{"title":"Allergic bronchopulmonary aspergillosis in a lung transplant recipient treated with mepolizumab","authors":"Foteini Ioakeim , Christophe Abellan , Alessio Casutt , Benoit Lechartier , Leslie Noirez , Catherine Beigelman-Aubry , John-David Aubert , Zisis Balmpouzis , Angela Koutsokera","doi":"10.1016/j.clim.2024.110265","DOIUrl":"10.1016/j.clim.2024.110265","url":null,"abstract":"<div><p>Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to <em>Aspergillus</em> spp. ABPA diagnosis may be challenging due to its non-specific presentation. Standard ABPA treatment consists of systemic corticosteroids and antifungal agents. Mepolizumab, a monoclonal antibody against interleukin-5 seems to be a promising treatment for ABPA. Data about ABPA following lung transplantation (LuTx) are scarce. LuTx recipients are at higher risk for adverse effects of ABPA treatment compared to the general population.</p><p>Here we present a case of a LuTx recipient who was successfully treated with mepolizumab for ABPA following LuTx. Prolonged administration of high dose prednisone was thus avoided. To our knowledge, this is the first case describing mepolizumab administration following LuTx. Mepolizumab seems particularly attractive as a corticosteroid-sparing agent or as an alternative option to antifungal treatments, because of its excellent safety profile and low risk of drug interactions.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157536","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}
Salem Al-Tamemi , Abdulhakim Al-Rawas , Murtadha Al-Khabori , Khalil Al-Farsi , Mohammed Al-Huneini , Amr Abdalla , Salam Al-Kindi , David Dennison
{"title":"Immune reconstitution and survival, following hematopoietic stem cell transplantation in Omani patients with inborn errors of immunity","authors":"Salem Al-Tamemi , Abdulhakim Al-Rawas , Murtadha Al-Khabori , Khalil Al-Farsi , Mohammed Al-Huneini , Amr Abdalla , Salam Al-Kindi , David Dennison","doi":"10.1016/j.clim.2024.110263","DOIUrl":"10.1016/j.clim.2024.110263","url":null,"abstract":"<div><h3>Background</h3><p>Hematopoietic stem cell transplantation (HSCT) is a curative treatment for certain inborn errors of immunity.</p></div><div><h3>Methods</h3><p>A 17-year retrospective cohort study was conducted on 40 immunodeficient patients who underwent HSCT.</p></div><div><h3>Results</h3><p>The median age at transplant was 11.0 months (4.6–61.0). Donors were primarily matched sibling donors (60%). 90% and 85% of patients received conditioning and graft-versus-host disease (GVHD) prophylaxis, respectively. The mean donor chimerism at the last follow-up was 88.6% ± 17.9% (40–100). Median serum immunoglobulin (Ig) G level, CD4+ T-cell count, and CD19+ B-cell count were 11.7 g/L (9.2–13.6), 0.9 × 10<sup>9</sup>/L 0.6–1.2), and 0.5 × 10<sup>9</sup>/L (0.2–0.7), respectively. 29 patients (72.5%) received intravenous immunoglobulins (IVIG) therapy, with a median duration of 10.0 months (4.0–14.0). The median post-transplant follow-up was 6.5 years (IQR:1.4–11.5). The 10-year overall probability of survival is 84.3%.</p></div><div><h3>Conclusion</h3><p>Monitoring IRC is important in ensuring adequate disease-free survival.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141141525","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}
Sahla El Mahdaoui , Marie Mathilde Hansen , Malene Bredahl Hansen , Victoria Hyslop Hvalkof , Helle Bach Søndergaard , Mie Reith Mahler , Jeppe Romme Christensen , Finn Sellebjerg , Marina Rode von Essen
{"title":"Effects of anti-CD20 therapy on circulating and intrathecal follicular helper T cell subsets in multiple sclerosis","authors":"Sahla El Mahdaoui , Marie Mathilde Hansen , Malene Bredahl Hansen , Victoria Hyslop Hvalkof , Helle Bach Søndergaard , Mie Reith Mahler , Jeppe Romme Christensen , Finn Sellebjerg , Marina Rode von Essen","doi":"10.1016/j.clim.2024.110262","DOIUrl":"10.1016/j.clim.2024.110262","url":null,"abstract":"<div><p>Follicular helper T (Tfh) cells and their interplay with B cells likely contribute to the pathogenesis of relapsing-remitting multiple sclerosis (RRMS). Tfh cells are enriched in cerebrospinal fluid (CSF) in RRMS, but effects of anti-CD20 therapy are unknown. We investigated Tfh cells in controls, untreated and anti-CD20-treated patients with RRMS using flow cytometry. CSF Tfh cells were increased in untreated patients. Compared to paired blood samples, CD25<sup>−</sup> Tfh cells were enriched in CSF in RRMS, but not in controls. Contrast-enhancing brain MRI lesions and IgG index correlated with CSF CD25<sup>−</sup> Tfh cell frequency in untreated patients with RRMS. Anti-CD20 therapy reduced the numbers of circulating PD1<sup>+</sup> Tfh cells and CD25<sup>−</sup> Tfh cells, and the frequency of CSF CD25<sup>−</sup> Tfh cells. The study suggests that CD25<sup>−</sup> Tfh cells are recruited to the CSF in RRMS, associated with focal inflammation, and are reduced by anti-CD20 therapy.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624003711/pdfft?md5=067c9241e5b14c9188b12b45b28eafd8&pid=1-s2.0-S1521661624003711-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141092672","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}
Ubaid Ullah Kalim , Rahul Biradar , Sini Junttila , Mohd Moin Khan , Subhash Tripathi , Meraj Hasan Khan , Johannes Smolander , Kartiek Kanduri , Tapio Envall , Asta Laiho , Alexander Marson , Omid Rasool , Laura L. Elo , Riitta Lahesmaa
{"title":"A proximal enhancer regulates RORA expression during early human Th17 cell differentiation","authors":"Ubaid Ullah Kalim , Rahul Biradar , Sini Junttila , Mohd Moin Khan , Subhash Tripathi , Meraj Hasan Khan , Johannes Smolander , Kartiek Kanduri , Tapio Envall , Asta Laiho , Alexander Marson , Omid Rasool , Laura L. Elo , Riitta Lahesmaa","doi":"10.1016/j.clim.2024.110261","DOIUrl":"10.1016/j.clim.2024.110261","url":null,"abstract":"<div><p>Gene regulatory elements, such as enhancers, greatly influence cell identity by tuning the transcriptional activity of specific cell types. Dynamics of enhancer landscape during early human Th17 cell differentiation remains incompletely understood. Leveraging ATAC-seq-based profiling of chromatin accessibility and comprehensive analysis of key histone marks, we identified a repertoire of enhancers that potentially exert control over the fate specification of Th17 cells. We found 23 SNPs associated with autoimmune diseases within Th17-enhancers that precisely overlapped with the binding sites of transcription factors actively engaged in T-cell functions. Among the Th17-specific enhancers, we identified an enhancer in the intron of RORA and demonstrated that this enhancer positively regulates RORA transcription. Moreover, CRISPR-Cas9-mediated deletion of a transcription factor binding site-rich region within the identified RORA enhancer confirmed its role in regulating RORA transcription. These findings provide insights into the potential mechanism by which the RORA enhancer orchestrates Th17 differentiation.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S152166162400370X/pdfft?md5=ec84d01de2fe59f7a407e8d211a2b03c&pid=1-s2.0-S152166162400370X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141092671","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}
Ivy L. Debreceni , Jennifer Y. Barr , Ellen M. Upton , Yi-Guang Chen , Scott M. Lieberman
{"title":"IL-27 promotes pathogenic T cells in a mouse model of Sjögren's disease","authors":"Ivy L. Debreceni , Jennifer Y. Barr , Ellen M. Upton , Yi-Guang Chen , Scott M. Lieberman","doi":"10.1016/j.clim.2024.110260","DOIUrl":"https://doi.org/10.1016/j.clim.2024.110260","url":null,"abstract":"<div><p>Sjögren's disease (SjD) is a chronic autoimmune disease characterized by focal lymphocytic inflammation in lacrimal and salivary glands. We recently identified IL-27 as a requisite signal for the spontaneous SjD-like manifestations in nonobese diabetic (NOD) mice. Here, we define T cell-intrinsic effects of IL-27 in lacrimal gland disease in NOD mice. IL-27 receptor was required by both CD4 T effector (Te) cells and CD8 T cells to mediate focal inflammation. Intrinsic IL-27 signaling was associated with PD-1 and ICOS expressing T follicular helper (Tfh)-like CD4 Te cells within lacrimal glands, including subsets defined by CD73 or CD39 expression. CD8 T cells capable of IL-27 signaling also expressed PD-1 with subsets expressing ICOS and CD73 demonstrating a T follicular cytotoxic (Tfc)-like cell phenotype and others expressing a CD39<sup>hi</sup> exhausted-like phenotype. These findings suggest IL-27 is a key early signal driving a follicular-type response in lacrimal gland inflammation in NOD mice.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141090966","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":"Itaconate reduces proliferation and migration of fibroblast-like synoviocytes and ameliorates arthritis models","authors":"Maria Tada , Yuki Kudo , Michihito Kono , Masatoshi Kanda , Shuhei Takeyama , Kodai Sakiyama , Hotaka Ishizu , Tomohiro Shimizu , Tsutomu Endo , Ryo Hisada , Yuichiro Fujieda , Masaru Kato , Olga Amengual , Norimasa Iwasaki , Tatsuya Atsumi","doi":"10.1016/j.clim.2024.110255","DOIUrl":"10.1016/j.clim.2024.110255","url":null,"abstract":"<div><p>Fibroblast-like synoviocytes (FLS) play critical roles in rheumatoid arthritis (RA). Itaconate (ITA), an endogenous metabolite derived from the tricarboxylic acid (TCA) cycle, has attracted attention because of its anti-inflammatory, antiviral, and antimicrobial effects. This study evaluated the effect of ITA on FLS and its potential to treat RA. ITA significantly decreased FLS proliferation and migration in vitro, as well as mitochondrial oxidative phosphorylation and glycolysis measured by an extracellular flux analyzer. ITA accumulates metabolites including succinate and citrate in the TCA cycle. In rats with type II collagen-induced arthritis (CIA), intra-articular injection of ITA reduced arthritis and bone erosion. <em>Irg1</em>-deficient mice lacking the ability to produce ITA had more severe arthritis than control mice in the collagen antibody-induced arthritis. ITA ameliorated CIA by inhibiting FLS proliferation and migration. Thus, ITA may be a novel therapeutic agent for RA.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064914","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}
M.Y. Hardy , L.M. Henneken , A.K. Russell , Y. Okura , A. Mizoroki , Y. Ozono , S. Kobayashi , Y. Murakami , J.A. Tye-Din
{"title":"A bispecific antibody targeting HLA-DQ2.5-gluten peptides potently blocks gluten-specific T cells induced by gluten ingestion in patients with celiac disease","authors":"M.Y. Hardy , L.M. Henneken , A.K. Russell , Y. Okura , A. Mizoroki , Y. Ozono , S. Kobayashi , Y. Murakami , J.A. Tye-Din","doi":"10.1016/j.clim.2024.110259","DOIUrl":"10.1016/j.clim.2024.110259","url":null,"abstract":"<div><p>The gluten-free diet for celiac disease (CeD) is restrictive and often fails to induce complete symptom and/or mucosal disease remission. Central to CeD pathogenesis is the gluten-specific CD4+ T cell that is restricted by HLA-DQ2.5 in over 85% of CeD patients, making HLA-DQ2.5 an attractive target for suppressing gluten-dependent immunity. Recently, a novel anti-HLA-DQ2.5 antibody that specifically recognizes the complexes of HLA-DQ2.5 and multiple gluten epitopes was developed (DONQ52).</p></div><div><h3>Objective</h3><p>To assess the ability of DONQ52 to inhibit CeD patient-derived T-cell responses to the most immunogenic gluten peptides that encompass immunodominant T cell epitopes.</p></div><div><h3>Methods</h3><p>We employed an in vivo gluten challenge model in patients with CeD that affords a quantitative readout of disease-relevant gluten-specific T-cell responses. HLA-DQ2.5+ CeD patients consumed food containing wheat, barley, or rye for 3 days with collection of blood before (D1) and 6 days after (D6) commencing the challenge. Peripheral blood mononuclear cells were isolated and assessed in an interferon (IFN)-γ enzyme-linked immunosorbent spot assay (ELISpot) testing responses to gluten peptides encompassing a series of immunodominant T cell epitopes. The inhibitory effect of DONQ52 (4 or 40 μg/mL) was assessed and compared to pan-HLA-DQ blockade (SPVL3 antibody).</p></div><div><h3>Results</h3><p>In HLA-DQ2.5+ CeD patients, DONQ52 reduced T cell responses to all wheat gluten peptides to an equivalent or more effective degree than pan-HLA-DQ antibody blockade. It reduced T cell responses to a cocktail of the most immunodominant wheat epitopes by a median of 87% (IQR 72–92). Notably, DONQ52 also substantially reduced T-cell responses to dominant barley hordein and rye secalin derived peptides. DONQ52 had no effect on T-cell responses to non-gluten antigens.</p></div><div><h3>Conclusion</h3><p>DONQ52 can significantly block HLA-DQ2.5-restricted T cell responses to the most highly immunogenic gluten peptides in CeD. Our findings support in vitro data that DONQ52 displays selectivity and broad cross-reactivity against multiple gluten peptide:HLA-DQ2.5 complexes. This work provides proof-of-concept multi-specific antibody blockade has the potential to meaningfully inhibit pathogenic gluten-specific T-cell responses in CeD and supports ongoing therapeutic development.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624003681/pdfft?md5=9fdf4526b65a872dc51c5c1e70e84367&pid=1-s2.0-S1521661624003681-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070807","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":"Regarding the “Renal dysfunction in AQP4 NMOSD and MS; a potential predictor of relapse and prognosis”","authors":"Jianfang Liao, Juan Cao","doi":"10.1016/j.clim.2024.110257","DOIUrl":"10.1016/j.clim.2024.110257","url":null,"abstract":"","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141049939","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":"Reconstruction of Sjögren's syndrome-like sialadenitis by a defined disease specific gut-reactive single TCR and an autoantibody","authors":"Mana Iizuka-Koga , Minako Ito , Noriko Yumoto , Setsuko Mise-Omata , Taeko Hayakawa , Kyoko Komai , Shunsuke Chikuma , Satoru Takahashi , Isao Matsumoto , Takayuki Sumida , Akihiko Yoshimura","doi":"10.1016/j.clim.2024.110258","DOIUrl":"10.1016/j.clim.2024.110258","url":null,"abstract":"<div><p>Lymphocytes such as CD4<sup>+</sup> T cells and B cells mainly infiltrate the salivary glands; however, the precise roles and targets of autoreactive T cells and autoantibodies in the pathogenesis of Sjögren's Syndrome (SS) remain unclear. This study was designed to clarify the role of autoreactive T cells and autoantibodies at the single-cell level involved in the development of sialadenitis. Infiltrated CD4<sup>+</sup> T and B cells in the salivary glands of a mouse model resembling SS were single-cell-sorted, and their T cell receptor (TCR) and B cell receptor (BCR) sequences were analyzed. The predominant TCR and BCR clonotypes were reconstituted in vitro, and their pathogenicity was evaluated by transferring reconstituted TCR-expressing CD4<sup>+</sup> T cells into Rag2<sup>−/−</sup> mice and administering recombinant IgG in vivo. The reconstitution of Th17 cells expressing TCR (#G) in Rag2<sup>−/−</sup> mice resulted in the infiltration of T cells into the salivary glands and development of sialadenitis, while an autoantibody (IgGr22) was observed to promote the proliferation of pathogenic T cells. IgGr22 specifically recognizes double-stranded RNA (dsRNA) and induces the activation of dendritic cells, thereby enhancing the expression of IFN signature and inflammatory genes. TCR#G recognizes antigens related to the gut microbiota. Antibiotic treatment severely reduces the activation of TCR#G-expressing Th17 cells and suppresses sialadenitis development. These data suggest that the anti-dsRNA antibodies and, TCR recognizing the gut microbiota involved in the development of sialadenitis like SS. Thus, our model provides a novel strategy for defining the roles of autoreactive TCR and autoantibodies in the development and pathogenesis of SS.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S152166162400367X/pdfft?md5=a89c51a62bd2d391439f22d442f68c69&pid=1-s2.0-S152166162400367X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956460","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":"Ionic reverberation modulates the cellular fate of CD8+tissue resident memory T cells (TRMs) in patients with renal cell carcinoma: A novel mechanism","authors":"Ashu Singh , Saumitra Dey Choudhury , Prabhjot Singh , Vishwendra Vikram Singh , Som Nath Singh , Alpana Sharma","doi":"10.1016/j.clim.2024.110256","DOIUrl":"10.1016/j.clim.2024.110256","url":null,"abstract":"<div><p>In metastatic renal cell carcinoma (mRCC), existing treatments including checkpoint inhibitors are failed to cure and/or prevent recurrence of the disease. Therefore, in-depth understanding of tumor tissue resident memory T cells (TRMs) dysfunction are necessitated to enrich efficacy of immunotherapies and increasing disease free survival in treated patients. In patients, we observed dysregulation of K<sup>+</sup>, Ca<sup>2+</sup>, Na<sup>2+</sup> and Zn<sup>2+</sup> ion channels leads to excess infiltration of their respective ions in tumor TRMs, thus ionic gradients are disturbed and cells became hyperpolarized. Moreover, overloaded intramitochondrial calcium caused mitochondrial depolarization and trigger apoptosis of tumor TRMs. Decreased prevalence of activated tumor TRMs reflected our observations. Furthermore, disruptions in ionic concentrations impaired the functional activities and/or suppressed anti-tumor action of circulating and tumor TRMs in RCC. Collectively, these findings revealed novel mechanism behind dysfunctionality of tumor TRMs. Implicating enrichment of activated TRMs within tumor would be beneficial for better management of RCC patients.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956457","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}