Circulation: Genomic and Precision Medicine最新文献

{"title":"ALPK3 Cardiomyopathy: Integrative Review With Systematic Variant Curation, Mechanisms, and Translation.","authors":"Chien-Wei Chang, Li Wang, Zeyu Chen, Julius Bogomolovas, Ju Chen","doi":"10.1161/CIRCGEN.125.005368","DOIUrl":"10.1161/CIRCGEN.125.005368","url":null,"abstract":"<p><p>Pathogenic variants in ALPK3 (α-protein kinase 3), an atypical α‑kinase acting as a sarcomeric M-band scaffold, cause cardiomyopathy with severity linked to zygosity. We present a comprehensive review with systematic curation of peer-reviewed clinical and experimental reports through June 9, 2025, encompassing 156 patient-level variants and all published preclinical models. Biallelic loss-of-function variants lead to severe, often lethal cardiomyopathy with prenatal or early onset presentation and extracardiac involvement. Heterozygous protein-truncating variants, defined as nonsense or frameshift (resulting from insertion/deletion events or splicing mutations), explain ≈1% to 4% of adult hypertrophic cardiomyopathy, often with apical/septal hypertrophy, right ventricular involvement, fibrosis, and risk of progression. ALPK3 lacks catalytic activity and maintains sarcomeric proteostasis by scaffolding MYOMs (myomesins), MuRF (muscle ring-finger protein) E3 ligases, and SQSTM1 (sequestosome-1)/p62. Loss of this scaffolding function displaces MYOMs, drives thick‑filament protein aggregation, and precipitates severe contractile dysfunction in human induced pluripotent stem cell-derived cardiomyocytes and multiple mouse models. Therapeutic proof‑of‑concept has now been achieved on 2 fronts: (1) pharmacological correction of sarcomeric hypercontractility with the myosin inhibitor mavacamten and (2) durable phenotypic rescue in global knockout mice using an adeno-associated virus-delivered miniALPK3 gene‑replacement construct. Together, these data position ALPK3 cardiomyopathy as a compelling target for precision medicine. Early genetic diagnosis, genotype-tailored surveillance, and focused development of gene-replacement or editing strategies, potentially combined with modulators of the ALPK3-MuRF proteostatic axis, offer a realistic path to disease-modifying therapy for this once enigmatic condition.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005368"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12755062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494660","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":"Exome Sequencing Enhances Screening for Familial Hypercholesterolemia Within a Multi-Site Healthcare System.","authors":"N Jewel Samadder, Mariah Schroeder, Molly M Voss, Fadi Shamoun, Iftikhar Kullo, Timothy B Curry, Elisa J F Houwink, Michelle L Bublitz, Lorelei A Bandel, Sebastian M Armasu, Robert A Vierkant, Matthew J Ferber, Rory Olson, Jennifer Tan-Arroyo, Joel A Morales-Rosado, Eric W Klee, Nicholas B Larson, Teresa M Kruisselbrink, Jan B Egan, Jennifer L Kemppainen, Jessa S Bidwell, Jennifer L Anderson, Tammy M McAllister, Linnea M Baudhuin, Katie L Kunze, Michael A Golafshar, Richard J Presutti, Jolene M Summer-Bolster, Konstantinos N Lazaridis","doi":"10.1161/CIRCGEN.125.005174","DOIUrl":"10.1161/CIRCGEN.125.005174","url":null,"abstract":"<p><strong>Background: </strong>Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder that increases risk for premature coronary artery disease and has accessible and effective interventions. The Dutch lipid clinic network is currently the most used diagnostic criterion; however, genetic sequencing provides a definitive diagnosis of FH. The goals of this study were to determine whether germline genetic screening using exome sequencing could be used to efficiently identify individuals who were genotype positive for FH.</p><p><strong>Methods: </strong>Participants were recruited from 3 geographically and racially diverse sites in the United States (Rochester, MN; Phoenix, AZ; and Jacksonville, FL). Participants underwent Exome+ sequencing (dba Helix, San Mateo, CA) and return of results for specific genetic findings in <i>APOB</i>, <i>LDLR</i>, or <i>PCSK9</i>. A chart review was performed to collect demographics, personal, and family cardiovascular history.</p><p><strong>Results: </strong>At the time of the study, 84 413 participants were enrolled in the Tapestry study. Annotation and interpretation of all variants in genes for FH resulted in the identification of 419 likely pathogenic and pathogenic variants (prevalence, 0.50%), which included 116 <i>APOB</i>, 298 <i>LDLR</i>, and 5 <i>PCSK9</i>. Sixty-six percent were female, the mean body mass index was 27.3, with 12.3% reporting a history of diabetes. Hypertriglyceridemia (≥150 mg/dL) was present in 39.5% and reduced HDL (<50 mg/dL) was present in 56.7% of patients. 27.5% of patients were not on cholesterol-lowering medications, and only 10% of FH carriers were at goal low-density lipoprotein cholesterol levels. A history of coronary artery disease was reported in 22.4% of the cohort. Nearly 90% of these participants were newly diagnosed carriers of FH. Only 30.8% of confirmed genetic diagnoses of FH satisfied clinical (Dutch lipid clinic network) criteria for a diagnosis.</p><p><strong>Conclusions: </strong>Our results emphasize the need for wider utilization of germline genetic sequencing for enhanced screening and detection of individuals who have familial hypercholesterolemia.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT05212428.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005174"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494608","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":"Neurocognitive Delay in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia.","authors":"Kristina D Chambers, Anjali Sadhwani, Ashley Robbins, Danielle A Heims-Waldron, Kimberlee Gauvreau, Dominic J Abrams, Vassilios J Bezzerides","doi":"10.1161/CIRCGEN.125.005291","DOIUrl":"10.1161/CIRCGEN.125.005291","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005291"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548520","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":"Fibroblasts Are the Primary Contributors to a Disrupted Micro-Environment in End-Stage Pediatric Hypertrophic Cardiomyopathy.","authors":"Hanna J Tadros, Diwakar Turaga, Yi Zhao, Chang-Ru Tsai, Iki A Adachi, Xiao Li, James F Martin","doi":"10.1161/CIRCGEN.125.005192","DOIUrl":"10.1161/CIRCGEN.125.005192","url":null,"abstract":"<p><strong>Background: </strong>Hypertrophic cardiomyopathy (HCM) is a relatively rare but debilitating diagnosis in the pediatric population, and patients with end-stage HCM require heart transplantation. Here, we have examined the transcriptome in ventricular tissue from this patient group to identify cell states and underlying cellular processes unique to pediatric HCM.</p><p><strong>Methods: </strong>We performed single-nucleus RNA sequencing (snRNA-seq) on explanted hearts at transplant in 3 pediatric patients with end-stage HCM and compared findings to pediatric control and adult HCM.</p><p><strong>Results: </strong>We identified distinct underlying cellular processes in cardiomyocytes, fibroblasts, endothelial cells, and myeloid cells compared with controls. Pediatric HCM was enriched in cardiomyocytes exhibiting stressed myocardium gene signatures and underlying pathways associated with cardiac hypertrophy; cardiac fibroblasts exhibited activation signatures and compared with adult patients, exhibited heightened downstream processes associated with fibrosis and a unique, myofibroblast-like cluster with increased metabolic stress and antiapoptotic properties. We noted depletion of tissue-resident macrophages and increased vascular remodeling in endothelial cells in pediatric HCM.</p><p><strong>Conclusions: </strong>Our analysis provides the first snRNA-seq analysis focused on end-stage pediatric HCM. Fibroblast-mediated cellular processes were the most prominent in pediatric HCM, which had more downstream processes associated with fibrosis than did adult HCM.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005192"},"PeriodicalIF":6.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231540","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":"Rare Variants in HTRA1, SGTB, and RBM12 Confer Risk of Atherosclerotic Cardiovascular Disease Independent of Traditional Cardiovascular Risk Factors.","authors":"Sam M Lockhart, Anuradhika Puri, Yajie Zhao, Vladimir Saudek, Eugene J Gardner, Katherine A Kentistou, Brian Y H Lam, Felix R Day, Stephen O'Rahilly, John R B Perry, Ken K Ong, Meredith E Jackrel","doi":"10.1161/CIRCGEN.125.005233","DOIUrl":"10.1161/CIRCGEN.125.005233","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis is a pathophysiological process common to a range of cardiovascular diseases. We reasoned that considering clinical presentations of atherosclerosis across the coronary, peripheral, and cerebrovasculature as a single entity would enhance statistical power to identify rare genetic variation driving pathological processes across multiple vascular beds.</p><p><strong>Methods: </strong>We performed an exome-wide association study of atherosclerotic cardiovascular disease in 434 438 UK Biobank participants of European ancestry.</p><p><strong>Results: </strong>We identified rare, predicted damaging variants in HTRA1, SGTB, and RBM12 to be associated with risk of atherosclerotic cardiovascular disease, independent of known risk factors. Both SGTB and HTRA1 were downregulated in the aorta of patients with coronary artery disease compared with controls. Loss-of-function variants in the RNA-binding protein RBM12 increased the risk of coronary, cerebrovascular, and peripheral vascular diseases to a similar extent. SGTB increased the risk of atherosclerotic cardiovascular disease in the coronary and peripheral circulations but not the cerebrovasculature. While loss-of-function variants in HTRA1 are known to cause monogenic stroke syndromes, we found that damaging missense variants in HTRA1 are associated with increased risk of disease in both the cerebrovascular and coronary circulation. Surprisingly, the increased risk of coronary artery disease was driven predominantly by a single missense variant (p.R227W; minor allele frequency, 0.009). In vitro, the R227W mutant HTRA1 efficiently proteolyzed the disordered substrate casein but not aggregated α-synuclein. In contrast, a stroke risk-raising variant (D320N) could not efficiently process any of the tested substrates.</p><p><strong>Conclusions: </strong>We identified novel genetic variants predisposing to atherosclerotic cardiovascular diseases that act independently of established cardiovascular risk factors. The observed phenotypic and functional heterogeneities between HTRA1 variants suggest that distinct biochemical mechanisms drive HTRA1-related vascular disease in the brain and heart.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005233"},"PeriodicalIF":6.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7618418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444142","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":"Plasma Protein Profile Associated With a Family History of Early-Onset Coronary Heart Disease.","authors":"Agnes Wahrenberg, Lars Lind, Natan Åberg, Henrike Häbel, Marika Ström, Anders Mälarstig, Patrik K E Magnusson, Ralf Kuja-Halkola, Göran Bergström, Gunnar Engström, Emil Hagström, Tomas Jernberg, Stefan Söderberg, Carl Johan Östgren, Per Svensson","doi":"10.1161/CIRCGEN.124.005220","DOIUrl":"10.1161/CIRCGEN.124.005220","url":null,"abstract":"<p><strong>Background: </strong>Proteins linked to heritable coronary heart disease (CHD) could uncover new pathophysiological mechanisms of atherosclerosis. We report on the protein profile associated with a family history of early-onset CHD and whether the relation between proteins and coronary atherosclerotic burden differs according to family history status, as well as inferences from Mendelian randomization.</p><p><strong>Methods: </strong>Data on coronary atherosclerotic burden from computed tomography angiography and Olink proteomics were retrieved for 4521 subjects, free of known CHD, from SCAPIS (the Swedish Cardiopulmonary Bioimage Study). Records of myocardial infarction and coronary revascularization therapies in any parent or sibling of subjects were retrieved from national registers. Linear associations between family history and proteins were adjusted for age, sex, and study site. Statistical interactions between proteins and family history for the association between proteins and the coronary atherosclerotic burden were also studied. Mendelian randomization for causal associations between proteins and CHD was performed with genome-wide association study summary data from UKB-PPP (UK Biobank Pharma Proteomics Project), CARDIoGRAMplusC4D, and FinnGen.</p><p><strong>Results: </strong>Of 4251 subjects, family history of early-onset CHD was present in 9.5%. Thirty-eight proteins, with biological features of inflammation, lipid metabolism, and vascular function, were associated with family history using a false discovery rate of 0.05. The strongest associations were observed with cathepsin D, paraoxonase 3, renin andfollistatin, neither of which was attenuated by adjusting for cardiovascular risk factors. Eighteen proteins were statistical interactors with family history in the association between each protein and the coronary atherosclerotic burden, most notably the LDL (low-density lipoprotein) receptor, transferrin receptor protein 1, and PECAM1 (platelet endothelial cell adhesion molecule 1). In 2-sample Mendelian randomization, a novel association was found for follistatin and myocardial infarction, and previous associations for PCSK9 (proprotein convertase subtilisin/kexin type 9) and PECAM1 were repeated.</p><p><strong>Conclusions: </strong>These findings highlight new potential mechanisms for heritable and general atherosclerosis.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005220"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12711270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457902","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":"Calmodulinopathies: The Need for a Registry.","authors":"Peter J Schwartz, Lia Crotti","doi":"10.1161/CIRCGEN.125.005503","DOIUrl":"10.1161/CIRCGEN.125.005503","url":null,"abstract":"<p><p>Calmodulinopathies are very rare genetic disorders associated with a high risk for sudden cardiac death. Disease-causing variants in 1 of the 3 identical <i>CALM</i> genes cause severe forms of long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, or idiopathic ventricular fibrillation, and there are many open questions concerning management and underlying mechanisms. What is currently known depends largely on the initial publications from the International Calmodulinopathy Registry. However, progress is delayed because the accrual of patients in the International Calmodulinopathy Registry is slow. As we did long ago for long QT syndrome, this is a call for action, requesting doctors all over the world to enroll even their isolated cases in the registry. This is the only way to obtain, for an adequate number of patients, the data necessary to define the spectrum of clinical manifestations and the genotype-phenotype correlation essential for an improved risk stratification and best therapeutic management. If you are willing to contribute, please contact us.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005503"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12711277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451192","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":"Precision Medicine and the FDA Modernization Act 2.0: Catalyzing Innovation in Cardiovascular Therapy.","authors":"Dominic E Fullenkamp, Lisa D Wilsbacher, Hanna J Tadros, Pankaj Arora, Thomas P Cappola","doi":"10.1161/CIRCGEN.125.005487","DOIUrl":"10.1161/CIRCGEN.125.005487","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005487"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12788729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437671","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":"Population Genomic Screening and Improved Lipid Management in Patients With Familial Hypercholesterolemia.","authors":"Matthew E Levy, Kelly M Schiabor Barrett, Megan N Betts, David Kann, Alexandre Bolze, Basil Khuder, Natalie Telis, Lisa M McEwen, Amy C Sturm, Chad Haldeman-Englert, Jeremy Cauwels, Douglas Stoller, C Anwar A Chahal, Christopher N Chapman, Ashley A Waring, Douglas A Olson, Joseph J Grzymski, Nicole L Washington, William Lee, Elizabeth T Cirulli, Catherine Hajek","doi":"10.1161/CIRCGEN.125.005206","DOIUrl":"10.1161/CIRCGEN.125.005206","url":null,"abstract":"<p><strong>Background: </strong>The Helix Research Network program is a large population genomics initiative that screens an all-comers population of patients for Centers for Disease Control and Prevention Tier 1 genetic conditions, including familial hypercholesterolemia (FH). We evaluated changes in clinical management and low-density lipoprotein cholesterol (LDL-C) levels among patients we identified to have FH.</p><p><strong>Methods: </strong>Participants across 9 US health systems provided samples that underwent clinical-grade exome sequencing. Individuals with a positive screening result for a Tier 1 condition were offered no-cost genetic counseling through their health system. Using medication and laboratory testing records, we evaluated changes in patients' lipid-lowering therapies and LDL-C levels.</p><p><strong>Results: </strong>Among 228 602 adults enrolled between 2017 to 2025, 1155 (≈1/198) had a pathogenic FH variant in <i>LDLR</i> (74%), <i>APOB</i> (25%), or <i>PCSK9</i> (1%). Of the 622 with retrospective and prospective electronic health record data available (mean of 11.8 and 2.1 years, respectively), 84% lacked a prior clinical FH diagnosis. Overall, 33% received new/modified lipid-lowering therapy within the first year, but this proportion was higher in those with a newly documented FH diagnosis code (57% versus 17% for those without documentation; <i>P</i><0.001). Patients with new/modified therapies had a mean LDL-C reduction of 52 mg/dL, compared with 20 mg/dL in patients with no therapeutic change (difference=32 mg/dL; <i>P</i><0.001).</p><p><strong>Conclusions: </strong>Following genetic screening, many patients with a pathogenic FH variant experienced improvements in clinical management and LDL-C levels. Electronic health record documentation of the diagnosis code was associated with a greater likelihood of therapeutic modifications, which, in turn, were associated with larger LDL-C reductions. Findings underscore the powerful potential of population genomic screening for supporting optimal lipid management in individuals with FH.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005206"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12711266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444117","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":"Comparing the Efficacy of Myosin Inhibition Versus Thin Filament Calcium Desensitization for Treatment of Pediatric Restrictive Cardiomyopathy Using a Patient-Derived hiPSC Model.","authors":"David W Staudt, Ricardo Serrano, Anna P Hnatiuk, Isaac Sanchez, Xiomara Carhuamaca, Dries A M Feyen, Mark Mercola","doi":"10.1161/CIRCGEN.125.005464","DOIUrl":"10.1161/CIRCGEN.125.005464","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005464"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12802102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494621","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}