Clinical and experimental immunology最新文献

{"title":"Peripheral Immune Biomarkers Associated with Response to Adoptive Cell Therapy with Tumor Infiltrating Lymphocytes.","authors":"Cecilie Oelvang Madsen, Marta Velasco Santiago, Evelina Martinenaite, Troels Holz Borch, Marco Donia, Inge Marie Svane, Morten Hansen","doi":"10.1093/cei/uxaf010","DOIUrl":"https://doi.org/10.1093/cei/uxaf010","url":null,"abstract":"<p><p>Adoptive cell therapy (ACT) with ex-vivo expanded tumor-infiltrating lymphocytes (TILs, TIL-ACT) has shown clinical efficacy in a significant proportion of patients with metastatic melanoma. To further target TIL-ACT towards responsive patients, identifying predictive biomarkers and understanding broader immune dynamics remain critical. This study investigated the peripheral blood immune landscape in 47 patients with metastatic melanoma undergoing TIL-ACT, assessing antitumor reactivity and peripheral immune cell profiles before and after treatment. Responders displayed increased frequency of circulating tumor-reactive cells post-treatment, and higher baseline levels of activated CD57-expressing T cells, serving as potential biomarkers of response. In contrast, persistent high serum levels of interleukin (IL)-6 and IL-8, higher frequencies of CD38-expressing T cells and regulatory T cells (Tregs) post-treatment, correlated with unfavorable outcomes. These findings contribute to understanding of the peripheral immune landscape associated with response to TIL-ACT, offering valuable insights into predictive biomarkers and mechanisms to improve patient selection.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447646","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":"The role of IgA and IgG in Mycobacterium tuberculosis infection: A cross-sectional study in Ethiopia.","authors":"Rubiyat E Islam, Meaza Zewdie, Daniel Mussa, Yonas Abebe, Tom H M Ottenhoff, Kees L M C Franken, Fekadu Abebe, Liya Wassie","doi":"10.1093/cei/uxaf001","DOIUrl":"https://doi.org/10.1093/cei/uxaf001","url":null,"abstract":"<p><strong>Introduction: </strong>Despite the high global prevalence of Mycobacterium tuberculosis (Mtb) infection in humans, most infected individuals achieve a stable immunological equilibrium, without showing clinical signs and symptoms of tuberculosis (TB). Although the role of antibodies in TB is assumed to be relatively small compared to cell-mediated immunity, their role in TB has been documented in a few recent studies.</p><p><strong>Methods: </strong>In this cross-sectional study, we quantitated antibody responses to Mtb antigens, lipoarabinomannan (LAM), and heparin-binding hemagglutinin adhesin (HBHA) by determining antigen-specific immunoglobulin A(IgA) and G(IgG) secretion levels using enzyme-linked immunosorbent assay (ELISA) in serum and saliva of pulmonary TB patients (PTB), their household contacts (HHC), and community controls (CC) (determined by QuantiFERON TB Gold assay QFT- test result).</p><p><strong>Results: </strong>The HBHA-specific IgA levels were significantly higher in both saliva and serum in HHC groups compared to PTB patients (P=0.013, P=0.023). Exposed contacts, who were QFT-negative had higher serum HBHA-specific IgA responses compared to PTB patients (P=0.04). QFT-negative HHC and QFT-positive CC showed higher HBHA and LAM-specific IgG responses (P=0.006, P=0.002, P=0.0009, P=0.006, respectively) than PTB patients. Generally, LAM and HBHA-specific IgA levels were significantly higher in saliva compared to serum (P<0.0001) in all study groups.</p><p><strong>Conclusion: </strong>Overall, the observed higher levels of IgA and IgG in controls, and exposed but QFT-negative contacts suggest a correlation with, and perhaps a role for these antibodies in preventing the development of active TB. The findings highlighted the potential involvement of saliva IgA in the immune response to Mtb, underscoring the relevance of mucosal immunity in TB infection.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413562","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 T-bet expressing B cells in lupus patients indicates a putative prognostic and therapeutic value of these cells for the disease.","authors":"Athanasios Sachinidis, Maria Trachana, Anna Taparkou, George Gavriilidis, Vasileios Vasileiou, Sofoklis Keisaris, Panayotis Verginis, Christina Adamichou, Dimitrios Boumpas, Fotis Psomopoulos, Alexandros Garyfallos","doi":"10.1093/cei/uxaf008","DOIUrl":"https://doi.org/10.1093/cei/uxaf008","url":null,"abstract":"<p><strong>Objective: </strong>To investigate whether T-bet+ B cells, as well as age-associated B cells/ABCs (CD19+CD21-CD11c+T-bet+) and double-negative B cells/DN (CD19+IgD-CD27- CXCR5-T-bet+), serve as prognostic and/or therapeutic tools for systemic lupus erythematosus (SLE) in humans.</p><p><strong>Methods: </strong>Flow cytometry was used for enumerating T-bet+ B cells and ABCs/DN subsets, found in the peripheral blood of 10 healthy donors and 22 active SLE patients. Whole blood assay cultures, combined with in vitro pharmacological treatments, were performed to evaluate the effects of hydroxychloroquine, anifrolumab and fasudil (a ROCK kinase inhibitor) on T-bet+ B cells' percentage. Moreover, previously published single-cell RNA sequencing (scRNA-seq) data were used in a meta-analysis to allow characterization of genes and pathways associated with the biology of T-bet in B cells.</p><p><strong>Results: </strong>T-bet+ B cells displayed an expansion in SLE patients [1.47 (1.9 - 0.7) vs 10.85 (37.4 - 3.6)]. Similarly, both ABCs and DN were found to be expanded. Interestingly, percentages of T-bet+ B cells positively correlated with patients' SLEDAI scores (rs=0.55, p=0.007). Cell culture experiments conducted, revealed that all three agents tested can deplete T-bet+ B cells (without affecting the cell viability of lymphocytes, T cells and B cells). According to bioinformatics analyses, T-bet is highly expressed in two B cell clusters with pathogenic characteristics for SLE (designated as atypical memory B cells and activated naïve B cells). These clusters can be targeted for therapeutic interventions.</p><p><strong>Conclusions: </strong>T-bet+ B cells can serve as a putative prognostic biomarker of lupus severity. Circumstantial data suggest that these cells may promote disease pathogenesis and may represent a novel therapeutic target.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370588","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":"Expression of Concern: Therapeutic effect of farnesylthiosalicylic acid on adjuvant-induced arthritis through suppressed release of inflammatory cytokines.","authors":"","doi":"10.1093/cei/uxae111","DOIUrl":"10.1093/cei/uxae111","url":null,"abstract":"","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/PMC11773795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806242","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":"Exhausted Lag-3+ CD4+ T cells are increased in pediatric Inflammatory Bowel Disease.","authors":"Alexander Schnell, Carmen Aicher, Philipp A Schnegelsberg, Benedikt Schwarz, Hannah Schmidt, Ida Allabauer, Aline Rueckel, Adrian P Regensburger, Joachim Woelfle, André Hoerning","doi":"10.1093/cei/uxae066","DOIUrl":"10.1093/cei/uxae066","url":null,"abstract":"<p><p>T cells are one of the main drivers of inflammatory bowel diseases (IBD). Infliximab (IFX) is used in the treatment of IBD as an anti-inflammatory drug to induce remission by neutralizing TNFα. We determined the individual chemokine/homing receptor and cytokine profile in pediatric IBD patients before and during IFX therapy to identify predictive biomarkers for therapy success. Peripheral blood CD4+ cells from pediatric patients with IBD were immunomagnetically isolated and either directly analyzed by FACS for cell distribution and chemokine/homing receptor expression or evaluated for cytokine production after in-vitro-stimulation. Twenty-one responders (RS) and 21 non-responders (NRS) were recruited. Before IFX therapy, flow cytometry revealed decreased percentages of naïve conventional T cells in pediatric IBD patients. The proportions of CD62-L+ T cells were decreased in both CD and UC therapy responders. The cytokine profile of T cells was highly altered in IBD patients compared to healthy controls (HC). During IFX therapy, the frequencies of conventional memory and regulatory memory T cells expanded in both cohorts. IFX response was marked by a decrease of α4β7+ and IFNγ+ memory T cells in both CD and UC. In contrast, frequencies of Lag-3+ T cells proved to be significantly increased in NRS. These observations were irrespective of the underlying disease. T cells of pediatric IBD patients display an activated and rather Th1/Th17-shifted phenotype. The increased expression of the checkpoint molecule Lag-3 on T cells of NRS resembles a more exhausted phenotype than in RS and HC which appeared to be a relevant predictive marker for therapy failure.</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/PMC11771200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751239","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":"C/EBPε and its acetylation in PMN enhance the tolerance to trauma.","authors":"Shaowen Cheng, Junyu Zhu, Yangyang Bian, Jiangling Yao, Wei Zhang, Shuangqin Yin, Tianyin Kuang, Lina Xian, Huaping Liang","doi":"10.1093/cei/uxae061","DOIUrl":"10.1093/cei/uxae061","url":null,"abstract":"<p><p>Severe trauma can lead to numerous serious complications, threating the well-being and vitality of the afflicted. The quantity and functionality of polymorphonuclear neutrophils (PMNs) undergo rapid transformations in response to severe trauma, playing a pivotal role in the trauma response. The absence of CCAAT/enhancer-binding protein ε (C/EBPε) profoundly impairs the functionality of PMNs, a function of paramount importance in trauma. In this study, by generating mice with C/EBPε knocked out or overexpressed, we substantiate that C/EBPε ensures the restoration of PMN function, enhancing the expression of antimicrobial proteins and thereby promoting trauma recovery. Furthermore, diminished expression of C/EBPε is observed in trauma patients, with levels displaying a negative correlation with ISS and APACHE II scores, suggesting its potential as a prognostic indicator for clinical treatment. Mechanistically, we uncover the upregulation of SIRT1 and the inhibition of P300 participating in the suppression of C/EBPε acetylation, consequently reducing the resilience of mice to trauma. Therapeutic interventions, whether through the sole administration of PMN, nicotinamide (NAM) treatment, or their combination, all result in an increased survival rate in traumatic mice. In conclusion, our study elucidates the role of C/EBPε in enhancing the resilience to trauma and identifies C/EBPε acetylation as a critical regulatory mechanism, offering potential therapeutic approaches involving PMN transfusion and NAM treatment.</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/PMC11771198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726986","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":"Amlexanox targeted inhibition of TBK1 regulates immune cell function to exacerbate DSS-induced inflammatory bowel disease.","authors":"Lu Hui, Meng-Ke Huang, Qing-Kai Dai, Cheng-Lin Miao, Yun-Long Yang, Chen-Xi Liu, Ting Liu, Yong-Mei Jiang","doi":"10.1093/cei/uxae082","DOIUrl":"10.1093/cei/uxae082","url":null,"abstract":"<p><p>Amlexanox (ALX) is a small-molecule drug for the treatment of inflammatory, autoimmune, metabolic, and tumor diseases. At present, there are no studies on whether ALX has a therapeutic effect on inflammatory bowel disease (IBD). In this study, we used a mouse model of dextran sulfate sodium-induced colitis to investigate the effect of ALX-targeted inhibition of TBK1 on colitis. We found that the severity of colitis in mice was correlated with TBK1 expression. Notably, although ALX inhibited the activation of the TBK1-NF-κB/TBK1-IRF3 pro-inflammatory signaling pathway, it exacerbated colitis and reduced survival in mice. The results of drug safety experiments ruled out a relationship between this exacerbating effect and drug toxicity. In addition, ELISA results showed that ALX promoted the secretion of IL-1β and IFN-α, and inhibited the production of cytokines IL-6, TNF-α, IL-10, TGF-β, and secretory IgA. Flow cytometry results further showed that ALX promoted T-cell proliferation, activation, and differentiation, and thus played a pro-inflammatory role; also, ALX inhibited the generation of dendritic cells and the polarization of macrophages to M1 type, thus exerting anti-inflammatory effect. These data suggest that the regulation of ALX on the function of different immune cells is different, so the effect on the inflammatory response is bidirectional. In conclusion, our study demonstrates that simply inhibiting TBK1 in all immune cells is not effective for the treatment of colitis. Further investigation of the anti-inflammatory mechanism of ALX on dendritic cells and macrophages may provide a new strategy for the treatment of IBD.</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/PMC11771202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153267","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":"Past, present, and future of Phase 3 vaccine trial design: rethinking statistics for the 21st century.","authors":"Leila Janani, Rachel Phillips, Ellie Van Vogt, Xinxue Liu, Claire Waddington, Suzie Cro","doi":"10.1093/cei/uxae104","DOIUrl":"10.1093/cei/uxae104","url":null,"abstract":"<p><p>Vaccines are crucial for protecting health globally; however, their widespread use relies on rigorous clinical development programmes. This includes Phase 3 randomized controlled trials (RCTs) to confirm their safety, immunogenicity, and efficacy. Traditionally, such trials used fixed designs with predetermined assumptions, lacking the flexibility to change during the trial or stop early due to overwhelming evidence of either efficacy or futility. Modern vaccine trials benefit from innovative approaches like adaptive designs, allowing for planned trial adaptations based on accumulating data. Here, we provide an overview of the evolution of Phase 3 vaccine trial design and statistical analysis methods from traditional to more innovative contemporary methods. This includes adaptive trial designs, which offer ethical advantages and enable early termination if indicated; Bayesian methods, which combine prior knowledge and observed trial data to increase efficiency and enhance result interpretation; modern statistical analysis methods, which enable more accurate and precise inferences; the estimand framework, which ensures the primary question of interest is addressed in a trial; novel approaches using machine learning methods to assess heterogeneity of treatment effects; and statistical advances in safety analysis to evaluate reactogenicity and clinical adverse events. We conclude with insights into the future direction of vaccine trials, aiming to inform clinicians and researchers about conventional and novel RCT design and analysis approaches to facilitate the conduct of efficient, timely trials.</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/PMC11754867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680412","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":"From acute lung injury to cerebral ischemia: a unified concept involving intercellular communication through extracellular vesicle-associated miRNAs released by macrophages/microglia.","authors":"Xianbin Wang, Ting Wang, Dong Zhu, Jing Wang, Weijie Han","doi":"10.1093/cei/uxae105","DOIUrl":"10.1093/cei/uxae105","url":null,"abstract":"<p><p>Ischemic stroke and acute lung injury are prevalent life-threatening conditions marked by intricate molecular mechanisms and elevated mortality rates. Despite evident pathophysiological distinctions, a notable similarity exists in the gene responses to tissue injury observed in both pathologies. This similarity extends to both protein-encoding RNAs and non-coding RNAs. Extracellular vesicles (EVs) are nano-scale vesicles derived through cell secretion, possessing unique advantages such as high biocompatibility, low immunogenicity, intrinsic cell targeting, and facile chemical and genetic manipulation. Importantly, miRNAs, the most prevalent non-coding RNAs, are selectively concentrated within EVs. Macrophages/microglia serve as immune defense and homeostatic cells, deriving from progenitor cells in the bone marrow. They can be classified into two contrasting types: classical proinflammatory M1 phenotype or alternative anti-inflammatory M2 phenotype. However, there exists a continuum of various intermediate phenotypes between M1 and M2, and macrophages/microglia can transition from one phenotype to another. This review will investigate recent discoveries concerning the impact of EVs derived from macrophages/microglia under various states on the progression of ischemic stroke and acute lung injury. The focus will be on the involvement of miRNAs within these vesicles. The concluding remarks of this review will underscore the clinical possibilities linked to EV-miRNAs, accentuating their potential as both biomarkers and therapeutic targets.</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/PMC11773807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806246","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":"Comparative efficacy of leniolisib (CDZ173) versus standard of care on rates of respiratory tract infection and serum immunoglobulin M (IgM) levels among individuals with activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS): an externally controlled study.","authors":"John Whalen, Anita Chandra, Sven Kracker, Stephan Ehl, Markus G Seidel, Ioana Gulas, Louis Dron, Russanthy Velummailum, Chenthila Nagamuthu, Sichen Liu, Joanne Tutein Nolthenius, Maria Elena Maccari","doi":"10.1093/cei/uxae107","DOIUrl":"10.1093/cei/uxae107","url":null,"abstract":"<p><p>Leniolisib, an oral, targeted phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, was well-tolerated and efficacious versus placebo in treating individuals with activated PI3Kδ syndrome (APDS), an ultra-rare inborn error of immunity (IEI), in a 12-week randomised controlled trial. However, longer-term comparative data versus standard of care are lacking. This externally controlled study compared the long-term effects of leniolisib on annual rate of respiratory tract infections and change in serum immunoglobulin M (IgM) levels versus current standard of care, using data from the leniolisib single-arm open-label extension study 2201E1 (NCT02859727) and the European Society for Immunodeficiencies (ESID) registry. The endpoints were chosen following feasibility assessment considering comparability and availability of data from both sources. Baseline characteristics between groups were balanced through inverse probability of treatment weighting. The leniolisib-treated group included 37 participants, with 62 and 49 participants in the control group for the respiratory tract infections and serum IgM analyses, respectively. Significant reductions in the annual rate of respiratory tract infections (rate ratio: 0.34; 95% confidence interval [CI]: 0.19, 0.59) and serum IgM levels (treatment effect: -1.09 g/L; 95% CI: -1.78, -0.39, P = 0.002) were observed in leniolisib-treated individuals versus standard of care. The results were consistent across all sensitivity analyses, regardless of censoring, baseline infection rate definition, missing data handling, or covariate selection. These novel data provide an extended comparison of leniolisib treatment versus standard of care, highlighting the potential for leniolisib to deliver long-term benefits by restoring immune system function and reducing infection rate, potentially reducing complications and treatment burden.</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/PMC11754865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823607","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}