Pathogens and Immunity最新文献

{"title":"Replication and Injury Associated With SARS-CoV-2 in Cultured Hepatocytes.","authors":"Suman Pradhan, Susan D Rouster, Jason T Blackard, Gary E Dean, Kenneth E Sherman","doi":"10.20411/pai.v8i2.648","DOIUrl":"10.20411/pai.v8i2.648","url":null,"abstract":"<p><strong>Background: </strong>Liver dysfunction is one of the hallmarks of SARS-CoV-2 infection. The mechanism(s) of hepatic injury in SARS-CoV-2 infection remains controversial with some reporting viral replication and cellular injury and others suggesting lack of replication and injury due to non-cytopathogenic etiologies. To investigate this further, we evaluated SARS-CoV-2 replication in immortalized hepatic cell lines and primary hepatocytes, examined whether cell injury was associated with apoptotic pathways, and also determined the effect of the antiviral remdesivir on these processes.</p><p><strong>Methods: </strong>Immortalized hepatocyte cell lines (HepG2 and Huh7.5), as well as primary human hepatocytes, were exposed to SARS-CoV-2 at a multiplicity of infection of 0.1 PFU/mL. Viral replication was evaluated by plaque assays, immunohistochemical staining for the viral spike protein, and caspase-3 expression evaluated with and without exposure to remdesivir.</p><p><strong>Results: </strong>All hepatocyte cell lines and primary hepatocytes supported active replication of SARS-CoV-2. Significant cytopathic effect was observed by light microscopy, and caspase-3 staining supported activation of apoptotic pathways. Remdesivir abrogated infection in a dose-dependent fashion and was not independently associated with hepatocyte injury.</p><p><strong>Conclusion: </strong>Hepatocytes appear to be highly permissive of SARS-CoV-2 replication which leads to rapid cell death associated with activation of apoptotic pathways. Viral replication and hepatocytes injury are abrogated with remdesivir. We conclude that active viral replication is most likely a key contributor to liver enzyme abnormalities observed in the setting of acute SARS-CoV-2 infection.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"8 2","pages":"59-73"},"PeriodicalIF":0.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10868721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stable Levels of Antibodies Against Unrelated Toxoid Vaccines After COVID-19: COVID-19 Infection Does Not Affect Toxoid Vaccine Antibody Levels.","authors":"Suvi T Jokiranta, Simo Miettinen, Sami Salonen, Lauri Kareinen, Ruut Uusitalo, Essi M Korhonen, Jenni Virtanen, Ilkka Kivistö, Kirsi Aaltonen, Dina A Mosselhy, Tinja Lääveri, Anu Kantele, T Petteri Arstila, Hanna Jarva, Olli Vapalahti, Santtu Heinonen, Eliisa Kekäläinen","doi":"10.20411/pai.v8i2.627","DOIUrl":"10.20411/pai.v8i2.627","url":null,"abstract":"<p><strong>Background: </strong>Lymphopenia is common in COVID-19. This has raised concerns that COVID-19 could affect the immune system akin to measles infection, which causes immune amnesia and a reduction in protective antibodies.</p><p><strong>Methods: </strong>We recruited COVID-19 patients (n = 59) in Helsinki, Finland, and collected plasma samples on 2 to 3 occasions during and after infection. We measured IgG antibodies to diphtheria toxin, tetanus toxoid, and pertussis toxin, along with total IgG, SARS-CoV-2 spike protein IgG, and neutralizing antibodies. We also surveyed the participants for up to 17 months for long-term impaired olfaction as a proxy for prolonged post-acute COVID-19 symptoms.</p><p><strong>Results: </strong>No significant differences were found in the unrelated vaccine responses while the serological response against COVID-19 was appropriate. During the acute phase of the disease, the SARSCoV-2 IgG levels were lower in outpatients when compared to inpatients. SARS-CoV-2 serology kinetics matched expectations. In the acute phase, anti-tetanus and anti-diphtheria IgG levels were lower in patients with prolonged impaired olfaction during follow up than in those without.</p><p><strong>Conclusions: </strong>We could not detect significant decline in overall humoral immunity during or after COVID-19 infection. In severe COVID-19, there appears to be a temporary decline in total IgG levels.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"8 2","pages":"74-87"},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10860543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning Bolsters Evidence That D1, Nef, and Tat Influence HIV Reservoir Dynamics.","authors":"LaMont Cannon, Sophia Fehrman, Marilia Pinzone, Sam Weissman, Una O'Doherty","doi":"10.20411/pai.v8i2.621","DOIUrl":"10.20411/pai.v8i2.621","url":null,"abstract":"<p><strong>Background: </strong>The primary hurdle to curing HIV is due to the establishment of a reservoir early in infection. In an effort to find new treatment strategies, we and others have focused on understanding the selection pressures exerted on the reservoir by studying how proviral sequences change over time.</p><p><strong>Methods: </strong>To gain insights into the dynamics of the HIV reservoir we analyzed longitudinal near full-length sequences from 7 people living with HIV between 1 and 20 years following the initiation of antiretroviral treatment. We used this data to employ Bayesian mixed effects models to characterize the decay of the reservoir using single-phase and multiphasic decay models based on near full-length sequencing. In addition, we developed a machine-learning approach utilizing logistic regression to identify elements within the HIV genome most associated with proviral decay and persistence. By systematically analyzing proviruses that are deleted for a specific element, we gain insights into their role in reservoir contraction and expansion.</p><p><strong>Results: </strong>Our analyses indicate that biphasic decay models of intact reservoir dynamics were better than single-phase models with a stronger statistical fit. Based on the biphasic decay pattern of the intact reservoir, we estimated the half-lives of the first and second phases of decay to be 18.2 (17.3 to 19.2, 95%CI) and 433 (227 to 6400, 95%CI) months, respectively.In contrast, the dynamics of defective proviruses differed favoring neither model definitively, with an estimated half-life of 87.3 (78.1 to 98.8, 95% CI) months during the first phase of the biphasic model. Machine-learning analysis of HIV genomes at the nucleotide level revealed that the presence of the splice donor site D1 was the principal genomic element associated with contraction. This role of D1 was then validated in an <i>in vitro</i> system. Using the same approach, we additionally found supporting evidence that HIV <i>nef</i> may confer a protective advantage for latently infected T cells while <i>tat</i> was associated with clonal expansion.</p><p><strong>Conclusions: </strong>The nature of intact reservoir decay suggests that the long-lived HIV reservoir contains at least 2 distinct compartments. The first compartment decays faster than the second compartment. Our machine-learning analysis of HIV proviral sequences reveals specific genomic elements are associated with contraction while others are associated with persistence and expansion. Together, these opposing forces shape the reservoir over time.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"8 2","pages":"37-58"},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10827039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139643053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Normospermic Patients Infected With Ureaplasma parvum: Role of Dysregulated miR-122-5p, miR-34c-5, and miR-141-3p","authors":"Marilena Galdiero, Carlo Trotta, Maria Teresa Schettino, Luigi Cirillo, Francesca Paola Sasso, Francesco Petrillo, A. Petrillo","doi":"10.20411/pai.v8i2.603","DOIUrl":"https://doi.org/10.20411/pai.v8i2.603","url":null,"abstract":"Background: Ureaplasma parvum (UP) is a causative agent of non-gonococcal urethritis, involved in the pathogenesis of prostatitis and epididymitis, and it could impair human fertility. Although UP infection is a frequent cause of male infertility the study evidence assessing their prevalence and the association in patients with infertility is still scarce. The molecular processes leading to defects in spermatozoa quality are not completely investigated. MicroRNAs (miRNAs) have been extensively reported as gene regulatory molecules on post-transcriptional levels involved in various biological processes such as gametogenesis, embryogenesis, and the quality of sperm, oocyte, and embryos.\u0000Methods: Therefore, the study design was to demonstrate that miRNAs in body fluids like sperm could be utilized as non-invasive diagnostic biomarkers for pathological and physiological conditions such as infertility. A post-hoc bioinformatics analysis was carried out to predict the pathways modulated by the miRNAs dysregulated in the differently motile spermatozoa.\u0000Results: Here it is shown that normospermic patients infected by UP had spermatozoa with increased quantity of superoxide anions, reduced expression of miR-122-5p, miR-34c-5, and increased miR-141-3p compared with non-infected normospermic patients. This corresponded to a reduction of sperm motility in normospermic infected patients compared with normospermic non-infected ones. A target gene prediction presumed that an essential role of these miRNAs resided in the regulation of lipid kinase activity, accounting for the changes in the constitution of spermatozoa membrane lipids caused by UP. \u0000Conclusions: Altogether, the data underline the influence of UP on epigenetic mechanisms regulating spermatozoa motility. ","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"92 14","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139381218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arterial Stiffness and Oxidized LDL Independently Associated With Post-Acute Sequalae of SARS-CoV-2","authors":"Sokratis N. Zisis, Jared C. Durieux, Christian Mouchati, Nicholas Funderburg, Kate Ailstock, Mary Chong, Danielle Labbato, Grace McComsey","doi":"10.20411/pai.v8i2.634","DOIUrl":"https://doi.org/10.20411/pai.v8i2.634","url":null,"abstract":"OBJECTIVE: COVID-19 survivors can experience lingering symptoms known as post-acute sequelae of SARS-CoV-2 (PASC) that appear in different phenotypes, and its etiology remains elusive. We assessed the relationship of endothelial dysfunction with having COVID and PASC.\u0000METHODS: Data was collected from a prospectively enrolled cohort (n=379) of COVID-negative and COVID-positive participants with and without PASC. Primary outcomes, endothelial function (measured by reactive hyperemic index [RHI]), and arterial elasticity (measured by augmentation index standardized at 75 bpm [AI]), were measured using the FDA approved EndoPAT. Patient characteristics, labs, metabolic measures, markers of inflammation, and oxidized LDL (ox-LDL) were collected at each study visit, and PASC symptoms were categorized into 3 non-exclusive phenotypes: cardiopulmonary, neurocognitive, and general. COVID-negative controls were propensity score matched to COVID-negative-infected cases using the greedy nearest neighbor method.\u0000RESULTS: There were 14.3% of participants who were fully recovered COVID positive and 28.5% who were COVID positive with PASC, averaging 8.64 ± 6.26 total number of symptoms. The mean RHI was similar across the cohort and having COVID or PASC was not associated with endothelial function (P=0.33). Age (P<0.0001), female sex (P<0.0001), and CRP P=0.04) were positively associated with arterial stiffness, and COVID positive PASC positive with neurological and/or cardiopulmonary phenotypes had the worst arterial elasticity (highest AI). Values for AI (P=0.002) and ox-LDL (P<0.0001) were independently and positively associated with an increased likelihood of having PASC. \u0000CONCLUSION: There is evidence of an independent association between PASC, ox-LDL, and arterial stiffness with neurological and/or cardiopulmonary phenotypes having the worst arterial elasticity. Future studies should continue investigating the role of oxidative stress in the pathophysiology of PASC.","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"56 24","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138957072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highlights from the Inaugural HIV Reservoirs and Immune Control Conference, October 1st–4th 2023, Malahide Ireland","authors":"Una O’Doherty, J. M. Picado, A. Sáez-Cirión","doi":"10.20411/pai.v8i1.653","DOIUrl":"https://doi.org/10.20411/pai.v8i1.653","url":null,"abstract":"The inaugural FASEB HIV Reservoirs and Immune Control Conference brought researchers together from across the globe to discuss reservoir dynamics in clinical cohorts. It extended over 4 days in the seaside town of Malahide, Ireland. The scientific sessions covered a broad range of topics, including: 1) HIV pathogenesis and control, 2) reservoirs and viral expression, 3) pediatric reservoirs, 4) innate immunity and B cell responses, 5) environmental factors affecting pathogenesis, 6) loss of virologic control, and 7) HIV-2. The following article provides a brief summary of the meeting proceedings and includes a supplementary document with the meeting abstracts. ","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"115 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138959589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbon Dioxide Monitoring Demonstrates Variations in the Quality of Ventilation on Public Transportation Buses and University Student Shuttle Vans and Identifies Effective Interventions.","authors":"David Henry Greentree, Brigid M Wilson, Curtis J Donskey","doi":"10.20411/pai.v8i1.619","DOIUrl":"10.20411/pai.v8i1.619","url":null,"abstract":"<p><strong>Background: </strong>There is a risk for transmission of severe acute respiratory syndrome 2 (SARS-CoV-2) and other respiratory viruses in motor vehicles, particularly if ventilation is inadequate.</p><p><strong>Methods: </strong>We used carbon dioxide monitoring to examine the quality of ventilation in several public transportation buses and in university student shuttle vans in the Cleveland metro area during peak and non-peak travel times. Carbon dioxide levels above 800 parts per million (ppm) were considered an indicator of suboptimal ventilation for the number of people present. In the shuttle vans, we evaluated the impact of an intervention to improve ventilation.</p><p><strong>Results: </strong>In large articulated buses with 2 ventilation systems, carbon dioxide concentrations never exceeded 800 ppm, whereas in standard buses with 1 ventilation system concentrations rose above 800 ppm during peak travel times and on some trips during non-peak travel times. In shuttle vans, the ventilation system was not turned on during routine operation, and carbon dioxide levels rose above 800 ppm on all trips during peak and non-peak travel times. In the shuttle vans, an intervention involving operation of the existing ventilation system resulted in a significant reduction in carbon dioxide levels (mean concentration, 1,042 no intervention versus 785 with intervention; <i>P</i> < 0.001).</p><p><strong>Conclusions: </strong>Our findings demonstrate substantial variability in the quality of ventilation in public transportation buses and university shuttle vans. There is a need for efforts to assess and optimize ventilation in motor vehicles used for public transportation to reduce the risk for aerosol-mediated transmission of respiratory viruses. Carbon dioxide monitoring may provide a useful tool to assess and improve ventilation.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"8 1","pages":"148-160"},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vishva Dixit Shares Insights on His Early Influences, Research Career, Key Findings, and What it Takes to Be Successful in Science.","authors":"Neil S Greenspan","doi":"10.20411/pai.v8i2.643","DOIUrl":"https://doi.org/10.20411/pai.v8i2.643","url":null,"abstract":"In this interview, Vishva Dixit, MD, talks with Neil S. Greenspan, MD, PhD, senior editor of Pathogens and Immunity aboutwhat his career in science has revealed about biology in humans, but also what it has revealed about how to be successful in science. Dr. Dixit is a world-famous immunologist and biochemist who has made major contributions to the study of innate immunity in general and particularly to understanding inflammasome activation. He is vice president and senior fellow in physiological chemistry at Genentech.","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"8 1","pages":"136-147"},"PeriodicalIF":0.0,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138465440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamics of T-cell Responses Following COVID-19 mRNA Vaccination and Breakthrough Infection in Older Adults.","authors":"Sneha Datwani, Rebecca Kalikawe, Francis Mwimanzi, Sarah Speckmaier, Richard Liang, Yurou Sang, Rachel Waterworth, Fatima Yaseen, Hope R Lapointe, Evan Barad, Mari L DeMarco, Daniel T Holmes, Janet Simons, Julio S G Montaner, Marc G Romney, Zabrina L Brumme, Mark A Brockman","doi":"10.20411/pai.v8i1.613","DOIUrl":"10.20411/pai.v8i1.613","url":null,"abstract":"<p><strong>Introduction: </strong>While older adults generally mount weaker antibody responses to a primary COVID-19 vaccine series, T-cell responses remain less well characterized in this population. We compared SARS-CoV-2 spike-specific T-cell responses after 2- and 3-dose COVID-19 mRNA vaccination and subsequent breakthrough infection in older and younger adults.</p><p><strong>Methods: </strong>We quantified CD4+ and CD8+ T-cells reactive to overlapping peptides spanning the ancestral SARS-CoV-2 spike protein in 40 older adults (median age 79) and 50 younger health care workers (median age 39), all COVID-19 naive, using an activation-induced marker assay. T-cell responses were further assessed in 24 participants, including 8 older adults, who subsequently experienced their first SARS-CoV-2 breakthrough infection.</p><p><strong>Results: </strong>A third COVID-19 mRNA vaccine dose significantly boosted spike-specific CD4+ and CD8+ T-cell frequencies to above 2-dose levels in older and younger adults. T-cell frequencies did not significantly differ between older and younger adults after either dose. Multivariable analyses adjusting for sociodemographic, health, and vaccine-related variables confirmed that older age was not associated with impaired cellular responses. Instead, the strongest predictors of CD4+ and CD8+ T-cell frequencies post-third-dose were their corresponding post-second-dose frequencies. Breakthrough infection significantly increased both CD4+ and CD8+ T-cell frequencies, to comparable levels in older and younger adults. Exploratory analyses revealed an association between HLA-A*02:03 and higher post-vaccination CD8+ T-cell frequencies, which may be attributable to numerous strong-binding HLA-A*02:03-specific CD8+ T-cell epitopes in the spike protein.</p><p><strong>Conclusion: </strong>Older adults mount robust T-cell responses to 2- and 3-dose COVID-19 mRNA vaccination, which are further boosted following breakthrough infection.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"8 1","pages":"117-135"},"PeriodicalIF":0.0,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Raymond Schinazi Discusses the Discovery of Early Antiretroviral Agents and Sofosbuvir","authors":"Michael M. Lederman, Neil Greenspan","doi":"10.20411/pai.v8i2.624","DOIUrl":"https://doi.org/10.20411/pai.v8i2.624","url":null,"abstract":"In this interview, Raymond Schinazi, PhD, Hon DSc, talks about his career with Michael M. Lederman, MD, and Neil S. Greenspan, MD, PhD, senior editors of Pathogens and Immunity. Dr. Schinazi has invented numerous powerful antiviral agents including the antiretrovirals lamivudine (3TC) and emtricitabine (FTC) and was instrumental in the discovery of the anti-hepatitis C agent sofosbuvir. These drugs have saved millions of lives and, here, Dr. Schinazi shares in detail how these agents were invented, how they work, and how they are being applied. He also offers his thoughts about newer approaches to treat viral infections.","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"14 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135679037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}