HGG Advances最新文献

{"title":"Two-sample bi-directional causality between two traits with some invalid IVs in both directions using GWAS summary statistics.","authors":"Siyi Chen","doi":"10.1016/j.xhgg.2025.100449","DOIUrl":"10.1016/j.xhgg.2025.100449","url":null,"abstract":"<p><p>Mendelian randomization (MR) is a widely used method for assessing causal relationships between risk factors and outcomes using genetic variants as instrumental variables (IVs). While traditional MR assumes uni-directional causality, bi-directional MR aims to identify the true causal direction. In uni-directional MR, invalid IVs due to pleiotropy can violate assumptions and introduce biases. In bi-directional MR, traditional MR can be performed separately for each direction, but the presence of invalid IVs poses even greater challenges. We introduce a new bi-directional MR method incorporating stepwise selection (Bidir-SW) designed to address these challenges. Our approach leverages public genome-wide association study (GWAS) datasets for two traits and uses model selection criteria to identify invalid IVs iteratively by stepwise selection. This method accounts for potential bi-directional causality in the presence of common invalid IVs for both directions, even if only GWAS summary statistics are provided. Through simulation studies, we demonstrate that our method outperforms traditional MR techniques, such as MR-Egger and inverse-variance weighted (IVW), with uncorrelated SNPs. We also provide simulations to compare our approach with existing transcriptome-wide association study (TWAS) to show its effectiveness. Finally, we apply the proposed method to genetic traits such as CRP levels and BMI to explore possible bi-directional relationships among these traits. We also used the proposed method to discover causal protein biomarkers. Our findings suggest that the Bidir-SW approach is a powerful tool for bi-directional MR or TWAS, which can provide a valuable framework for future genetic epidemiology studies.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100449"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044175","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":"Breaking barriers in rare disease research: The RARE-X Open Science Data Challenge as a model for collaborative innovation and community partnership.","authors":"Karmen Trzupek, Ravi Bhargava, Cynthia Kuan, Fanny Sie, Vanessa Vogel-Farley, Katelyn Hobbs, Verena Chung, Maria Diaz, Charlene Son-Rigby, Joseph Geraci, Jacob Albrecht","doi":"10.1016/j.xhgg.2025.100462","DOIUrl":"10.1016/j.xhgg.2025.100462","url":null,"abstract":"<p><p>Trzupek et al. describe a rare disease Open Science Data Challenge, using data collected systematically on RARE-X across 27 neurodevelopmental disorders. Clinical diagnoses, symptoms, genetic data, and PROs were included. Researchers and statisticians generated solutions that identified previously underappreciated symptoms and used machine learning to test predictive models for diagnosis.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100462"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226963","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":"MED13L pathogenic missense variants impair protein stability and interaction, underlying diverse clinical outcomes.","authors":"Thomas Smol, Frédéric Frenois, Morgane Billotte, Roseline Caumes, Leonie A Menke, Amara Nassar-Sheikh Rashid, Caroline Thuillier, Didier Monté, Florence Petit, Alexis Verger, Jamal Ghoumid","doi":"10.1016/j.xhgg.2025.100467","DOIUrl":"10.1016/j.xhgg.2025.100467","url":null,"abstract":"<p><p>Heterozygous pathogenic variants in the Mediator complex subunit 13-like gene located in the locus 12q21.21 (MED13L) are associated with intellectual disability, developmental delay, and distinctive facial features. While nonsense and frameshift variants typically cause haploinsufficiency, resulting in a well-characterized clinical presentation, missense variants have been associated with a broader range of phenotypes, including epilepsy and severe motor delay. In this study, we investigated five pathogenic missense variants in MED13L-c.2597C>T p.Pro866Leu, c.2605C>T p.Pro869Ser, c.3392G>A p.Cys1131Tyr, c.5695G>A p.Gly1899Arg, and c.6485C>T p.Thr2162Met-associated with different clinical severities. We identified significant reductions in protein stability across these variants, with some exhibiting aberrant cytoplasmic localization, suggesting disruptions in structural integrity and function. In particular, exon 15 variants (p.Pro866Leu and p.Pro869Ser) correlated with severe phenotypes, including epilepsy and severe motor impairment, whereas p.Gly1899Arg and p.Thr2162Met were associated with milder manifestations. 3D protein modeling suggested that these missense variants may disrupt MED13L's interaction with the CDK8 kinase module, leading to functional deficits. Our findings highlight different pathogenic mechanisms, ranging from protein instability to altered molecular interactions, that contribute to the clinical variability observed in MED13L-related disorders.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100467"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276162","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":"Aortic valve-specific genes dysregulated in calcific aortic valve stenosis as potential biomarkers and therapeutic targets.","authors":"Pardis Zamani, Ursula Houessou, Hasanga D Manikpurage, Zhonglin Li, Manel Dahmene, Nathalie Gaudreault, François Dagenais, Marie-Annick Clavel, Philippe Pibarot, Benoit J Arsenault, Patrick Mathieu, Yohan Bossé, Sébastien Thériault","doi":"10.1016/j.xhgg.2025.100448","DOIUrl":"10.1016/j.xhgg.2025.100448","url":null,"abstract":"<p><p>Calcific aortic valve stenosis (CAVS) is the most frequent heart valve disease. Elucidating specific gene expression patterns in the aortic valve could provide new insights for understanding disease pathophysiology. We used local RNA sequencing data from 500 explanted human aortic valves to identify aortic valve-specific genes and compared their expression according to disease status and CAVS severity. We identified 100 specific protein-coding genes in the aortic valve compared to 45 other tissues from the Genotype-Tissue Expression (GTEx) project. Among them, 38 were differentially expressed in CAVS. Ten had a gradient of expression between severity levels and were central in a protein-protein interaction network, most of which were involved in extracellular matrix regulation or inflammation. Among the aortic valve-specific genes, four of the corresponding proteins had a significantly different plasma level in individuals with CAVS. These findings represent a robust foundation for the development of specific biomarkers and therapies for CAVS.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100448"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019627","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":"A multi-level gene-diet interaction analysis of fish oil and 14 polyunsaturated fatty acid traits identifies the FADS and GPR12 loci.","authors":"Susan Adanna Ihejirika, Alexandra Huong Chiang, Aryaman Singh, Eunice Stephen, Han Chen, Kaixiong Ye","doi":"10.1016/j.xhgg.2025.100459","DOIUrl":"10.1016/j.xhgg.2025.100459","url":null,"abstract":"<p><p>Fish oil supplements (FOS) are known to alter circulating levels of polyunsaturated fatty acids (PUFAs) but in a heterogeneous manner across individuals. These varied responses may result from unidentified gene-FOS interactions. To identify genetic factors that interact with FOS to alter the circulating levels of PUFAs, we performed a multi-level genome-wide interaction study (GWIS) of FOS on 14 plasma measurements in 200,060 unrelated European-ancestry individuals from the UK Biobank. From our single-variant tests, we identified genome-wide significant interacting SNPs (p < 5 × 10^-8) in the FADS1-FADS2 gene cluster for total omega-3, omega-3%, docosapentaenoic acid (DHA), DHA%, and the omega-6 to omega-3 ratio. Among the interaction signals for omega-3%, the lead SNP, rs35473591 (C>CT, CT allele frequency = 0.34), had a lower association effect size in the FOS-taking group (β = 0.35 for allele C) than that in the group without FOS (β = 0.42). Likewise, the effect sizes of associations between FOS and omega-3% varied across the three genotype groups (β = 0.45, 0.50, and 0.59, respectively, in C/C, C/CT, and CT/CT). Our gene-level aggregate and transcriptome-wide interaction analyses identified significant signals at two loci around FADS1-FADS2 and GPR12. The contribution of genome-wide gene-FOS interactions to phenotypic variance was statistically significant in omega-3-related traits. This systematic gene-FOS GWIS contributes to our understanding of the genetic architecture of circulating PUFAs underlying FOS response and informs personalized dietary recommendations.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100459"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128950","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 genetic services in African healthcare: Challenges, opportunities, and strategic insights from a scoping review.","authors":"Karen Kengne Kamga, Pallissa Fonkam Marlyse, Seraphin Nguefack, Ambroise Wonkam","doi":"10.1016/j.xhgg.2025.100439","DOIUrl":"10.1016/j.xhgg.2025.100439","url":null,"abstract":"<p><p>The implementation of genetic medicine services in African healthcare systems is a complex process that presents both challenges and opportunities. The primary objective of this study was to provide evidence-based recommendations to policymakers and healthcare organizations to help ensure the successful integration of genetic services into African healthcare systems. To achieve this goal, we conducted a scoping review of peer-reviewed studies published between 2003 and 2023. The studies were sourced from PubMed, Scopus, and Africa-wide information databases. We based their findings on eight relevant research studies conducted between 2016 and 2023, covering a wide range of genetic topics in six African countries, including Cameroon, Kenya, Nigeria, Rwanda, South Africa, and Tanzania. The studies identified several challenges associated with the implementation of genetic services in African healthcare systems. These challenges include a lack of awareness and education about genetic diseases, barriers to genetic testing, resource limitations, ethical dilemmas, and challenges in follow-up and retention. However, the authors also highlighted opportunities and strategies for successful implementation, emphasizing preventive measures through community engagement, advocacy, and supportive networks. Apart from the potential to improve healthcare outcomes, implementing genetic services in Africa presents opportunities and challenges for healthcare and biotech companies. To address gaps in disease awareness, we recommend that healthcare providers should invest in education, collaborate with local institutions, and utilize digital platforms. Furthermore, businesses should explore innovative, cost-effective genetic testing models and create dialog platforms like online forums to positively impact African health care.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":"6 3","pages":"100439"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054259","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":"Meta-analysis of uveal melanoma genome-wide association studies identifies novel risk loci and population effect size heterogeneity.","authors":"Georgia Mies, Noah L Tsao, Alexandre Houy, Sarah E Coupland, Helen Kalirai, Asta Försti, Kari Hemminki, Hauke Thomsen, Marc-Henri Stern, Carol L Shields, Scott M Damrauer, Katheryn G Ewens, Arupa Ganguly, Iain Mathieson","doi":"10.1016/j.xhgg.2025.100465","DOIUrl":"10.1016/j.xhgg.2025.100465","url":null,"abstract":"<p><p>Uveal melanoma (UM) is a rare but frequently metastasizing cancer. Genome-wide association studies have identified three common genome-wide significant germline risk loci. Here, we perform a genome-wide association study on 401 new cases and conduct a meta-analysis with three independent previously published cohorts for a total sample size of 2,426 cases. We confirm the three previously identified risk loci and identify four additional genome-wide significant loci. We find that eye pigmentation-decreasing variants are systematically associated with increased UM risk and that selection for lighter pigmentation in the past 5,000 years explains about 73% of the difference in UM incidence between Northern and Southern Europe. We find evidence of effect size heterogeneity at significant loci across cohorts, in particular, a weaker association between eye pigmentation and UM in a Finnish cohort. Finally, we confirm differential effect sizes between uveal melanoma cases with and without loss of chromosome 3, the major determinant of metastatic risk. Our study identifies novel germline risk factors for UM and highlights genetic and environmental heterogeneity in its etiology.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100465"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267446","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":"Severe Joubert syndrome in family with homozygous POC1B p.Arg106Pro variant is due to a co-inherited deep-intronic mutation in the neighboring CEP290 gene.","authors":"Christian Betz, Björn Reusch, Thomas Langmann, Sandra Habbig, Bodo B Beck, Hanno J Bolz","doi":"10.1016/j.xhgg.2025.100429","DOIUrl":"10.1016/j.xhgg.2025.100429","url":null,"abstract":"<p><p>\"En bloc\" inheritance of point mutations in adjacent genes has rarely been described. We have previously reported a family with severe, mostly early-lethal Joubert syndrome (JBTS) with early-onset severe retinal dystrophy (EOSRD) and polycystic kidney disease (PKD), which at that time had been attributed to a homozygous pathogenic missense variant, p.Arg106Pro (c.317G>C), in the ciliary POC1B gene. Because this and other POC1B variants were, in subsequent studies, only reported in patients with non-syndromic childhood or early-adult-onset macular dystrophy, we have now reassessed our index patient by long-read high-fidelity (HiFi) whole-genome sequencing (LR-WGS). We identified a homozygous deep-intronic variant, c.2818-657T>G, in CEP290, a JBTS/Meckel syndrome-associated gene on chromosome 12q21, only 1.28 Mb from the N terminus of POC1B. cDNA analysis revealed aberrant splicing with the frame-shifting inclusion of 37 bp from CEP290 intron 25, predicting the loss of CEP290 function. EOSRD and PKD can fully be ascribed to this CEP290 variant, whose effect outshines the \"background\" non-syndromic POC1B retinopathy and co-segregates with the severe syndromic phenotype. Our novel findings in this family no longer justify POC1B as a JBTS gene. This co-inheritance of two ciliopathies, with the clinically decisive variant hidden deep in an intron, exemplifies the importance of WGS for achieving the complete diagnosis in challenging cases.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100429"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765313","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":"Multiple molecular diagnoses identified through genome sequencing in individuals with suspected rare disease.","authors":"Alka Malhotra, Erin Thorpe, Alison J Coffey, Revathi Rajkumar, Josephine Adjeman, Naomi Dianne Naa Adjeley Adjetey, Sharron Aglobitse, Felix Allotey, Todor Arsov, Joyce Ashong, Ebenezer Vincent Badoe, Donald Basel, Yvonne Brew, Chester Brown, Kerri Bosfield, Kari Casas, Mario Cornejo-Olivas, Laura Davis-Keppen, Abbey Freed, Kate Gibson, Parul Jayakar, Marilyn C Jones, Martina Kawome, Aimé Lumaka, Ursula Maier, Prince Makay, Gioconda Manassero, Marilyn Marbell-Wilson, Charles Marcuccilli, Diane Masser-Frye, Julie McCarrier, Hannah-Sharon Mills, Jeny Balazar Montoya, Gerrye Mubungu, Mamy Ngole, Jorge Perez, Eniko Pivnick, Milagros M Duenas-Roque, Hildegard Pena Salguero, Arturo Serize, Marwan Shinawi, Fabio Sirchia, Claudia Soler-Alfonso, Alan Taylor, Lauren Thompson, Gail Vance, Adeline Vanderver, Keith Vaux, Danita Velasco, Samuel Wiafe, Ryan J Taft, Denise L Perry, Akanchha Kesari","doi":"10.1016/j.xhgg.2025.100430","DOIUrl":"10.1016/j.xhgg.2025.100430","url":null,"abstract":"<p><p>Genome sequencing is a powerful and comprehensive test that detects multiple variants of different types. The interrogation of variants across the genome enables the identification of multiple molecular diagnoses (MMDs) in a single individual. In this retrospective study, we describe individuals in whom MMDs were associated with the proband's indication for testing (IFT), secondary findings, or incidental findings. An MMD is considered where at least one of the findings is associated with the primary IFT and all variants are classified as either likely pathogenic or pathogenic. Clinical genome sequencing was performed for all individuals as part of the iHope program at the Illumina Laboratory Services between September 2017 and December 2023. The iHope cohort included 1,846 affected individuals, with 872 (47.2%) found to have at least one likely pathogenic or pathogenic variant associated with the primary IFT. Of these, 81 (9.3%) individuals had multiple clinically significant molecular findings, including 76 individuals with reported variants associated with 2 different conditions, and 5 individuals with more than 2 molecular findings. A total of 32 individuals (3.7%) had at least 2 molecular diagnoses related to the primary IFT, while in 49 (5.6%) individuals, the variant(s) reported for the second condition constituted a secondary or incidental finding. Our study highlights that among individuals with a likely pathogenic or pathogenic finding identified through genome sequencing, 9% have MMDs, which may have been missed with different testing methods. Of note, approximately 60% of the 81 individuals with an MMD had a potentially actionable secondary or incidental finding.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100430"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804350","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":"Interaction between genetic risk and comorbid conditions in endometriosis.","authors":"Isabelle M McGrath, Valentina Rukins, Triin Laisk, Sally Mortlock, Grant W Montgomery","doi":"10.1016/j.xhgg.2025.100456","DOIUrl":"10.1016/j.xhgg.2025.100456","url":null,"abstract":"<p><p>Endometriosis is a complex disease, and many genetic and environmental risk factors contribute to disease risk. The genetic risk of endometriosis has been well characterized in genome-wide association studies. While few physiological risk factors are known, endometriosis is associated with many comorbid disorders. This study examines the interplay between genetic risk factors, comorbid disorders, and endometriosis. Genetic and health record data from the UK Biobank (5,432 cases; 92,344 controls) and Estonian Biobank (3,824 cases; 15,296 controls) was used to estimate the correlation between comorbidity burden, endometriosis and genetic risk, and to estimate the interactive effects between endometriosis polygenic risk score (PRS) and diagnosis of prevalent comorbidities (uterine fibroids, heavy menstrual bleeding, dysmenorrhea, irritable bowel syndrome, diverticular disease, and asthma) on endometriosis prevalence. The comorbidity burden was significantly higher in endometriosis cases and was positively correlated with endometriosis PRS in women without endometriosis but negatively correlated in women with endometriosis. The absolute increase in endometriosis prevalence conveyed by the presence of several comorbidities (uterine fibroids, heavy menstrual bleeding, dysmenorrhea) was greater in individuals with a high endometriosis PRS compared to a low endometriosis PRS. These findings, consistent across two biobanks, highlight significant interactions between polygenic risk for endometriosis and the diagnosed comorbidities in endometriosis susceptibility that have implications for understanding the underlying mechanisms contributing to disease risk.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100456"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081082","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}