Viral immunology最新文献

{"title":"Monocyte Transcriptome in Different Phases of Chronic Hepatitis B Virus Infection Uncovers Potential Functional Roles.","authors":"Prakriti Sinha, Vaishali Bhardwaj, Abaranjitha Muniyasamy, K Varsha Mohan, Kshama Jain, Kiran Chaudhary, Pramod Upadhyay","doi":"10.1089/vim.2024.0006","DOIUrl":"10.1089/vim.2024.0006","url":null,"abstract":"<p><p>The hepatitis B virus (HBV) chronic infection goes through different phases, i.e., immune tolerant (IT), immune clearance (IC), and inactive carrier (IN) resulting from the interplay of viral replication and immune response. Although the adaptive immune response is central to viral control, roles of the innate immune cells are less prominent. We explored monocyte transcriptome in these different phases of HBV infection to understand the nature of its involvement and identify unique differentially expressed genes (DEGs) in each phase. CD14+ peripheral blood monocytes were isolated from patients in the IT, IC, and IN phases and from healthy subjects and their RNA was sequenced. The significant DEGs were studied through gene annotation databases to understand differentially modulated pathways. The DEGs were further validated by qRT-PCR to identify genes that were uniquely expressed in each phase. It was found that <i>TNFRSF12A</i> was upregulated in all the HBV samples. The IN phase had six uniquely upregulated genes, i.e., <i>PI3, EMP1, STX1A, RRAD, SPINK1,</i> and <i>SNORD3B-2</i>. <i>E2F7</i> was most consistently downregulated in the IT phase, and in the IC phase, <i>IL23A</i> and <i>PI3</i> were specifically downregulated. Cut-off values were generated by ROC curve analysis to differentiate between the groups based on their expression levels. The monocyte functions are majorly suppressed in the IT and IC phases and are, however, somewhat metabolically active in the IN phase.</p>","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":" ","pages":"287-297"},"PeriodicalIF":1.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Immunodeficiency Virus-Human Pegivirus Coinfected Individuals Display Functional Mucosal-Associated Invariant T Cells and Follicular T Cells Irrespective of PD-1 Expression.","authors":"Jaisheela Vimali, Yean K Yong, Amudhan Murugesan, Sakthivel Govindaraj, Sivadoss Raju, Pachamuthu Balakrishnan, Marie Larsson, Vijayakumar Velu, Esaki M Shankar","doi":"10.1089/vim.2024.0007","DOIUrl":"10.1089/vim.2024.0007","url":null,"abstract":"<p><p>Human pegivirus (HPgV) appears to alter the prognosis of HIV disease by modulating T cell homeostasis, chemokine/cytokine production, and T cell activation. In this study, we evaluated if HPgV had any 'favorable' impact on the quantity and quality of T cells in HIV-infected individuals. T cell subsets such as CD4^lo, CD4^hi, and CD8⁺ T cells, CD4⁺ MAIT cells, CD8⁺ MAIT cells, follicular helper T (TFH) cells, and follicular cytotoxic T (TFC) cells were characterized based on the expression of markers associated with immune activation (CD69, ICOS), proliferation (ki67), cytokine production (TNF-α, IFN-γ), and exhaustion (PD-1). HIV⁺HPgV⁺ individuals had lower transaminase SGOT (liver) and GGT (biliary) in the plasma than those who were HPgV^-. HIV/HPgV coinfection was significantly associated with increased absolute CD4⁺ T cell counts. HIV⁺HPgV⁺ and HIV⁺HPgV^- individuals had highly activated T cell subsets with high expression of CD69 and ICOS on bulk CD4⁺ and CD8⁺ T cells, CD4⁺ MAIT cells, CD8⁺ MAIT cells, and CXCR5⁺CD4⁺ T cells and CXCR5⁺CD8⁺ T cells compared with healthy controls. Irrespective of immune activation markers, these cells also displayed higher levels of PD-1 on CD4⁺ T and CD8⁺ T cells . Exploring effector functionality based on mitogen stimulation demonstrated increased cytokine production by CD4⁺ MAIT and CD8⁺ MAIT cells. Decrease in absolute CD4⁺ T cell counts correlated positively with intracellular IFN-γ levels by CD4^lo T cells, whereas increase of the same correlated negatively with TNF-α in the CD4^lo T cells of HIV⁺HPgV⁺ individuals. HIV/HPgV coinfected individuals display functional CD4⁺ and CD8⁺ MAIT, TFH, and TFC cells irrespective of PD-1 expression.</p>","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":" ","pages":"240-250"},"PeriodicalIF":1.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knowledge on Human Papillomavirus Infections, Cancer Biology, Immune Interactions, Vaccination Coverage and Common Treatments: A Comprehensive Review.","authors":"Nika Nikmanesh, SeyedehZahra Hosseini, Fatemehsadat Mirbagheri, Kimiya Asadsangabi, Mohammad Reza Fattahi, Ali Reza Safarpour, Ebrahim Fallahzadeh Abarghooee, Ali Moravej, Seyedeh Azra Shamsdin, Hassan Akrami, Seyyed Amirreza Saghi, Yousef Nikmanesh","doi":"10.1089/vim.2023.0144","DOIUrl":"10.1089/vim.2023.0144","url":null,"abstract":"<p><p>Human papillomavirus (HPV) is a circular, double-stranded DNA virus and recognized as the most prevalent sexually transmitted infectious agent worldwide. The HPV life cycle encompasses three primary stages. First, the virus infiltrates the basal cells of the stratified epidermis. Second, there is a low-level expression of viral genes and preservation of the viral genome in the basal layer. Lastly, productive replication of HPV occurs in differentiated cells. An effective immune response, involving various immune cells, including innate immunity, keratinocytes, dendritic cells, and natural killer T cells, is instrumental in clearing HPV infection and thwarting the development of HPV-associated tumors. Vaccines have demonstrated their efficacy in preventing genital warts, high-grade precancerous lesions, and cancers in females. In males, the vaccines can also aid in preventing genital warts, anal precancerous lesions, and cancer. This comprehensive review aims to provide a thorough and detailed exploration of HPV infections, delving into its genetic characteristics, life cycle, pathogenesis, and the role of high-risk and low-risk HPV strains. In addition, this review seeks to elucidate the intricate immune interactions that govern HPV infections, spanning from innate immunity to adaptive immune responses, as well as examining the evasion mechanisms used by the virus. Furthermore, the article discusses the current landscape of HPV vaccines and common treatments, contributing to a holistic understanding of HPV and its associated diseases.</p>","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":" ","pages":"221-239"},"PeriodicalIF":1.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Interleukin-6 (rs1800795) and Interleukin-10 (rs1800896) Genetic Polymorphisms with the Outcome of COVID-19 Infection: A Single Center Study.","authors":"Mahmoud El-Bendary, Mustafa Naemattalah, Hatem Elalfy, Ahmed Elhawary, Abdel-Hady El-Gilany, Hosam Zaghloul, Sara Anber, Mohamed Elegezy","doi":"10.1089/vim.2024.0029","DOIUrl":"10.1089/vim.2024.0029","url":null,"abstract":"<p><p>The corona virus disease-2019 (COVID-19) pandemic has affected most of the world with varying degrees of morbidity and mortality. The presence of genetic polymorphisms may be associated with the severity and outcome of COVID-19 infection. This work aimed to evaluate the genetic polymorphisms of interleukin (IL-6) and IL-10 genes with the outcome of COVID-19 infection. This cross-sectional study was conducted on 354 patients who were classified into moderate and severe cases (including alive and deceased cases). All individuals were genotyped for one SNP for IL-6 (rs1800795) and one SNP for IL10 (rs1800896) using allelic discrimination real-time PCR technique. In this study, 198 cases were moderate, and 156 cases were severe. The risk of allele carriage of the minor allele of IL-6 rs1800795 (C) was significantly higher among the severe group when compared with that of the moderate group (<i>p</i> < 0.0001), while there was a mild significant difference of same allele carriage among alive cases when compared to that of deceased one (<i>p</i> < 0.04). Furthermore, the risk of the C allele of IL-10 rs1800896 was significantly increased in severe cases when compared with the moderate group (<i>p</i> < 0.0001), while there was no significant difference of the risk of the C allele in deceased cases when compared with that of alive ones (<i>p</i> > 0.05). In conclusion, the C allele (rs1800795) of IL-6 and the C allele (rs1800896) of IL-10 were highly significant in severe cases than in moderate cases. The C allele carriage of IL-6 showed only a significant difference between alive and deceased patients and not with the C allele of IL-10.</p>","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":" ","pages":"251-258"},"PeriodicalIF":1.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Letter to the Editor:</i> Should Viruses Exist? A Brief Reflection on the (Re)evolution of the Virus-Life Relationship.","authors":"José Valter Joaquim Silva Júnior, Eduardo Furtado Flores","doi":"10.1089/vim.2024.0037","DOIUrl":"10.1089/vim.2024.0037","url":null,"abstract":"","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":" ","pages":"266-267"},"PeriodicalIF":1.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IGH Complementarity Determining Region-3-Cytomegalovirus Protein Chemical Complementarity Linked to Better Overall Survival Probabilities for Glioblastoma.","authors":"Tabitha R Hudock, Joanna J Song, Andrea Chobrutskiy, Boris I Chobrutskiy, George Blanck","doi":"10.1089/vim.2024.0013","DOIUrl":"10.1089/vim.2024.0013","url":null,"abstract":"<p><p>Cytomegalovirus (CMV) has long been thought to have an association with glioblastoma multiforme (GBM), although the exact role of CMV and any subsequent implications for treatment have yet to be fully understood. This study addressed whether IGH complementarity determining region-3 (CDR3)-CMV protein chemical complementarity, with IGH CDR3s representing both tumor resident and blood-sourced <i>IGH</i> recombinations, was associated with overall survival (OS) distinctions. <i>IGH</i> recombination sequencing reads were obtained from (a) the Clinical Proteomic Tumor Analysis Consortium, tumor RNAseq files; and (b) the cancer genome atlas, blood exome-derived files. The Adaptive Match web tool was used to calculate chemical complementarity scores (CSs) based on hydrophobic interactions, and those scores were used to group GBM cases and assess survival probabilities. We found a higher OS probability for cases whose hydrophobic IGH CDR3-CMV protein chemical complementarity scores (Hydro CSs) were in the upper 50th percentile for several CMV proteins, including UL99 and UL123, as well as for CSs based on known B cell epitopes representing these proteins. We also identified multiple immune signature genes, including CD79A and TNFRSF17, for which higher RNA expression was associated with higher Hydro CSs. Results were consistent with the idea that stronger immunoglobulin responses to CMV are associated with better OS probabilities for GBM.</p>","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":" ","pages":"259-265"},"PeriodicalIF":1.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Efficacy of the Modified Vaccinia Ankara-Bavaria Nordic Vaccine Against Mpox in the Real World: Systematic Review and Meta-Analysis.","authors":"Yi Pang, Demin Cao, Xiaoying Zhu, Qinqin Long, Fengqin Tian, Xidai Long, Yulei Li","doi":"10.1089/vim.2023.0147","DOIUrl":"10.1089/vim.2023.0147","url":null,"abstract":"<p><p>In May 2022, mpox began to spread worldwide, posing a serious threat to human public health. Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN) is a live attenuated orthopoxvirus vaccine that has been authorized by the U.S. Food and Drug Administration as the vaccine of choice for the prevention of mpox. In this study, we conducted a meta-analysis of all currently published literature on the efficacy and safety of the MVA-BN vaccine in the real world, showing that the MVA-BN vaccine is effective and safe, with efficacy of up to 75% with a single dose and up to 80% with a two-dose vaccine. Meanwhile, we found that subcutaneous injection has lower local and systemic adverse events than intradermal injection, regardless of single- or two-dose vaccination, and subcutaneous injection is better tolerated in children, the elderly, or people with underlying medical conditions. These results have important reference value for clinical practice.</p>","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":"37 4","pages":"216-219"},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformation Analysis of Differential Expression Proteins in Different Processes of COVID-19.","authors":"Nana Guo, Xu Han, Guangyue Han, Mingyan Dai, Zhanying Han, Qi Li","doi":"10.1089/vim.2023.0094","DOIUrl":"10.1089/vim.2023.0094","url":null,"abstract":"<p><p>COVID-19 is a highly infectious respiratory disease whose progression has been associated with multiple factors. From SARS-CoV-2 infection to death, biomarkers capable of predicting different disease processes are needed to help us further understand the molecular progression of COVID-19 disease. The aim is to find differentially expressed proteins that are associated with the progression of COVID-19 disease or can be potential biomarkers, and to provide a reference for further understanding of the molecular mechanisms of COVID-19 occurrence, progression, and treatment. Data-independent Acquisition (DIA) proteomics to obtain sample protein expression data, using R language screening differentially expressed proteins. Gene Ontology and Kyoto Encyclopedia for Genes and Genomes analysis was performed on differential proteins and protein-protein interaction (PPI) network was constructed to screen key proteins. A total of 47 differentially expressed proteins were obtained from COVID-19 incubation patients and healthy population (L/H), mainly enriched in platelet-related functions, and complement and coagulation cascade reaction pathways, such as platelet degranulation and platelet aggregation. A total of 42 differential proteins were obtained in clinical and latent phase patients (C/L), also mainly enriched in platelet-related functions and in complement and coagulation cascade reactions, platelet activation pathways. A total of 10 differential proteins were screened in recovery and clinical phase patients (R/C), mostly immune-related proteins. The differentially expressed proteins in different stages of COVID-19 are mostly closely associated with coagulation, and key differential proteins, such as FGA, FGB, FGG, ACTB, PFN1, VCL, SERPZNCL, APOC3, LTF, and DEFA1, have the potential to be used as early diagnostic markers.</p>","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":"37 4","pages":"194-201"},"PeriodicalIF":2.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Levels of Secreted Cytokines in Virologically Controlled HIV-Infected Aging Adult Individuals on Long-Term Antiretroviral Therapy.","authors":"Maria Love, Nicole Behrens-Bradley, Aasim Ahmad, Anne Wertheimer, Stephen Klotz, Nafees Ahmad","doi":"10.1089/vim.2023.0123","DOIUrl":"10.1089/vim.2023.0123","url":null,"abstract":"<p><p>HIV-infected (HIV⁺) aging adult individuals who have achieved undetectable viral load and improved CD4 T cell counts due to long-term antiretroviral therapy (ART) may continue to experience inflammation and immunosenescence. Therefore, we evaluated the plasma levels of proinflammatory and anti-inflammatory cytokines in 173 HIV⁺ aging adult individuals with age ranging from 22 to 81 years on long-term ART with viral load mostly <20 HIV RNA copies/mL and compared with 92 HIV-uninfected (HIV^- or healthy controls) aging individuals. We found that the median levels of TNF-α, IFN-γ, IL-1β, IL-6, and IL-10 were higher (<i>p</i> < 0.001 to <0.0001) and IL-17 trended lower in HIV⁺ individuals than healthy controls. Increasing CD4 T cell counts in the HIV⁺ cohort did not significantly change the circulating cytokine levels, although levels of IL-1β increased. However, IL-17 levels significantly decreased with increasing CD4 counts in the healthy controls and yet unchanged in the HIV⁺ cohort. Of note, the levels of circulating IL-17 were significantly reduced comparatively in the healthy controls where the CD4 count was below 500, yet once above 500 the levels of CD4, IL-17 levels were comparable with the HIV⁺ cohort. With increasing CD8 T cell counts, the levels of these cytokines were not significantly altered, although levels of TNF-α, IFN-γ, and IL-6 declined, whereas IL-1β and IL-17 were slightly elevated. Furthermore, increasing age of the HIV⁺ cohort did not significantly impact the cytokine levels although a slight increase in TNF-α, IL-6, IL-10, and IL-17 was observed. Similarly, these cytokines were not significantly modulated with increasing levels of undetectable viral loads, whereas some of the HIV⁺ individuals had higher levels of TNF-α, IFN-γ, and IL-1β. In summary, our findings show that HIV⁺ aging adult individuals with undetectable viral load and restored CD4 T cell counts due to long-term ART still produce higher levels of both proinflammatory and anti-inflammatory cytokines compared with healthy controls, suggesting some level of inflammation.</p>","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":"37 4","pages":"202-215"},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11238844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon-Induced Transmembrane Protein-3 Rs12252-G Variant Increases COVID-19 Mortality Potential in Egyptian Population.","authors":"Sara M Elessawy, Abeer Shehab, Dina A Soliman, Mai A Eldeeb, Sara I Taha","doi":"10.1089/vim.2024.0015","DOIUrl":"10.1089/vim.2024.0015","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) represented an international health risk. Variants of the interferon-induced transmembrane protein-3 (<i>IFITM3</i>) gene can increase the risk of developing severe viral infections. This cross-sectional study investigated the association between <i>IFITM3</i> rs12252A>G single nucleotide polymorphism (SNP) and COVID-19 severity and mortality in 100 Egyptian patients. All participants were subjected to serum interleukin-6 (IL-6) determination by ELISA and <i>IFITM3</i> rs12252 genotyping by real-time polymerase chain reaction. Of all participants, 85.0% had the <i>IFITM3</i> rs12252 homozygous AA genotype, whereas 15.0% had the heterozygous AG genotype. None of our participants had the homozygous GG genotype. The <i>IFITM3</i> rs12252A allele was found in 92.5% and the G allele in only 7.5%. There was no significant association (<i>p</i> > 0.05) between the <i>IFITM3</i> rs12252 SNP and COVID-19 severity, intensive care unit (ICU) admission, or IL-6 serum levels. The heterozygous AG genotype frequency showed a significant increase among participants who died (32.0%) compared with those who had been cured (9.3%). The mutant G allele was associated with patients' death. Its frequency among cured participants was 8.5%, whereas in those who died was 24.2% (<i>p</i> = 0.024) with 3.429 odds ratio [95% confidence interval: 1.1-10.4]. In conclusion, this study revealed a significant association between the G allele variant of <i>IFITM3</i> rs12252 and COVID-19 mortality. However, results were unable to establish a significant link between rs12252 polymorphism, disease severity, ICU admission, or serum IL-6 levels.</p>","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":"37 4","pages":"186-193"},"PeriodicalIF":2.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}