Virus Evolution最新文献

{"title":"Kuafuorterviruses, a novel major lineage of reverse-transcribing viruses.","authors":"Zhen Gong, Guan-Zhu Han","doi":"10.1093/ve/veae110","DOIUrl":"10.1093/ve/veae110","url":null,"abstract":"<p><p>Reverse-transcribing viruses (RTVs) characterized by reverse transcription required for their replication infect nearly all the eukaryotes. After decades of extensive analyses and discoveries, the understanding of the diversity of RTVs has largely stagnated. Herein, we discover a previously neglected lineage of RTVs, designated Kuafuorterviruses, in animals. Through screening over 8000 eukaryote genomes, we identify the presence of endogenous Kuafuorterviruses in the genomes of 169 eumetazoans dispersed across 11 animal phyla. Phylogenetic analyses and sequence similarity networks indicate that Kuafuorterviruses constitute a novel major lineage of RTVs. The discovery of Kuafuorterviruses refines our understanding of the diversity, evolution, and classification of RTVs and has implications in annotating animal genomes.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae110"},"PeriodicalIF":5.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11673190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurring incursions and dissemination of novel Eurasian-origin H5Nx avian influenza viruses in Atlantic Canada.","authors":"Ishraq Rahman, Cassidy N G Erdelyan, Anthony V Signore, Ifeoluwa Ayilara, Jordan Wight, Megan E B Jones, Daniel S Sullivan, Oliver Lung, Tamiko Hisanaga, Sabina I Wilhelm, Joshua T Cunningham, Christopher R E Ward, Johanna Bosch, Gregory J Robertson, Karen Gosse, Meghan Baker, Beverly Dawe, Stéphane Lair, Jennifer F Provencher, Kathryn E Hargan, Yohannes Berhane, Andrew S Lang","doi":"10.1093/ve/veae111","DOIUrl":"10.1093/ve/veae111","url":null,"abstract":"<p><p>Wild birds are important hosts of influenza A viruses (IAVs) and play an important role in their ecology. The emergence of the A/goose/Guangdong/1/1996 H5N1 (Gs/GD) lineage marked a shift in IAV ecology, leading to recurrent outbreaks and mortality in wild birds from 2002 onwards. This lineage has evolved and diversified over time, with a recent important derivative being the 2.3.4.4b sub-lineage, which has caused significant mortality events in wild bird populations. An H5N1 clade 2.3.4.4b virus was transmitted into North America from Eurasia in 2021, with the first detection being in Newfoundland and Labrador in Atlantic Canada, and this virus and its reassortants then spread broadly throughout North America and beyond. Following the first 2021 detection, there have been three additional known incursions of Eurasian-origin strains into Atlantic Canada, a second H5N1 strain in 2022 and two H5N5 strains in 2023. In this study, we document a fifth incursion in Atlantic Canada that occurred in 2023 by another H5N5 strain. This strain spread throughout Atlantic Canada and into Quebec, infecting numerous species of wild birds and mammals. Genomic analysis revealed mammalian-adaptive mutations in some of the detected viruses (PB2-E627K and PB2-D701N) and mutations in the hemagglutinin (HA) and neuraminidase (NA) genes that are associated with enhanced viral fitness and avian transmission capabilities. Our findings indicate that this virus is continuing to circulate in wildlife, and confirms Atlantic Canada is an important North American entry point for Eurasian IAVs. Continued surveillance and genomic analysis of IAVs detected in the region is crucial to monitor the evolution of these viruses and assess potential risks to wildlife and public health.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae111"},"PeriodicalIF":5.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Major change in swine influenza virus diversity in France owing to emergence and widespread dissemination of a newly introduced H1N2 1C genotype in 2020.","authors":"Gautier Richard, Séverine Hervé, Amélie Chastagner, Stéphane Quéguiner, Véronique Beven, Edouard Hirchaud, Nicolas Barbier, Stéphane Gorin, Yannick Blanchard, Gaëlle Simon","doi":"10.1093/ve/veae112","DOIUrl":"10.1093/ve/veae112","url":null,"abstract":"<p><p>Swine influenza A viruses (swIAVs) are a major cause of respiratory disease in pigs worldwide, presenting significant economic and health risks. These viruses can reassort, creating new strains with varying pathogenicity and cross-species transmissibility. This study aimed to monitor the genetic and antigenic evolution of swIAV in France from 2019 to 2022. Molecular subtyping revealed a marked increase in H1_avN2 cases from 2020 onwards, altering the previously stable subtypes' distribution. Whole-genome sequencing and phylogenetic analyses of H1_av (1C) strains identified 10 circulating genotypes, including 5 new genotypes. The most predominant genotype from 2020 onwards, denominated H1_avN2#E, was characterized by an HA-1C.2.4, an N2-Gent/84, and internal protein-encoding genes belonging to a newly defined subclade within the Eurasian avian-like (EA) lineage termed EA-DK. H1_avN2#E emerged in Brittany, the country's most pig-dense region, and rapidly became the most frequently detected swIAV genotype across France. This drastic change in the swIAV lineage proportions at a national scale was unprecedented, making H1_avN2#E a unique case for understanding swIAV evolution and spreading patterns. Phylogenetic analyses suggested an introduction of the H1_avN2#E genotype from a restricted source, likely originating from Denmark. It spread rapidly with low genetic diversity at the start of the epizootic in 2020, showing increasing diversification in 2021 and 2022 as the inferred population size grew and stabilized, and exhibited reassortments with other enzootic genotypes. Amino acid sequence alignments of H1_avN2#E antigenic sites revealed major mutations and deletions compared to commercial vaccine 1C strain (HA-1C.2.2) and previously predominant H1_avN1 strains (HA-1C.2.1). Antigenic cartography confirmed significant antigenic distances between H1_avN2#E and other 1C strains, suggesting that the new genotype has escaped the pre-existing immunity of the swine population. Epidemiologically, the H1_avN2#E virus exhibited epizootic hallmarks with more severe clinical outcomes compared to H1_avN1 viruses. These factors likely contributed to the spread of H1_avN2#E within the pig population. The rapid rise of H1_avN2#E highlighted the dynamic nature of swIAV genetic and antigenic diversity, underscoring the importance of tailored surveillance programs to support risk assessment during potential new outbreaks. It also demonstrates the need to strengthen biosecurity measures when introducing pigs into a herd, including swIAV positivity assessment followed by quarantine, and restrict the trade of swIAV-excreting live swine between European countries.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"11 1","pages":"veae112"},"PeriodicalIF":5.5,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diversity and cross-species transmission of viruses in a remote island ecosystem: implications for wildlife conservation.","authors":"Rebecca K French, Sandra Anderson, Kristal Cain, Andrew Digby, Terry C Greene, Colin M Miskelly, Chris G Muller, Michael W Taylor, Kākāpō Recovery Team, Jemma L Geoghegan, Edward C Holmes","doi":"10.1093/ve/veae113","DOIUrl":"10.1093/ve/veae113","url":null,"abstract":"<p><p>The ability of viruses to emerge in new species is influenced by aspects of host biology and ecology, with some taxa harbouring a high diversity and abundance of viruses. However, how these factors shape virus diversity at the ecosystem scale is often unclear. To better understand the pattern and determinants of viral diversity within an ecosystem, and to describe the novel avian viruses infecting an individual avian community, we performed a metagenomic snapshot of the virome from the entire avian community on remote Pukenui/Anchor Island in Aotearoa New Zealand. Through total RNA sequencing of 18 bird species, we identified 50 avian viruses from 9 viral families, of which 96% were novel. Of note, passerines (perching birds) exhibited high viral abundance and diversity, with viruses found across all nine viral families identified. We also identified numerous viruses infecting seabirds on the Island, including megriviruses, hepaciviruses, and hepatoviruses, while parrots exhibited an extremely low diversity of avian viruses. Within passerines, closely related astroviruses and hepatoviruses, and multiple identical hepe-like viruses, were shared among host species. Phylogenetic reconciliation analysis of these viral groups revealed a mixture of co-divergence and cross-species transmission, with virus host-jumping relatively frequent among passerines. In contrast, there was no evidence for recent cross-species virus transmission in parrots or seabirds. The novel pegiviruses and a flavivirus identified here also pose intriguing questions regarding their origins, pathogenicity, and potential impact on vertebrate hosts. Overall, these results highlight the importance of understudied remote island ecosystems as refugia for novel viruses, as well as the intricate interplay between host ecology and behaviour in shaping viral communities.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"11 1","pages":"veae113"},"PeriodicalIF":5.5,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increase of niche filling with increase of host richness for plant-infecting mastreviruses.","authors":"Sélim Ben Chéhida, Heemee Devi Bunwaree, Murielle Hoareau, Oumaima Moubset, Charlotte Julian, Laurence Blondin, Denis Filloux, Christophe Lavergne, Philippe Roumagnac, Arvind Varsani, Darren P Martin, Jean-Michel Lett, Pierre Lefeuvre","doi":"10.1093/ve/veae107","DOIUrl":"10.1093/ve/veae107","url":null,"abstract":"<p><p>Now that it has been realized that viruses are ubiquitous, questions have been raised on factors influencing their diversity and distribution. For phytoviruses, understanding the interplay between plant diversity and virus species richness and prevalence remains cardinal. As both the amplification and the dilution of viral species richness due to increasing host diversity have been theorized and observed, a deeper understanding of how plants and viruses interact in natural environments is needed to explore how host availability conditions viral diversity and distributions. From a unique dataset, this study explores interactions of <i>Mastrevirus</i> species (family <i>Geminiviridae</i>) with Poales order hosts across 10 sites from three contrasting ecosystems on La Réunion. Among 273 plant pools, representing 61 Poales species, 15 <i>Mastrevirus</i> species were characterized from 22 hosts. The analysis revealed a strong association of mastreviruses with hosts from agroecosystems, the rare presence of viruses in coastal grasslands, and the absence of mastreviruses in subalpine areas, areas dominated by native plants. This suggests that detected mastreviruses were introduced through anthropogenic activities, emphasizing the role of humans in shaping the global pathobiome. By reconstructing the realized host-virus infection network, besides revealing a pattern of increasing viral richness with increasing host richness, we observed increasing viral niche occupancies with increasing host species richness, implying that virus realized richness at any given site is conditioned on the global capacity of the plant populations to host diverse mastreviruses. Whether this tendency is driven by synergy between viruses or by an interplay between vector population and plant richness remains to be established.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae107"},"PeriodicalIF":5.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On modes of disease transmission and the hidden shape of pandemics: A review of <i>Asymptomatic</i> by Joshua Weitz.","authors":"C Brandon Ogbunugafor","doi":"10.1093/ve/veae109","DOIUrl":"10.1093/ve/veae109","url":null,"abstract":"<p><p>The importance of asymptomatic transmission was a key discovery in our efforts to study and intervene in the COVID-19 pandemic. In <i>Asymptomatic</i> (Johns Hopkins University Press, 2024), Joshua Weitz uses this aspect of SARS-CoV-2 natural history to discuss many counterintuitive characteristics of the pandemic. In this essay, I engage the arguments in the book, and discuss why asymptomatic transmission is such a critical dimension of the study of infectious diseases. I explore ideas contained within <i>Asymptomatic</i> and connect them to related issues in evolutionary virology and disease ecology, including epistemic uncertainty and the evolution of virulence. Furthermore, I comment on the broader messages in the text, including the gap between scientific knowledge and social understanding.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae109"},"PeriodicalIF":5.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIV-1 Vif global diversity and possible APOBEC-mediated response since 1980.","authors":"Eric Lewitus, Yifan Li, Morgane Rolland","doi":"10.1093/ve/veae108","DOIUrl":"10.1093/ve/veae108","url":null,"abstract":"<p><p>HIV-1 Vif's principal function is to counter the antiretroviral activities of DNA-editing APOBEC3 cytidine deaminases. Unconstrained APOBEC3 activity introduces premature stop codons in HIV-1 genes and can lead to viral inactivation. To investigate the evolution and diversification of Vif over the HIV-1 pandemic and document evidence of APOBEC3-mediated pressure, we analyzed 4612 publicly available sequences derived from 10 dominant subtypes and circulating recombinant forms (CRFs) using the Hervé platform. We found widespread evidence of diversifying selection that was convergent across subtypes and CRFs, but remarkable stability in consensus sequences over time. Divergence and selection did not favor APOBEC3-interacting sites. We furthermore found that APOBEC3-induced substitutions in <i>env</i> and <i>gag-pol</i> genes increased over time and were positively associated with <i>vif</i> diversity. These results suggest that APOBEC3-driven adaptation in Vif is relatively rare and that permissiveness to human APOBEC3-induced substitution as a mechanism for generating diversity may be advantageous to HIV-1 evolution.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"11 1","pages":"veae108"},"PeriodicalIF":5.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Origin, spread, and interspecies transmission of a dominant genotype of BJ/94 lineage H9N2 avian influenza viruses with increased threat.","authors":"Yong Zhou, Yudong Li, Hongzhuang Chen, Sicheng Shu, Zhixin Li, Honglei Sun, Yipeng Sun, Jinhua Liu, Lu Lu, Juan Pu","doi":"10.1093/ve/veae106","DOIUrl":"10.1093/ve/veae106","url":null,"abstract":"<p><p>The H9N2 subtype of avian influenza viruses (AIVs) is widely prevalent in poultry and wild birds globally, with occasional transmission to humans. In comparison to other H9N2 lineages, the BJ/94 lineage has raised more public health concerns; however, its evolutionary dynamics and transmission patterns remain poorly understood. In this study, we demonstrate that over three decades (1994-2023), BJ/94 lineage has undergone substantial expansion in its geographical distribution, interspecies transmission, and viral reassortment with other AIV subtypes, increasing associated public health risks. These changes were primarily driven by the emergence of a dominant genotype G57. In the first decade, G57 emerged in East China and rapidly adapted to chickens and spread across China. Since 2013, the G57 genotype has expanded beyond China into eight other countries and reassorted with various AIV subtypes to form new zoonotic reassortants. Chickens have played a key role in the generation and circulation of the G57 viruses, with ducks and other poultry species likely assuming an increasingly importantly role. Over the past decade, G57 has been more frequently detected in wild birds, mammals, and humans. Additionally, Vietnam has emerged as a new hotspot for the international spread of G57. Our results suggest that the BJ/94 lineage H9N2 virus may continue to overcome geographical and species barriers, with potentially more severe consequences.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae106"},"PeriodicalIF":5.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11673197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A meta-analysis highlights the idiosyncratic nature of tradeoffs in laboratory models of virus evolution.","authors":"Ketty Kabengele, Wendy C Turner, Paul E Turner, C Brandon Ogbunugafor","doi":"10.1093/ve/veae105","DOIUrl":"10.1093/ve/veae105","url":null,"abstract":"<p><p>Different theoretical frameworks have been invoked to guide the study of virus evolution. Three of the more prominent ones are (i) the evolution of virulence, (ii) life history theory, and (iii) the generalism-specialism dichotomy. All involve purported tradeoffs between traits that define the evolvability and constraint of virus-associated phenotypes. However, as popular as these frameworks are, there is a surprising paucity of direct laboratory tests of the frameworks that support their utility as broadly applicable theoretical pillars that can guide our understanding of disease evolution. In this study, we conduct a meta-analysis of direct experimental evidence for these three frameworks across several widely studied virus-host systems: plant viruses, fungal viruses, animal viruses, and bacteriophages. We extracted 60 datasets from 28 studies and found a range of relationships between traits in different analysis categories (e.g., frameworks, virus-host systems). Our work demonstrates that direct evidence for relationships between traits is highly idiosyncratic and specific to the host-virus system and theoretical framework. Consequently, scientists researching viral pathogens from different taxonomic groups might reconsider their allegiance to these canons as the basis for expectation, explanation, or prediction. Future efforts could benefit from consistent definitions, and from developing frameworks that are compatible with the evidence and apply to particular biological and ecological contexts.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae105"},"PeriodicalIF":5.5,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inferring strain-level mutational drivers of phage-bacteria interaction phenotypes arising during coevolutionary dynamics.","authors":"Adriana Lucia-Sanz, Shengyun Peng, Chung Yin Joey Leung, Animesh Gupta, Justin R Meyer, Joshua S Weitz","doi":"10.1093/ve/veae104","DOIUrl":"10.1093/ve/veae104","url":null,"abstract":"<p><p>The enormous diversity of bacteriophages and their bacterial hosts presents a significant challenge to predict which phages infect a focal set of bacteria. Infection is largely determined by complementary-and largely uncharacterized-genetics of adsorption, injection, cell take-over, and lysis. Here we present a machine learning approach to predict phage-bacteria interactions trained on genome sequences of and phenotypic interactions among 51 <i>Escherichia coli</i> strains and 45 phage λ strains that coevolved in laboratory conditions for 37 days. Leveraging multiple inference strategies and without <i>a priori</i> knowledge of driver mutations, this framework predicts both who infects whom and the quantitative levels of infections across a suite of 2,295 potential interactions. We found that the most effective approach inferred interaction phenotypes from independent contributions from phage and bacteria mutations, accurately predicting 86% of interactions while reducing the relative error in the estimated strength of the infection phenotype by 40%. Feature selection revealed key phage λ and <i>Escherchia coli</i> mutations that have a significant influence on the outcome of phage-bacteria interactions, corroborating sites previously known to affect phage λ infections, as well as identifying mutations in genes of unknown function not previously shown to influence bacterial resistance. The method's success in recapitulating strain-level infection outcomes arising during coevolutionary dynamics may also help inform generalized approaches for imputing genetic drivers of interaction phenotypes in complex communities of phage and bacteria.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae104"},"PeriodicalIF":5.5,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}