ImmunoTargets and Therapy最新文献

{"title":"IL-6 Signaling in Immunopathology: From Basic Biology to Selective Therapeutic Intervention.","authors":"Tim Schumertl, Juliane Lokau, Christoph Garbers","doi":"10.2147/ITT.S485684","DOIUrl":"https://doi.org/10.2147/ITT.S485684","url":null,"abstract":"<p><p>Interleukin-6 (IL-6) is a cytokine with pro- and anti-inflammatory functions. Interestingly, its divergent biological activities are mediated by different signaling pathways: In IL-6 classic signaling, which is associated with the regenerative and anti-inflammatory properties of the cytokine, IL-6 binds to and signals via the membrane-bound IL-6 receptor (IL-6R) on its target cells. In contrast, the pro-inflammatory properties of IL-6 are mediated via the soluble (s)IL-6R (IL-6 trans-signaling). Recently, a third mode of IL-6 signaling was revealed, which was termed cluster signaling and is required for the generation of pathogenic Th17 cells. In all pathways, intracellular signaling cascades are activated via the formation of a gp130 homodimer. The involvement of IL-6 in the pathogenesis of inflammatory diseases, autoimmune diseases and even cancer has made IL-6 and the IL-6R important therapeutic targets. Consequently, antibodies that block either IL-6 itself or the IL-6R are in clinical use and have been approved for different inflammatory diseases, including rheumatoid arthritis (RA). This review gives an overview about the complex biology of this important cytokine, summarizes the current usage of anti-IL-6 therapeutics in clinical use and highlights the pre-clinical and clinical development of novel therapeutic agents that specifically block only the trans-signaling pathway of IL-6.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"681-695"},"PeriodicalIF":6.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Advances and Challenges in CAR-T Therapy for Hematological and Solid Tumors.","authors":"Gengtian Zhang, Mengyao Bai, Hanzhi Du, Yue Yuan, Yidan Wang, Weijing Fan, Huachao Zhu, Di Wu, Pengcheng He, Busheng Xue","doi":"10.2147/ITT.S519616","DOIUrl":"10.2147/ITT.S519616","url":null,"abstract":"<p><strong>Introduction: </strong>Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of refractory hematological malignancies, yet significant challenges persist in extending its success to solid tumors. This review aims to provide a comprehensive overview of the current landscape and future perspectives of CAR-T therapy in both hematological malignancies and solid tumors.</p><p><strong>Methods: </strong>A thorough literature search was conducted to identify relevant preclinical and clinical studies, as well as review articles, focusing on CAR-T therapy in various hematological malignancies and solid tumors. The collected information was synthesized to discuss the current applications, challenges, and strategies for improving CAR-T therapy in these settings.</p><p><strong>Results: </strong>CAR-T therapy has demonstrated impressive clinical outcomes in treating certain hematological malignancies, such as B-cell lymphoma, leukemia, and multiple myeloma. However, the efficacy of CAR-T cells in solid tumors has been limited due to various obstacles, including tumor heterogeneity, immunosuppressive microenvironment, and off-tumor toxicities. Strategies to overcome these challenges involve advanced CAR designs, combination therapies, and novel approaches to CAR-T cell manufacturing and engineering.</p><p><strong>Conclusion: </strong>While CAR-T therapy has revolutionized the treatment of some hematological malignancies, significant hurdles remain in extending its success to solid tumors. Continued research efforts focusing on improving CAR-T cell efficacy, safety, and accessibility will be crucial in unlocking the full potential of this innovative immunotherapeutic approach across a broad spectrum of cancer types.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"655-680"},"PeriodicalIF":6.2,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Adjuvant Immunotherapy in Hepatocellular Carcinoma: A Comprehensive Review.","authors":"Miho Akabane, Odysseas P Chatzipanagiotou, Yuki Imaoka, Austin Schenk, Timothy M Pawlik","doi":"10.2147/ITT.S528709","DOIUrl":"10.2147/ITT.S528709","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality globally, with high rates of recurrence even after curative-intent treatments such as hepatectomy and liver transplantation (LT). In recent years, immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape for HCC, demonstrating significant efficacy among advanced-stage tumors through combination regimens, such as anti-programmed cell death ligand-1 (PD-L1)/PD-1 inhibitors with anti-vascular endothelial growth factor agents. Recent advances have highlighted the potential of ICIs as adjuvant therapy to improve recurrence-free survival among high-risk patients post-resection. However, challenges such as low immunogenicity, the immunosuppressive tumor microenvironment, and immune resistance remain substantial barriers to the broader success of ICIs. In the context of LT, the use of ICIs is further complicated by the concurrent need for immunosuppressive agents, which can exacerbate the risk of recurrence. Emerging strategies focusing on the optimization of the timing of ICI therapy and the utilization of novel biomarkers are being explored to mitigate graft rejection while maintaining antitumor efficacy. Additionally, immune-cell-based therapies based on chimeric antigen receptor-T and natural killer (NK) cells, adoptive cell transfer, and liver-resident NK cell approaches are also being investigated for their potential to reduce recurrence and improve survival outcomes. This review focuses on the current landscape of adjuvant immunotherapy and immune-cell therapy in the postoperative management of HCC, highlighting ongoing clinical trials, therapeutic potential, and associated risks. With continued advancements in immunotherapeutic strategies and personalized approaches, these therapies hold the promise of transforming outcomes for patients undergoing curative resection or LT.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"631-654"},"PeriodicalIF":6.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotargets and Therapy for Systemic Lupus Erythematosus.","authors":"Chi Chiu Mok","doi":"10.2147/ITT.S485650","DOIUrl":"10.2147/ITT.S485650","url":null,"abstract":"<p><p>The pathophysiology of systemic lupus erythematosus (SLE) is complex and involves most cell types of the innate and adaptive immune system. Impaired clearance of apoptotic bodies and self-antigens, dysregulated cytokine network and aberrated functions of the immune cells lead to overproduction of autoantibodies, activation of complements, immune complex deposition and tissue injury. Novel biological and newer generation immunosuppressive agents have been developed to target the B cells, T cells, T/B cell interaction, plasmacytoid dendritic cells and the cytokines. With the advances in the knowledge about the intracellular pathways, small molecules that inhibit the downstream signal transduction from surface receptors and intracellular protein degradation by the ubiquitin-proteasome system are being developed in the pipeline. This article summarizes the evidence of various immunotargets for the treatment of SLE. These novel agents target specific cellular mechanisms, and further works are necessary to stratify patients according to biomarkers to receive individualized therapies that could help maximize the clinical response. With the availability of more therapeutic choices, a combination approach to achieve synergistic effects while reducing adverse events by dosage reduction of individual drugs is being explored for SLE patients at risk of disease progression or refractory to conventional therapies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"605-629"},"PeriodicalIF":6.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGF-β Decreases NK Cell Mobility and Cytotoxic Efficacy in Complex in vitro Models of the Leukemia Microenvironment.","authors":"Veronika Švubová, Lucie Janstová, Marek Jedlička, Eva Mašínová, Jana Szabová, Tereza Feglarová, Kateřina Kuglerová, Veronika Bosáková, Barbora Brodská, Kristýna Boráková, David Kundrát, Iva Trsová, Martina Böhmová, Kateřina Kuželová, Jiří Hrdý, Zdenka Gašová, Jan Vydra, Michaela Dostálová Merkerová, Marcela Hortová-Kohoutková, Jan Frič","doi":"10.2147/ITT.S512700","DOIUrl":"10.2147/ITT.S512700","url":null,"abstract":"<p><strong>Background: </strong>Natural killer (NK) cell-based therapies represent a promising approach for acute myeloid leukemia (AML) relapse, yet their efficacy is hindered by immunosuppressive factors such as transforming growth factor beta (TGF-β) in the tumor microenvironment. This study investigated the effects of TGF-β on NK cell cytotoxicity and migration using 2D and 3D co-culture models that mimic the leukemic microenvironment.</p><p><strong>Methods: </strong>TGF-β production was evaluated in AML-derived leukemic cell lines and mesenchymal stromal cells (hTERT-MSCs) using ELISA. Bulk RNA sequencing (RNA-seq) was performed to analyze global gene expression changes in TGF-β-treated primary human NK cells. NK cell cytotoxicity and migration were assessed in 2D monolayer and 3D spheroid co-cultures containing hTERT-MSCs and leukemic cells using flow cytometry and confocal microscopy.</p><p><strong>Results: </strong>Both leukemic cells and MSCs produced TGF-β, with increased levels observed in MSCs after co-culture with primary AML blasts. RNA sequencing revealed that TGF-β altered key gene pathways associated with NK cell cytotoxicity, adhesion, and migration, supporting its immunosuppressive role. In functional assays, TGF-β exposure significantly reduced NK cell-mediated cytotoxicity in a time-dependent manner and impaired NK cell infiltration into 3D spheroids, particularly in models incorporating MSCs. Additionally, MSCs themselves provided a protective environment for leukemic cells, further reducing NK cell effectiveness in 2D co-cultures.</p><p><strong>Conclusion: </strong>TGF-β suppresses both NK cell cytotoxicity and migration, limiting their ability to eliminate leukemic cells and infiltrate the bone marrow niche (BMN). These findings provide novel insights into TGF-β-mediated immune evasion mechanisms and provide important insights for the future design of NK-based immunotherapies and clinical trials.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"589-604"},"PeriodicalIF":6.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Significance of Circulating Immune Subset Counts in Nasopharyngeal Carcinoma.","authors":"Honghui Xie, Lin Zhang, Lizhi Chen, Wenchao Zhou, Lijuan Zhang, Yong Su, Bocheng Li, Peng Ding, Yun Xiao, Tianzhu Lu, Xiaochang Gong, Jingao Li","doi":"10.2147/ITT.S516853","DOIUrl":"10.2147/ITT.S516853","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to assess the prognostic value of circulating immune cells in newly diagnosed, non-metastatic nasopharyngeal carcinoma (NPC) and to develop a nomogram combining immune cell counts with clinical characteristics.</p><p><strong>Methods: </strong>In this retrospective study, patients with non-metastatic NPC treated between January 2015 and December 2018 were included. Circulating immune cell subtypes were measured using cellular immunochip technology. Survival outcomes were assessed using Kaplan-Meier analysis, and independent prognostic factors were identified through multivariate analysis (MVA). A prognostic nomogram was constructed and evaluated using Harrell's concordance index (C-index).</p><p><strong>Results: </strong>A total of 459 patients were included, with a median follow-up of 62 months. Optimal cutoff values for CD4+ T cells (420 cells/μL), CD8+ T cells (430 cells/μL), CD3+ T cells (1100 cells/μL), and CD4/CD8 ratio (1.00) were determined using X-tile. Higher levels of CD4+ T cells (78.6% vs 64.2%, p < 0.001), CD8+ T cells (77.5% vs 71.4%, p = 0.113), CD3+ T cells (83.1% vs 70.0%, p = 0.003), and CD4/CD8 ratio (77.6% vs 60.0%, p = 0.001) were associated with better 5-year progression-free survival. MVA confirmed high CD4/CD8 ratio and CD3+ T cell count as independent prognostic factors. The nomogram combining CD3+ T cells, CD4/CD8 ratio, and N classification showed superior prognostic accuracy compared with the clinical model alone (C-index: 0.686 vs 0.648, p < 0.001).</p><p><strong>Conclusion: </strong>Circulating immune cells, particularly CD3+ T cells and CD4/CD8 ratio, are significant prognostic indicators in NPC. The proposed nomogram may help predict disease progression and support individualized treatment planning.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"577-587"},"PeriodicalIF":6.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Regulatory Network of Transcription Factors in Macrophage Polarization.","authors":"Jie Liu, Mengran Wang, Yong Zhao","doi":"10.2147/ITT.S494550","DOIUrl":"10.2147/ITT.S494550","url":null,"abstract":"<p><p>Macrophage polarization, a dynamic process crucial for immune responses and tissue homeostasis, is tightly regulated by transcription factors. Understanding the transcriptional regulation of macrophage polarization holds significant therapeutic implications for various diseases, including cancer, autoimmune disorders, and metabolic syndromes. Studies have shown that transcription factors, including signal transducer and activator of transcription (STAT), nuclear transcription factor-κB (NF-κB), peroxisome proliferator-activated receptors (PPARs), interferon regulatory factors (IRFs), BTB and CNC homology (BACH), CCAAT-enhancer binding proteins (C/EBPs), kruppel-like factors (KLFs), Cellular Myc (c-Myc), the SNAIL family, v-Maf Musculoaponeurotic Fibrosarcoma Oncogene Homolog (Maf), and hypoxia-inducible factor alpha (HIFα), are highly involved in shaping macrophage polarization. Targeting transcription factors involved in macrophage polarization may provide promising avenues for immunomodulatory therapies aimed at restoring immune homeostasis and combating pathological conditions characterized by dysregulated macrophage activation. Here, we review the intricate transcriptional networks that govern macrophage polarization, highlighting the pivotal role of transcription factors in orchestrating these processes.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"555-575"},"PeriodicalIF":6.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"JAK-STAT Signaling in Autoimmunity and Cancer.","authors":"Sana Parveen, Mariyam Fatma, Snober Shabnam Mir, Said Dermime, Shahab Uddin","doi":"10.2147/ITT.S485670","DOIUrl":"https://doi.org/10.2147/ITT.S485670","url":null,"abstract":"<p><p>The JAK-STAT pathway is an essential cell survival signaling that regulates gene expressions related to inflammation, immunity and cancer. Cytokine receptors, signal transducer and activator of transcription (STAT) proteins, and Janus kinases (JAKs) are the critical component of this signaling cascade. When JAKs are stimulated by cytokines, STAT phosphorylation, dimerization, and nuclear translocation occur, which eventually impacts gene transcription. Dysregulation of JAK-STAT signaling is linked with various autoimmune diseases, including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. This pathway is constitutively activated in human malignancies and leads to tumor cell survival, proliferation, and immune evasion. Oncogenic mutations in the JAK and STAT genes have been found in solid tumors, leukemia, and lymphoma. Targeting the JAK-STAT pathway is a viable and promising therapeutic strategy for the treatment of autoimmune diseases and cancers.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"523-554"},"PeriodicalIF":6.2,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How to Choose Treatment Regimens for Idiopathic Membranous Nephropathy Patients with PLA2R-Negative: A Single-Center Retrospective Cohort Study.","authors":"Zijian Zhou, Yijing Zou, Ben Ke, Wen Shen","doi":"10.2147/ITT.S512451","DOIUrl":"https://doi.org/10.2147/ITT.S512451","url":null,"abstract":"<p><strong>Background: </strong>Cyclophosphamide, tacrolimus, and rituximab (RTX) are first-line treatments for idiopathic membranous nephropathy (IMN), regardless of PLA2R status. While the efficacy of RTX in IMN patients with PLA2R-positive has been well-documented, its effectiveness in IMN patients with PLA2R-negative remains understudied. This study aimed to evaluate the efficacy and adverse events of these three treatment regimens in IMN patients with PLA2R-negative.</p><p><strong>Methods: </strong>This study included 46 PLA2R-negative IMN patients confirmed by renal biopsy and immunofluorescence from the Department of Nephrology, the Second Affiliated Hospital of Nanchang University between September 2021 and October 2023. We compared clinical remission rates, and side effects at 3, 6, and 12 months follow-up in 14 patients who received prednisolone combined with cyclophosphamide (cyclophosphamide group), in 11 patients who treated with prednisolone combined with tacrolimus (tacrolimus group), and 21 patients who treated with rituximab (RTX group).</p><p><strong>Results: </strong>Baseline characteristics were similar among the three groups. At the 12-month follow-up, the complete response rate was significantly higher in the cyclophosphamide and tacrolimus groups compared to the RTX group (<i>p</i> = 0.029). However, there were no significant differences in cumulative complete remission rates or cumulative composite remission rates among the three groups during the follow-up period (<i>p</i> = 0.192, <i>p</i> = 0.212). Severe adverse events occurred in all groups, but the differences were not statistically significant (<i>p</i> > 0.05).</p><p><strong>Conclusion: </strong>Cyclophosphamide and tacrolimus appear to offer long-term benefits for PLA2R-negative IMN patients, with tacrolimus demonstrating superior efficacy among the treatment options evaluated. These insights offer important guidance for clinical decision-making in the management of PLA2R-negative IMN. However, further large-scale, multicenter studies with long-term follow-up are necessary to confirm these findings.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"515-522"},"PeriodicalIF":6.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-Based Therapeutic Strategies for Autoimmune Diseases.","authors":"Francisco B Quero, Tays Troncoso-Bravo, Mónica A Farías, Alexis M Kalergis","doi":"10.2147/ITT.S513629","DOIUrl":"https://doi.org/10.2147/ITT.S513629","url":null,"abstract":"<p><p>Currently, the management of autoimmune disorders still being a challenge in terms of safety, efficiency, and specificity. Cell-based therapeutic strategies have emerged as a novel approach for autoimmune disease treatment, employing different cell therapy platforms, including tolerogenic dendritic cells, regulatory T cells, conventional and regulatory chimeric antigen receptor-T cells, mesenchymal and hematopoietic stem cells, each with their biological features. Here, we discuss the different cell therapy platforms, their immunological mechanisms of action, their therapeutic potential and benefits in autoimmune diseases, and challenges related to their production, scaling up, risks, and patient safety.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"501-514"},"PeriodicalIF":6.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12047289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}