Clinical immunology最新文献

{"title":"Optimizing iNKT-driven immune responses against cancer by modulating CD1d in tumor and antigen presenting cells","authors":"Ritis Kumar Shyanti ,&nbsp;Mazharul Haque ,&nbsp;Rajesh Singh ,&nbsp;Manoj Mishra","doi":"10.1016/j.clim.2024.110402","DOIUrl":"10.1016/j.clim.2024.110402","url":null,"abstract":"<div><div>Two major antigen processing pathways represent protein Ags through major histocompatibility complexes (MHC class I and II) or lipid Ags through CD1 molecules influence the tumor immune response. Invariant Natural Killer T cells (iNKT) manage a significant role in cancer immunotherapy. CD1d, found on antigen-presenting cells (APCs), presents lipid Ags to iNKT cells. In many cancers, the number and function of iNKT cell are compromised, leading to immune evasion. Additionally impaired motility of iNKT cells may contribute to poor tumor prognosis. Emerging evidences suggest that CD1d, itself also influences cancer progression. Patient databases further highlight the importance of CD1d expression in different cancers and its correlation with patient survival outcomes. The ability of iNKT cells to activate and enhance the immune response renders them an attractive target for cancer immunotherapy. This review discusses all the possible ways of cancer immune evasion and restoration of immune responses mediated by CD1d-iNKT interactions.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"269 ","pages":"Article 110402"},"PeriodicalIF":4.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674987","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":"HLA evolutionary divergence effect on bacterial infection risk in cirrhotic liver transplant candidates","authors":"Alessandra Mazzola ,&nbsp;Clémentine Roger ,&nbsp;Romain Lhotte ,&nbsp;Maxime Mallet ,&nbsp;Dominique Thabut ,&nbsp;Jean-Luc Taupin ,&nbsp;Filomena Conti","doi":"10.1016/j.clim.2024.110399","DOIUrl":"10.1016/j.clim.2024.110399","url":null,"abstract":"<div><div>Bacterial infections are common in cirrhosis patients, increasing the risk of decompensation and death. The impact of HLA evolutionary divergence (HED) on infection risk hasn't been studied in humans before. We conducted a retrospective study on cirrhosis patients awaiting liver transplantation (LT) from January 2019 to February 2022, examining class I and II-HED effects on bacterial infections and cirrhosis decompensation.</div><div>We included 269 cirrhosis patients. Among them, 98 experienced 153 bacterial infections. Multivariable analysis after variable selection revealed that higher class II-HED was linked to fewer bacterial infections (<em>p</em> = 0.034), while class I-HED showed no effect (<em>p</em> = 0.074). Independent risk factors for bacterial infections included invasive procedures (<em>p</em> &lt; 0.001), ICU hospitalization (p &lt; 0.001), recent antibiotic treatment (<em>p</em> = 0.046), rifaximin use (<em>p</em> = 0.043), and cirrhosis decompensation (<em>p</em> = 0.002). Neither class I nor II-HED affected decompensation risk.</div><div>This pioneering study shows that high class II-HED levels may protect against bacterial infections in cirrhosis patients awaiting LT, suggesting an immunological mechanism at play.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"270 ","pages":"Article 110399"},"PeriodicalIF":4.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674736","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":"Clinical characterization of NOD2 variants in patients with common variable immunodeficiency","authors":"Ashley Sang Eun Lee ,&nbsp;Jin Feng ,&nbsp;Alp Kazancioglu ,&nbsp;Charlotte Cunningham-Rundles","doi":"10.1016/j.clim.2024.110401","DOIUrl":"10.1016/j.clim.2024.110401","url":null,"abstract":"","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"270 ","pages":"Article 110401"},"PeriodicalIF":4.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674732","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 randomised, placebo-controlled, phase III trial of leniolisib in activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS): Adolescent and adult subgroup analysis","authors":"V. Koneti Rao ,&nbsp;Anna Šedivá ,&nbsp;Virgil A.S.H. Dalm ,&nbsp;Alessandro Plebani ,&nbsp;Catharina Schuetz ,&nbsp;Anna Shcherbina ,&nbsp;Antonino Trizzino ,&nbsp;Yulia Zharankova ,&nbsp;Alanvin Orpia ,&nbsp;Elaine Kulm ,&nbsp;Sharon Webster ,&nbsp;Julia Körholz ,&nbsp;Vassilios Lougaris ,&nbsp;Yulia Rodina ,&nbsp;Niall Conlon ,&nbsp;Tanya Coulter ,&nbsp;Jason Bradt ,&nbsp;Anurag Relan ,&nbsp;Gulbu Uzel","doi":"10.1016/j.clim.2024.110400","DOIUrl":"10.1016/j.clim.2024.110400","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) is an ultra-rare, progressive genetic disease, characterised by immune deficiency and dysregulation, affecting individuals from birth. In a 12-week phase III randomised placebo-controlled trial, leniolisib, a selective PI3Kδ inhibitor, was well-tolerated and met both co-primary endpoints (change from Baseline in log&lt;sub&gt;10&lt;/sub&gt;-transformed sum of product of diameters of index lymph nodes and percentage of naïve/total B cells at Day 85). Here, prespecified subgroup analyses are reported in adolescents aged 12–17 years (leniolisib, &lt;em&gt;n&lt;/em&gt; = 8; placebo, &lt;em&gt;n&lt;/em&gt; = 4) and adults aged ≥18 (leniolisib, &lt;em&gt;n&lt;/em&gt; = 13; placebo, &lt;em&gt;n&lt;/em&gt; = 6). In both subgroups, leniolisib reduced lymphadenopathy (least squares mean change versus placebo: adolescents, −0.4 versus −0.1; adults, −0.3 versus 0.1) and increased the percentage of naïve B cells (least squares mean change: adolescents, 44.5 versus −16.5; adults, 28.4 versus −1.1). Leniolisib was well-tolerated in both adolescents and adults. These results show leniolisib is an effective APDS treatment in both subpopulations.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Plain Language Summary&lt;/h3&gt;&lt;div&gt;&lt;em&gt;What is activated PI3Kδ syndrome (APDS)?&lt;/em&gt;&lt;/div&gt;&lt;div&gt;APDS is an ultra-rare disease in which the immune system does not work correctly. People with APDS have a wide range of symptoms, including infections, certain organs associated with the immune system becoming larger, and worse quality of life. These symptoms generally start in childhood.&lt;/div&gt;&lt;div&gt;&lt;em&gt;Why was this study carried out?&lt;/em&gt;&lt;/div&gt;&lt;div&gt;Current treatments only treat the symptoms of APDS, rather than correcting the cause of the problem. These treatments can also have significant side effects. A new medication for APDS called leniolisib aims to treat the underlying cause of the disease. This publication reports results from a clinical trial of leniolisib which compared patients who received leniolisib with patients who received a placebo. The aim of this report was to examine these clinical trial results to understand if leniolisib is effective and safe when treating both adolescents (12–17 years old) and adults (18 years and older) with APDS.&lt;/div&gt;&lt;div&gt;&lt;em&gt;What were the results of this study?&lt;/em&gt;&lt;/div&gt;&lt;div&gt;Leniolisib improved the number of certain immune cells, compared to patients who did not receive leniolisib, in both adolescents and adults with APDS. Leniolisib also reduced the size of the enlarged immune system organs in both adolescents and adults with APDS. There were no major safety concerns for either age group who received leniolisib.&lt;/div&gt;&lt;div&gt;&lt;em&gt;What do these results mean?&lt;/em&gt;&lt;/div&gt;&lt;div&gt;These results show that leniolisib can help the immune system to work in a way that is closer to those without APDS. This new treatment is effective and generally well-tolerated for both adolescents and adults. These results indicate that people with APDS are able to start treatment with ","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"270 ","pages":"Article 110400"},"PeriodicalIF":4.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674727","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":"IL-1β mediated fibroblast-neutrophil crosstalk promotes inflammatory environment in skin lesions of SLE","authors":"Xiaoyun Chen ,&nbsp;Lianlian OuYang ,&nbsp;Bao Qian ,&nbsp;Yueqi Qiu ,&nbsp;Limin Liu ,&nbsp;Fangqi Chen ,&nbsp;Wenjuan Jiang ,&nbsp;Meiling Zheng ,&nbsp;Zhi Hu ,&nbsp;Xiaoli Min ,&nbsp;Lifang Wen ,&nbsp;Qiaolin Wang ,&nbsp;Di Yu ,&nbsp;Sujie Jia ,&nbsp;Qianjin Lu ,&nbsp;Ming Zhao","doi":"10.1016/j.clim.2024.110396","DOIUrl":"10.1016/j.clim.2024.110396","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is characterized by immune dysregulation, with neutrophil infiltration in skin lesions contributing to inflammation and disease progression. However, the interaction between fibroblasts and neutrophils in SLE skin lesions has not been fully explored. Using single-cell RNA sequencing, we identified a unique CXCL1⁺ fibroblast subset in SLE lesions. We found that CXCL1⁺ fibroblasts recruit and activate neutrophils, increasing the production of inflammatory mediators, reactive oxygen species, and neutrophil extracellular traps. These fibroblasts also facilitated the transition of neutrophils to a low-density phenotype. Notably, these fibroblasts delayed neutrophil apoptosis, extending their survival and amplifying inflammation. Serum amyloid A1, secreted by CXCL1⁺ fibroblasts, emerged as a key activator of neutrophils. Activated neutrophils, in turn, secreted IL-1β to induce CXCL1⁺ fibroblasts differentiation via activating the NF-κB pathway. In conclusion, our findings reveal that IL-1β-induced CXCL1⁺ fibroblasts significantly modulate pro-inflammatory neutrophils, underscoring the critical crosstalk between fibroblasts and neutrophils in SLE pathogenesis.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"269 ","pages":"Article 110396"},"PeriodicalIF":4.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616142","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":"Assessing humoral immunity in daily practice: A retrospective study in a pediatric tertiary center","authors":"Isabel Fernandez ,&nbsp;Hélène Decaluwe ,&nbsp;Jean-Jacques DeBruycker ,&nbsp;Elie Haddad ,&nbsp;Fabien Touzot","doi":"10.1016/j.clim.2024.110395","DOIUrl":"10.1016/j.clim.2024.110395","url":null,"abstract":"<div><div>The evaluation of humoral immunity is usually performed through the assessment of serum immunoglobulin levels, vaccine titer responses, and B-cell enumeration and phenotyping. We performed a retrospective study assessing humoral immunity in 469 pediatric patients referred at the Sainte-Justine University Hospital Center. Almost half of the patients had at least one abnormal humoral immunological parameter at their evaluation, with low vaccine response titer to protein antigen being the most frequent. Fifteen patients (3.2 %) had a proven monogenic IEI, and 21 patients (4.5 %) required Ig replacement. Besides the infectious burden, hypoIgG remains the only parameter associated with Ig replacement therapy after the age of 6 years. Low antibody titers against conjugate vaccines had low sensitivity and positive predictive values for starting Ig replacement. Our study highlights the challenge of evaluating the humoral function in the pediatric population with suspected IEI with significant age and sex-dependent variability between parameters.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"269 ","pages":"Article 110395"},"PeriodicalIF":4.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616144","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":"Carrier frequency and incidence estimation of deficiency of adenosine deaminase 2 in the Chinese population based on massive exome sequencing data","authors":"Lulu Yan ,&nbsp;Xiangwei Sun ,&nbsp;Biying Lou ,&nbsp;Yuxin Zhang ,&nbsp;Danyan Zhuang ,&nbsp;Jia Jia ,&nbsp;Li Zhang ,&nbsp;Yan He ,&nbsp;Limin Xu ,&nbsp;Shanshan Wu ,&nbsp;Qing Zhou ,&nbsp;Changshui Chen ,&nbsp;Xiaomin Yu ,&nbsp;Haibo Li","doi":"10.1016/j.clim.2024.110394","DOIUrl":"10.1016/j.clim.2024.110394","url":null,"abstract":"<div><div>Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disease characterised by early onset stroke, recurrent fever, and diverse vascular pathologies, caused by loss-of-function homozygous or compound heterozygous variants of <em>ADA2</em>. This research aimed to determine the carrier frequency and expected incidence of DADA2 in China, using massive exome sequencing (ES) data. A total of 50 likely pathogenic/pathogenic variants (LP/PVs) were identified among 69,413 Chinese individuals, including 20 novel and rare variants (&lt;0.0022 % allele frequency), expanding the known spectrum of PVs in <em>ADA2</em>. The overall carrier frequency in the Chinese population was 1.05 % (732/69,413) and the estimated incidence of DADA2 was approximately one in 92,251 individuals. The present study provides an accurate estimation of the prevalence of DADA2 in China, supporting genetic counseling, early diagnosis treatment, and prognostic evaluation.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"269 ","pages":"Article 110394"},"PeriodicalIF":4.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557310","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":"Aberrant overexpression of the autoantigen protein vimentin promotes Th17 cell differentiation and autoimmune arthritis via activation of STAT3 signaling","authors":"Seon-Yeong Lee ,&nbsp;Young-Mee Moon ,&nbsp;Eun-Kyung Kim ,&nbsp;A Ram Lee ,&nbsp;Su Been Jeon ,&nbsp;Chae Rim Lee ,&nbsp;Jeong Won Choi ,&nbsp;Mi-La Cho","doi":"10.1016/j.clim.2024.110383","DOIUrl":"10.1016/j.clim.2024.110383","url":null,"abstract":"<div><div>Vimentin contributes to the positioning and function of organelles, cell migration, adhesion, and division. However, secreted vimentin accumulates on the cell surface (Mor-Vaknin et al., 2003; Ramos et al., 2020 [<span><span>1</span></span>,<span><span>2</span></span>]) where it acts as a coreceptor for viral infection and as an autoantigen in inflammatory and autoimmune diseases. The roles of vimentin in Th17 cells were examined in mice with knockdown of vimentin. We also examined whether STAT3 is required for vimentin expression.</div><div>Vimentin expression was significantly increased in Th17 cells through STAT3 activation, and vimentin⁺ IL-17⁺ T cells were markedly increased in the joint and spleen tissues of CIA mice. The arthritis score and expression levels of proinflammatory cytokines were significantly decreased in CIA mice treated with vimentin shRNA vector.</div><div>In this study, we demonstrated that vimentin is significantly expressed in Th17 cells through STAT3 activation. Our results provide new insights into the role of vimentin in Th17 cells and the complex pathogenesis of RA.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"269 ","pages":"Article 110383"},"PeriodicalIF":4.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496320","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":"Characterization of primary Sjögren's syndrome in the Taiwan Han population through a genome-wide association study and polygenic risk score analysis","authors":"Ting-Yuan Liu ,&nbsp;Min-Rou Lin ,&nbsp;Hsing-Fang Lu ,&nbsp;Yu-Chia Chen ,&nbsp;Hui-Ju Lin ,&nbsp;Wan-Hsuan Chou ,&nbsp;Chun-Yu Wei ,&nbsp;Poppy Diah Palupi ,&nbsp;Chi-Chou Liao ,&nbsp;Yen-Ting Chang ,&nbsp;Wei-Chiao Chang ,&nbsp;Fuu-Jen Tsai","doi":"10.1016/j.clim.2024.110381","DOIUrl":"10.1016/j.clim.2024.110381","url":null,"abstract":"<div><h3>Background</h3><div>Sjögren's syndrome (SS) is an autoimmune disorder that primarily affects the exocrine glands, leading to dryness of mucous membranes and systemic manifestations. This study aimed to identify genetic markers associated with primary SS (pSS) in the Taiwan Han population through a hospital-based genome-wide association study (GWAS) and polygenic risk score (PRS) analysis, addressing the lack of genetic research.</div></div><div><h3>Results</h3><div>This study included 11,390 patients diagnosed with pSS and 113,900 controls. GWAS identified one known locus and eight novel loci. Known HLA alleles, including HLA-DRB1*15:01 and HLA-DQA1*03:01, were successfully replicated in a consistent effect direction. PRS analysis revealed that several autoimmune diseases share similar genetic backgrounds with pSS, including rheumatoid arthritis and systemic lupus erythematosus.</div></div><div><h3>Conclusion</h3><div>This study represents the largest cohort to date on the genetics of pSS in the Taiwan Han population. Our findings provide valuable insights into the pathogenesis of pSS and emphasize the comorbidities associated with it as an autoimmune disease.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"269 ","pages":"Article 110381"},"PeriodicalIF":4.5,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496321","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":"DOCK8 deficiency due to a deep intronic variant in two kindreds with hyper-IgE syndrome","authors":"Fatma Betul Oktelik ,&nbsp;Muyun Wang ,&nbsp;Sevgi Keles ,&nbsp;Hatice Eke Gungor ,&nbsp;Murat Cansever ,&nbsp;Salim Can ,&nbsp;Elif Karakoc-Aydiner ,&nbsp;Safa Baris ,&nbsp;Klaus Schmitz-Abe ,&nbsp;Mehdi Benamar ,&nbsp;Talal A. Chatila","doi":"10.1016/j.clim.2024.110384","DOIUrl":"10.1016/j.clim.2024.110384","url":null,"abstract":"<div><div>Dedicator of cytokinesis 8 (DOCK8) deficiency underlies the majority of cases of patients with autosomal recessive form of the hyper-immunoglobulin E syndrome (HIES). Most <em>DOCK8</em> mutations involve deletions and splice junction mutations that abrogate protein expression. However, a few patients whose presentation is reminiscent of DOCK8 deficiency have no identifiable mutations. Using Whole Exome Sequencing (WES), we identified a deep intronic homozygous <em>DOCK8</em> variant located in intron 36 (c.4626 + 76 A &gt; G) in two unrelated patients with features of HIES that resulted in an in-frame 75 base pair intronic sequence insertion in <em>DOCK8</em> cDNA, resulting in a premature stop codon (p.S1542ins6Ter). This variant resulted in variable decrease in DOCK8 expression that was associated with impaired T cell receptor-triggered actin polymerization, decreased IL-6-induced STAT3 phosphorylation, reduced expression of the Th17 cell markers CCR6 and IL-17, and higher frequencies of GATA3⁺ T cells indicative of Th2 skewing. Our approach extends the reach of WES in identifying disease-related intronic variants. It highlights the role of non-coding mutations in immunodeficiency disorders, including DOCK8 deficiency, and emphasizes the need to explore these mutations in unexplained inborn errors of immunity.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"268 ","pages":"Article 110384"},"PeriodicalIF":4.5,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496322","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}