Infection and Immunity最新文献

{"title":"Correction for Castelli et al., \"Extracellular Vesicle Formation in <i>Cryptococcus deuterogattii</i> Impacts Fungal Virulence and Requires the <i>NOP16</i> Gene\".","authors":"Rafael F Castelli, Alana Pereira, Leandro Honorato, Alessandro Valdez, Haroldo C de Oliveira, Jaqueline M Bazioli, Ane W A Garcia, Tabata D'Maiella Freitas Klimeck, Flavia C G Reis, Charley C Staats, Leonardo Nimrichter, Taicia P Fill, Marcio L Rodrigues","doi":"10.1128/iai.00049-24","DOIUrl":"10.1128/iai.00049-24","url":null,"abstract":"","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11003222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Specific interaction between Group B <i>Streptococcus</i> CC17 hypervirulent clone and phagocytes.","authors":"Anne-Sophie Bourrel, Amandine Picart, Jose-Carlos Fernandez, Constantin Hays, Virginie Mignon, Bruno Saubaméa, Claire Poyart, Agnès Fouet, Asmaa Tazi, Julie Guignot","doi":"10.1128/iai.00062-24","DOIUrl":"10.1128/iai.00062-24","url":null,"abstract":"<p><p><i>Streptococcus agalactiae</i> also named Group B <i>Streptococcus</i> (GBS) is the most significant pathogen causing invasive infections, such as bacteremia and meningitis, in neonates. Worldwide epidemiological studies have shown that a particular clonal complex (CC) of capsular serotype III, the CC17, is strongly associated with meningitis in neonates and is therefore, designated as the hypervirulent clone. Macrophages are a permissive niche for intracellular bacteria of all GBS clones. In this study, we deciphered the specific interaction of GBS CC17 strains with macrophages. Our study revealed that CC17 strains are phagocytosed at a higher rate than GBS non-CC17 strains by human monocytes and macrophages both in cellular models and in primary cells. CC17-enhanced phagocytosis is due to an initial enhanced-attachment step to macrophages mediated by the CC17-specific surface protein HvgA and the PI-2b pilus (Spb1). We showed that two different inhibitors of scavenger receptors (fucoidan and poly(I)) specifically inhibited CC17 adhesion and phagocytosis while not affecting those of non-CC17 strains. Once phagocytosed, both CC17 and non-CC17 strains remained in a LAMP-1 positive vacuole that ultimately fuses with lysosomes where they can survive at similar rates. Finally, both strains displayed a basal egress which occurs independently from actin and microtubule networks. Our findings provide new insights into the interplay between the hypervirulent GBS CC17 and major players of the host's innate immune response. This enhanced adhesion, leading to increased phagocytosis, could reflect a peculiar capacity of the CC17 lineage to subvert the host immune defenses, establish a niche for persistence or disseminate.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11003227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrected and republished from: \"Extracellular Vesicle Formation in <i>Cryptococcus deuterogattii</i> Impacts Fungal Virulence\".","authors":"Rafael F Castelli, Alana Pereira, Leandro Honorato, Alessandro Valdez, Haroldo C de Oliveira, Jaqueline M Bazioli, Ane W A Garcia, Tabata D'Maiella Freitas Klimeck, Flavia C G Reis, Amanda C Camillo-Andrade, Marlon D M Santos, Paulo C Carvalho, Oscar Zaragoza, Charley C Staats, Leonardo Nimrichter, Taícia P Fill, Marcio L Rodrigues","doi":"10.1128/iai.00037-24","DOIUrl":"10.1128/iai.00037-24","url":null,"abstract":"<p><p>Small molecules are components of fungal extracellular vesicles (EVs), but their biological roles are only superficially known. <i>NOP16</i> is a eukaryotic gene that is required for the activity of benzimidazoles against <i>Cryptococcus deuterogattii</i>. In this study, during the phenotypic characterization of <i>C. deuterogattii</i> mutants expected to lack <i>NOP16</i> expression, we observed a reduced EV production. Whole-genome sequencing, RNA-Seq, and cellular proteomics revealed that, contrary to our initial findings, these mutants expressed Nop16 but exhibited altered expression of 14 genes potentially involved in sugar transport. Based on this observation, we designated these mutant strains as Past1 and Past2, representing <u>p</u>otentially <u>a</u>ltered <u>s</u>ugar <u>t</u>ransport. Analysis of the small molecule composition of EVs produced by wild-type cells and the Past1 and Past2 mutant strains revealed not only a reduced number of EVs but also an altered small molecule composition. In a <i>Galleria mellonella</i> model of infection, the Past1 and Past2 mutant strains were hypovirulent. The hypovirulent phenotype was reverted when EVs produced by wild-type cells, but not mutant EVs, were co-injected with the mutant cells in <i>G. mellonella</i>. These results connect EV biogenesis, cargo, and cryptococcal virulence.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11003230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Salmonella</i> Enteritidis antitoxin DinJ inhibits NLRP3-dependent canonical inflammasome activation in macrophages.","authors":"Dan Gu, Ang Li, Xirui Zang, Tingting Huang, Yaxin Guo, Xinan Jiao, Zhiming Pan","doi":"10.1128/iai.00505-23","DOIUrl":"10.1128/iai.00505-23","url":null,"abstract":"<p><p>The inflammasome is a pivotal component of the innate immune system, acting as a multiprotein complex that plays an essential role in detecting and responding to microbial infections. <i>Salmonella</i> Enteritidis have evolved multiple mechanisms to regulate inflammasome activation and evade host immune system clearance. Through screening <i>S</i>. Enteritidis C50336Δ<i>fliC</i> transposon mutant library, we found that the insertion mutant of <i>dinJ</i> increased inflammasome activation. In this study, we demonstrated the genetic connection between the antitoxin DinJ and the toxin YafQ in <i>S</i>. Enteritidis, confirming their co-transcription. The deletion mutant Δ<i>fliC</i>Δ<i>dinJ</i> increased cell death and IL-1β secretion in J774A.1 cells. Western blotting analysis further showed elevated cleaved Caspase-1 product (p10 subunits) and IL-1β secretion in cells infected with Δ<i>fliC</i>Δ<i>dinJ</i> compared to cells infected with Δ<i>fliC</i>. DinJ was found to inhibit canonical inflammasome activation using primary bone marrow-derived macrophages (BMDMs) from <i>Casp</i>^-/- C57BL/6 mice. Furthermore, DinJ specifically inhibited NLRP3 inflammasome activation, as demonstrated in BMDMs from <i>Nlrp3</i>^<i>-/-</i> and <i>Nlrc4</i>^<i>-/-</i> mice. Fluorescence resonance energy transfer (FRET) experiments confirmed the translocation of DinJ into host cells during infection. Finally, we revealed that DinJ could inhibit the secretion of IL-1β and IL-18 <i>in vivo</i>, contributing to <i>S</i>. Enteritidis evading host immune clearance. In summary, our findings provide insights into the role of DinJ in modulating the inflammasome response during <i>S</i>. Enteritidis infection, highlighting its impact on inhibiting inflammasome activation and immune evasion.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11003228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140109970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotic treatment modestly reduces protection against <i>Mycobacterium tuberculosis</i> reinfection in macaques.","authors":"Sharie Keanne Ganchua, Pauline Maiello, Michael Chao, Forrest Hopkins, Douaa Mugahid, Philana Ling Lin, Sarah M Fortune, JoAnne L Flynn","doi":"10.1128/iai.00535-23","DOIUrl":"10.1128/iai.00535-23","url":null,"abstract":"<p><p>Concomitant immunity is generally defined as an ongoing infection providing protection against reinfection . Its role in prevention of tuberculosis (TB) caused by <i>Mycobacterium tuberculosis</i> (Mtb) is supported by epidemiological evidence in humans as well as experimental evidence in mice and non-human primates (NHPs). Whether the presence of live Mtb, rather than simply persistent antigen, is necessary for concomitant immunity in TB is still unclear. Here, we investigated whether live Mtb plays a measurable role in control of secondary Mtb infection. Using cynomolgus macaques, molecularly barcoded Mtb libraries, positron emission tomography-computed tomography (PET CT) imaging, flow cytometry, and cytokine profiling, we evaluated the effect of antibiotic treatment after primary infection on immunological response and bacterial establishment, dissemination, and burden post-secondary infection. Our data provide evidence that, in this experimental model, treatment with antibiotics after primary infection reduced inflammation in the lung but was not associated with a significant change in bacterial establishment, dissemination, or burden in the lung or lymph nodes. Nonetheless, treatment of the prior infection with antibiotics did result in a modest reduction in protection against reinfection: none of the seven antibiotic-treated animals demonstrated sterilizing immunity against reinfection, while four of the seven non-treated macaques were completely protected against reinfection. These findings support that antibiotic-treated animals were still able to restrict bacterial establishment and dissemination after rechallenge compared to naïve macaques, but not to the full extent of non-antibiotic-treated macaques.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11003231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-domain antibodies reveal unique borrelicidal epitopes on the Lyme disease vaccine antigen, outer surface protein A (OspA).","authors":"David J Vance, Saiful Basir, Carol Lyn Piazza, Graham G Willsey, H M Emranul Haque, Jacque M Tremblay, Michael J Rudolph, Beatrice Muriuki, Lisa Cavacini, David D Weis, Charles B Shoemaker, Nicholas J Mantis","doi":"10.1128/iai.00084-24","DOIUrl":"10.1128/iai.00084-24","url":null,"abstract":"<p><p>Camelid-derived, single-domain antibodies (V_HHs) have proven to be extremely powerful tools in defining the antigenic landscape of immunologically heterogeneous surface proteins. In this report, we generated a phage-displayed V_HH library directed against the candidate Lyme disease vaccine antigen, outer surface protein A (OspA). Two alpacas were immunized with recombinant OspA serotype 1 from <i>Borrelia burgdorferi sensu stricto</i> strain B31, in combination with the canine vaccine RECOMBITEK Lyme containing lipidated OspA. The phage library was subjected to two rounds of affinity enrichment (\"panning\") against recombinant OspA, yielding 21 unique V_HHs within two epitope bins, as determined through competition enzyme linked immunosorbent assays (ELISAs) with a panel of OspA-specific human monoclonal antibodies. Epitope refinement was conducted by hydrogen exchange-mass spectrometry. Six of the monovalent V_HHs were expressed as human IgG1-Fc fusion proteins and shown to have functional properties associated with protective human monoclonal antibodies, including <i>B. burgdorferi</i> agglutination, outer membrane damage, and complement-dependent borreliacidal activity. The V_HHs displayed unique reactivity profiles with the seven OspA serotypes associated with <i>B. burgdorferi</i> genospecies in the United States and Europe consistent with there being unique epitopes across OspA serotypes that should be considered when designing and evaluating multivalent Lyme disease vaccines.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11003225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibodies from chlamydia-infected individuals facilitate phagocytosis via Fc receptors.","authors":"Kevin Hybiske, Shahrokh Paktinat, Katherine Newman, Dorothy Patton, Christine Khosropour, Alison C Roxby, Nelly R Mugo, Lynda Oluoch, Kenneth Ngure, Robert Suchland, Florian Hladik, Lucia Vojtech","doi":"10.1128/iai.00503-23","DOIUrl":"10.1128/iai.00503-23","url":null,"abstract":"<p><p>Non-neutralizing functions of antibodies, including phagocytosis, may play a role in <i>Chlamydia trachomatis</i> (CT) infection, but these functions have not been studied and assays are lacking. We utilized a flow-cytometry-based assay to determine whether serum samples from a well-characterized cohort of CT-infected and naïve control individuals enhanced phagocytosis via Fc-receptor-expressing THP-1 cells, and whether this activity correlated with antibody titers. Fc-receptor-mediated phagocytosis was detected only in CT+ donors. Phagocytosis generally did not correlate well with antibody titer. In addition, we found that complement from both CT+ and negative individuals enhanced phagocytosis of CT into primary neutrophils. These results suggest that anti-CT antibodies can have functions that are not reflected by titer. This method could be used to quantitively measure Fc-receptor-mediated function of anti-CT antibodies or complement activity and could reveal new immune correlates of protection.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11003224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress toward a vaccine for extraintestinal pathogenic E. coli (ExPEC) II: efficacy of a toxin-autotransporter dual antigen approach","authors":"Yikun Xing, Justin R. Clark, James D. Chang, Jacob J. Zulk, Dylan M. Chirman, Felipe-Andres Piedra, Ellen E. Vaughan, Haroldo J. Hernandez Santos, Kathryn A. Patras, Anthony W. Maresso","doi":"10.1128/iai.00440-23","DOIUrl":"https://doi.org/10.1128/iai.00440-23","url":null,"abstract":"Extraintestinal pathogenic Escherichia coli (ExPEC) represents the most prevalent Gram-negative bacterial pathogen and is a primary\u0000contributor to mortality due to antimicrobial resistance (AMR) globally (both deaths\u0000attributable to and associated with AMR) (1, 2). ExPEC comprises the pathotypes of uropathogenic E. coli (UPEC), neonatal meningitis E. coli, and septicemia-associated isolates (3). ExPEC is the primary cause of bacteremia and urinary tract infections (UTIs) and\u0000a frequent cause of neonatal meningitis (4, 5). In the United States, over 970,000 sepsis cases are admitted annually, with an\u00008.7% yearly increase in incidence among hospitalized patients, accounting for over\u000050% of hospital deaths (6, 7). Based on the Centers for Disease Control and Prevention (CDC) multiple cause-of-death\u0000data (1999–2014), 6% of all deaths involved sepsis, 22% of these cases listing sepsis\u0000as the underlying cause (8). Moreover, in 2017, approximately 48.9 million new cases of sepsis were recorded\u0000globally, with 11 million sepsis-related deaths reported, accounting for 19.7% of\u0000all worldwide deaths (9). In addition, sepsis management remains a major challenge for healthcare systems\u0000worldwide, resulting in a disproportionately high burden in terms of cost and hospital\u0000resource utilization. In the United States, sepsis management costs surpass those\u0000for any other disease, exceeding $24 billion in 2013, representing 13% of total hospital\u0000expenses and growing at three times the rate of other admissions (10). E. coli has emerged as the predominant causative agent of bloodstream infections (BSIs) in\u0000both community and hospital settings over the past decade, accounting for 27.1% of\u0000all bacteremia cases. Moreover, the incidence rate of E. coli bacteremia is estimated at 48 per 100,000 person-years, exhibiting a notable increase\u0000with advancing age (11).","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140602721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cathelicidin boosts the antifungal activity of neutrophils and improves prognosis during <i>Aspergillus fumigatus</i> keratitis.","authors":"Xiaochen Hou, Cui Li, Jingyi Liu, Shanshan Yang, Xudong Peng, Qian Wang, Chengxiu Liu, Xing Liu, Junjie Luan, Guiqiu Zhao, Jing Lin","doi":"10.1128/iai.00483-23","DOIUrl":"10.1128/iai.00483-23","url":null,"abstract":"<p><p><i>Aspergillus fumigatus</i> (<i>A. fumigatus</i>) is one of the common pathogens of fungal keratitis. Fungal growth and invasion cause excessive inflammation and corneal damage, leading to severe vision loss. Neutrophils are the primary infiltrating cells critical for fungal clearance. Cathelicidin [LL-37 in humans and cathelicidin-related antimicrobial peptide (CRAMP) in mice], a natural antimicrobial peptide, can directly inhibit the growth of many pathogens and regulate immune responses. However, the role of cathelicidin and its effect on neutrophils in <i>A. fumigatus</i> keratitis remain unclear. By establishing <i>A. fumigatus</i> keratitis mouse models, we found that cathelicidin was increased in <i>A. fumigatus</i> keratitis. It could reduce fungal loads, lower clinical scores, and improve corneal transparency. Restriction of CRAMP on fungal proliferation was largely counteracted in <i>CD18^-/-</i> mice, in which neutrophils cannot migrate into infected sites. When WT neutrophils were transferred into <i>CD18^-/-</i> mice, corneal fungal loads were distinctly reduced, indicating that neutrophils are vital for CRAMP-mediated resistance. Furthermore, cathelicidin promoted neutrophils to phagocytose and degrade conidia both <i>in vitro</i> and <i>in vivo</i>. CXC chemokine receptor 2 (CXCR2) was reported to be a functional receptor of LL-37 on neutrophils. CXCR2 antagonist SB225002 or phospholipase C (PLC) inhibitor U73122 weakened LL-37-induced phagocytosis. Meanwhile, LL-37 induced PLC γ phosphorylation, which was attenuated by SB225002. SB225002 or the autophagy inhibitors Bafilomycin-A1 and 3-Methyladenine weakened LL-37-induced degradation of conidia. Transmission electron microscopy (TEM) observed that LL-37 increased autophagosomes in <i>Aspergillus</i>-infected neutrophils. Consistently, LL-37 elevated autophagy-associated protein expressions (Beclin-1 and LC3-II), but this effect was weakened by SB225002. Collectively, cathelicidin reduces fungal loads and improves the prognosis of <i>A. fumigatus</i> keratitis. Both <i>in vitro</i> and <i>in vivo</i>, cathelicidin promotes neutrophils to phagocytose and degrade conidia. LL-37/CXCR2 activates PLC γ to amplify neutrophils' phagocytosis and induces autophagy to eliminate intracellular conidia.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11003229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140158070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Article of Significant Interest in This Issue","authors":"","doi":"10.1128/iai.00139-24","DOIUrl":"https://doi.org/10.1128/iai.00139-24","url":null,"abstract":"Infection and Immunity, Volume 92, Issue 4, April 2024. <br/>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}