Clinical and experimental immunology最新文献

{"title":"Reduced response to SARS-CoV-2 vaccination is associated with impaired immunoglobulin class switch recombination in SLE patients.","authors":"Guillem Montamat, Claire E Meehan, Hannah F Bradford, Reşit Yıldırım, Francisca Guimarães, Marina Johnson, David Goldblatt, David A Isenberg, Claudia Mauri","doi":"10.1093/cei/uxae119","DOIUrl":"10.1093/cei/uxae119","url":null,"abstract":"<p><strong>Introduction: </strong>Systemic lupus erythematosus (SLE) patients exhibit B-cell abnormalities. Although there are concerns about reduced antibody responses to SARS-CoV-2 vaccines, detailed data on B-cell-specific responses in SLE remain scarce. Understanding the responsiveness to novel vaccine antigens, and boosters number, is important to avoid unnecessarily prolonged isolation of immunocompromised individuals. We assessed humoral and antigen-specific B-cell subset responses, including changes in isotype switching, prior to and after several doses of SARS-CoV-2 vaccines.</p><p><strong>Methods: </strong>Blood samples were obtained prior to and after SARS-CoV-2 vaccination from cross-sectional and longitudinal cohorts of previously uninfected patients with SLE (n = 93). Healthy participants receiving SARS-CoV-2 vaccines were recruited as controls (n = 135). We measured serum antibody titres, their neutralizing capacity, and vaccine-specific memory B-cell subsets.</p><p><strong>Results: </strong>Impaired IgG, IgA, and neutralizing responses against the original and various SARS-CoV-2 variants were observed following two doses of vaccine in SLE patients. Follow-up booster doses increased humoral responses compared to baseline, but they remained lower, with poorer neutralisation capacity against most strains, compared to healthy individuals after three or more doses. Analysis of memory B-cell subsets in SLE patients revealed an increase of SARS-CoV-2-specific isotype unswitched IgM+ over SARS-CoV-2-specific isotype switched IgG+/IgA+ memory B-cells compared to healthy individuals. Culturing healthy naive B-cells with high levels of IFNα, a hallmark of SLE pathogenesis, prevented B-cells from switching to IgG under IgG-polarizing conditions.</p><p><strong>Conclusion: </strong>SLE patients' protection against SARS-CoV-2 is overall impaired compared to healthy individuals and is associated with a class switch defect possibly due to chronic exposure of B-cells to IFNα.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806254","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":"In-depth immune profiling of a patient with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2 caused by a novel mutation in ZBTB24.","authors":"Colleen M Roark, Diana Ramírez-Vásquez, Jenniffer Yissel Giron Martinez, Xin Zhen, Alexa N Del Bene, Shannon E Gibson, Megan M Dobrose, Natasha B Halasa, Lizbeth Blancas-Galicia, Ruben Martinez-Barricarte","doi":"10.1093/cei/uxaf016","DOIUrl":"10.1093/cei/uxaf016","url":null,"abstract":"<p><p>Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare genetic disorder characterized by recurrent, severe infections. Mutations in DNA methylation genes such as DNMT3B (ICF1), ZBTB24 (ICF2), CDCA7 (ICF3), and HELLS (ICF4) cause ICF. ICF2 syndrome has been previously described, yet the extent of its clinical presentation and immunological consequences needs to be further elucidated. We describe a patient with a novel homozygous mutation in ZBTB24 (Q375Hfs*3). While infections with extracellular pathogens are frequent in other reported ICF2 patients, our patient also displays infections by intracellular pathogens. At the molecular level, we showed that the novel mutation results in a truncated ZBTB24 protein that disrupts its function in DNA methylation. We thoroughly characterized the immunological consequences of ZBTB24 deficiency using mass cytometry coupled with state-of-the-art computational methods. Our analysis revealed reduced frequencies of natural killer cells and class-switched memory B cell populations in our patient, along with low levels of the immunoglobulin isotypes IgG4 and IgM. Despite observing normal cell frequencies within the T and myeloid compartments, the clinical presentation of this patient suggests a functional defect in immune cells known to be critical to combat intracellular pathogens. Overall, this study expands the clinical and immunological features of ZBTB24 deficiency and highlights the importance of ZBTB24 to the human immune response.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656477","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":"Correction to: Antibody-mediated glomerulonephritis in mice: the role of endotoxin, complement and genetic background.","authors":"","doi":"10.1093/cei/uxaf004","DOIUrl":"10.1093/cei/uxaf004","url":null,"abstract":"","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":"219 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022329","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":"Pneumococcal serotype-specific antibodies in children with recurrent oto-sinopulmonary infections.","authors":"Hanadys Ale, Jose G Calderon, Joshua Gruber, Thomas Taylor, William R Blouin, Vivian P Hernández-Trujillo","doi":"10.1093/cei/uxae086","DOIUrl":"10.1093/cei/uxae086","url":null,"abstract":"<p><p>Low titers to pneumococcal vaccine are a frequent finding in pediatric patients with recurrent oto-sinopulmonary infections. To characterize the pre- and post-immunization antibody trend for each serotype included in the pneumococcal 13-valent conjugate vaccine, in a cohort of pediatric patients with recurrent oto-sinopulmonary infections, this retrospective review identified 182 patients with recurrent oto-sinopulmonary infections (131 required an immune workup and 99 had low pneumococcal titers leading to a pneumococcal 13-valent conjugate vaccine booster). Baseline pneumococcal serotype-specific antibody titers at the initial visit and 6 weeks after the vaccine booster were obtained. An adequate response to the pneumococcal conjugate vaccine was deemed to be a 4-fold increase over baseline and/or a post-immunization titer of 1.3 µg/ml or greater. Overall, The pneumococcal 13-valent conjugate vaccine booster provided a significant improvement in the number of protective titers, increasing from 3.6 serotypes at baseline to 11.1 serotypes at 6 weeks (P < 0.001). This increase correlated with improved clinical outcomes (81% showed no signs of recurrent infection after the first booster and 94% after a second booster). Post-immunization antibody concentrations were significantly higher than at baseline for all serotypes (P < 0.05), and only 8, 9N, and 12F did not exhibit a greater than 4-fold increase (P > 0.05) 6 weeks following booster. There were no differences between patients at different ages in post-immunization titer levels for all serotypes. In pediatric patients with recurrent oto-sinopulmonary infections, an additional pneumococcal booster proved to be effective in the protection of these children against further infections, across all age groups.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388481","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-cell analysis of lung epithelial cells reveals age and cell population-specific responses to SARS-CoV-2 infection in ciliated cells.","authors":"Raven M Osborn, Christopher S Anderson, Justin R Leach, Chin Yi Chu, Stephen Dewhurst, Thomas J Mariani, Juilee Thakar","doi":"10.1093/cei/uxae118","DOIUrl":"https://doi.org/10.1093/cei/uxae118","url":null,"abstract":"<p><strong>Introduction: </strong>The ability of SARS-CoV-2 to evade antiviral immune signaling in the airway contributes to the severity of COVID-19 disease. Additionally, COVID-19 is influenced by age and has more severe presentations in older individuals. This raises questions about innate immune signaling as a function of lung development and age.</p><p><strong>Method: </strong>Therefore, we investigated the transcriptome of different cell populations of the airway epithelium using pediatric and adult lung tissue samples from the LungMAP Human Tissue Core Biorepository. Specifically, lung lobes were digested and cultured into a biomimetic model of the airway epithelium on an air-liquid interface. Cells were then infected with SARS-CoV-2 and subjected to single-cell RNA sequencing. Transcriptional profiling and differential expression analysis were carried out using Seurat.</p><p><strong>Results: </strong>The clustering analysis identified several cell populations: club cells, proliferating epithelial cells, multiciliated precursor cells, ionocytes, and two biologically distinct clusters of ciliated cells (FOXJ1high and FOXJ1low). Interestingly, the two ciliated cell clusters showed different infection rates and enrichment of processes involved in ciliary biogenesis and function; we observed a cell-type-specific suppression of innate immunity in infected cells from the FOXJ1low subset. We also identified a significant number of genes that were differentially expressed in lung cells derived from children as compared to adults, suggesting the differential pathogenesis of SARS-CoV-2 infection in children versus adults.</p><p><strong>Conclusion: </strong>We discuss how this work can be used to identify drug targets to modulate molecular signaling cascades that mediate an innate immune response and begin to understand differences in COVID-19 outcomes for pediatric vs. adult populations.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945589","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":"A multi-centre UK-based survey on angioedema secondary to acquired C1 inhibitor deficiency.","authors":"Hadeil Morsi, Aarnoud Huissoon, Alexandros Grammatikos, Andrew Whyte, Ania Manson, Anjali Ekbote, Anju Sivadasan, Anne Pacita Rosillo Boulton, Archana Herwadkar, Ariharan Anantharachagan, Arthur Price, Cathal Steele, Catherine Stroud, Charu Chopra, Dilani Arnold, Efrem Eren, Elizabeth Cleave, Elizabeth Drewe, Emily Moon, Emily Zinser, Grant Hayman, Hana Alachkar, Harichandana Ghanta, Helen Bourne, Intisar Abdelhakam, John Dempster, Katie Townsend, Kavitha Sooriyakumar, Lorena Lorenzo, Magdalena Dziadzio, Manisha Ahuja, Maria Prasinou, Marina Frleta-Gilchrist, Michael Zhang, Moira Thomas, Pavaladurai Vijayadurai, Prashantha Madhuri Vaitla, Ravishankar Sargur, Richard Herriot, Robert L Yellon, Sai Hurng Kham Murng, Sara Drinkwater, Sarah Denness, Sarah Denman, Shuayb Elkhalifa, Sinisa Savic, Sorena Kiani-Alikhan, Tanya I Coulter, Tariq El-Shanawany, Tasneem Rahman, Tomaz Garcez, Patrick F K Yong, Rashmi Jain","doi":"10.1093/cei/uxae121","DOIUrl":"https://doi.org/10.1093/cei/uxae121","url":null,"abstract":"<p><strong>Background: </strong>Acquired angioedema due to C1-inhibitor deficiency (AAE-C1-INH) is very rare compared to its prototype, hereditary angioedema. An updated characterisation of the AAE-C1-INH cohort in UK is required to inform management.</p><p><strong>Objectives: </strong>To describe the disease burden of AAE-C1-INH, long-term prophylaxis (LTP) and the clinical, immunochemical and treatment profiles of AAE-associated diseases in UK.</p><p><strong>Method: </strong>Retrospective data on 117 AAE-C1-INH patients were collected using a national survey proforma across 25/34 Adult Clinical Immunology and Allergy centres in UK. Other European cohorts were compared.</p><p><strong>Results: </strong>Median age at AAE-C1-INH diagnosis was 65 years with 3.4% of patients diagnosed below 40 years. The median delay in diagnosis was one year. Antifibrinolytics and attenuated androgens showed comparable efficacy as LTP 88.9% and 89.5%, respectively. A haematological disorder was identified in 83.8% AAE-C1-INH patients compared to 3.4% autoimmune diseases. The predominant haematological disorders were splenic marginal zone lymphoma (SZL) 34% followed by MGUS 16%. The severity of angioedema did not depend on the associated disease. Anti-C1INH-autoantibodies testing was limited at 23.1%. Rituximab monotherapy was effective in treating 9/9 SZL and 1/2 MGUS-associated AAE-C1-INH. Rituximab efficacy was independent of anti-C1INH-autoantibodies detection with response in 3/3 seronegative and 4/4 seropositive patients.</p><p><strong>Conclusion: </strong>The diagnosis of AAE-C1-INH should not be overlooked below the age of 40 years. The choice of oral LTP should be informed by propensity to side-effects. B-cell depletion could be considered in treating monoclonal B cell disorder-associated-AAE-C1-INH in the absence of haematological indications. Further studies are required to address the clinical utility of anti-C1INH-autoantibodies.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930715","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":"My highlights as Editor-in-Chief of Clinical & Experimental Immunology, 2017-2024.","authors":"Leonie Taams","doi":"10.1093/cei/uxae112","DOIUrl":"https://doi.org/10.1093/cei/uxae112","url":null,"abstract":"","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806251","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":"A homogeneous bioluminescent inhibition immunoassay to detect anti-interferon gamma antibodies.","authors":"Peter Bradhurst, Alex Stoyanov, Arnone Nithichanon, Christine Bundell, Nicolás Urriola","doi":"10.1093/cei/uxae055","DOIUrl":"10.1093/cei/uxae055","url":null,"abstract":"<p><p>Adult-onset immunodeficiency with antibodies to interferon-γ (AOID with AIGA) is a rare, acquired immunodeficiency causing susceptibility to disseminated non-tuberculous mycobacteria and other intracellular opportunistic infections. The diagnosis depends on demonstrating the presence of endogenous anti-interferon-γ antibodies (AIGA) that suppress Th1 cell-mediated immunity. Bioluminescent immunoassays are a newly emerging immunoassay format which utilize the action of bioluminescent enzymes on a substrate for specific analyte detection. In short, detecting antibodies are conjugated with a bioluminescent enzyme. The detecting antibodies bind the analyte of interest and produce light (luminescence) after addition of a substrate. The purpose of this study was to evaluate two newly developed bioluminescent immunoassays using Lumit® (Promega) technology as a diagnostic test for AOID with AIGA. Specific aims included the clinical validation of a new inhibition bioluminescent immunoassay technique to detect AIGA which block detection of interferon-γ (IFN-γ) in vitro and correlation of inhibition bioluminescent immunoassay results with AOID with AIGA disease status. Two bioluminescent inhibition immunoassays were developed. One which adapted an existing kit from Promega (Lumit® Human IFN-γ Immunoassay) and the other which was developed in house. Eighty-seven healthy controls and 48 patients with previously diagnosed AOID with AIGA were recruited and tested using these two methods. Results showed both bioluminescent inhibition immunoassays were able to clearly discriminate between AOID with AIGA patients and healthy controls. The mean inhibition percentage between patient groups correlated with disease activity. Both assays appeared to be more sensitive when compared to the existing inhibition ELISA.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":"283-290"},"PeriodicalIF":3.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554236","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":"Unveiling immunological signatures and predictors of response to immunosuppressive therapy in acquired aplastic anemia.","authors":"Maya Gupta, Chandrakala Shanmukhaiah, Babu Rao Vundinti, Amrutha Jose, Shashank Tiwari, Amiya Bhowmick, Manisha Madkaikar","doi":"10.1093/cei/uxae076","DOIUrl":"10.1093/cei/uxae076","url":null,"abstract":"<p><p>Acquired aplastic anemia (AA) often results from immune destruction of hematopoietic stem and progenitor cells. However, only 60%-70% of patients with AA respond to immunosuppressive therapy (IST). There is a lack of strong predictive markers for response to IST which can help therapy. Our study sought to pinpoint unique immune markers in AA patients and validate established predictors for response to IST. We enrolled 51 severe AA patients and analyzed 57 immunological parameters via flow cytometry. Additionally, we measured paroxysmal nocturnal hemoglobinuria (PNH) clone, telomere length, and thrombopoietin (TPO) levels prior to IST. After a 6-month follow-up, a response was observed. Patients with AA had a distinct immunological signature characterized by absolute lymphopenia, skewed CD4/CD8 ratio with expansion of CD8 T cells with activated and senescent phenotype. Treg counts were reduced, while the proportion of Treg A and B was comparable to controls. Treatment response was correlated with elevated absolute neutrophil count (ANC), absolute reticulocyte count (ARC), and reduced CD57+ CD8+ naive cells and B cell % before therapy. However, predictors like TPO, telomere length, and PNH did not emerge as indicators of treatment response. Identifying predictors for treatment response in AA is challenging due to abnormal hematopoiesis, genetic mutations, and treatment variables.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":"291-299"},"PeriodicalIF":3.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970765","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":"The immune landscape of the inflamed joint defined by spectral flow cytometry.","authors":"Meryl H Attrill, Diana Shinko, Vicky Alexiou, Melissa Kartawinata, Lucy R Wedderburn, Anne M Pesenacker","doi":"10.1093/cei/uxae071","DOIUrl":"10.1093/cei/uxae071","url":null,"abstract":"<p><p>Cellular phenotype and function are altered in different microenvironments. For targeted therapies it is important to understand site-specific cellular adaptations. Juvenile idiopathic arthritis (JIA) is characterized by autoimmune joint inflammation, with frequent inadequate treatment responses. To comprehensively assess the inflammatory immune landscape, we designed a 37-parameter spectral flow cytometry panel delineating mononuclear cells from JIA synovial fluid (SF) of autoimmune inflamed joints, compared to JIA and healthy control blood. Synovial monocytes and NK cells (CD56bright) lack Fc-receptor CD16, suggesting antibody-mediated targeting may be ineffective. B cells and DCs, both in small frequencies in SF, undergo maturation with high 4-1BB, CD71, CD39 expression, supporting T-cell activation. SF effector and regulatory T cells were highly active with newly described co-receptor combinations that may alter function, and suggestion of metabolic reprogramming via CD71, TNFR2, and PD-1. Most SF effector phenotypes, as well as an identified CD4-Foxp3+ T-cell population, were restricted to the inflamed joint, yet specific SF-predominant CD4+ Foxp3+ Treg subpopulations were increased in blood of active but not inactive JIA, suggesting possible recirculation and loss of immunoregulation at distal sites. This first comprehensive dataset of the site-specific inflammatory landscape at protein level will inform functional studies and the development of targeted therapeutics to restore immunoregulatory balance and achieve remission in JIA.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":"221-241"},"PeriodicalIF":3.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888657","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}