialing system. The sample size provided us with a sample error of 5%. Proportional quota sampling based on age and sex was used to ensure a demographically representative sample of the general population in each city. Calls were placed three times at different hours on the same day before being classified as invalid. Local residents who were aged 18 years and above and were currently living in the selected cities were eligible to participate. Verbal informed consent was obtained from all participants. Figure S1 presents the flow chart of participant recruitment.", "Possible responses for each question were yes or no." ] },{ "paper_id": "ba3efcd6b74e55327fd7db470d824fc18943f30e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "results indicate multiple countries (many with low IDVI, hence highly vulnerable) might see (or already have seen) case emergence in the month of February.", "We select the countries for which there have been no imported cases, and compute their new estimated time of ar-3 Figure generated using https://github.com/benmaier/radial-distance-layout All rights reserved. No reuse allowed without permission.", "author/funder, who has granted medRxiv a license to display the preprint in perpetuity.", "While providing a preliminary analysis using COVID-19 official reports and airline suspensions, this work also lays out a framework for rapid risk assessment for an emerging and ongoing outbreak. We believe that using near real-time multi-modal mobility datasets and detailed disease surveillance with qualitative and quantitative inputs on ongoing interventions and preparedness efforts will aid in swift and efficient global response to such outbreaks." ] },{ "paper_id": "ba92c589f077b55e9cd13264d619c2ffe9d3ce7a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(b) Based on the growing number of cases worldwide within a short period, the disease is assumed to spread sufficiently fast that the birth and the natural death rates can be considered as negligible in the model.", "The transmission model was formulated based on the epidemiology aspects of the disease:", "!'" ] },{ "paper_id": "baabfb35a321ea12028160e0d2c1552a2fda2dd5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The medical records of 148 patients were collected and analyzed by the research team from the Department of Gastroenterology and Hepatology, Shanghai Public Health Clinical Center, Fudan University. Epidemiological, clinical, laboratory characteristics and treatment and outcomes data were acquired by the hospitalization management system.", "All patients rested in bed and received nutritional support. The basic principle of treatment is symptomatic treatment to maintain the balance of water and electrolyte, stable internal environment. Monitor vital signs and finger oxygen saturation, and give effective oxygen therapy in time. Antiviral therapy can be tried with interferon, lopinavir/litonavir, abidol and dnrunavir. Antibiotics can be used if necessary.", "Up to January 31, 2020, a total of 148 cases with COVID-19 had been admitted to the Table 1 . " ] },{ "paper_id": "bad4192bbc6d41c066bc947eaeeafc53024c98be", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Similarly, SNVs accumulate on most viral genes proportionally to gene length and sequencing depth ( Fig. 1D, E) . Only exception is the ORF6 gene, which modulates interferon signaling (30), 10 where the editing rate is higher compared to that of the other genes.", "Consequently, editing rate per gene has been calculated as follows:", "The analysis of the trinucleotide contexts was performed normalizing the mutated trinucleotide with respect to its presence in the 2019-nCoV genome as follows:" ] },{ "paper_id": "bb8e3d331bb2975e1c644c8729b842797da2d626", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "bb97f90ff5bfd41f2f1148c5cbdb257fdba535df", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Patient 1 was a 41-year-old man with no history of hepatitis, tuberculosis or diabetes.", "He was admitted and hospitalized in Wuhan Central Hospital 6 days after the onset of illness.", "The patient reported fever, chest tightness, unproductive cough, pain and weakness for one 66 week on presentation. Physical examination of cardiovascular, abdominal and neurologic 67 examination was normal. Mild lymphopenia (less than 900 cells per cubic milli-meter) was" ] },{ "paper_id": "bbba5ff9ab9eccef99a0bbc6ea557a373158bbcd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "bc65a0655d7b88cade3fbec16f3e9706c4cfc5aa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A massively parallel reporter assay accurately measures PRF rates and provides evidence for bidirectional frameshifting", "We identified the most predictive combination of features based on our results from the designed data set (Fig 3A, pairedness of nucleotides after the frameshifting site and amino acid class) and trained a Gradient Boosting Regressor on 80% of our HIV clinical isolates. Our prediction for 93 novel HIV variants showed good correlation with the experimentally measured values (r=0.32, Fig 4E) , which could be further improved by applying more restrictive filtering (r=0.44, Fig 4F; see Methods). This shows that a model based on data from our assay is sensitive enough to detect even subtle differences between HIV variants and allows prediction of frameshifting rates with an accuracy of clinical relevance.", "The distribution of mean GFP expression of all library variants shows clear peaks corresponding to background green fluorescence and maximum GFP levels from variants with GFP in frame with mCherry ( Fig S1C) . We set the lowest mean GFP fluorescence we observed to 0% and the highest to 100%. Accordingly, we assigned a percentage to every variant that passed filtering for read number, bin profile and expression levels (by gating for a narrow range of mCherry fluorescence to minimize effects coming from the influence of the variable region on overall expression levels, Methods). This percentage value does not necessarily denote the precise rate of frameshifting events, but gives us a meaningful measure of frameshifting efficiencies across PRF events. Based on the peak of negative, non-frameshifting variants we assigned a noise threshold (corresponding to 1.7% Figure 1 . A massively parallel reporter assay quantitatively measures PRF rates and reveals bidirectional shifting." ] },{ "paper_id": "bca15ad98e1d08c6a62c9c0486de84bc15a9f661", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Chinese people are facing unprecedented panic induced by the outbreak of 2019 Novel Coronavirus (2019-nCov) infected pneumonia (NCIP) in Wuhan, China since December 2019 [1] . Currently, during Spring Festival travel rush, millions of people leave Wuhan city, and the 2019-nCov would spread quickly especially along with people coming out from Wuhan. By 10 Feb 2020, a total of 3,7626 people have been confirmed NCIP in China [2] .", "The NCIP is considered a relative of the deadly Middle East respiratory syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS) coronaviruses. They are characterized by pneumonia symptoms, such as fever, radiographic evidence of pneumonia, respiratory symptoms and possibly transmitted from animal to human [3] [4] [5] . The public health authorities proposed NCIP definitions that combined clinical features (e.g., fever, cough, and anhelation) with epidemiological factors (e.g., travel to a seafood and wet animal wholesale market in Wuhan or direct contact with another patient with NCIP) to improve diagnostic accuracy [6, 7] . Unfortunately, these epidemiological features are not specific and have poor positive predictive value during the outbreak.", "Routine hematological and serum biochemical examination was ordered at the discretion of the physicians and were measured using standard methods in our hospital. Fasting whole blood from every patient was collected in an EDTA anticoagulant-treated tube and analyzed within 30 minutes of collection." ] },{ "paper_id": "bcef0894cf382a83c2aa4d9c803978780c2809db", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Pseudotypes expressing H17 and N10 genes were produced as described previously 32, 53 . 298", "Friebertsh\u00e4user, Philipps University of Marburg, Germany) were co-transfected using 302 polyethylenimine transfection reagent (Sigma Aldrich, UK) into HEK293T/17 cells, plated on 303 6-well Nunclon \u00a9 plates (Thermo Fisher Scientific, UK). Supernatants were collected 48-72 h 304 post transfection and filtered through a 0.45 \u00b5m filter (Millipore, UK). To remove viral titer 305 bias between different PV stocks, pseudotypes were concentrated and (re-) titrated by serial 306 dilution. Concentration was carried out by ultra-centrifugation for 2 h at 25,000 rpm, 4\u00b0C in 307 the SW32 rotor of a L2-65B Beckman ultra-centrifuge. 308", "Bright-Glo\u2122 substrate (Promega, UK) was added. Luciferase readings were conducted with a 313 luminometer (FLUOstar OPTIMA, BMG Labtech) after a 5-minute incubation period and 314 luciferase reading recorded in relative luminescence units (RLU). Data were normalized using 315 \u0394-env and cell-only measurements and expressed as RLU/ml. 316" ] },{ "paper_id": "bd872a86902d848bd94694469bb0c5cb05bea483", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "One study directly observed recurring infection amongst a herd of dromedaries in Egypt.", "Three studies have found dromedaries to be shedding MERS-CoV RNA despite having high 266 antibody titres months or weeks prior to detectable infection. Both older animals whose 267 antibodies reflect past exposure (29, 76, 79) , and young calves whose high antibody titres 268 were maternally-acquired immediately post-partum, became infected (79).", "Phylogenetic analysis of viral sequences isolated from dromedaries and humans indicates that 59 hundreds of camel-to-human spillover events are likely to have occurred since 2012 (6). Taken 60 together, recurring dromedary-to-human transmission is driving ongoing human infection." ] },{ "paper_id": "bd8f57ea4aadeda075d557f566a1909d68e658c4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "COVID-19 virus RNA was reverse transcribed using random primer with Super-Script\u00ae III Reverse Transcriptase First-Strand Synthesis System (Invitrogen, USA).", "Sample collection and analysis of samples were approved by the local CDC. The internal use of samples was agreed under the medial and ethical rules of each participating individuals.", "After the specificity analysis, we retained one primer set with several pairs of loop primers ( Table 1, ", "In December 2019, the first case of cluster unidentified pneumonia was found in Wuhan, named 2019-Novel Coronavirus (2019-nCoV), a beta subtype, highly homologous with SARS(1). As of February 18, 2020, there were in total 75,201 confirmed cases worldwide. With the rapid spreading speed of R0 3.28, there is a heavy pres-sure for hospital assistant diagnosis, as some infected individuals without any symptoms could still transfer the virus to others (2) . Thus, there is an urgent need to develop a diagnostic method that is sensitive, accurate, rapid and low-cost to screen infected individuals, facilitate proper isolation and help controlling the disease spread.", "The present study describes an isothermal LAMP based method-iLACO (isothermal LAMP based method for COVID-19), for rapid colorimetric detection of 2019-Novel Coronavirus.", "RNA was extracted from clinic samples with COVID-19 virus infection during the epidemic in Shenyang in 2020 with the Thermo nuclear acid extraction workstation in the P3 laboratory of CDC Shenyang. Before the experiment, the concentration of virus RNA sample was measured with Qubit 3.0 (Thermo Fisher)." ] },{ "paper_id": "bf04c9ddc80690a5e2d3c74d79a797319e36e5b6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "functions. Yet the mechanism how Huntingtin proteins are regulated remains unknown.", "The IE is therefore calculated as:", ", respectively):" ] },{ "paper_id": "bf39a81c9aab9e0569f33d93d5e203d320dac024", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "medRxiv preprint", "Early identification of risk factors for critical conditions is urgently warranted not only to identify the defining clinical and epidemiological characteristics with greater precision, but also facilitated appropriate supportive care and promptly access to the intensive care unit (ICU) if necessary.", "Importance: The recent outbreak of Novel Coronavirus (SARS-CoV-2) Disease has put the world on alert, that is reminiscent of the SARS outbreak seventeen years ago." ] },{ "paper_id": "bfb0852ef4dd124ba671303aee7a71a08c7c21a7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Membrane proteins (MPs) are crucial for the normal functioning of an organism as they are involved in essential processes including signalling, nutrient and ion transport, maintaining biological membrane structure and integrity (1) (2) (3) (4) . They are encoded by about 30% of the human genome (5) and are major targets for modern therapeutic drugs. This makes structural studies of MP solutions extremely important both scientifically and medically (6) (7) (8) (9) (10) .", "At present the majority of investigators studying MPs utilize readily available and inexpensive surfactant systems or detergents (small amphiphilic molecules) (6, 8) . However, a common problem observed is the destabilization of protein structure following exposure to detergent molecules (11, 12) . Fortunately, the development of milder detergents and detergent stabilized bilayer systems (bicelles) has helped to overcome this problem (7, 8, 13, 14) . Importantly, the solution behaviour of many commercially available detergents has been well characterised using a range of techniques, including small angle X-ray scattering (SAXS) (15) . Micellar solutions of such detergents have been shown to adopt characteristic sizes, which can be reliably separated from detergent-protein complexes of interest using chromatographic techniques, eg. high performance liquid chromatography (HPLC)." ] },{ "paper_id": "bfed3ce6a6df2d442d96d0cab07d4bc1f2347255", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Primary Outcomes: All rights reserved. No reuse allowed without permission.", "All rights reserved. No reuse allowed without permission." ] },{ "paper_id": "c04c7fb330a409a00f67040dde0f83b3da88eacb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Among all know RNA viruses, coronaviruses have the largest genomes ranging from 26 to 32 kb in length (Regenmortel et al., 2000; Schoeman and Fielding, 2019) ." ] },{ "paper_id": "c04e10858012bdd666d50c0d69c3d1e7224ccbea", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The results indicate no relationship between the C. elegans odr4TM or human CD23 TM and TM helices of the RC subunits (L/M/H) of T. tepidum or R. viridis (Fig. S2A/B) .", "Abbreviations: A2AR, adenosine A2A receptor; 3HA-A2AR, A2AR tagged with a triple HA epitope; Bchl, bacteriochlorophyll; BRET, bioluminescence resonance energy transfer; C, carboxy-terminal; CD, cluster of differentiation; D2LR and D2SR, the long and short form of dopamine D2 receptor, respectively; Fab, antigen binding fragment; Fc, Fc fragment; Fc\uf065RI, high affinity receptor for IgE; FRET, fluorescence resonance energy transfer; G4S, an amino acid sequence consisting of a four-glycine-repeat followed by a serine residue;", "On immunoblot analysis, cell membranes were subjected to SDS-PAGE and transferred to a nitrocellulose membrane as previously described [10] . Immunofluorescence studies were performed as previously described [10] ." ] },{ "paper_id": "c08c3b98a956287a6eaf99f6d90969d7dd1410d1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "RNA was then isolated following the standard protocol of the NucleoSpin RNA II kit (Machery-Nagel).", "Homogenized samples were centrifuged at 9,500 x g for 5 min and supernatants were collected.", "Subsequently, samples were centrifuged at 9,500 x g for 5 min and supernatants were aliquoted." ] },{ "paper_id": "c10661c9b35e068691b879661bcebeba3bd6aad9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c124701d09545e0117cca7a3a5f449584223899f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c12ad8b411c24fe215be91d1f990645743e55ab5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "d\u03b8 I t dt \" \u03b2\u03b8 S t \u03b8 I t\u00b4\u03b3 \u03b8 I t , and", "f p\u03b8 t\u00b41 , \u03b2, \u03b3q \"\u00a8\u03b8 S t\u00b41`1 {6rk S 1 t\u00b41`2 k S 2 t\u00b41`2 k S 3 t\u00b41`k S 4 t\u00b41 s \u03b8 I t\u00b41`1 {6rk I 1 t\u00b41`2 k I 2 t\u00b41`2 k I 3 t\u00b41`k", "3 Implementation: Markov Chain Monte Carlo Algorithm", "where all these k t terms are given in the appendix A. Denote the set of model parameters by \u03c4 \" p\u03b2, \u03b3, \u03b8 0 , \u03bb, \u03baq J , which will be estimated using the MCMC method [2] ." ] },{ "paper_id": "c14d50924f959d38ff7857e6db3a60c929448956", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Inactivation of virus was confirmed by RT-qPCR following infection of cells. Sodium arsenite, 112 cycloheximide, puromycin and emetine were purchased from Sigma.", "Here we investigated stress granule regulation by Gammacoronavirus infectious bronchitis 23 virus (IBV), which causes the economically important poultry disease, infectious bronchitis.", "30 31 32 105 Cells, viruses and reagents 106" ] },{ "paper_id": "c15f8c23eedbedf8d48bbc88b8225ae9c9d234bf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nevertheless, Nsp15 is essential in coronavirus biology.", "EndoU enzymes are present in all kingdoms of life, where they play various biological functions associated with RNA processing. All characterized family members display an RNA endonuclease activity producing 2'-3' cyclic phosphodiester and 5\u00b4-hydroxyl termini (Ulferts & Ziebuhr, 2011) .", "The entire process from protein expression to structure deposition to PDB took 5 days." ] },{ "paper_id": "c1a08ce8f2c5d5311b19822c3df5aa9d25c4d93c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Procedures: Epidemiological data was collected from patients' medical records. If more information was needed, we communicated with attending health care providers, patients, and their families. Throat-swab specimens from the upper respiratory tract were obtained for Real-Time Reverse Transcription Polymerase Chain Reaction(RT-PCR). The Wuhan Institute of Virology provided the RT-PCR detection reagents.", "There were three limitations in this study. First, only 213 patients diagnosed with COVID-19 were included. Second, the unconfirmed suspected cases in the early stages were excluded in the analyses.", "Patients: For this retrospective study, we recruited patients in the First People's Hospital of Jingmen from January 12 to February 14, 2020. All the confirmed COVID-19 patients at our hospital were study was approved by the First People's Hospital of Jingmen Ethics Committee. The patients' written informed consent was obtained before data was collected." ] },{ "paper_id": "c1ae608c7ffb926a0f50a6a34c0780983274ea74", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We collected a dataset with 59 officially confirmed COVID-19 cases from 10 regions in China except for Hubei province, the assumed origin of the virus. The patient data was dated from Dec 29, 2019, to Feb 5, 2020. We only involved the officially confirmed cases with a clear history of exposure and time of onset in data collection. We exclude those without relevant epidemiological descriptions, working or living in Wuhan for a long time, or hard to determine the possible exposure time.", "where (0,1) is added Gaussian noise and \u2208 [0,1] is a variance control parameter in simulation. Such a procedure is repeated times, the population median . =", "Our data consists of 34 male cases, 24 female cases and 1 unidentified gender case from ten regions in China." ] },{ "paper_id": "c2510fbc213aa74c6c3195cbc8033c7d0f11b248", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "the entirety of this autophagic process and is regulated by lots of signaling [17, 18] .", "159 entry.", "Twenty-seven out of eighty piglets (BW= 5.5 \u00b1 0.5 kg) were selected and randomly 360 divided into three groups, with 3 replicates per group and 3 piglets per replicate. Piglets " ] },{ "paper_id": "c2af4db8591a8ef84229eb08359c0a50efa24544", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Escherchia coli for the formation of recombinant bacmids, DH10Bac (Genotype: F \u2212mcrA \u0394(mrrhsdRMS-mcrBC) \u03d580lacZ\u0394M15 \u0394lacX74 recA1 endA1 araD139 \u0394(ara,leu)7697 galU galK \u03bb\u2212rpsL nupG/bMON14272/pMON7124) carries the recombinant baculovirus genome, Autographica californica, on a bacterial artificial chromosome. These cells are propagated at 37\u02daC in LB broth or on LB agar supplemented with 50 \u00b5g/mL kanamycin, 10 \u00b5g/mL tetracycline. ", "swine sera used in the study were collected from pigs on day 76 PI (i.e., 20 days after the 2nd inoculation). The negative swine serum was from one of age-matched control pigs. The positive serum had an antibody titer of 8 to 32 against PEDV as measured by serum-virus neutralization test.", "Proteins were concentrated for structural studies using ultrafiltration (Sigma-Millipore, AmiconUltra 4 mL, 30K MWCO, Cat. #UFC903024)." ] },{ "paper_id": "c3e5af129cd3332c6a01776cbb9534bceb46e21a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "73 Interestingly, Valastro et al., (2016), confirmed what previously proposed by Franzo et al., [7] about 74 the clustering of 624/I and Q1 genotypes in the same group (currently named GI-16).", "225 226 The time-calibrated spreading process provided further information. Particularly, GI-16 lineage was", "120 A phylogenetic tree was then reconstructed using PhyML [25] selecting as the most appropriate 121 substitution model the one with the lowest Akaike Information Criterion (AIC) calculated using 122 Jmodeltest [26]. The phylogenetic tree was used to classify the strains and those 123 potentially belonging to the GI-16 lineage were extracted. The presence of 124 recombinant strains was evaluated using RDP4 [27] on a dataset including the selected GI-16 like 125 strains plus the reference ones. The RDP4 settings for each method were adjusted accounting for the 126 dataset features according to the RDP manual recommendations. Only recombination events", "106 . Viral RNA was extracted from isolates using the TRIzol reagent (Invitrogen, Carlsbad, CA, USA) 107 according to the manufacturer's protocol. IBV was detected using RT-PCR as previously described 108 [23]. Partial sequencing of the S1 gene (464-bp), covering the hypervariable region 3 (HVR3), was 109 performed using the same primers that were used for RT-PCR. The obtained chromatogram quality 110 was evaluated by FinchTV (http://www.geospiza.com) and the consensus sequences were 111 reconstructed using CromasPro (CromasPro Version 1.5). 112 113 International database preparation 114 To download all available IBV sequences overlapping with the region of interest (HVR3), one of 115 the Italian sequences was used as query in BLAST and all sequences with a genetic distance lower 116 than 30% were downloaded. Obtained sequences plus the Italian ones were merged with the 117 reference set provided by Valastro et al., [6] and aligned using MAFFT [24]. Partial sequences (i.e. 118 covering only part of the HVR3) and those with unknown nucleotides, frameshift mutations and 119 premature stop codons, suggestive of poor sequence quality, were removed from the dataset." ] },{ "paper_id": "c41fdb2efd6d61384a92a84cbba3f8233629a41b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The microbial communities comprising the human microbiome are now recognised as playing important roles in the aetiology and pathogenesis of myriad diseases (1) . However elucidation of these complex roles requires targeted characterization of microbial communities present in relevant spatial niche(s) during critical periods of pathogenesis. The focus of this study is the respiratory tract, in particular the nasopharynx (NP) which is an accessible source of airway microbial communities (2) and serves as a conduit for pathogens associated with lower respiratory illnesses (LRI) that are responsible for substantial morbidity and mortality worldwide." ] },{ "paper_id": "c42a617a00afe6a36bde0a8e3638e0f55bfee4f7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "for cities i and j within a group of cities having similar parameter sets. This also means", "for the group of cities having similar rates of infection and recovery. Thus, provided the historical archive has adequately covered the possible dynamical profiles, we are able to perform fast prediction for any city o, by fitting an incomplete set of data (corresponding to an early outbreak stage in city o) and using the model parameters already obtained previously, as detailed in the following subsection.", ". Thus, (1) can be represented in normalized form as", "where i = 1, 2, \u00b7 \u00b7 \u00b7 , 367, and K i is the length of the data recorded in city i. Superscript \"(c)\" denotes data of Chinese cities. Now, suppose an outbreak occurs in city o, and only k o days of data have been obtained in normalized form as\u012a" ] },{ "paper_id": "c4ce14ce42fa4360dfe3515ec9d1584847381c27", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "where I o = I(t = 0) is a constant. Considering the existence of an infectious period, the transition time of R(t) will be different from that of I(t). Therefore, R(t) can be expressed as", "Our model and results can be compared to the classic Susceptible-Infective-Removed (SIR) model. The SIR model divides the population into compart-1 All uncertainties of predictions in the paper are reported on 95% confidence level.", "Resolving \u03b2 and \u03b3, we can estimate the basic reproduction number" ] },{ "paper_id": "c4dc1c0360d3fe9ceddc4650aea022f24d88cd99", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To confirm the expression of cloned genes in pSFTSV and pSFTSV-IL12, HEK 293T cells Overexpressed recombinant proteins in supernatants were purified by AKTA start affinity confirmed by ELISA and immunoblot analysis (Fig. 2) . All the viral antigens were detected 312 in cell culture supernatants, as well as in cellular lysates (Fig. 2B) . KO mice to a Korean SFTSV isolate was examined by inoculating the mice with 1 x 10 1 to 1 375 x 10 5 FFU (S3 Fig A) . Upon infection, all the mice gradually lost body weight and became 376 moribund from the third to fifth day after infection, depending on the infection dose. All the 377 infected mice died at 5 ~ 9 d after infection (S3 Fig A) . Similar survival kinetics were 378 previously reported in IFNAR KO mice infected with other SFTSV strains [11, 14] , 379 indicating that our Korean SFTSV isolate possesses an equivalent degree of virulence to prior 380 Chinese isolates. The platelet counts in mice infected with 1 x 10 5 FFU of SFTSV 381 significantly declined up to 4 d after infection, and the mean platelet volumes of the infected 382 mice were significantly higher than those of control animals (S3 Fig B) , suggesting that 383 platelet destruction and the activation of platelet production simultaneously occur during 384 lethal infection [14] .", "53 54 Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infection 58 endemic to East Asia including China, Korea, and Japan. Gradual rise of disease incidence 59 and relatively high mortality have become a serious public health problem in the endemic 60 countries. In this study, we developed a recombinant plasmid DNA encoding four antigens, 61 Gn, Gc, NP, and NS, of SFTS virus (SFTSV) as a vaccine candidate. In order to enhance cell-62 mediated immunity, the viral antigens were fused with Flt3L and IL-2 gene was incorporated 63 into the plasmid. Immunization with the DNA vaccine provides complete protection against 64 lethal SFTSV infection in IFNAR KO mice. Antigen-specific T cell responses might play a 65 major role in the protection since we observed enhanced T cell responses specific to the viral 66 antigens but failed to detect neutralizing antibody in the immunized mice. When we 67 immunized with either viral glycoprotein, Gn protein induced relatively higher neutralizing 68 activity and better protection against SFTSV infection than Gc antigen, but neither generated 69 complete protection. Therefore, an optimal combination of DNA and protein elements, as 70 well as proper selection of target antigens, might be required to produce an effective SFTSV 71 vaccine. 72 73 74 75 76 77 78 79 . CC-BY 4.0" ] },{ "paper_id": "c5bf5beb177c16aa29255e89e0cf47e4e9467cce", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The advent of the digital era has radically changed the way individuals search for information and this is particularly relevant for health-related information 1 . A 2013 study 2 found that 59% of U.S.", "Combining both features, the linear model achieves R 2 = 0.63 and r = 0.82. As model performance is evaluated via state-wise cross-validation, these results highlight that national-level media signals are highly informative of state-level pageview time series, once they are rescaled to take into account population size." ] },{ "paper_id": "c6012a6141f5ad05ac983aa9f1a7c57938363b16", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Investigating prognostic markers for severe patients are required to supply important information for early therapeutic strategy.", "Data are presented as mean \u00b1 SEM, frequency (%) or median (interquartile ranges)." ] },{ "paper_id": "c6039f8933305c9f44a44c81a15b321b6c2848dc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A key advantage of the UVC based approach, which is in clear contrast to vaccination 102 approaches, is that UVC light is likely to be effective against all airborne microbes. For example, while 103 there will almost certainly be variations in UVC inactivation efficiency as different influenza strains 104 appear, they are unlikely to be large 7,10 . Likewise, as multi-drug-resistant variants of bacteria emerge, 105 their UVC inactivation efficiencies are also unlikely to change greatly 9 .", "138 All rights reserved. No reuse allowed without permission.", "All rights reserved. No reuse allowed without permission.", "Airborne-mediated microbial diseases represent one of the major challenges to worldwide public 26 health 1 . Common examples are influenza 2 , appearing in seasonal 3 and pandemic 4 forms, and bacterially-27 based airborne-mediated diseases such as tuberculosis 5 , increasingly emerging in multi-drug resistant 28 form." ] },{ "paper_id": "c672f5b0d7c0a40f7cc1bdf079066d72eb8f64ec", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In this article, we made use of some online renal single cell RNA-seq (scRNA-seq) gene expression data sets that were publicly usable. These contained the data reported in GSE131685 and GSE107585.", "Novel coronavirus-infected pneumonia outbroke in Wuhan in December 2019 and January 2020, which has posed a major threat to global public health [18] . The numbers of confirmed cases and deaths are still rising quickly, posing higher challenges for disease control and patient treatment.", "Raw reads were processed to generate gene expression matrices as described previously. Reads with the same cell barcode, UMI and gene were grouped together to generate the number of UMIs per gene per cell. Cell number was then determined based on the inflection point of the number of UMI versus sorted cell barcode curve.", "Results of GSE132023 confirm the previous results (data not shown)." ] },{ "paper_id": "c6ec1380338cb2467dc6fc14add09ca5bea18411", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The candidates harvested from docking were deeply analyzed for atom-based affinity contributions and physical-chemical properties by SeeSAR (version 9.2;", "BioSolveIT GmbH, Sankt Augustin, Germany, 2019, www.biosolveit.de/SeeSAR).", "The 3D molecule images were displayed by PyMOL v2.3 [7] ." ] },{ "paper_id": "c72595eda8a721e9bff19fcc18ecbb8510054f37", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c8437a45bfb84fb206fe03fd18d28858bae32651", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Totally, 75 patients diagnosed with COVID-19 were included in this study. Among 128 them, 61 (81.33%) patients had been to Wuhan or exposed to people who came from diabetes, chronic kidney disease, respiratory system disease, nervous system disease, 135 chronic liver diseases, and malignant tumor (Table 1) .", "Elevated IL-6 (n=14) Normal IL-6 (n=35) P value", "36" ] },{ "paper_id": "c8559b6ddd6213bc91524397933bce33aea7d50f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Then, we linked weekly observed incidence O t,X to past incidence with:", "The NI prior distributions expressed vague characteristics of the parameters: R 0,Z will be positive and likely not greater than 20; and \u03c1 Z will range between 0 and 1.", "The predictive distributions were compared using two measures of forecasting quality: (i) accuracy, i.e. the root-mean-square dierence between predicted and observed values, and (ii) sharpness," ] },{ "paper_id": "c85f571a674c7fed0ccb9176e9cf9f3d3659ca32", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We expected that the international travel from Wuhan was relatively stable during this period. This motivated our working model for ? : 1.", "log( [ # ]) \u2212 log( \u2212 + 1) = log( \u00d7 ' ) + . We compared the fit of this model with the other two choices of the travel rate.", "To aide comparison, we included lines in panels B, C, and D, in Figure 2 corresponding to a growth rate of = 0.11 or a doubling time of 6.4 days reported by a previous analysis . This estimate did not fit the average infection counts well." ] },{ "paper_id": "c8b6f2752a842dd9eb9c50a82112748ef10ba259", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Coronaviruses utility the spike (S) proteins to select and enter target cells.", "HEK293 and HEK293T were cultured in Dulbecco's modified Eagle's medium (DMEM, Gibco, USA) with 10% heat-inactivated fetal bovine serum (FBS, Gibco, USA). poly (I:C) (Sigma P1530) was transfected into cells using Lipofectamine 2000 (Thermo Fisher, USA).", "Three independent experiments are performed in all studies. Two-tailed unpaired Student's t test by GraphPad Prism 7.0 was used to perform statistical analysis. P < 0.05 was considered as statistically significant in all experiments." ] },{ "paper_id": "c8c052d27aaf8015316dcd2644fa5e0b3870cea1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In a low feasibility setting, and remained above one, even with ( Figure 2 , 3).", "As COVID-19 continues to spread, better understanding how to contain it becomes critical.", "We calculate this quantity from the model under varying assumptions about p.", "This work was supported in part by Award Number U54GM088558 from the US National Institute Of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute Of General Medical Sciences, the National Institutes of Health, or other contributing agencies." ] },{ "paper_id": "c8d206a4f9af0709b6e9ee90c4d854d482cb0784", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Critical patients should have any of the following conditions:", "1. Respiratory failure occurs and mechanical ventilation required; 2. Shock occurs;", "3. Combining other organ failure and requiring treatment in ICU." ] },{ "paper_id": "c8df44a3612e85e267351e936ddeb8fc5867afa1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Our goal is not to provide specific predictions for a specific population, but rather to demonstrate the generic impact of delaying a one-off intervention and to show its robustness.", "We will measure three quantities of interest:", "\u2022 the time of peak, or t p at which I is maximized.", "The Influenza pandemic of 1918 was one of the deadliest epidemics of infectious disease the world has ever seen. In response, many cities introduced widespread interventions intended to reduce the spread. There is evidence [3] that those cities which implemented these interventions later had fewer deaths. This seemingly counter-intuitive observation suggests that those cities which were slow to respond were the most successful.", "where S, I, and R denote the susceptible, infected and recovered fractions of the population with S + I + R = 1. There are a few important quantities to consider." ] },{ "paper_id": "c8e940f25e802de4fb2abd917b76b8dffc5a23ae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Fasting paradigms elicit a wide-range of health benefits including suppressing inflammation.", "The authors declare no conflicts of interest.", "RNeasy " ] },{ "paper_id": "c9533866dd77deaa65ee1015b57bca5486f93326", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "c954675ee859e2f7b8f352a398a67469b50f05de", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ca88735399ff43d0e673876200655099f06f5567", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Maximum likelihood estimates were obtained by maximizing the equation (1) 7 and the profile likelihood-based confidence intervals were computed. 8", "Considering the possibility of underreporting or biased age distribution, the 19 nature of this age distribution may lead to underestimation. 20", "We analyzed the epidemiological dataset of confirmed cases with 13 COVID-19 in Japan as of 28 February 2020. The confirmatory diagnosis was 14 made by means of reverse transcriptase polymerase chain reaction (RT-PCR). 15" ] },{ "paper_id": "cb346b64e20934bc01f7727cf51494b22f172de0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The non-survival hypnotic \u03b1-chloralose (mechanism unknown) provides light long-lasting anesthesia with minimal analgesia, and minimal effect on normal spinal and sympathetic reflex function 2, 11 . Unfortunately, \u03b1-chloralose is not recommended for survival studies due to involuntary excitement and prolonged recovery 11 although several studies have successfully recovered animals following \u03b1-chloralose anesthesia 41, 42 .", "Isoflurane (exact mechanism of action unknown 16, 38 , but suspected to affect GABA receptors 39 ) is the primary inhalant anesthetic used in veterinary medicine, especially in prolonged invasive procedures 16 .", "During terminal procedures in conjunction with other studies, cats were anesthetized with the same dexmedetomidine/ketamine/butorphanol combination as for the VAP surgery, and transitioned to isoflurane, then \u03b1-chloralose (70 mg/kg induction, 20 mg/kg maintenance every 4-6 hours or as needed [MilliporeSigma, Burlington, MA]), supplemented with 0.01 mg/kg buprenorphine 20 ." ] },{ "paper_id": "cb3974f33a1d54369d630e62052d603148bb12e7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Genomic assembly and sequence analyses. After examining the high similarity among the samples from three animals, to maximize the coverage of the virus genome, clean reads from three animals were pooled together and de novo assembled using MEGAHIT v1. 2.9 [19] . The assembled contigs were used as references for mapping those the rest unmapped reads using Salmon v0.14. 1 [20] , and multiple rounds were implemented to maximize the mapping (Table S2) .", "SARS-CoV uses angiotensin-converting enzyme 2 (ACE2) as one of the main receptors [7] with CD209L as an alternative receptor [8] , whereas MERS-CoV uses dipeptidyl peptidase 4 (DPP4, also known as CD26) as the primary receptor.", "Pangolin-CoV-2020 Nucleotide Identity", "Approximate 30-thousand-base genome of coronavirus codes up to 11 proteins, and the surface glycoprotein S protein binds to receptors on the host cell, initiating virus infection. Different coronaviruses can use distinct host receptors due to structural variations in the receptor binding domains of the virus S protein.", "To effectively control the diseases and prevent new spillovers, it is critical to identify the animal origin of this newly emerging coronavirus. In this wet market of Wuhan, high viral loads were reported in the environmental samples. However, variety of animals, including some wildlife, were sold on this market, and the number and species were very dynamics. It remains unclear which animal initiated the first infections." ] },{ "paper_id": "cbc05d14c57b91081970a232ab83bc993f998fe2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The data were processed using R version 3.6.2 [12], MLE was computed using Julia version 1.3 [13] , and the Markov chain Monte Carlo (MCMC) simulations were performed in Stan (cmdStan version 2.22.1 [14] ). All code is freely available at the github repository [15].", "(", "The authors declare no conflicts of interest." ] },{ "paper_id": "cc41c51293ed24a57ddf467e462ec9399463ee33", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The vast majority of COVID-19 genomic data available at the time of writing are partially or fully assembled genomes. There is no public access to sequence reads that were used to produce these assemblies: as of Feb 19, 2020-more than two months since the beginning of the outbreak-there are only six raw datasets (Table S1 ).", "Finally, we performed a branch-level test for positive selection on a codon-alignment of the S gene from COVID-19, SARS-Tor2 as well as Bat ZC45, ZXC21, and Rp3 coronaviruses, specifically to identify if there was any evidence of diversifying selection along the ancestral branch leading to COVID-19 isolates. We found statistically significant evidence of positive diversifying selection (~7% of S -gene sites) along the branch leading to COVID-19 (Fig. 4) .", "5,6 , usegalaxy.be 7,8 and hyphy.org 9 development teams" ] },{ "paper_id": "cc5e36a8d22f6b1708b1c43764806b1722aa1754", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Scheme 1: Chemical structures of a-ketoamide inhibitors 11r, 13a, and 13b", "Hence, it has been proposed to rename the new virus as SARS-CoV-2 (Gorbalenya et al., 2020) ." ] },{ "paper_id": "cddff59aa11d3d8005e389b47cb7c4501a21d593", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "cdfc8be07677f50c91106e5b56379acb0d0eb289", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Lysosomal activity and caspase cleavage have both been reported to degrade parkin [86] [87] [88] [89] ,", "mutant.", "For both differentiated and undifferentiated cells, half of the medium was replaced every 2-3 days with fresh medium and cells were kept in an incubator under 7.5% CO2." ] },{ "paper_id": "ce16fdcdc9f5932ac2e66646317a33f142ee1eb6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ce97f5b8be9e2d7eeb169762fc07a08bacb3e8cf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "56 Introduction", "136", "Results" ] },{ "paper_id": "d010cc0209bc5a0eee6259f72c42590c448da1cf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Page 13 of 44 All statistical analyses were performed using R (version 3.6.0). We tested the effect of bee 272 type on bacterial loads, diversity indices, and wet gut weight using Student's t-test (in case 273 of two group comparisons) or general linear models (in case of three group comparisons)." ] },{ "paper_id": "d01e580a45c457c7c200cd884e746b4d836e2ea9", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.", "Movie micrographs were aligned and dose weighted with MotionCor2 81 and CTF estimation was performed with Gctf 82 . Single-particle data processing was performed using CryoSparc v.2 83 and Relion v.3 84 . 3D variability analyses were performed in SPARX 85, 86 . Map filtering and visualisation was performed in UCSF chimera 87 ." ] },{ "paper_id": "d069dfb7f0aefcdc2c890a1bbe773ebd26b01a55", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Pragmatic effectiveness trials are increasingly recognized as an essential component of medical evidence and good prediction models can help formulate scientific prevention and treatment programs 4, 5 .", "We define the states in this model. Medical Observation (MO) is a close contact of a known infected patient is identified and put into medical observation. In the next day, outcome could be any of the three: confirmed infection, discharged without infection, or stay in MO. Discharge (dis) is a terminal state for a close contact, until he or she becomes another incident of close contact again. Infected is an intermediate state, where the patient becomes a confirmed infected case. The outcome is binary:" ] },{ "paper_id": "d0b33d173f1d32662e2ad8d7e85181f9b23f010c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d10525ee12ac8eb0941e0b21d04b3552baaeb79d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "However, it is also possible that the modification of NSP4 could impair VP7 trimerization." ] },{ "paper_id": "d12b31daa935e9043a9f526a2547b6216ada7cde", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All authors declare no competing interests. All rights reserved. No reuse allowed without permission.", "Eight of nine patients had an obvious history of epidemiological exposure to SARS-CoV-2. All patients presented with a fever. Other symptoms were cough, sore throat, fatigue and diarrhea. Four patients had a lymphopenia. Elevated C-reactive protein and erythrocyte sedimentation rate were found in 6 and 5 cases respectively. All patients had normal serum levels of procalcitonin, alanine transaminase, creatinine, myocardial enzyme and arterial partial oxygen pressure. All rights reserved. No reuse allowed without permission.", "author/funder, who has granted medRxiv a license to display the preprint in perpetuity." ] },{ "paper_id": "d14f165645f21a60d224c6286c5e51799797eceb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Seizure propagation is the process by which a focal seizure spreads within the brain and cause more severe behavioral manifestations. All strains we tested showed progression of seizures from transient involuntary jerks (i.e. MS) to full-blown continuous generalized clonus (i.e. GS) after flurothyl exposure 42 . The decoupling of MS and GS in CC058 and CC032", "To assess whether the resistance to epileptogenesis in a particular CC strain was generalizable to another induction paradigm, and based on MST kindling slope of our initial cohort (cohort 1), we challenged CC055 (lowest), B6J (highest), and CC027 (intermediate) mice", "The authors declare no competing interests." ] },{ "paper_id": "d1b26388670660f66249b55ece2beccee4c18d1a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d1c77a93f69b5dbcf3806674bff9fe4677209ae5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d23c6a066a58dbe5ec5fa57e67f1b795337299f7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Zoonotic coronaviruses (CoVs) are significant threats to global health, as exemplified by the recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 1 . Host immune responses to CoV are complex and regulated in part through antiviral interferons.", "Up-(red) or down-regulated (blue) pathways indicated by activation z-score. Numbers show significantly dysregulated genes as percentage of total gene number included in pathway. d-e, Expression of select genes in liver (d) and spleen (e). f-g, Immune cell counts from liver (f) and spleen ", "Differences in data were tested for significance using GraphPad Prism v8.3.1 for Windows (GraphPad)." ] },{ "paper_id": "d2609c4d8837558f4b8f32170422ce1cd12425a6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d2616cd5feadf2f63508144580ce2b9e172decf5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Human cells. De-identified blood samples were obtained from healthy donors, as defined by Hoxworth Blood Center guidelines (https://hoxworth.org/donors/eligibility.html), with the approval of Cincinnati Children's Hospital Medical Center Institutional Review Board.", "DEO: conceptualization, investigation, data curation, writing-original draft. AA, PCA, and DK: investigation, data curation, writing-editing. LCK: data curation, writing-editing. MB: data curation, writing-editing. SNW: conceptualization, data curation, writing-original draft, study supervision." ] },{ "paper_id": "d29c253b473969c4d92ea9911d3badb9a7ee63f2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d2c7ac58cc309df9d3da8e766184d09c32d16dca", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For each candidate taxon (i.e. species in primary and strains in secondary iteration, respectively), raw counts are calculated by summing over all assigned PSMs including non-unique matches. To account for taxonomic biases caused by shared matches, we integrate a weighting scheme based on the level of uniqueness using the global frequency of a PSM. Here, a PSM count per taxon is adjusted by the number of occurrences in all candidate taxa. Thereby, unique PSMs gain in value for the final taxa selection without fully neglecting the importance of high numbers of non-unique matches that are often highly present within closely related taxa such as strains.", "The TaxIt workflow for strain identification consists of several recurring modules interconnected, controlled (in terms of input and output) and automatically executed by the Snakemake computational workflow management system 46 . The designed workflow executes up to three stages including (i) an optional host filter, (ii) species identification (primary iteration) and (iii) strain identification (secondary iteration). A concise overview of the workflow is illustrated in Figure 1 . The main steps of each iteration are the execution of a peptide search engine, false discovery rate (FDR) control, taxonomic classification, taxa counting and adjustment as well as candidate selection and visualization. The automated download of strain proteomes bridges the primary and secondary iteration. The procedures of the main modules are described in detail below.", "The central step in the analysis of MS/MS spectra is an efficient peptide search for comprehensive protein identification. Therefore, we rely on established and reliable open-source database search engines such as X!Tandem 47 in combination with the XTandem Parser 48 and MS-GF+ 49 . However, any command-line search engine including proprietary ones could be implemented via additional Snakemake rules. We apply a classic target-decoy approach for false discovery rate (FDR) control 50 . Decoy sequences are created upfront and independently of the search engine with fasta-decoy.pl 51 by reversing the target sequences (including contaminant proteins, for instance cRAP 52 ) and both target and decoy databases are concatenated as suggested by Jeong et al. 20 . PSMs are subjected to an FDR cutoff based on a per-match FDR calculated as Ndecoy/Ntarget, with Ndecoy being the number of decoys in between targets (Ntarget) in a list of matches sorted by e-value 20, 53 . To acknowledge established false positive hits of previous iterations, decoy sequences with an e-value above the FDR-cutoff are passed on and concatenated to the database of the next iteration." ] },{ "paper_id": "d34a47b592e9c6e84b5b4115474349acbc0fb925", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "It follows from (1) and (2) that", "In [4] the equations (1-3) were solved by introducing the function ( ) ( )", "yields:" ] },{ "paper_id": "d37a760a6ae9f4df3da850e9a71b88d340c54588", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "is the", "The calibration curves were used to compare the observed probability with the predicted probability.", "Dots on the calibration plot would be close to a 45\u00b0 diagonal line if the model calibration is correct.", "The outbreak of COVID-19 has laid unprecedented psychological stress on health workers (HWs). We aimed to assess the immediate psychological impact on HWs at Tongji Hospital in Wuhan, China." ] },{ "paper_id": "d3c2e2839498c613ee95739dce7052109750362c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "23 BACKGROUND 24 The ongoing worldwide outbreak of the 2019-nCoV is markedly similar to the severe acute 25 respiratory syndrome (SARS) outbreak 17 years ago. During the 2002-2003 SARS outbreak, 26 healthcare workers formed a special population of patients. Although virus-specific IgG play 27 important roles in virus neutralization and prevention against future infection, limited information is 28 available regarding the long term persistence of IgG after infection with SARS-like coronavirus.", "To analyze the general IgG distributions, subjects were divided into 2 groups: group 1 (n=46),", "29", "Boxplots and heatmaps were used to show the temporal trends and variations in the antibody levels." ] },{ "paper_id": "d418cdee18b07a0adfb553d43b4a08f7736fa9f3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The limitations of current microbiologic tests drive excessive use of empiric broadspectrum antimicrobials, which potentiates the emergence of drug resistance and increases risk of Clostridium difficile infection (8) . In some situations, empiric regimens may lack activity against an underlying microbe, leading to treatment failure, disease progression, and consequent adverse outcomes (5, 9) . Furthermore, in transplant patients, concern for GVHD may compel clinicians to initiate empiric immunosuppressive agents that could inadvertently exacerbate disease in the presence of an unrecognized infection (10) .", "To mitigate spurious taxonomic assignments due to laboratory background contaminants, we calculated a standard Z-score for each microbial genus relative to a control group of 17 \"no-template\" water-only controls (detailed in Table E1 ) derived from sequencing runs performed in our laboratory over the past 2 years (24). Z-scores were calculated based on unique reads aligned to either NCBI nt or nr, per million sequence input reads (rpM nt , rpM nr ).", "Abstract Word Count: 249", "This retrospective study evaluated sequentially enrolled adult HCT recipients who underwent bronchoscopy with bronchoalveolar lavage (BAL) at the University of Michigan Medical Center between January 25 th , 2012 and May 20 th , 2013. All patients met established clinical definitions of community-acquired or hospital-acquired pneumonia and had two or more of the following: cough, fever, chills, dyspnea, pleuritic chest pain, crackles, or bronchial breathing; in addition, an opacity, infiltrate or nodules on chest radiograph was required (17) (18) (19) " ] },{ "paper_id": "d47377d0da60ea7aab2522c204ad65753b0545fe", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "In 615 extracts (52.2% of those tested) at least one virus was detected. The most frequently detected virus or virus group was a picornavirus ( Figure 1 and Table 1 ; ", "Notably, RVs and influenza A viruses (IFAV) seldom co-occurred, supporting their roles as primary pathogens of the airway among acutely ill infants. Whether RV circulation has a moderating or controlling effect on the IFAV season or is controlled by it cannot be determined from these data." ] },{ "paper_id": "d485fce0c7ad92a1e1606eb81043bf9e12714562", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "\u2022 R 0 =1.5, 2, 3, 4, 5", "For each infectious case i:" ] },{ "paper_id": "d49f8ba7212183bc1b7f2cb6dd709dd197303b3d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Obviously, the initial condition is," ] },{ "paper_id": "d4cfb1fc4fc53abbc1d4b0ca60276c6af6632c3c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d4dde806ec1cfa2209b422f67ed42bcaf6bd7201", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "the results showed that these 560-bp bands could be segments from the bovine genome. 112", "it still can not rule out the possibilities of this segment from unknown species. The further work is to obtain 128 the complete genome sequence of ASFV from hard ticks or sheep. The cleaning and quality control of sRNA-seq data were performed using the pipeline Fastq_clean [12] 139 that was optimized to clean the raw reads from Illumina platforms. used for all the data analysis in this study. 143", "The RNA extraction of D. nuttalli and cDNA synthesis were performed using the protocol published in 144 our previous study [14] . The DNA extraction of D. nuttalli, D. silvarum, sheep and bovine was performed 145" ] },{ "paper_id": "d4e1b8705646c89433773a9f67bdb8c12fcf4cef", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Influenza A virus (FLUAV;", "Attachment and entry into a host cell is the first bottleneck virions encounter during infection. Virion entry requires efficient use of the host cell environment while simultaneously evading cellular immune responses.", "293T cells were transfected with plasmids encoding WSN PA, PB1, PB2, and NP, a vNA-luciferase reporter, a Renilla luciferase control reporter, and EPS8 or an empty vector. Firefly luciferase and Renilla luciferase activity were assayed 24 hours post-transfection. Firefly luciferase was normalized to Renilla luciferase within each sample. Expression of EPS8 was determined by immunoblot of cell lysates." ] },{ "paper_id": "d5efae48a9bbfccac8d9e6c1a80c8c605d80ee21", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Regardless, no direct correlation between SERINC5 exclusion from virions and resistance to its antiviral effects was evident.", "The mechanism by which virion-associated SERINC5 inhibits HIV-1 entry is unknown." ] },{ "paper_id": "d5f14e63b86239f491c9dd1749cff01dc4d633cb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We obtained a total of 87 genomic sequences from human subjects that were available via the GISAID EpiFlu Database\u2122 1 as of Monday, February 10th 2020.", "number of dif f erent nucleotides length of compared nucleotide sequence" ] },{ "paper_id": "d5f7332f6dba1d990d54b5887a175e530d144130", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "139 140", "(2).", "As \u039b s+1 only depends on I s s\u2212k+1 (see Methods) there are no unknowns. Solving 152 using this and Eq. (1) gives" ] },{ "paper_id": "d618a596def847bdfc19991c694e09bdeccf2287", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Most emerging human infectious diseases have an animal origin. Yet, while zoonotic diseases originate from a primary reservoir, most theoretical studies have principally focused on single-host processes, either exclusively humans or exclusively animals, without considering the importance of animal to human transmission for understanding the dynamics of emerging infectious diseases.", "Recent decades have seen a surge of emerging infectious diseases (EIDs), with up to forty new diseases recorded since the 1970s [1] . Sixty percent of emerging human infectious diseases have an animal origin [1, 2] . The World", "\"any animal, person, plant, soil, substance or combination of any of these in which the infectious agent normally lives\"" ] },{ "paper_id": "d7111b44f2d13b24a11d55c8be2d2bbe6b245eac", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d75c48f51b2a5c26a41fe615339e5947d5e9cb30", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "d7701711485f822c0f43df58b48faf6a433028c4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For s>0, F(s) represents the cumulative distribution function of the gamma distribution.", "We characterized the expected number of new incident cases E[c i,t ] in type i at symptom onset week t as follows,", "where r ij denotes the average number of cases of type i infected by a single individual of type j. Here we assume that the incidence, c i,t , follows a Poisson sampling process with" ] },{ "paper_id": "d810f78f8850d9386abc6fdd8d652f2f85191753", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We also estimate the growth rates of the epidemic in all other provinces (Materials and Methods).", "We fitted a truncated gamma distribution (0 to 30 days) and estimated the mean and variance of the incubation period using Markov Chain Monte Carlo (MCMC) in a Bayesian framework using an uninformative prior distribution. We derived the likelihood as follows:", "A Metropolis-Hastings algorithm was implemented in R. Marginal posteriors were sampled from a chain of 5,000 steps after discarding a burn-in of 50 steps. Convergence was inspected visually.", "Comparing predictive models of epidemic trajectories: To evaluate hypotheses regarding the effect of mobility and testing on COVID-19 dynamics, we fit three different Generalized Linear Models (GLM)." ] },{ "paper_id": "d82fe700418fb6494ffb9a2c0cf4f6b8012b3824", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "GAT GAA", "GCA GCT" ] },{ "paper_id": "d83e3c028de1950c4f8dedae21eb90f90c4ed6c3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "255 Remarkably, inhibition of eIF4A activity using silvestrol abrogated TGF-\u03b2 induction in L.", ". CC-BY 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2019.12.20.884338 doi: bioRxiv preprint", ". CC-BY 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2019.12.20.884338 doi: bioRxiv preprint 28 534 The authors have declared that no competing interests exist." ] },{ "paper_id": "d85d142716f7f85cd27b54fc38a9e2968cf14346", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "that were peaking when the disruption occurred and least for viruses in early epidemic phase.", "\u2022 prospective enrollment of community members with acute respiratory illness (ARI) through standalone kiosks at university campuses, airports, workplaces, homeless shelters, and high-traffic tourist areas;", "Nucleic acids extracted from respiratory swab specimens from study participants were screened for the presence of multiple respiratory pathogens by reverse-transcription and Taqman. Screened pathogens included influenza A/H1N1, A/H3N2, and B; respiratory syncytial virus (RSV) A and B; human coronavirus (229E, NL63, OC43, HKU1) (hCoV); human metapneumovirus (hMPV); rhinovirus (HRV), and adenovirus (AdV)." ] },{ "paper_id": "d8c2466863d8ff87bc1aaf5218ce6f3f7fb29c3b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Eq. (1):", "= + ' + ) + + + -+ / + 1 \u00d7 ( = 2) + : : + ,", "= + T + Q + ' + ) + + + -+ / + ( \u00d7 T ) '\u00d7U V + ( \u00d7 Q ) '\u00d7U W + ( \u00d7 T ) )\u00d7U V + ( \u00d7 Q ) )\u00d7U W + ( \u00d7 T ) +\u00d7U V + ( \u00d7 Q ) +\u00d7U W + ( \u00d7 T ) -\u00d7U V + ( \u00d7 Q ) -\u00d7U W + ( \u00d7 T ) /\u00d7U V + ( \u00d7 Q ) /\u00d7U W + + ," ] },{ "paper_id": "d91120d80916351170b34715ea4ab141f02c51fb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The activation and movement of a prophage from one host to another enables phages to act as mediators of horizontal gene transfer, via either generalized or specialized transduction (4) . This phagemediated horizontal gene transfer may account for up to 10 15 transduction events per second (5, 6) .", "Computational work was conducted on the Edwards Bioinformatics Lab compute cluster.", "Prophage genometrics" ] },{ "paper_id": "d92e6ddc127c4dd588cfa8fd584a9a1adb4bbe86", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Ahlgren, N. A., et al. (2016) . \"Alignment-free oligonucleotide frequency dissimilarity measure improves prediction of hosts from metagenomically-derived viral sequences.\" Nucleic acids research 45(1): 39-53.", "The model not only had the best overall performance, with accuracy of 0.90 and AUC of 0.92, respectively, but also had the best ability of capturing the human-infecting virus, with recall rate of 0.94. ", "All the statistical analysis was conducted in R (version 3.5.0)." ] },{ "paper_id": "d9eeeb81d17be6a722b11081f13576de197d249f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The medical records of all participants were analyzed by the research team of the", "Measurement data were expressed using median and interquartile range (IQR) values and compared using independent group t test. Enumeration data were described as number (%). All statistical analyses were performed using SPSS (Statistical Package for Statistical analysis), and a P value of less than 0.05 is considered as significant difference.", "According to chest CT scans reports, 15 (41%) patients showed unilateral involvement (13 cases in right lung and 2 cases in left lung) and 22 (59%) patients showed bilateral involvement. 23 (62%) patients had multiple \"ground-glass opacity\" lesions in the lung which were regarded as the characteristics of COVID-19 pneumonia (Table 3 and Figure 3 )." ] },{ "paper_id": "da3aa20131ac2805c0d9e1b29f094683479ab5b7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Fifth, the INO80 \u2206N , HQ1 and HQ2 mutations most drastically affected distance to BamHI sites, but in opposite ways ( Figures 5C,D, 6C,D) .", "The pGP546 yeast genomic plasmid library was expanded from the clonal plates provided by Open Biosystems. For generation of genomic plasmid libraries, the S. pombe strain Hu0303 (Ekwall group) and E. coli strain (ATCC 11303 strain, 14380, Affymetrix) were used. INO80 wild-type and mutant complexes, Chd1 and FACT were expressed in Trichoplusiani insect cells. Spodoptera frugiperda sf21 insect cells were used for virus production. The Saccharomyces cerevisiae ISW1a and Fun30 remodelers were purified from the correspondingly TAP-tagged yeast strains, Ioc3-TAP, Fun30-Tap, as provided by Open Biosystems. Yeast ISW2 was purified from strain YTT480 (ISW2-2xFLAG, Tsukiyama et al., 1999) . Reb1 was purified from E. coli BL21 (DE3) cd+ cells. The Drosophila embryo histones were prepared from the Drosophila melanogaster strain OregonR.", "Whole-genome plasmid library expansion. The S. cerevisiae genomic plasmid library (pGP546) was originally described in Jones et al. 2008 and purchased as a clonal glycerol stock collection from Open Biosystems. Library expansion was carried out via a Singer ROTOR plating machine (Singer Instruments) (8-12 rounds, 3 replicas). After 16 hours, colonies were combined into 3x2 L of LB medium containing 50 \u00b5g/mL kanamycin and grown for 4 hours. Cells were harvested and subjected to Plasmid Giga Preparation (PC 10 000 Kit, Macherey&Nagel). For S. pombe and E. coli plasmid library generation, genomic S. pombe (Hu0303) and E. coli (type B cells, ATCC 11303 strain, 14380, Affymetrix) DNA was fragmented by a limited SauIIIA or AluI digest. Fragmented DNA was ligated into pJET1.2 vector (ThermoFisher Scientific) and transformed into electrocompetent DH5\u03b1 cells. Cells were plated on LB plates containing 100 \u00b5g/mL ampicillin, grown for 16 -20 hours, combined in LB medium containing 100 \u00b5g/mL ampicillin and grown for another 4 hours. Plasmids was extracted with Plasmid Mega Preparation Kit (PC 2000 Kit, Macherey&Nagel) .", "For low, medium and high assembly degrees, 10 \u00b5g of plasmid library DNA (S. cerevisiae, S. pombe or E. coli) was mixed with ~2, 4 or 8 \u00b5g of Drosophila embryo histone octamers, respectively, in 100 \u00b5l assembly buffer (10 mM Tris\u00b7HCl, pH 7.6, 2 M NaCl, 1 mM EDTA, 0.05 % IGEPAL CA630, 0.2 \u00b5g BSA). Samples were transferred to Slide-A-lyzer mini dialysis devices, which were placed in a 3 L beaker containing 300 mL of high salt buffer (10 mM Tris\u00b7HCl pH 7.6, 2 M NaCl, 1 mM EDTA, 0.05 % IGEPAL CA630, 14.3 mM \u03b2-mercaptoethanol), and dialyzed against a total of 3 L low salt buffer (10 mM Tris\u00b7HCl pH 7.6, 50 mM NaCl, 1 mM EDTA, 0.05 % IGEPAL CA630, 1.4 mM \u03b2-mercaptoethanol) added continuously via a peristaltic pump over a time course of 16 h while stirring. \u03b2mercaptoethanol was added freshly to all buffers. After complete transfer of low salt buffer, samples were dialyzed against 1 L low salt buffer for 1 h at room temperature. DNA concentration of the SGD chromatin preparations was estimated with a DS-11+ spektrophotometer (Denovix) and could be stored at 4 \u00b0C for several weeks. To estimate the extent of the assembly degree, an aliquot of the sample was subjected to MNase digestion (as described below) for MNase-ladder read out." ] },{ "paper_id": "da5ecffba8c5d1b7afee057ff61149fb976501ce", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "dac1b1607ae72b9509ab26367e0d55016e8132a8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The data are from the official website of China Health and Health Committee and Hubei Health and Health Committee. From December 1, 2019 to February 14, 2020 [10] [11] , WPS software was used to analyze and summarize; WPS software and GraphPad Prism 6 software were used for mapping.", "Objective] Analyze the occurrence of novel coronavirus pneumonia(NCP) in China mainland, explore the epidemiological rules, and evaluate the effect of prevention and control. [Methods] From", "From January 21, 2020 to January 24, 2020, the spread index is around 100%, indicating that the novel coronavirus spreads rapidly in these four days." ] },{ "paper_id": "daf32e013d325a6feb80e83d15aabc64a48fae33", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As illustrated by Fig. 3 a, air traffic network acts as a major channel serving human long-range travels, which mediates the pandemic transmission on a large geographic scale. The epidemic dynamics occurred under this scenario is well characterized by the reaction-diffusion processes [88] , which are also widely applied to model phenomena as diverse as genetic drift, chemical reactions, and population evolution [2] .", "encounters per day [115] [116] [117] [118] [119] , which implies the presence of a characteristic contact rate within each subpopulation.", "The above studies focus on understanding the influence of inter-subpopulation human mobility patterns, generally assuming that the individuals behave identically in each subpopulation. However, the diversity of individual behaviors in different subpopulations also affects the pandemic spreading.", "Aside from the above conceptual descriptions, it is also essential to verify the validity of the model from theoretical as well as empirical perspectives." ] },{ "paper_id": "daf507bcd9337e05d4bdc3da73e05639837f2031", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Polymorphisms Registry (35), a NIEHS-supported cohort, to recruit carriers of this allele, as well 129 as \"wildtype\" controls. Others have reported that whole blood from rs5744168 minor-allele carriers 130", "were not affected by obesity-, microbiome-or breeding-related immune perturbations, we 90 performed experiments with mice that were either purchased from a commercial vendor (using 91 C57BL/6 as controls) or bred in our NIEHS colony (using wild-type littermates as controls) and 92 treated some mice with neomycin to reduce bacterial burden in the intestinal tract. Our results did 93 not vary regardless of mouse provenance or antibiotic treatment (Supplementary Fig. 1B) . 94", "We exposed human volunteers to O3, and isolated alveolar macrophages through bronchoscopy 141 24 hours after exposure, which represents the peak of O3-induced inflammation and symptoms 142 in humans. TLR5 expression was modestly increased in alveolar macrophages of human 143 volunteers after O3 exposure (Fig. 4B , p=0.05 by Wilcoxon pairwise signed rank test). There was 144 no association between TLR5 expression and TLR4 expression after O3 exposure. We found, that 145" ] },{ "paper_id": "db142fe07544dcf0e454f8a9f39452f0aa92a6ca", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Identifying and eliminating factors that predict a negative outcome is the key to improve survival from COVID-19, especially in Wuhan.", "However, the clinical characteristics of COVID-19 cases remain largely unclear." ] },{ "paper_id": "dbefc8ad2a3de5d1696b7e604de8bce1da2ea8cd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "With the current severe outbreak of coronavirus disease emerging from Wuhan in China in late 2019, several countries worldwide battle to control the spread of this devastating virus.", "The ongoing outbreak is accompanied by many human casualties and significant socio-economic losses globally and has now reached the proportions of a pandemic, with more than 81,000 COVID-19 confirmed cases and more than 2,760 related fatalities worldwide (February 26, 2020) .", "Unfortunately, CoV-specific FDA-approved drugs are still not available in the clinics." ] },{ "paper_id": "dc3d8b94ae9acb1ec585507d0d77164a7f688d10", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "One limitation of this study is that only one pneumococcal serotype 6B isolate was used, future 268 studies using other isolates with a more or less invasive phenotype will be able to answer how 269 generalizable these findings across pneumococcal isolates are. Nonetheless, the observation that ", "Log counts per million (CPM) from raw counts were calculated using the 'edgeR' package." ] },{ "paper_id": "dca8ced82157924ed86c698a7dd482be81b4b266", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The proteolytic processing of the SARS-CoV S protein is essential for the Moreover, the cleavage site of cathepsin L was consistent among the epidemic strains of 2019-nCoV retrieved from the GenBank database, including 9 from Wuhan, 2 from Shenzhen, and 5 from USA ( Figure 1B ).", "Statistical analysis was performed with GraphPad Prism 7. For data with a normal distribution, we used a Student's t test. For multiple comparisons a one-way or two-way ANOVA (for parametric data) followed by Bonferroni's correction (only two groups were compared) were used. P values < 0.05 were considered statistically significant. the author/funder. All rights reserved. No reuse allowed without permission.", "The genome sequences of SARS-CoV and 2019-nCoV were collected from the GenBank database (https://www.ncbi.nlm.nih.gov/nuccore/). Consensus sequences were created using the BioEdit software (http://www.mbio.ncsu.edu/bioedit/bioedit.html) based on the multiple alignment of SARS-CoV and 2019-nCoV, respectively. The amino acid sequence logos generated by using WebLogo 29 ." ] },{ "paper_id": "dcd7a1235ea74e3ef71d051103bf8a64c3c8f457", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Year. We believe our estimation is close to the real situation and is helpful for 2019-65 nCoV control. 66 ", "Hubei Province, and none of the prediction closes to the real situation. 17" ] },{ "paper_id": "dd2cd004a197872cfce1c31a9685d6972f838efa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Adding a more explicit fatality compartment is straightforward. However, more complex models incorporating significantly time-delayed or nonlinear costs are much more accurate for measuring the effectiveness of QIT policies.", "The authors declare that they have no competing interests.", "This effort was funded by Defense Threat Reduction Agency." ] },{ "paper_id": "ddbf32ef7d7bd337dbfe05cbf8239b0fb698bb6a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "As the essential elements of virus transmission, the expression of virus receptor ACE2 in target organs is another determining factor for fetus vulnerable to SARS-CoV-2.", "[10]" ] },{ "paper_id": "ddefea974fdb2730133e762ece41335b3d3cb94d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "1 transmission routes 2 Sk Shahid Nadim a , Indrajit Ghosh 1a , Joydev Chattopadhyay a 3 Abstract 5", "The mode of transmission of some infectious diseases may be through both direct and indirect con-9 tact. In direct transmission, a pathogen can infect a susceptible host through infected host, and in 10 indirect transmission, a pathogen can infect a susceptible host through an infected vector. For instance, 11 Middle East respiratory syndrome coronavirus (MERS-CoV) (1) and Zika virus (2) may be spread both policies have been found very effective (5; 6) in decreasing the rate of infection at the late stage of SARS outbreak, even when the number of infective individuals were getting larger relatively. Additionally, the influenza pandemic of 2009 has triggered a psychological effect that caused adoption of preventive 23 measures by a significant portion of the population (4). Recent MERS-CoV outbreak in Arabian penin-24 sula also imposed a significant behaviour change in the local people (1) . Thus, psychological effects 25 are necessary in modelling infectious disease transmission. The general incidence rate in this context at time t is given by N v (t) = S v (t) + I v (t). We assume all newborn hosts are fully susceptible. The susceptible host population increases at a constant rate \u03a0 h . The susceptible population decreases due to 66 getting infection from infected vectors and infected hosts and natural mortality at a rate \u00b5 h . Therefore ", "(3.5)" ] },{ "paper_id": "de3ae7971891058db2f4b36cd216531e6f533332", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The cytotoxic T lymphocytes (CTLs) and their immune responses are common to various 43 genera of jawed vertebrates. Common CTLs include CD8 + T cells, which recognize only 44 antigens presented by classical major histocompatibility complex class I (MHC-I) molecules 45", "His 99 , Tyr 156 and Tyr 159 , which have large side chains and provide a clear boundary to pocket D. 160", "Ile 124 , Thr 143 , Lys 146 and Trp 147 , as well as the poorly conserved residues Ala 73 , Phe 74 , Asp 77 , 170" ] },{ "paper_id": "df6013a1630aa41627cc84c8e780d40ff93785cc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The user should paste one or two RNA sequences in FASTA format into the dedicated form, providing an email address (optional) to receive a notification when the job is completed. The algorithm can be launched in 4 different modes, each of them being a specific variation of the DTW algorithm (Supplementary Figure 1) .", "To test the performances and functionality of CROSS combined with DTW ( Supplementary Figures 1 and 2) , we selected a dataset of 22 structures for which crystallographic (exact base pairing between nucleotides) and Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE; chemical probing of flexible regions used to assess whether a nucleotide is in double-or single-stranded state) data are available [12] . Using DTW, we calculated the structural distances between all possible pairs in the dataset considering crystallographic (dots and parentheses were transformed into binary code) data as well as 1) SHAPE profiles ( [20] .", "This result suggests that HIV could have evolved maintaining a similar sequence but different structures, as previously reported in literature [30] .", "Thermodynamic approaches, such as RNAstructure [14] or RNAfold [12] , cannot be directly used for such a task since they are restricted on the sequence length [36] ." ] },{ "paper_id": "dfb0fedbeed56bd2b795a67faab28295afc14c96", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "dfb2f07149617b0c2911899ac61563e808e2cee1", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "dff716159738acd6bd53b4be12af45358a58752e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "These pathogens were analyzed in a more detailed study. The results of analysis of Gardnerella vaginalis were previously published [2] .", "DNA from blood and saliva and tumor tissues was isolated using lysis buffer containing 5M guanidinium thiocyanate, 50mM Tris (pH 7.5), 10mM EDTA, 0.5% Triton X-100, then extracted with equal volume of phenol:chlorophorm and then chlorophorm. DNA was precipitated by 2.5 volumes of ice-cold 96% ethanol in the presence of 0.3M ammonium acetate. Tumor was grinded in liquid nitrogen with addition of lysis buffer before extraction." ] },{ "paper_id": "e01948b342544a5fcd8c14d757501779029c6d6d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "is scaled from -1 to 1, where -1 represents an entirely segregated network and 1 represents an entirely nested network.", "pathogens is an open question in disease ecology. Importantly, patterns like these would be missed without incorporating high-resolution pathogen data." ] },{ "paper_id": "e046a06f262d74d025272ad697d358c4afb5d9bd", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The study was approved by The Fifth Affiliated Hospital of Sun Yat-sen University Ethics Committee and written informed consent was obtained from patients involved before enrolment when data were collected retrospectively.", "Negative: no Ct value or Ct 40.", "Positive: a Ct value < 37." ] },{ "paper_id": "e05c39ce913edc81f93c9247f9714d6cddd30073", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e066fdbb4a9338a57477424cb66fd4d75b2fd66d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "According to title and abstract, two independent researchers selected and classified literatures, and reviewed all followed criteria.", "Articles from PubMed, Embase, Cochrane database, and google up-to 24 February 2020 were systematically reviewed. Eighteen Literatures were identified with cases of COVID-19 pneumonia. The extracted data includes clinical symptoms, age, gender, sample size and region et al were systematic reviewed and meta analyzed." ] },{ "paper_id": "e0a53c258ee0483666329ccab591c0753ff49531", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Our institutional review board approved this retrospective study analyzing existing patient data with patient information de-identified and all subjects gave written informed consent. And this study involved no potential risk to patients.", "Highlights:" ] },{ "paper_id": "e0fd364797eb02a280e25e2649dfe6d6c0d33e05", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "proposed Alphacoronavirus 2 species, as an improved way to classify the diverse Alphacoronavirus 38 genus.", "FCoV and CCoV serotypes. 138" ] },{ "paper_id": "e1008925754f127b74ab07e83fd64c0260b980a2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e1632ff25e6c30d4d89828154be1389a90109db8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The developed assay will serve as a practical tool for screening of propagative material, monitoring the presence and distribution, and quantification of target pathogens in a breeding program. The assay also has applications in routine diagnostics, biosecurity and microbial forensics.", "New York, USA Prunus avium --Soil --Healthy potato ---Indicates no amplification; \u00b1 standard deviation of cycle threshold (Ct) values of three replicates; *95% identity with P. wasabiae and 94% with P. parmentieri (BLASTn results on 5.22.18); SD is standard deviation; a sequencing quality was poor. Therefore, sequence was not submitted to NCBI GenBank." ] },{ "paper_id": "e18620d5cff022d18aa23da2fa4634331fa54860", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Protease-activated receptors (PARs) are G protein-coupled receptors (GPCRs) that can drive inflammation in asthma, chronic rhinosinusitis (CRS), and allergic rhinitis. 1, 2 PARs are activated by proteolytic cleavage of the extracellular N-terminus, exposing an intramolecular tethered ligand. 1, 2 PAR-2 may be activated by mast cell tryptase, 3 neutrophil elastase, 4 Alternaria fungal proteases, 5 and house dust mite proteases 6 and may promote Th2 inflammation in bronchial epithelial cells. 7 We previously found that PAR-2 is expressed on the basolateral membrane of healthy well-polarized differentiated primary sinonasal epithelial ciliated cells, where it elevates intracellular calcium to increase ciliary beating and apical membrane Clsecreation, 8 suggesting PAR-2 promotes epithelial mucociliary clearance in response to protease activity.", "While Alternaria proteases are well documented to activate PAR-2, 32, 33 ", "Basolateral 2FLI caused an increase in ASL height in both groups (Figs 4A-C) that was inhibited by basolateral application of the Na + K + 2Clco-transporter (NKCC) inhibitor bumetanide (Fig 4C) ,", "Objective: We tested if epithelial remodeling during diseases characterized by loss of cilia and squamous metaplasia may alter PAR-2 polarization." ] },{ "paper_id": "e226beab8af4202a5182f7603fe468dedd5dee6a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "HIV/AIDS continues to be a major global health epidemic. In 2017, there were 36.9 million 39 axially chiral dimeric naphthylisoquinolone alkaloids first isolated from Anicistrocladus 84 korupensis in 1991 and later named the michellamines, exhibit selective anti-HIV activity. 15-19 85 Given these facts taken together with the existence of other antiviral biaryl natural products (e.g., 86", "HIV-1 pseudotyped viruses were prepared as previously described. 68 Briefly, HEK 293T 433 cells were transfected with an envelope expression plasmid (pHxB2, pYU2, or p89.6) and an 434 envelope deficient HIV-1 backbone vector (pSG3\u0394env) using XtremeGENE HP DNA 435", "Effects from non-specific binding were removed using double referencing. Residual baseline 536 drift was calculated by fitting the response during baseline periods to an exponential decay and 537 then subtracting this drift. The resulting response curves were globally fit to a 1:1 Langmuir 538 model. 72 All fits were performed using a constrained, non-linear least squares minimization 539 (MATLAB R2018a, lsqnonlin function implementing the trust region reflective algorithm). 540" ] },{ "paper_id": "e29b287d326be9c2c0a7dcd7a81cb49cc2125360", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Word Count: 204 (Excludes title and key words)", "The authors declare that there are no competing interests.", "Correspondence and requests for reprints should be sent to Dr. Rhoel R. Dinglasan. His e-mail address is rdinglasan@epi.ufl.edu. His FAX number is 352-392-9704 and his telephone number is 352-294-8448. His professional address is 2055 Mowry Road, 32611, Gainesville, FL." ] },{ "paper_id": "e350e1b4aab99c73d0e0d03121b50c059c04fd61", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nidoviruses are an ancient group of lipid-enveloped viruses with non-segmented RNA genomes, which 35 are known to infect oomycetes and animals, including molluscs, arthropods and vertebrates (1). Among 36 them are the coronaviruses (CoVs) which possess the largest known monopartite RNA genomes and are 37 classified into four genera-Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and 38", "The host-pathogen arms-race has selected for a disparate complement of viral genes involved in 127 pathogenesis. These genes often rapidly diversify through recombination and mutations to keep up with 128 the evolution of host resistance. To identify proteins with potential pathogenic roles in COVID-19, we 129 conducted a comparative genomic analysis of the coronaviruses. Similarity plots show that the bat CoV 130", "Deltacoronavirus (2) . Over the past two decades, Beta-CoVs, including the viruses responsible for 39", "CoVZXC45, first in the 5' half of ORF1 and again after nucleotide number 20,000 of the genome. 133" ] },{ "paper_id": "e3f19f88e7e3d1279b4d93e4db041e44a8d35dbb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We conducted a literature review to establish plausible ranges for model parameters, and developed a deterministic system of ordinary differential equations to model the general dynamics of these five viruses.", "(4) Everyone who recovers gains full immunity.", "The equations governing common upper respiratory virus dynamics are given by", "Influenza-like illness (ILI) accounts for a large burden of annual morbidity and mortality worldwide (WHO 2020) . Despite this, diagnostic testing for specific viruses underlying ILI is relatively rare (CDC 2019) . This results in a lack of information about the pathogens that make between 9 million and 49 million people sick every year in the United States alone (CDC 2020 ). Yet knowledge of the specific diseases is necessary for timely treatment to prevent unnecessary suffering and death (Nguyen 2016 , Van Asten et al. 2012 , Pawelek et al. 2015 ." ] },{ "paper_id": "e4701bdf5d414ea8ca38a4d8d3f69540805293b0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e476334b4f415f8fde5e2f560fd1ad0fa314af90", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Phenotypes are plotted as Tukey box plots with strain (y-axis) by relative residual animal length (x-axis). Statistical significance of each deletion strain compared to its parental strain (ECA1132 to N2 and ECA1134 to CB4856) is shown above each strain and colored by the parent strain against which it was tested (ns = non-significant (p-value > 0.05);", "Broad-sense heritability was calculated from the dose response phenotypes using the lmer function in the lme4 R package (Bates et al. 2014 ) with the formula phenotype ~ 1 + (1|strain) for each dose. All statistical tests of phenotypic differences between strains were performed using the TukeyHSD function (R Core Team 2017) on an ANOVA model with the formula phenotype ~ strain .", "MATERIALS AND METHODS" ] },{ "paper_id": "e4cb4af2f4ec6f023096afcf7b3d4410584e1393", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Promoting angiogenesis subsequently enhances the rate of tumor growth and progression.", "Gremlin-1 regulates the transition of epithelial cells to mesenchymal cells, thus contributing to the progression of cancers [15] .", "However, [24] reported that intramolecular hairpin secondary structure of strand does not significantly affect siRNA efficacy." ] },{ "paper_id": "e4d752fd72eb7b1089e4b820598b1f69f50bc636", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All rights reserved. No reuse allowed without permission.", "We present an R package, \"NobBS,\" intended to provide easy and flexible implementation of this approach to a wide audience of public health officials and researchers. This package is currently being finalized and is installable from https://github.com/sarahhbellum/NobBS, and will be moved to CRAN in final form." ] },{ "paper_id": "e4e5e67fd4f75548dffab7f75484bc14fa15c0c2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Given the high mutation rates (9) , potentially large population sizes and fast replication of many emergent RNA viruses (10) , they are capable of generating and maintaining substantial genetic variation (11, 12) . This variation fuels adaptation, and selective sweeps leave genetic marks of past ecological history in viral genomes. These fixed mutations can alter the fitness landscape and constrain evolutionary trajectories of viruses due to epistatic interactions between mutations (13) . Virus evolution is known to be shaped by epistasis, detected by both laboratory experimentation and phylogenetic analysis (14) (15) (16) , and increased understanding of epistasis promises to improve our predictions of why some viral emergence events are more successful than others (17) .", "where n=4 for 4 nucleotides, ( ! ) is the proportion of a single nucleotide over all nucleotides read at that position. When comparing levels of polymorphism between populations directly, the SNPs in each protein-coding gene were considered as independent observations for a paired t-test (Microsoft Excel, Redmond, WA)." ] },{ "paper_id": "e4f66cfdaf836895e7d37941223f11ebc41dbb57", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "However, current plant pathogen PoUD strategies use a range of approaches including antibody-based detection which lacks sensitivity (9) , or isothermal amplification that by itself does not generate convenient visual outputs that are amenable to field use.", "Synthetic 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 stranddisplacement (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 PCR-based approaches." ] },{ "paper_id": "e5163021a1b88e2c2335cca27fbfcf883f870830", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e53f5a6c4cbac340f0d97a4ba3289c30b7222dd5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The inclusion criteria for this study were as follows: (a) age older than 18 years old; " ] },{ "paper_id": "e560eb28bb3f35099d2632f80adaa14436516474", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e5f19b6daf956e815c779228cc0cad1293d65bbb", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "After the outbreak of the middle east respiratory syndrome (MERS) worldwide in 2012.", "All statistical analyses and graphs were generated and plotted using GraphPad Prism version 7.00 software (GraphPad Software Inc). The p value < 0.05 suggests significant difference." ] },{ "paper_id": "e60640bfc445db0f53b5d92cb9f69cd943f1b73a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Virus annotation was instrumented as described in Debat (2017) RPs are depicted clockwise, and sequence similarity is visualized from blue to red ribbons representing low-to-high sequence identity. F) Unrooted radial phylogenetic tree visualization of (B), genera of depicted viruses are indicated by colors.", "studies are exploring and elucidating the expression profiles of a global plethora of organisms." ] },{ "paper_id": "e62e453735dc2022f4d81aa9b22769de30d0bb90", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This is an ordinary differential equation model, described by the following equations:", "The simulation used the fourth-order Runge-Kutta algorithm [5] to solve it numerically, with a step size fixed at 0.01 for R 0 , and at 0.1 for TE and TI.", "All data and materials used in this work were publicly available." ] },{ "paper_id": "e6fe63419fe399f9c77513c1c11a043db006a2f3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "1 0", "The originally proposed Z-curve variables might reflect the composition of a single nucleotide considering the features derived from phase heterogeneity of a single nucleotide (Zhang and Zhang 1991; Zhang and Chou 1994; Zhang 1997) . Herein, we provided a summary of the Z-curve method used for gene identification (Zhang and Wang 2000) . Let us suppose that the frequencies of bases A, C, G and T occurring in an ORF or a gene fragment at positions 1, 4, 7, \u2026 , 2, 5,", "(1)", "(" ] },{ "paper_id": "e7bdd52badd2d2ca8ce7bd838ca42d02ca3396ee", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Supplementary Table 1 Sensitivity and specificity of LCN2, CRP and combined LCN2 and CRP Supplementary ", "Correspondence: ccasals@clinic.cat" ] },{ "paper_id": "e7c3ec3dcb3469ee4d608029e7aa3068a4c90c54", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Two quantities are fundamental in measurements on channel gating: gating current and gating charge.", "(1)", "These are linked through the Y266, the other two members of the second triad being R303 and E226." ] },{ "paper_id": "e7ff9455c483c237c3ee08b9d230b7be65c064bf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "(GT)6 oligonucleotides were purchased from Integrated DNA Technologies (IDT, Standard Desalting). HiPCo SWNT were purchased from NanoIntegris (Batch # HR27-104). (GT)6-SWNT colloidal suspension (nIRCat) was prepared by mixing 1 mg of (GT)6 and 1 mg of SWNT in 1 mL of a 100 mM NaCl solution. The solution was bath sonicated (Branson Ultrasonic 1800) for 10 minutes and probe-tip sonicated for 10 minutes at 5 W power (Cole Parmer Ultrasonic Processor, 3 mm tip diameter) in an ice-bath. The sonicated solution was incubated at room temperature for 30 minutes. The product was subsequently centrifuged at 16,000 g (Eppendorf 5418) for 90 minutes to remove unsuspended SWNT bundles and amorphous carbon, and the supernatant was recovered for characterization and use. Each nanosensor suspension was stored at 4\u00b0C until use.", "To characterize nIRCats post-synthesis, the full visible and near-infrared absorption spectrum was taken for each nanosensor batch (UV-VIS-NIR spectrophotometer, Shimadzu UV-3600 Plus) or UV-VIS (ThermoFisher Scientific Genesys 20) . SWNT concentrations of as-made nanosensor batches were determined using absorbance at 632 nm (UV-VIS) with an extinction coefficient of \uf065 = 0.036 (mg/L) -1 cm -1 . Full spectrum absorbance measurements were made with UV-VIS-NIR after dilution to 5 mg/L SWNT concentration in 100 mM NaCl. For fluorescence spectroscopy, each sensor batch was diluted to a working concentration of 5 mg/L in 100 mM NaCl, and aliquots of 198 \u00b5L were placed in each well of a 96-well plate (Corning). Fluorescence measurements were obtained with a 20 X objective on an inverted Zeiss microscope (Axio Observer.D1) coupled to a Princeton Instruments spectrograph (SCT 320) and liquid nitrogen cooled Princeton Instruments InGaAs linear array detector (PyLoN-IR). A 721nm laser (OptoEngine LLC) was used as the excitation light source for all characterization experiments.", "All rights reserved. No reuse allowed without permission." ] },{ "paper_id": "e8b2e667f2145ec96fbb6400fb41b05cafa26e37", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "245 mallacophyla (6), P. murchronata (7), P. morifolia (8) P. racemosa (10), P. setacea (11), P.", "165 mg/mL) was added, followed by incubation at 37\u00b0C in an atmosphere of 5% CO 2 for 3 hours.", "The cytotoxic activity of natural bioactive products against cancer cells is attributed to 295 the chemical composition of the product, and this practice of identification is the most 296 successful source of potential drug discovery and development (7). " ] },{ "paper_id": "e8b8e0f027881d2480d808b05d9281a7ff4e9b4d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "e901cf35efbad09a224f2c500f7aef1f6d2d3b6a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "3. Our modelling approach provided enhanced predictive performance compared to more 51 traditional approaches, as well as new insights into disease risks in a wild population. We 52 were able to efficiently capture and visualise strong non-linear patterns, as well as model 53 complex interactions between variables in shaping exposure risk from CDV and feline 54 parvovirus. For example, we found that lions were more likely to be exposed to CDV at a 55 young age but only in low rainfall years. 56 57 . CC-BY-NC-ND 4.0 International license is made available under a", "1. Predicting infectious disease dynamics is a central challenge in disease ecology. Models 36 that can assess which individuals are most at risk of being exposed to a pathogen not only 37 provide valuable insights into disease transmission and dynamics but can also guide 38 management interventions. Constructing such models for wild animal populations, 39 however, is particularly challenging; often only serological data is available on a subset 40 of individuals and non-linear relationships between variables are common. 41 42 2. Here we take advantage of the latest advances in statistical machine learning to construct 43 pathogen-risk models that automatically incorporate complex non-linear relationships 44 with minimal statistical assumptions from ecological data with missing values. Our 45 approach compares multiple machine learning algorithms in a unified environment to 46 find the model with the best predictive performance and uses game theory to better 47 interpret results. We apply this framework on two major pathogens that infect African 48 lions: canine distemper virus (CDV) and feline parvovirus.", "49 50" ] },{ "paper_id": "e93ba7d8a047795d5ec114741f32f5b18e8567c7", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We expect individuals of different ages to show different antibody profiles due to differences in lifetime influenza exposures. However, we found that our summary metrics did not monotonically increase with age. There is a gradual increase in the overall (nAUC) and breadth of immunity (nW 40 ) throughout childhood consistent with the accumulation of exposures (Fig. 3 , J and K and fig. S1) (3) (4) (5) . The observed decrease in nAUC and nW 40 among people aged 40 to 50 and age-independent changes in these metrics (Fig. 3 D and H) could suggest low HAI antibody among this age group, which could be due to high non-specific immune responses [e.g. antibodies against HA stalk and neuraminidase (NA) and cellular immune responses; (18) (19) (20) (21) (22) ]. These non-specific immunities, which may accumulate over multiple exposures and are not measured in our assay, could preventing people from being infected and producing updated, strain specific HA responses (19, 20, 23) ." ] },{ "paper_id": "ea17aad7692bb5040f3b2ba1d01b8249e4969469", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ " 33 ", "Emergency Use Authorization (EUA)-approved assay developed by the US CDC 6 . 58", "for an in-vitro transcription (IVT) reaction at 37\u00b0C for 2 hours. The IVT reaction was then 232 treated with TURBO DNase (Thermo) for 30 minutes at 37\u00b0C, followed by a heat-233 denaturation step at 75\u00b0C for 15 minutes. RNA was purified using RNA Clean and 234", "In early January 2020, a cluster of cases of pneumonia from a novel coronavirus, 51 SARS-CoV-2 (with the disease referred to as COVID-19), was reported in Wuhan, 52" ] },{ "paper_id": "ea7cf2347337e379e62c9bf09b2db9b44fb2e812", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "replication 201" ] },{ "paper_id": "ea84759e67802b696a5c60503c024546e542d572", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Simulations of polarized filamentous viruses on surfaces with freely-diffusing sialic acid (green). Simulations correspond to D = 10 -7 \u03bcm 2 /s, D = 10 -5 \u03bcm 2 /s, and D = 10 -1 \u03bcm 2 /s, as plotted in 10 Figure 3E .", "Virus imaging at air-liquid interface of Calu-3 cell cultures. Calu-3 cells grown on plastic dishes for fewer than 10 passages were split at 80% confluence and seeded onto 6mm transwell supports at 50000 cells per insert. Approximately 3 days after seeding, media from the apical compartment was removed (the \"airlift\") and cells were provided with fresh media in the basal compartment every other day until being collected for experiments, 8-12 days following the airlift.", "Modeling virus diffusion. To model diffusion of the virus, we use expressions derived for dilute 5 suspensions of cylindrical rods (Brenner, 1974) :", "Montage of IAV particles acquired using total internal reflectance microscopy at 30 s intervals. Labeled HA is shown in blue and labeled NA is shown in red. Panels are shown at equivalent scales.", "For quantification and localization of blinking events, we use the ImageJ plugin Thunderstorm (Ovesn\u00fd et al., 2014) , combined with custom Matlab scripts for additional drift correction and 5 removal of fluorophores that remain in the \"on\" state for more than one frame. This analysis results in a list of coordinates for each localization that we then use to reconstruct images of virus at varying resolutions. Reconstructed STORM images (e.g. Fig. 1C & D) are displayed by representing each localization as a gaussian with a standard deviation of 30nm." ] },{ "paper_id": "ea94779ce166bcbf3813ccaab028524ff397089b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Two and half microliters of reverse transcriptase reaction (obtained from a reaction mixture before its incubation with glutathione Sepharose binding a GST-eIF4E fusion protein; see above) was subjected to Real-Time PCR amplification (5 min at 94\u00b0C; then 55 cycles of 20 sec at 94\u00b0C, 30 sec at 50\u00b0C, and 45 sec at 72\u00b0C; and finally, 4 min at 72\u00b0C) using an iCycler iQ Real-Time PCR Detection System (BioRad) and SYBR Green Master Mix (BioRad).", "A fusion PCR approach was used to assembly the desired construct for SAM mutagenesis.", "Both primary PCR products, which had defined overlapping ends, were synthesized as follows: 5 min at 95\u00b0C; then 30 cycles of 30 sec at 94\u00b0C, 30 sec at 56.2\u00b0C, and 90 sec at 72\u00b0C; and finally, 10 min at 72\u00b0C. Then, 1 \u00b5l of each PCR mixture was used without purification for a second PCR reaction using Pfu DNA polymerase (Fermentas), the primers ORF3_SAM_del_F1 and ORF3_SAMdel_R2 and following conditions: 5 min at 95\u00b0C; then 35 cycles of 30 sec at 94\u00b0C, 30 sec at 60.1\u00b0C, and 2 min at 72\u00b0C; and finally, 10 min at 72\u00b0C)." ] },{ "paper_id": "eae11a3f01b79e76a968bfb84886432f04584596", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "293T transfected to express the viral surface glycoprotein under study were inoculated with a 34 replication-deficient VSV vector that contains expression cassettes for eGFP (enhanced green 35 author/funder. All rights reserved. No reuse allowed without permission." ] },{ "paper_id": "eaf0b485f290fa884dd18de71be79d86de20eb31", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Each respondent was also asked at what point they started paying attention to this outbreak.", "*Fever or cough symptoms in the past 2 weeks." ] },{ "paper_id": "eb5e5088c41f976387784acd57dbb683932c6002", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We thank George Church, Didier Trono, David Sabatini, and Feng Zhang for sharing plasmids through Addgene. P.V.J. was supported by NIH grants R01GM094972 and P30CA008748. ", "Cells were fixed with 2.5% glutaraldehyde (Sigma) in PBS, pH 7.4-7.6 for 30 min, rinsed with PBS (3 x 5 min), and mounted in Rose chambers. Multimode (DIC and 3-color fluorescence) datasets were obtained on a Nikon TE2000 microscope equipped with a PlanApo 100x 1.45 NA objective lens at 53-nm XY pixels and 200-nm Z-steps. All LM images were deconvolved in SoftWoRx (v5.0) with lens-specific PSFs. Post-fixation, embedding, and sectioning were done as previously described [53] . Thin sections (70-80 nm) were imaged on a JEOL 1400 microscope operated at 80 kV using a side- " ] },{ "paper_id": "eb7fc5004191e8fce0d6e4ff98de6865872e665f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "About the antibody such as CR3022 [30] that the structure was not revealed, we performed the antibody strcture 148 149 author/funder. All rights reserved. No reuse allowed without permission.", "To suggest possible SARS-CoV-2 neutralizing antibodies, monoclonal antibodies were selected from the 174 author/funder. All rights reserved. No reuse allowed without permission.", "Based on antibody-antigen docking simulation, we calculated the binding scores between 11 antibodies and S-215 RBD structures. The antibody-antigen docking simulation generated not only the crystal structures of SARS-216 CoV and MERS-CoV S-RBD proteins, but also the high-quaility homology models with SARS-CoV-2 S-RBD." ] },{ "paper_id": "eb8ac60527db35b10881cb4fd86b8a6e21983d02", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ebb553a859d31ebcfc57d489ca84af0df894dab8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ebed882da10cbf669cbb86802e9fa07a4a33ef91", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ec223563f366aa8ed21ec84d1b0d21a911362cfa", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "RdRp is attenuated but elicits a protective immune response in mice that is at least as robust as the 83 immune response elicited by the type 1 Sabin vaccine strain (6).", "40 41 Significance 42", "Results" ] },{ "paper_id": "ec6adb9dc121bcbb8215cb16b880d6dc6497d209", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Thus MPAR can be calculated for loci that are not represented in either the pre-miR-seq or miR-seq library. Loci with no coverage in either sequencing library were omitted from this analysis.", "In vivo icSHAPE data from mouse ES cells was downloaded from GEO using the accession number GSE60034. Only scores in the top or bottom 10 th percentile were used for analysis. icSHAPE reactivity scores were overlaid on RNAfold diagrams using RNAplot (36) .", "The first 20 nt of the 3' adapter sequence CTGTAGGCACCATCAATAGA was used to trim adapter sequence from the raw reads using cutadapt (v1.4.2).", "This work was supported by NSF Career Award MCB-1053846 to BDG and NIH Grant GM-072777 to ZM." ] },{ "paper_id": "ec90b0b861d31f910433d388370344024ca7c35d", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The test device, which is developed based on the principle of fluorescence Immunochromatographic assay, is composed of a sample pad, a conjugate pad, a nitrocellulose membrane, an absorbent pad, and a supporting plastic cassette (Fig. 1A) .", "The current epidemic situation of COVID-19 still remains severe and it quickly spread all over China and to more than 20 other countries. Early diagnosis is critical to prevent its spreading and clinical treatment." ] },{ "paper_id": "eca1cf50bd67a7efbcaf78864f5f5b3b850243d6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "46", "(which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.02.25.20028043 doi: medRxiv preprint", "The copyright holder for this preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity." ] },{ "paper_id": "eccef80cfbe078235df22398f195d5db462d8000", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "times and is described as follows:", "and", "\u2022 A per day mutation rate and an initial source index sequence." ] },{ "paper_id": "ed0a318f34fe2d65cce6127be009ad7d5f3c7cae", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "3", "ProGest automated digestion unit. The resulting peptides were fractionated using a 867", "Dionex Ultimate 3000 nanoHPLC system in line with an LTQ-Orbitrap Velos or 868" ] },{ "paper_id": "ee986ee9617cddea4f905898fc76512afd10ae1f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For well-annotated genomes, we compile a ranking of genes (or other genomic features) sorted by the average infectious potential within a given region. In addition to that, we scan the genome with the learned filters of the first convolutional layer to find genes enriched in subsequences yielding nonzero filter activations. We use Gene Ontology to connect the identified genes of interest with their molecular functions and biological processes they are engaged in.", "We use an all-zero reference. As reads from real sequencing runs are usually not equally long, shorter reads must be padded with N s; the \"unknown\" nucleotide is also called whenever there is not enough evidence to assign any other to the raw sequencing signal. Therefore, N s are \"null\" nucleotides and are a natural candidate for the reference input. We do not consider alternative solutions based on GC content or dinucleotide shuffling, as the input reads originate from multiple different species, and the sequence composition may itself be a strong marker of both virus and host taxonomy.", "Using the formalism of DeepLIFT's multipliers (Shrikumar et al., 2019a) and their reinterpretation in SHAP (Lundberg & Lee, 2017) , we backpropagate the activation differences only along the paths \"passing through\" y j . In Eq. 1, we define partial multipliers \u00b5 (yj ) xiz and express them in terms of Shapley values \u03c6 and activation differences w.r.t. the expected activation values (reference activation). Calculating partial multipliers is equivalent to zeroing out the multipliers m y k z for all k = j before backpropagating m yj z further.", "In each of the evaluated settings, we used a total of 20 million (80%) reads for training, 2.5 million (10%) reads for validation and 2.5 million (10%) paired reads as the heldout test set. Read number per genome was proportional to genome length, keeping the coverage uniform on average. While the original datasets are heavily imbalanced, we generated the same number of negative and positive data points (reads) regardless of the negative class definition used.", "We wanted the networks to yield accurate predictions for both 250bp (our data, modelling a sequencing run of an Illumina MiSeq device) and 150bp long reads (as in the Human Blood Virome dataset). As shorter reads are padded with zeroes, we expected the CNNs trained using average pooling to misclassify many of them. Therefore, we prepared a modified version of the \"Stratified\" dataset, in which the last 100bp of each read were turned to zeros, mocking a shorter sequencing run while preserving the error model. Then, we retrained the CNN which had performed best on the original dataset. Since in principle, the Human Blood Virome dataset should not contain viruses infecting non-human Chordata, a \"Chordata\"-trained classifier was not used in this setting." ] },{ "paper_id": "eeae21c913759e8cf4c345e561457fe7ef84480f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "eec5b4ce2de8d9d00be664e6af79cac476991bbf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "These results will provide valuable information for the disease prevention for both individuals and organizations.", "Population migration data were collected from Baidu dataset (http://qianxi.baidu.com/)." ] },{ "paper_id": "f056da9c64fbf00a4645ae326e8a4339d015d155", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All methods were able identify the bulk of organisms in their databases at high abundances (75% and 18%, Figure 3 ), however performance varied considerably at lower abundances and depended on the particular organism and method used. SIANN detected each organism at high confidence, even at levels as low as 0.3% and 0.07% of the total.", "Steps to construct a custom database:", "To run SIANN:" ] },{ "paper_id": "f0cd43222c9a51d619357babc4d0ac984e8e45a0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f0e75c4697317cbd0e3a5cdd722fe0526595db64", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f0f3f4ab41fdd2d12c3fa45dc53a17d7c58a4068", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Purified library DNA was prepared for deep sequencing as in Kowalsky et al. (2015) using the primers listed in Supplemental Table S2 and gene tiling as specified in Table 1 . DNA was Illumina sequenced on a Mi-Seq platform with 250 BP paired end reads. The University of Colorado BioFrontiers Sequencing Core performed the Illumina sequencing. Data was processed using PACT (Klesmith and Hackel 2018) to determine the library coverage with the following changes to the default options in the configuration file: fast_filter_translate: qaverage = 20, qlimit = 0; enrichment: ref_count_threshold = 5, sel_ count_threshold = 0, strict_count_threshold = True. Library coverage statistics are shown in Supplemental Table S3 and S4.", "Segmentation of the \u03a6X174 genome A phage assembly platform for \u03a6X174 was devised following (Donaldson et al. 2008 ). The \u03a6X174 chromosome was divided into 14 genomic fragments designed to avoid host cell toxicity by separating genes from their promoters and breaking large genes into multiple segments (Supplemental Note S1). Each segment is flanked by unique five nucleotide overlaps of WT \u03a6X174 sequence so that they can be amplified from the ancestral \u03a6X174 using PCR primers designed to incorporate terminal BsmB1 restriction sites. Amplicons were cloned into pCR2.1 using the Invitrogen TOPO TA cloning system (Life Technologies, Grand Island, NY) and verified by Sanger sequencing.", "All purchased enzymes and DNA purification kits were from New England Biolabs, antibiotics were purchased from GoldBio, other chemicals were purchased from Sigma-Aldrich. Individual primers were purchased from Integrated DNA Technologies." ] },{ "paper_id": "f122e125c2cd3580b1a38e27c780b99f671fd78f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ ". CC-BY-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/140954 doi: bioRxiv preprint", "This study was approved by the local Institutional Review Boards and is in compliance with Helsinki principles. Informed consent was obtained from all participating patients if they were 18 years or older, from both parents and patients if they were 12-18 years of age, and from parents only if they were younger than 12 years old.", "Genotype data from 394 unrelated and unaffected Dutch samples were used as population controls and had been previously genotyped using the same platform as the JIA and uveitis samples contained in this study. 74", "Post-imputation, we checked the sum of the dosages across each HLA gene for each individual. Samples with dosages >2.5 at any one of the HLA genes (induced through imprecision in the imputation) were dropped from further analysis." ] },{ "paper_id": "f126b7f9c8ba02a0f872b51cf95d08086e0bd4ac", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Nucleoside and base analog sensitivity assays. 5-azacytidine (AZC), 5-fluorouracil (5-FU), and 480 ribavirin (RBV) were purchased from Sigma (product numbers A2385, F6627, and R9644, 481 respectively). Stock solutions of 5-FU and RBV were prepared in dimethyl sulfoxide (DMSO). 482", "2'-C-methyladenosine (CMeA) was received from Gilead Sciences, Inc (Foster City, CA). 483" ] },{ "paper_id": "f162829ffeba4cedd16aaf7f09902182c5cf903c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Introduction different mechanistic basis but affecting the same process (transcription-translation coupling) also cause DNA breaks.", "Results", "75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 All rights reserved. No reuse allowed without permission.", "Resistant mutants additionally carry different chromosomal alleles conferring antibiotic resistance. The fluorescent constructions were generated by Lambda-Red recombineering (86) (87) (88) , followed by transference to a clean background by P1 transduction (89) , and subsequent transduction of the resistance alleles. The clean deletion of rnhA was constructed by markerless recombineering using a tetR-Ptet-ccdB-cat selection/counterselection cassette as described by Figueroa " ] },{ "paper_id": "f17c6ac4986aecba2dc22f67b32f2d16b369117b", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "[Abstract] Objectives Latest epidemic data of Severe Acute Respiratory Syndrome", "The ", "The authors declare that they have no competing interests.", "Our results showed the following epidemiological characteristics related to COVID-19:" ] },{ "paper_id": "f19e2df932f90f387fe71533f3802875d9042160", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The presentation of dynamic changes of blood markers is descriptive. The consistence between Guideline and TLM-based disease classification was tested using kappa statistic. Kappa\u22670.75 indicates a high consistence and 0.75\ufe65Kappa\u22670.4 indicates a general consistence.", "Therefore, we suggested that LYM% should be used as an indicator for evaluating the effectiveness of clinical drugs or therapies. We suggest more medical staff apply and improve our proposed TLM to give patients more timely and appropriate treatments.", "Lymphopenia can be used as an indicator of disease severity and prognosis of COVID-19 patients. TLM is worth of application in the clinical practice.", "Coronavirus disease-2019 (COVID-19) is a rapidly escalating epidemic caused by SARS-CoV-2. Identification of a simple and effective indicator to assess disease severity and prognosis is urgently needed.", "Lymphocytes play a decisive role in maintaining immune homeostasis and inflammatory response throughout the body. Understanding the mechanism of reduced blood lymphocyte levels is expected to provide an effective strategy for the treatment of COVID-19. We speculated four potential mechanisms leading to lymphocyte deficiency. (1) The virus might directly infect lymphocytes, resulting in lymphocyte death. Lymphocytes express the coronavirus receptor ACE2 and may be a direct target of viruses. 9 (2) The virus might directly destroy lymphatic organs. Acute lymphocyte decline might be related to lymphocytic dysfunction, and the direct damage of novel coronavirus virus to organs such as thymus and spleen cannot be ruled out." ] },{ "paper_id": "f24d3b4b4af138be06b7452b7acefc8948bc1056", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "China are very necessary. This study further validates the concerns of international and domestic experts regarding asymptomatic transmission (E-status).", "As of 20:30 on January 27, 2020, 2844 cases were confirmed nationwide, 5794 were suspected, 58 were cured, and 81 died. Such a major epidemic is a serious challenge to people's lives and an important test of public health emergency management capabilities." ] },{ "paper_id": "f32841f22efe8c2bccd0d04a0c0b47e6ecf86b61", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "disease severity and that they may also interfere with each other's spread within a host population.", "word count: 247 12 Text word count: 5,657 Abstract 15 Influenza viruses and rhinoviruses are responsible for a large number of acute respiratory 16 viral infections in human populations and are detected as co-pathogens within hosts. Clinical and 17 epidemiological studies suggest that co-infection by rhinovirus and influenza virus may reduce 18", "To determine how co-infection by these two unrelated respiratory viruses affects pathogenesis, 20 we established a mouse model using a minor serogroup rhinovirus (RV1B) and mouse-adapted 21 influenza A virus (PR8). Infection of mice with RV1B two days before PR8 reduced 22 pathogenesis of mild to moderate, but not severe PR8 infections. Disease attenuation was 23 associated with an early inflammatory response in the lungs and enhanced clearance of PR8." ] },{ "paper_id": "f339a22cebc1bc0099beb7aea41be09cc916e5dc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "ratio of 1.2:1).", "Structure and sequence comparison of Arenavirus exonuclease with other viral exonuclease.", "Sequence retrieval of mammarenavirus L and analysis." ] },{ "paper_id": "f33c6d94b0efaa198f8f3f20e644625fa3fe10d2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "IGLV2-NL1 matched CH17 at this locus with 100% sequence identity, suggesting that IGLV2-NL1 and IGLV2-34 genes are allelic rather than distinct loci. No additional exact matches between the CH17 haplotype and other \"not-located\" V genes were observed.", "Using the program miropeats 56 CH17 contigs for IGK and IGL loci were compared individually to the sequences from the Kawasaki haplotypes (IGL, accession NG_000002.1;", "In addition to those noted above, several other IGKV genes are also classified as ORF genes based on irregular regulatory sequence motifs 27 . Notably, IGKV2D-29*02, previously referred to as \"VA2c\", has a non-canonical V-heptamer, but has also been shown to occur in productive rearrangements; thus, like IGKV1-8 and IGKV1D-13 alleles described in CH17, the expression of IGKV2D-29*02 could be explained by a previously undescribed regulatory sequence variant.", "Supplementary Figure 2A ). Interestingly, SNP density within 1 Mbp of the q arm telomere of chr14 harbouring IGHV (0.002) was higher than all other telomeric regions, >2-fold higher than the telomeric average (Supplementary Figure 2B) . In contrast, when CHM1 SNP densities within 3 Mbp of all telomeres were compared, the region on the q arm of ch14 (including both IGHV and non-IGHV sequence) no longer stands out, suggesting that IGHV may have some unique properties contributing to higher than average genetic diversity. To place this in the context of the analysis conducted within the IG regions above, we also found that the q arm of ch14 has the second highest overlap with SDs (34%; Supplementary Figure 3 )." ] },{ "paper_id": "f3ff1ecae96700f41b83d2a034a3a959428388b0", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "and chest computed tomographic (CT) images were obtained and analyzed.", "People's Hospital (No. 2020GCP012).", "Categorical data were described using frequency and percentage. Normalibility of continuous data was tested. We used mean (standard deviation, SD) to describe variables with normal distribution, otherwise median were used. All the analyses were performed in Stata 14.", "However, in Xiangyang area, the patients were mostly secondary cases. In the process of transmission, the sex difference was gradually diluted, indicating that there might be no gender difference in being infected." ] },{ "paper_id": "f40eaec892778166e4f8f8eeb576893e82a591be", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The importance of non-pharmaceutical control measures requires further research to quantify their impact [3] . Mathematical models are useful to evaluate the possible effects on epidemic dynamics of preventive measures, and to improve decision-making in global health [5, 6] .", "Plentiful infected patients could not be hospitalized or quarantined for treatment. Then they would contact more susceptible persons and infect more people. Besides, unhospitalised and under-treated patients suffered a higher death rate. Taken together, the accumulation of Several issues to be noted when interpreting our work." ] },{ "paper_id": "f47af9fe364fd9bac5e061142208d801667c5aca", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "qRT-PCR was repeated at least 3 times with different specimens.", "Statistical analysis was done with SPSS, version 25.0. Continuous variables were directly expressed as median, and interquartile range (IQR) values. Categorical variables were expressed as number (%). Means for continuous variables were compared using independent group t tests when the data were normally distributed; otherwise, the Mann-Whitney test was used. Proportions for categorical variables were compared using the \u03c72 test or Fisher exact test." ] },{ "paper_id": "f49a9b36227a498495c9788a4e5e4d6429b71eab", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For studies with high risk of publication the adjusted trim and fill statistics were presents in table.1" ] },{ "paper_id": "f4d76fb8161f4cee6987d7d412798e1276348858", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All rights reserved. No reuse allowed without permission.", "author/funder, who has granted medRxiv a license to display the preprint in perpetuity.", "(1 0)" ] },{ "paper_id": "f4f4b045dce8ff5ff1f5aaa48a6bdbaaa7b05179", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "A new transmission route for the propagation of the SARS-CoV-2 coronavirus, Danchin, Ng, Turinici", "The mathematical model of epidemic propagation is the following (see Figure 1 ):" ] },{ "paper_id": "f53e10f9cd4b97134ded58b3de4bcc36a55304d3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f5d9ab798adf8face1655d476644ebb75fbfef18", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Cleavage of Spike protein by tissue factor Xa is required for the infectivity of SARS-CoV [4] .", "Colonic biopsies from 17 children (6 control, 6 colitis, 2 ulcerative colitis, 3 Crohn's disease)", "Significantly correlated genes were chosen (p-value<0.05) for downstream GO enrichment analysis via GENEONTOLOGY at http://geneontology.org/. GO terms with False Detection Rate (FDR) <0.05 were selected.", "Here we report the expression pattern of ACE2 in the human intestine at single-cell resolution." ] },{ "paper_id": "f6312e7233ad4c0780492db3c05a61abe4fb6b22", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The majority of human coronaviruses (CoVs) cause mild disease phenotypes. However, when novel coronaviruses like severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV emerge from their animal reservoirs to infect humans they elicit a robust and aberrant immune response that can lead to a very serious and deadly pneumonia (1) (2) (3) . Importantly, there are no effective vaccines or therapeutics to treat these CoVs. Efforts to develop long-term therapeutic strategies to combat novel, highly pathogenic CoVs will be aided by increased understanding of conserved viral mechanisms at the level of their cell and molecular biology.", "Coronaviruses (CoVs) are important human pathogens with significant zoonotic potential." ] },{ "paper_id": "f634f2b73197fdda1d444dcdd6bd84a96ea148ad", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Regardless its limitations, at least, this approach provides a metric for ranking viral strains according to their performance in a particular environment/host. Such a fitness measure has been pivotal for quantitatively understanding many virus evolution processes: the effect of genetic bottlenecks and accumulation of deleterious mutations in RNA virus populations 6-8 , the rates and dynamics of adaptive evolution into novel hosts 9, , the pleiotropic cost of host range expansion 10-12 , the cost of genome complexity 13,14 , the cost of antiviral escape mutations 15-17 , the topography of adaptive fitness landscapes 18-20 , and the role of robustness in virus evolution 21-23 .", "Total RNAs were extracted, its quality verified, concentration normalized and used to hybridize N. tabacum Gene Expression 4\u00d744K Microarrays (Agilent). Slides were handled as described in the Methods section; intensity signals were normalized using tools in BABELOMICS 41 .", "Within clusters, r > 0.85, whilst between clusters the correlations ranged 0.65 < r < 0.75, except for plants infected with AS13, whose similarity with other infected plants was always r < 0.65.", "But differences in viral fitness should also matter in genome wide studies seeking to understand the mode of action of the viruses (i.e., the precise way they interact with their hosts)." ] },{ "paper_id": "f6f1ec12291f743de1504003929ea654217f2af6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "MERS-CoV consensus were selected for use in epitope sequence analysis.", "Protein regions that are conserved across relatively long evolutionary distances suggest that they are structurally or functionally constrained. Vaccination strategies designed to target the immune response toward these conserved epitope regions could generate immunity that is not only crossprotective across Betacoronaviruses but also relatively resistant to ongoing virus evolution." ] },{ "paper_id": "f7891683eecd12b3908862fc7ef1d341ca7a293c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "f810de29894bfa40d93bc6dde3efc22c9d0d3f4c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The first host-switching event HS1 in the Alpha 3 cluster (Fig 4) also in Guangxi province, with positive rates of 3/19 and 2/10, respectively." ] },{ "paper_id": "f82372b109168b411344f537210c63cc6ed323ed", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All rights reserved. No reuse allowed without permission.", "Primary outcome:", "For longitudinal data such as viral kinetics, we are conducting a descriptive analysis of group means over time and using mixed models, general estimating equations, and quantile regression to assess for change over time, adjusting for potential confounders, including age, comorbidities, and vaccination status.", "Data quality Data are checked for missing or unusual values and checked for consistency in the centralized data capture system. Computerized checks are conducted weekly to identify missing, inconsistent or out of range data. Any suspect data is raised as data queries, and are investigated by the study coordinators." ] },{ "paper_id": "f8360b0e64d444215d21a61e056b070f12417e53", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The outbreak of coronavirus disease 2019 continues to expand across the world.", "The methods of data curation for each of the used line lists has been previously published. 4 Chinese local, provincial, and national health authorities. 4 Their data is freely available online via Google Drive.", "reporting. When available, travel history, information on infected relatives, and symptomatology were also collected.", "The coronavirus disease 2019 outbreak is rapidly expanding across the world and presents a significant public health emergency with the potential of becoming pandemic. 1 As of March 1, 2020, cases of COVID-19 have been reported in over 60 countries. In early stages of epidemics with emerging pathogens, real-time analysis of accurate and robust epidemiological and clinical data is essential to developing interventional strategies and guiding public health decisionmaking. 2, 3 Such data can provide insight into infectivity, routes of transmission, disease severity, and outcomes, thus enabling epidemiologic modelling and improved public health responses. 4, 5 Line list data, which includes individual patient-level data on important epidemiological and clinical variables, is rarely available early during an outbreak with a novel pathogen. 5 However, recognizing the utility of such data and its ability to provide for real-time analyses, multiple academic groups have been curating line list data using crowdsourcing and openly sharing the data with the scientific community. 4, 5 Crowdsourcing enables the collection of data from multiple platforms including health-care-oriented social networks, government and public health agencies, and global news sources.", "After collecting cases from both databases, overlap of patients was assessed using age, location, and the three above mentioned dates. In the event of suspected duplicate patients, one case was removed from the dataset.", "Secondary outcomes included days between symptoms onset and first visit to hospital or clinic, and days between first visit to hospital or clinic and reporting. Tertiary outcomes included rate of travel to Wuhan, China, rate of family members with a positive COVID-19 diagnosis, and rates of symptoms." ] },{ "paper_id": "f854d7b750541d65c48df953a65028a50ce57881", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All data were provided by Hankou Hospital. The data collected include demographic characteristics, comorbidities, clinical signs, and symptoms, laboratory testing results, chest computed tomography (CT) scan images and clinical outcomes from the hospital information system, nursing records, and laboratory reports.", "<0.001), respectively ( Figure 2) .", "White blood cell count, \u00d710 9 /L 4.7 (3.6 -6.8) 4.6 (3.6 -6.6) 5. 8 Abbreviations: RT-PCR, reverse transcription polymerase chain reaction; COPD, chronic obstructive pulmonary disease; CT, computed tomography.", "The high mortality rates in our study may be due to differences in the population composition. Patients in three first designated hospitals are reasonable to have much progressed disease and higher mortality than the national-wide population, as reported by Huang et al and Chen et al. 1, 8 Notably, Hankou", "A total of 577 patients with at least one post-admission evaluation were included in the final analysis." ] },{ "paper_id": "f863247dc84916a96448088399badefd09d54fb8", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Since the beginning of the 21 st century, public health infrastructures have been required 28 to periodically respond to new and reemerging zoonotic viral diseases, including influenza, 29 Ebola, and Zika virus outbreaks (1). Severe acute respiratory syndrome coronavirus (SARS- ", "18", "Importance" ] },{ "paper_id": "f879c69d61f14d7efc51023258d1361bc681d403", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "This multi-center, retrospective, observational study was designed and conducted by the ", "There were 41 patients (91.1%) presented with lymphopenia (lymphocyte < 1.0*10 9 /L).", "Secondary infections, including bacterial co-infection and fungal co-infection, were identified in 17 (37.8%) and 12 (26.7%) patients, respectively (table 3) ." ] },{ "paper_id": "f87eec8279bc79900914c5689bb42f49f41aace5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ " 5 ", "of China, countries are at the most critical stage to avoid outbreaks of domestic cluster 48", "Many studies or reports have started revealing that SARS-CoV-2 is very infectious (Li 50 et al., 2020; Wu, Leung, & Leung, 2020) Many clinical cases are asymptomatic or 51 mildly diagnosed patients (Liu, Liao, Chang, Chou, & Lin, 2020), which greatly 52 increases the potential for transmission and makes epidemic prevention very difficult. 53" ] },{ "paper_id": "f89618a7949b8ff9b92c87ca5b839a3107957b5c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "These analyses revealed that the new type 2 recombinant EV-G genome was approximately 6.7 kb- ", "To confirm the genome sequence of the newly identified type 2 recombinant EV-G obtained by 114 metagenomics analysis, we performed long RT-PCR to amplify the viral genome approximately 115 every 1 kb with overlapping regions and subjected the PCR products for direct sequencing (Fig. 1B) .", "Enterovirus G (EV-G) is an enveloped RNA virus, belonging to the family of Picornaviridae. 54 More than 20 types of EV-G, known as EV-G1 to EV-G20, have been identified [1, 2] . The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/510131 doi: bioRxiv preprint 3 60" ] },{ "paper_id": "f8e8a9c6f5662c1739be031e6134284ef08ea8b2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We thank Andy Berglund, Carl Shotwell, and Jared Richardson for facilitating use of the RNA fragment analyzer; Darren Yang and Wesley P. Wong for assistance and suggestion on adapting the E-gel system with the nanoswitches; Gabriele Fuchs and Bijan K. Dey for providing comments and suggestions on the experiments and manuscript.", "Oligonucleotides were purchased from Integrated DNA Technologies (IDT) with standard desalting, and the full sequences of all strands is listed in Supporting information Table S1 to S9. Nanoswitches were constructed as described previously. 24, 27 A genomic single-stranded DNA (New England Biolabs M13mp18) was linearized using targeted cleavage with BtsCI restriction enzyme. The linearized ssDNA was then mixed with a molar excess of an oligonucleotide mixture containing backbone oligos and detectors, and annealed from 90\u00b0C to 20\u00b0C at 1 \u00b0C min \u22121 in a T100\u2122 Thermal Cycler (Bio-Rad, USA). Following construction, the nanoswitches were purified using liquid chromatography (LC) purification 29 to remove excess oligonucleotides. The concentration of purified nanoswitches were determined by measuring A260 absorbance with a Thermo Scientific NanoDrop 2000.", "Funding: Research reported in this publication was supported by the NIH under award R35GM124720 to K. H. and awards R01GM123050 & R21AI133617 to C.P. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or in the Supplementary Materials. Additional data related to this paper may be requested from the authors." ] },{ "paper_id": "f8eee21acf147a7088fa376af6c3d85e606b47c4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The sequence starts with a signal peptide motif, followed by pairs of G5 domain/E domain (Pfam key factor for the cooperative folding multidomain protein [14] . Once folded, the two domains form an 207 elongated structure, made of small beta strands which correspond on the HCA plot to small clusters.", "Examples of PDB sequences with high HCA scores." ] },{ "paper_id": "f905f78b32f63c6d14a79984dfb33f1b358b8ab4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Analyses of interactions were performed using COCOMAPS (37) and LigPlot + (38) . Lysine Crosslinking: Homobifunctional BS 3 (Pierce, 2.5 mM) was added to full-length IN (20 \u00b5M) that was initially mixed with increasing concentrations of inhibitory peptide or Y3molecule (4-Acetamido-5-hydroxy-2,7-naphthalenedisulfonic acid, (Sigma, S981680)). Reactions were incubated for 30 minutes at room temperature, and quenched by adding Tris-HCl (pH 7.5) to a final concentration of 10 mM and analyzed on SDS-PAGE. Affinity Measurements: IN proteins were labeled with Monolith NT protein labeling kit BLUE-NHS (NanoTemper Technologies) and eluted in microscale thermophoresis (MST) buffer (50 mM Tris-HCl pH 7.0, 300 mM NaCl and 0.05% Tween-20). Labeled IN proteins were incubated with serial dilutions of inhibitor peptide, and MST measurements were carried out using the Monolith NT.115 in standard capillaries with 40% LED and 20% MST power.", "IN constructs were expressed and purified as previously described (24) . Lysis buffer contained 50 mM potassium phosphate (pH 7.5), 5 mM Imidazole, 5 mM \u03b2mercaptoethanol and 1M NaCl for the full-length protein or 0. ", "Fluorescence based IN activity assays were performed as previously described (30) . Fab was used at a 1:1 molar ratio and the peptide at an excessive ratio of ~ 20 folds. and were processed with iMosflm (31) . The structure was solved by Phaser molecular replacement (32) using IN CCD (PDB code: 1BIS (33)) as a search model. Electron densities were fitted using Coot (34) and refined in the CCP4 suite (35) using REFMAC5 (36) . Structural superposition and figures were prepared using PyMOL Molecular Graphics System (Schr\u00f6dinger, LLC). Table-1 summarizes data collection and refinement statistics." ] },{ "paper_id": "f93daa3d8d53761cfcf4c9fb8ff03dace02a858c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CsA-3 contained mutations leading to substitutions in nsp2 (A199T) and again nsp5 (L8S and Q21R). 268", "To assess the importance of the identified mutations for CsA sensitivity, each mutation was 273 individually reverse engineered into the EAV genome, using full-length cDNA clone pEAN900. 274", "Novartis (Basel, Switzerland) and DebioPharm (Lausanne, Switzerland) for providing Alisporivir. 533" ] },{ "paper_id": "f9b108c052ded463773a9838a8157ac7d5ba6d1a", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Zika virus with a single stranded, positive sense RNA genome of 10.7 kb belongs to the flavivirus genus, which also contains Dengue, yellow fever, West Nile, Japanese encephalitis, and tick-borne encephalitis viruses (4, 10) . Zika virus shares a high degree of sequence and structural homology with other flaviviruses particularly Dengue virus, thus resulting in immunological cross-reactivity (11). Seriously, the current Zika outbreaks are largely localized within dengue-endemic areas, it is thus proposed that preexisting dengueinduced antibodies may enhance Zika infection by antibody-dependent enhancement (ADE), a factor that makes the vaccine approaches extremely challenging (11).", "The authors declare that they have no conflicts of interest with the contents of this article.", "first two authors contribute equally.", "Zika virus was originally isolated from a sentinel rhesus monkey in the Zika Forest of Uganda in 1947 (1) , which is transmitted to humans by Aedes species mosquitoes. Since 2007, large epidemics of Asian genotype Zika virus have been reported around the world (2, 3) ." ] },{ "paper_id": "f9c6a656d0ce352cc1fa0df8d83e6d4a1f53d7c2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "174 (updated to 218 later on 13 Februarysee comments)", "In jurisdictions outside China (and excluding Hong Kong, Macao and Taiwan) the CFR as detailed in the 13 February WHO Report [3] was 1/447 = 0.22% (95% confidence interval (CI) = 0.40% to 1.26%). But this estimate also did not account for possible missed mild cases in those countries or the lag time between hospitalisation and death.", "Our provisional CFR estimate for COVID-19 is less than that estimated for MERS-CoV and SARS-CoV, but is broadly comparable with two of the three previous influenza pandemics (when considering the range of estimated values) ( Table 2 ). These values could, however, be over-estimates given the possibility of mild cases not being detected (see main text). Pandemic influenza in 2009 0% to 1.2% (but mainly 0.05% to 0.005%)", "A systematic review considered 77 estimates from 50 published studies [19] . The values for symptomatic cases had point estimates ranging from 0 to 1,200 per 100,000 cases. Nevertheless, \"most of the estimates in this category [symptomatic cases] fell in the range of 5 to 50 deaths per 100,000 cases.\" Pandemic influenza in 1957 (US data) 0.2% Calculated using US data from: [20] ." ] },{ "paper_id": "fa6c14304fc37470639d55f97f7903035d768bd2", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Lectins are glycan-binding proteins with no catalytic activity and ubiquitously expressed in nature. Numerous bacteria employ lectins to efficiently bind to epithelia, thus facilitating tissue colonisation. Wounded skin is one of the preferred niches for Pseudomonas aeruginosa, which has developed diverse strategies to impair tissue repair processes and promote infection.", "By following LecB trafficking we sought to characterise the nature of LecBmediated vacuoles, which, from a structural point of view, shows similarities with multivesicular bodies (MVBs), as they contain numerous intraluminal vesicles.", "After three additional washes, glass cover slips were mounted with mowiol and imaged using an A1R Nikon confocal microscopy system with a 60x oil immersion objective (NA = 1.49).", "Z-stacks of at least 3 different areas per condition were acquired and analysed with Fiji ImageJ 1.0 software. Coloc2 Fiji's plugin was employed for colocalisation analysis." ] },{ "paper_id": "fb7371ad31cd501854660876a282060402082537", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Sequence data and all analytical code is publicly available at https://github.com/blab/ structured-mers.", "This left 70 000 states on which to base posterior inference. Posterior sets of typed trees were summarised using TreeAnnotator v2.4.3 with the common ancestor heights option (Heled and Bouckaert, 2013) .", "(1)", "As a secondary analysis to test robustness to choice of prior, we set up an analysis where we increased the mean of the exponential distribution prior for migration rate to 10.0. All other parameters were identical to the primary analysis and as before 10 independent MCMC chains were run. In this case, two chains did not converge. This left 80 000 states on which to base posterior inference. Posterior sets of typed trees were summarised using TreeAnnotator v2.4.3 with the common ancestor heights option (Heled and Bouckaert, 2013) ." ] },{ "paper_id": "fbc41a8e025cd6eb2d7c156aad3b6923af2349c4", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ ". These data indicated that ACE2 is likely to be the receptor for 2019-nCov.", "The copyright holder for this preprint . " ] },{ "paper_id": "fbebe4b66073c44cface2e842754bce26e3e2913", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We used a machine learning algorithm, random forest, to classify the risk levels.", "Another reason is that the numbers of cases are unbalanced among cities. In Wuhan, there are 39,249 confirmed cases by Feb. 16, whereas other large cities have a few hundred cases. Traditional linear models can not fit well with such a data distribution." ] },{ "paper_id": "fc15f433048e4d9464964930c36a1e7057ba1088", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 10 nCoV-2019 S, suggesting antibody cross-reactivity may be limited between the two virus RBDs. 11", "The atomic-resolution structure of 2019-nCoV S should enable rapid development and evaluation", "1" ] },{ "paper_id": "fc7a6b5d1852c5ecce2d20fd0d73d5f957ed7055", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We introduce public containment leverage P = \u03ba 0 \u03ba 0 + \u03ba that reflects how strong isolation measures affect the general public in comparison to quarantine measures imposed on symptomatic infecteds alone. We further define", "as the quarantine probability, i.e. the probability that an infected is identified and quarantined either in specialized hospital wards or at home.", "All data and the analysis material is available online [21] .", "The current outbreak of the new coronavirus in Mainland China (COVID-19, previously named 2019-nCoV) is closely monitored by governments, researchers, and the public alike [1] [2] [3] [4] [5] [6] [7] . The rapid increase of positively diagnosed cases in Mainland China and subsequent exportation and confirmation of cases in more than 20 countries worldwide raised concern on an international scale. The World Health Organization (WHO) therefore announced the COVID-19 outbreak a Public Health Emergency of International Concern [4] ." ] },{ "paper_id": "fcb76f0907f67a850fd4560218034f214fa28bcc", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Selection of a faster diffusing clone through in vitro validation using Transwell and multichannel diffusion assay Ex vivo uptake validation of the selected clone followed by comparison of diffusivity of peptide-coated nanoparticle with gold standards using multiple particle tracking", "Studies indicated that positively charged liposomes 34 and poly(lactic-co-glycolic) (PLGA) nanoparticles 35 improved penetration in tumors, whereas in other studies, negatively charged liposomes 36 and gold nanoparticles 37 exhibited improved penetration in spheroids and tumors.", "Peptides are attractive biological materials for surface modification of nanomedicines.", "PEG-coated PLGA and polystyrene nanoparticles exhibited enhanced diffusive transport and penetration through ECM gels 33, 38 and tumor tissues [39] [40] [41] [42] than uncoated positive and/or negative charged particles. While PEGylation has been an attractive strategy for tumor penetration, there are some challenges that limit its feasibility. PEGylation has been shown to hinder cell internalization [43] [44] [45] and endosomal escape 46 needed for drug and gene delivery. Numerous studies have also shown that people possess pre-existing anti-PEG antibodies, which reduces the efficacy and clinical feasibility of PEG-conjugated therapeutics [47] [48] [49] [50] . In addition, repeated systemic dosing of PEGylated formulations can result in the development of anti-PEG antibodies in living subjects [51] [52] [53] . These findings suggest while PEGylation can improve tumor penetration, there are challenges that motivate the need to find alternative surface chemistries." ] },{ "paper_id": "fccf6791aac676cf26c0be7745e217f9b8d6336c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "= 0 + 2 * + 3 * + 4 * * + \u2211 5 =1 + .", "= 0 + + 3 * + 1 1 + 2 2 + 4 4 + ." ] },{ "paper_id": "fd14ed7c073b7ff03afa517e9c0fd1e849878252", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Coverage statistics were determined from the resulting read alignments." ] },{ "paper_id": "fd3fc2c49f5cc27e4262261d0c9045911d65cb6e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "To differentiate between models where Xrn1p restricts L-A through a passive 158 mechanism that is incidental to its inherant exonuclease activity, or through an active 159 mechanism where Xrn1p evolves to optimally suppress L-A replication, we first looked 160 for evidence of positive selection (dN/dS > 1) within the genes encoding the major 161 components of the SKI complex, the exosome, and Xrn1p ( Fig 1B) . Importantly, cerevisiae, S. paradoxus, S. mikatae, S. kudriavzevii, S. arboricolus, and S. bayanus) 171 [44] [45] [46] and created a multiple sequence alignment. We then analyzed each alignment 172 for evidence of codons with dN/dS > 1 using four commonly employed tests for positive 173 selection [47, 48] . We see some evidence for positive selection of specific codon sites in 174 several of these genes, however, only XRN1 and the exosome subunit gene RRP40 175 passed all four tests ( Fig 1C; Table S1 ). Other genes are determined to be under surprising for a critical and conserved gene involved in RNA quality control, but 203 consistent with the signatures of positive selection which suggest that certain parts of 204 this protein are highly divergent between species. ", "has been shown previously that Xrn1p can inhibit the expression of the killer phenotype 239 by degrading uncapped killer virus RNAs [14, 57] . Therefore, we use the presence and 240 size of kill zones produced by killer yeasts as a quantitative measurement of killer virus 241 RNA production in the presence of each Xrn1p ortholog." ] },{ "paper_id": "fd847a97e6fce134345b25ae9240c4ebb680cca5", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "All rights reserved. No reuse allowed without permission.", "With 14/25 of cloacal swab samples and rest of Nasal Swabs or oropharynx swab samples testing, these patients presented the repeated positive COVID-19 mRNA within 3 (2-7) days after the hospital. Notably, the median time from their last negative result to turning positive was 6 (4-10) days. These patients were then hospitalized again and continued the quarantine protocol. All these patients were asymptomatic and chest CT scanning indicated that 12 of them even showed improvement while rest of them represented with no obvious change compared with previous images. With a few days of prophylactic intervention with Chinese herbal medicine, the RT-PCR results of virus mRNA detection were all turning to negative in both nasopharyngeal swab and cloacal swab samples.", "Since Dec 8 th 2019, many cases has been reported by investigators who described the clinical characteristics of hospitalized patients with COVID-19 infection [1] [2] [3] . We noticed the recent report 4 from Lan et al. that 4 medical staff were still virus carriers after recovery from COVID-19 infection. Here we gave a report on 25 discharged patients with their medical record review and further analysis." ] },{ "paper_id": "fd8d54106cd0cc2d09b1fda70f668736b5d0bd5c", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Influenza epidemics are caused by influenza A (IAV) and influenza B (IBV) viruses. IBV causes 45 substantial disease, however it is far less studied than IAV. While IAV originates from animal 46 reservoirs, IBV circulates in humans only. Virus spread requires that the viral hemagglutinin (HA) 47 is active and sufficiently stable in human airways. We here resolve how these mechanisms differ 48 between IBV and IAV. Whereas human IAVs rely on one particular protease for HA activation, this 49", "(B, C) Transduction efficiency (relative to the trypsin control) of TTSP-activated 973 pseudoparticles tested as such (in color) or after additional trypsin treatment (in white). 974 Data are the mean \u00b1 SEM (N=3 with triplicate read-outs). P-value versus no trypsin: 975 *\u2264 0.05; ***\u2264 0.001; ****\u2264 0.0001 (Kruskall-Wallis, followed by Dunnett's test). 976 49 All rights reserved. No reuse allowed without permission.", "Importance" ] },{ "paper_id": "fd96fc1859201e13e35526c188e022fa6e335327", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "days (95% confidence interval [CI], 4.4 to 5.4) days, ranging from 0.8 to 11.1 days (2.5th to 97.5th percentile) (Fig. 1 )." ] },{ "paper_id": "fda076d8d8b2fb52990e3db1982e4af2ff0fb08e", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "The flow chart demonstrates the overall process of peptide vaccine designing is illustrated in Figure1 ", "The retrieved sequences were aligned to allocate the conserved regions using multiple sequence alignment (MSA). The retrieved antigen sequences were run against the NCBI Reference Protein (RefSeq) using ClustalW as implemented in BioEdit sequence alignment editor software Version 7.2.5 (129) . After which, the epitope candidates were analyzed by a variety of prediction methods through Immune Epitope Database IEDB analysis resource tools (http://www.iedb.org/).", "The kolaskar and tongaonker antigenicity method was used to differentiate the immunogenic sites with a default cut-off value of 1.024 (137)." ] },{ "paper_id": "fda16c1ee2fbae3368f64a138aa27d972a83e020", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Statistical analysis: Data are presented as mean \u00b1 SD and groups compared using two-tailed unpaired Student's t test. p < 0.05 was considered statistically significant. All statistical analyses were performed using Graphpad Prism8. " ] },{ "paper_id": "fe09ebcf10de441c0ad0a90f0926ec0aed5a0577", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fe66306680e5be9820e2cc3742b663a782eb1b31", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "fe685aa676e739bd52ba2585a7e5b27c55e2d0d6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "feb8807e8418fdd6c4b8816ea761c9a68767a407", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "subspecies identification is then routinely performed by MLST, but this method while accurate and 90 portable is time consuming, labor intensive and expensive. From 2018, sequences of only two 91 housekeeping genes (rpoD and cysG or rpoD and malF) are required for subspecies identification in 92", "France, while other sets of gene pairs are recommended by EPPO (EPPO, 2018b). 93", "Rhizobium, TSA (tryptone soy broth 30 g.L -1 ; agar 15 g.L -1 ) for Clavibacter, Ensifer, 127" ] },{ "paper_id": "fec0c97b9bdc012b76f082b8bcd6ba0efbb4f5c3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "We calculated gap entropy at each position as:", "Our results provide evidence for widespread host-shift evolution in nature and a proof of concept for integrating experiments with genomic epidemiology." ] },{ "paper_id": "ff067164497bcfbd9145be223dcd2b05f159dd63", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "For many known pathogenic viruses, it has been a routine practice to make a diagnosis of acute infection according to the serological findings for a long time.", "For continue variables description, mean with standard deviation was used for normal distribution data and median with interquartile range (IQR) was used for non-normal distribution data. Cumulative seroconversion rates were calculated by Kaplan-Meier method. The association between antibody level and severity of illness were estimated by generalized estimating equations (GEE) model with logit link function. All statistical analysis was conducted by SAS 9.4 (SAS Institute, Cary, NC, USA).", "In conclusion, the findings demonstrate that antibody tests have important diagnosis value in addition to RNA tests. These findings provide strong evidence for the routine application of serological antibody assays in the diagnosis and clinical management of COVID-19 patients." ] },{ "paper_id": "ff54e3e961a72eb1d2500166809b3651b2f98cf6", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Coronaviruses (CoVs), belonging to the family Coronaviridae, are positive-sense enveloped RNA viruses and cause infections in birds, mammals, and humans (1) (2) (3) . The family includes four genera, such as Alphacoronavirus, Betacoronavirus, Deltacoronavirus, and Gammacoronavirus (4) . Two infamous infectious coronaviruses in the genus Betacoronavirus are severe acute respiratory syndrome coronavirus (SARS-CoV) (5) and Middle East respiratory syndrome coronavirus (MERS-CoV) (6) , which have infected more than 10,000 people around the world in the past two decades. Unfortunately, the incidence was accompanied by high mortality rates (9.6% for SARS-CoV and 34.4% for MERS-CoV), indicating that there is an urgent need for effective treatment at the beginning of the outbreak to prevent the spread (7, 8) . However, this cannot be achieved with current drug development or an application system, taking several years for newly developed drugs to come to the market.", "To train the model, the Drug Target Common (DTC) database (11) and BindingDB (12) database were manually curated and combined. Three types of efficacy value, Ki, Kd, and IC50 were integrated by a consistence-score-based averaging algorithm (13) to make the Pearson correlation score over 0.9 in terms of Ki, Kd, and IC50. Since the BindingDB database includes a wide variety of species and target proteins, the MT-DTI model has the potential power to predict interactions between antiviral drugs and 2019-nCoV proteins." ] },{ "paper_id": "ff6bd29c8ecd325c4edddb2b050d5f4919db6112", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Influenza viruses cause acute and highly contagious seasonal respiratory disease in all age 43 groups. Between 3-5 million cases of severe influenza-related illness and over 250 000 deaths are 44", "regulates the innate immune response in a clinically relevant in vitro human model of H5N1 39 infection. 40" ] },{ "paper_id": "ff6c0b549e3f20ec78845f981f19687eece4addf", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ffbd7555a337706238c211197b221795e4e35146", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [] },{ "paper_id": "ffbf8ea9948d73572fd052a74afa01b19e6758a3", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "Probability an infectious agent recovers. d", "Probability Description Probability to parameter parameter rate conversion on behavior X (denoted T X|DX ),", "Pr", "Reduction in the transmission probability or rate when adopting prophylactic behavior: b P = \u03c1b S (0 \u2264 \u03c1 \u2264 1). Note that we refer to 1 \u2212 \u03c1 as the protection. g", "Probability an agent in the susceptible or prophylactic state decides which behavior to engage in. \u03ba" ] },{ "paper_id": "ffc9bc4ac6548cb1c03c2c6f088ab1c1c2067c6f", "task": 3, "abstract": "HELP US UNDERSTAND HOW GEOGRAPHY AFFECTS VIRALITY?", "body_text": [ "ACKNOWLEDGMENTS. This research is supported by Columbia University, which has filed a patent application on the work described in this manuscript.", ". CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.01.30.927574 doi: bioRxiv preprint", "All RNA viruses are known to mutate at a high frequency, due to the low fidelity of the viral polymerase, resulting in the development of resistance to treatment. The promiscuous nature of the viral polymerase will allow incorporation of our newly designed nucleotide analogues as anti-viral agents." ] }]