Journal of Clinical Immunology最新文献

{"title":"Allogeneic Hematopoietic Stem Cell Transplantation in Immunodeficiency-Centromeric Instability-Facial Dysmorphism (ICF) Syndrome: an EBMT/ESID Inborn Errors Working Party Study.","authors":"Dagmar Berghuis, Lubna S Mehyar, Rolla Abu-Arja, Michael H Albert, Jessie L Barnum, Horst von Bernuth, Reem Elfeky, Philippe Lewalle, Alexandra Laberko, Sujal Ghosh, Mary A Slatter, Corry M R Weemaes, Akif Yesilipek, Tiarlan Sirait, Bénédicte Neven, Andrew R Gennery, Arjan C Lankester","doi":"10.1007/s10875-024-01786-7","DOIUrl":"10.1007/s10875-024-01786-7","url":null,"abstract":"<p><p>Immunodeficiency-Centromeric instability-Facial dysmorphism (ICF) syndrome is an inborn error of immunity characterized by progressive immune dysfunction and multi-organ disease usually treated with antimicrobial prophylaxis and immunoglobulin substitution. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment, but data on outcome are scarce. We provide a detailed description of disease characteristics and HSCT outcome in an international cohort of ICF syndrome patients. Eighteen patients (including all four genotypes) were enrolled. Main HSCT indications were infections (83%), enteropathy/failure to thrive (56%), immune dysregulation (22%) and myelodysplasia/haematological malignancy (17%). Two patients underwent pre-emptive HSCT after early diagnosis. Patients were transplanted between 2003-2021, at median age 4.3 years (range 0.5-19), after myeloablative or reduced-intensity conditioning, from matched sibling or matched family donors, matched unrelated or mismatched donors in 39%, 50% and 12% of cases respectively. Overall survival was 83% (all deaths occurred within the first 5 months post-HSCT; mean follow-up 54 months (range 1-185)). Acute GvHD occurred in 35% of patients, severe (grade III) in two (12%), while none developed chronic GvHD. At latest follow-up (median 2.2 years (range 0.1-14)), complete donor chimerism was achieved in 15/17 surviving patients. All survivors demonstrated normalized T and B cell numbers. Immunoglobulin substitution independence was achieved in all but two patients. All survivors recovered from pre-transplant infections, enteropathy/failure to thrive and immune dysregulation. All three patients transplanted at young age (≤ 3 years), after early diagnosis, survived. The favourable clinical and immunological HSCT outcome in this cohort of patients supports the timely use of this curative treatment in ICF syndrome.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 8","pages":"182"},"PeriodicalIF":7.2,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Safety of Facilitated Subcutaneous Immunoglobulin 10% Treatment in US Clinical Practice in Patients with Primary Immunodeficiency Diseases: Results from a Post-Authorization Safety Study.","authors":"Arye Rubinstein, Mohsen Mabudian, Donald McNeil, Niraj C Patel, Richard L Wasserman, Sudhir Gupta, Paz Carrasco, Jie Chen, Enrique Garcia, Andras Nagy, Leman Yel","doi":"10.1007/s10875-024-01769-8","DOIUrl":"10.1007/s10875-024-01769-8","url":null,"abstract":"<p><p>Facilitated subcutaneous immunoglobulin (fSCIG) 10% is an immunoglobulin replacement therapy that utilizes recombinant human hyaluronidase (rHuPH20) to enhance immunoglobulin dispersion and absorption, allowing for longer treatment intervals similar to intravenous immunoglobulin (up to once monthly). fSCIG 10% is indicated in the USA for treating adults and children aged ≥ 2 years with primary immunodeficiency diseases (PIDs). This prospective, non-interventional, open-label, multicenter, post-authorization safety study (NCT02593188) was conducted in the USA from November 2015 to October 2021 to assess the long-term safety of fSCIG 10% in routine clinical practice. Patients with PIDs aged ≥ 16 years who were prescribed and/or had started fSCIG 10% treatment were enrolled. In total, 253 patients were enrolled and included (full analysis set). Participants received fSCIG 10% treatment for a median (interquartile range) of 10.0 (3.5-11.8) months, with the majority of infusions administered every 4 weeks (54.4% [1197/2201 infusions]) and at home (62.6% [1395/2230 infusions]). Overall, 98.5% of infusions were administered without rate reduction, interruption, or discontinuation due to adverse events (AEs). Treatment-related, non-serious AEs were experienced by 52 patients (20.6%, 284 events). Two patients (0.8%) each experienced one treatment-related serious AE (aseptic meningitis and deep vein thrombosis). Development of antibodies against rHuPH20 was uncommon; 14/196 patients (7.1%) tested positive for binding antibodies (titer ≥ 1:160) with no neutralizing antibodies detected. There was no relationship between anti-rHuPH20 antibody positivity and the occurrence of treatment-related serious or non-serious AEs. Long-term, repeated self-administration of fSCIG 10% was well tolerated in US clinical practice by patients with PIDs.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 8","pages":"181"},"PeriodicalIF":7.2,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profound T Lymphocyte and DNA Repair Defect Characterizes Schimke Immuno-Osseous Dysplasia.","authors":"Ondřej Vladyka, Jakub Zieg, Ondřej Pátek, Markéta Bloomfield, Zuzana Paračková, Anna Šedivá, Adam Klocperk","doi":"10.1007/s10875-024-01787-6","DOIUrl":"10.1007/s10875-024-01787-6","url":null,"abstract":"<p><p>Schimke immuno-osseous dysplasia is a rare multisystemic disorder caused by biallelic loss of function of the SMARCAL1 gene that plays a pivotal role in replication fork stabilization and thus DNA repair. Individuals affected from this disease suffer from disproportionate growth failure, steroid resistant nephrotic syndrome leading to renal failure and primary immunodeficiency mediated by T cell lymphopenia. With infectious complications being the leading cause of death in this disease, researching the nature of the immunodeficiency is crucial, particularly as the state is exacerbated by loss of antibodies due to nephrotic syndrome or immunosuppressive treatment. Building on previous findings that identified the loss of IL-7 receptor expression as a possible cause of the immunodeficiency and increased sensitivity to radiation-induced damage, we have employed spectral cytometry and multiplex RNA-sequencing to assess the phenotype and function of T cells ex-vivo and to study changes induced by in-vitro UV irradiation and reaction of cells to the presence of IL-7. Our findings highlight the mature phenotype of T cells with proinflammatory Th1 skew and signs of exhaustion and lack of response to IL-7. UV light irradiation caused a severe increase in the apoptosis of T cells, however the expression of the genes related to immune response and regulation remained surprisingly similar to healthy cells. Due to the disease's rarity, more studies will be necessary for complete understanding of this unique immunodeficiency.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 8","pages":"180"},"PeriodicalIF":7.2,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypogammaglobulinemia and Infection Events in Patients with Autoimmune Diseases Treated with Rituximab: 10 Years Real-Life Experience.","authors":"Yuxue Nie, Nianyi Zhang, Jingna Li, Di Wu, Yunjiao Yang, Li Zhang, Wei Bai, Nan Jiang, Lin Qiao, Can Huang, Shuang Zhou, Xinping Tian, Mengtao Li, Xiaofeng Zeng, Linyi Peng, Wen Zhang","doi":"10.1007/s10875-024-01773-y","DOIUrl":"10.1007/s10875-024-01773-y","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate predictors of hypogammaglobulinemia (HGG) and severe infection event (SIE) in patients with autoimmune disease (AID) receiving rituximab (RTX) therapy.</p><p><strong>Methods: </strong>This was a retrospective study conducted in a tertiary medical center in China. Predictors of HGG or SIE were assessed using Cox analysis. Restricted cubic spline (RCS) analysis was applied to examine the correlation between glucocorticoid (GC) maintenance dose and SIE.</p><p><strong>Results: </strong>A total of 219 patients were included in this study, with a cumulative follow-up time of 698.28 person-years. Within the study population, 117 patients were diagnosed with connective tissue disease, 75 patients presented with ANCA-associated vasculitis, and 27 patients exhibited IgG4-related disease. HGG was reported in 63.3% of the patients, where an obvious decline in IgG and IgM was shown three months after RTX initiation. The rate of SIE was 7.2 per 100 person-years. An increase in the GC maintenance dose was an independent risk factor for both hypo-IgG (HR 1.07, 95% CI 1.02-1.12, p = 0.003) and SIE (HR 1.06, 95% CI 1.02-1.1, p = 0.004). Further RCS analysis identified 7.48 mg/d prednisone as a safe threshold dose for patients who underwent RTX treatment to avoid a significantly increased risk for SIE.</p><p><strong>Conclusion: </strong>HGG was relatively common in RTX-treated AID patients. Patients with chronic lung disease or who were taking ≥ 7.5 mg/d prednisone during RTX treatment were at increased risk for SIE and warrant attention from physicians.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 8","pages":"179"},"PeriodicalIF":7.2,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the Clinical Phenotype of Autosomal Recessive Chronic Granulomatous Disease.","authors":"Jennifer G Chester, Alani M Estrella, Douglas B Kuhns, Christine K Garcia, Ramsay L Fuleihan","doi":"10.1007/s10875-024-01782-x","DOIUrl":"10.1007/s10875-024-01782-x","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 8","pages":"177"},"PeriodicalIF":7.2,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Exclusive Characteristics of the p.E555K Dominant-Negative Variant in Autosomal Dominant E47 Deficiency.","authors":"Takanori Utsumi, Miyuki Tsumura, Masato Yashiro, Zenichiro Kato, Kosuke Noma, Fumiaki Sakura, Reiko Kagawa, Yoko Mizoguchi, Shuhei Karakawa, Hidenori Ohnishi, Charlotte Cunningham-Rundles, Peter D Arkwright, Masao Kobayashi, Hirokazu Kanegane, Dusan Bogunovic, Bertrand Boisson, Jean-Laurent Casanova, Takaki Asano, Satoshi Okada","doi":"10.1007/s10875-024-01785-8","DOIUrl":"10.1007/s10875-024-01785-8","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 8","pages":"178"},"PeriodicalIF":7.2,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Pathogenic Role of Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in the Nocardiosis with the Central Nervous System Involvement.","authors":"Yu-Fang Lo, Shang-Yu Wang, Yi-Hui Wu, Mao-Wang Ho, Chun-Fu Yeh, Tsai-Yi Wu, Jhan-Jie Peng, You-Ning Lin, Jing-Ya Ding, Han-Po Shih, Chia-Chi Lo, Yu-Pei Chan, Cheng-Shyuan Rau, Chen-Yen Kuo, Kun-Hua Tu, Wei-Te Lei, Yi-Chun Chen, Cheng-Lung Ku","doi":"10.1007/s10875-024-01775-w","DOIUrl":"10.1007/s10875-024-01775-w","url":null,"abstract":"<p><strong>Purpose: </strong>Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are implicated in the pathogenesis of Cryptococcus gattii (C. gattii) infection and pulmonary alveolar proteinosis (PAP). Their presence has also been noted in nocardiosis cases, particularly those with disseminated disease. This study delineates a case series characterizing clinical features and specificity of anti-GM-CSF Abs in nocardiosis patients.</p><p><strong>Methods: </strong>In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients.</p><p><strong>Results: </strong>Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated.</p><p><strong>Conclusion: </strong>The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 8","pages":"176"},"PeriodicalIF":7.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon Alpha Therapy in MSMD.","authors":"Vaishnavi V Iyengar, Akshaya Chougule, Vijaya Gowri, Prasad Taur, Minnie Bodhanwala, Mukesh M Desai","doi":"10.1007/s10875-024-01779-6","DOIUrl":"10.1007/s10875-024-01779-6","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 8","pages":"174"},"PeriodicalIF":7.2,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DIAPH1-Deficiency is Associated with Major T, NK and ILC Defects in Humans.","authors":"Zehra Busra Azizoglu, Royala Babayeva, Zehra Sule Haskologlu, Mustafa Burak Acar, Serife Ayaz-Guner, Fatma Zehra Okus, Mohammad Bilal Alsavaf, Salim Can, Kemal Erdem Basaran, Mehmed Fatih Canatan, Alper Ozcan, Hasret Erkmen, Can Berk Leblebici, Ebru Yilmaz, Musa Karakukcu, Mehmet Kose, Ozlem Canoz, Ahmet Özen, Elif Karakoc-Aydiner, Serdar Ceylaner, Gülsüm Gümüş, Huseyin Per, Hakan Gumus, Halit Canatan, Servet Ozcan, Figen Dogu, Aydan Ikinciogullari, Ekrem Unal, Safa Baris, Ahmet Eken","doi":"10.1007/s10875-024-01777-8","DOIUrl":"10.1007/s10875-024-01777-8","url":null,"abstract":"<p><p>Loss of function mutations in Diaphanous related formin 1 (DIAPH1) are associated with seizures, cortical blindness, and microcephaly syndrome (SCBMS) and are recently linked to combined immunodeficiency. However, the extent of defects in T and innate lymphoid cells (ILCs) remain unexplored. Herein, we characterized the primary T, natural killer (NK) and helper ILCs of six patients carrying two novel loss of function mutation in DIAPH1 and Jurkat cells after DIAPH1 knockdown. Mutations were identified by whole exome sequencing. T-cell immunophenotyping, proliferation, migration, cytokine signaling, survival, and NK cell cytotoxicity were studied via flow cytometry-based assays, confocal microscopy, and real-time qPCR. CD4⁺ T cell proteome was analyzed by mass spectrometry. p.R351* and p.R322*variants led to a significant reduction in the DIAPH1 mRNA and protein levels. DIAPH1-deficient T cells showed proliferation, activation, as well as TCR-mediated signaling defects. DIAPH1-deficient PBMCs also displayed impaired transwell migration, defective STAT5 phosphorylation in response to IL-2, IL-7 and IL-15. In vitro generation/expansion of Treg cells from naïve T cells was significantly reduced. shRNA-mediated silencing of DIAPH1 in Jurkat cells reduced DIAPH1 protein level and inhibited T cell proliferation and IL-2/STAT5 axis. Additionally, NK cells from patients had diminished cytotoxic activity, function and IL-2/STAT5 axis. Lastly, DIAPH1-deficient patients' peripheral blood contained dramatically reduced numbers of all helper ILC subsets. DIAPH1 deficiency results in major functional defects in T, NK cells and helper ILCs underlining the critical role of formin DIAPH1 in the biology of those cell subsets.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 8","pages":"175"},"PeriodicalIF":7.2,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11315734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidermodysplasia Verruciformis and Vδ2 γδ T-cell Expansion in STK4 Deficiency.","authors":"Wenjing Ying, Xin Long, Travis Vandergriff, Hemanth Karnati, Meghan Heberton, Mingyi Chen, Xiaochuan Wang, Christian Wysocki, Xiao-Fei Kong","doi":"10.1007/s10875-024-01780-z","DOIUrl":"10.1007/s10875-024-01780-z","url":null,"abstract":"<p><p>The clinical penetrance of infectious diseases varies considerably among patients with inborn errors of immunity (IEI), even for identical genetic defects. This variability is influenced by pathogen exposure, healthcare access and host-environment interactions. We describe here a patient in his thirties who presented with epidermodysplasia verruciformis (EV) due to infection with a weakly virulent beta-papillomavirus (HPV38) and CD4⁺ T-cell lymphopenia. The patient was born to consanguineous parents living in the United States. Exome sequencing identified a previously unknown biallelic STK4 stop-gain mutation (p.Trp425X). The patient had no relevant history of infectious disease during childhood other than mild wart-like lesion on the skin, but he developed diffuse large B-cell lymphoma (DLBCL) and EBV viremia with a low viral load in his thirties. Despite his low CD4⁺ T-cell count, the patient had normal counts of CD3⁺ cells, predominantly double-negative T cells (67.4%), which turned out to be Vδ2⁺ γδ T cells. γδ T-cell expansion has frequently been observed in the 33 reported cases with STK4 deficiency. The Vδ2 γδ T cells of this STK4-deficient patient are mostly CD45RA^-CD27⁺CCR7⁺ central memory γδT cells, and their ability to proliferate in response to T-cell activation was impaired, as was that of CD4⁺ T cells. In conclusion, γδ T-cell expansion may act as a compensatory mechanism to combat viral infection, providing immune protection in immunocompromised individuals.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 8","pages":"172"},"PeriodicalIF":7.2,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}