HGG Advances最新文献

{"title":"CUL3-related neurodevelopmental disorder: Clinical phenotype of 20 new individuals and identification of a potential phenotype-associated episignature.","authors":"Liselot van der Laan, Ananília Silva, Lotte Kleinendorst, Kathleen Rooney, Sadegheh Haghshenas, Peter Lauffer, Yasemin Alanay, Pratibha Bhai, Alfredo Brusco, Sonja de Munnik, Bert B A de Vries, Angelica Delgado Vega, Marc Engelen, Johanna C Herkert, Ron Hochstenbach, Saskia Hopman, Sarina G Kant, Ryutaro Kira, Mitsuhiro Kato, Boris Keren, Hester Y Kroes, Michael A Levy, Ngu Lock-Hock, Saskia M Maas, Grazia M S Mancini, Carlo Marcelis, Naomichi Matsumoto, Takeshi Mizuguchi, Alessandro Mussa, Cyril Mignot, Anu Närhi, Ann Nordgren, Rolph Pfundt, Abeltje M Polstra, Slavica Trajkova, Yolande van Bever, Marie José van den Boogaard, Jasper J van der Smagt, Tahsin Stefan Barakat, Mariëlle Alders, Marcel M A M Mannens, Bekim Sadikovic, Mieke M van Haelst, Peter Henneman","doi":"10.1016/j.xhgg.2024.100380","DOIUrl":"10.1016/j.xhgg.2024.100380","url":null,"abstract":"<p><p>Neurodevelopmental disorder with or without autism or seizures (NEDAUS) is a neurodevelopmental disorder characterized by global developmental delay, speech delay, seizures, autistic features, and/or behavior abnormalities. It is caused by CUL3 (Cullin-3 ubiquitin ligase) haploinsufficiency. We collected clinical and molecular data from 26 individuals carrying pathogenic variants and variants of uncertain significance (VUS) in the CUL3 gene, including 20 previously unreported cases. By comparing their DNA methylation (DNAm) classifiers with those of healthy controls and other neurodevelopmental disorders characterized by established episignatures, we aimed to create a diagnostic biomarker (episignature) and gain more knowledge of the molecular pathophysiology. We discovered a sensitive and specific DNAm episignature for patients with pathogenic variants in CUL3 and utilized it to reclassify patients carrying a VUS in the CUL3 gene. Comparative epigenomic analysis revealed similarities between NEDAUS and several other rare genetic neurodevelopmental disorders with previously identified episignatures, highlighting the broader implication of our findings. In addition, we performed genotype-phenotype correlation studies to explain the variety in clinical presentation between the cases. We discovered a highly accurate DNAm episignature serving as a robust diagnostic biomarker for NEDAUS. Furthermore, we broadened the phenotypic spectrum by identifying 20 new individuals and confirming five previously reported cases of NEDAUS.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100380"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584446","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":"Large-scale brainstem neuroimaging and genetic analyses provide new insights into the neuronal mechanisms of hypertension.","authors":"Tiril P Gurholt, Torbjørn Elvsåshagen, Shahram Bahrami, Zillur Rahman, Alexey Shadrin, Daniel E Askeland-Gjerde, Dennis van der Meer, Oleksandr Frei, Tobias Kaufmann, Ida E Sønderby, Sigrun Halvorsen, Lars T Westlye, Ole A Andreassen","doi":"10.1016/j.xhgg.2024.100392","DOIUrl":"10.1016/j.xhgg.2024.100392","url":null,"abstract":"<p><p>While brainstem regions are central regulators of blood pressure, the neuronal mechanisms underlying their role in hypertension remain poorly understood. Here, we investigated the structural and genetic relationships between global and regional brainstem volumes and blood pressure. We used magnetic resonance imaging data from n = 32,666 UK Biobank participants, and assessed the association of volumes of the whole brainstem and its main regions with blood pressure. We applied powerful statistical genetic tools, including bivariate causal mixture modeling (MiXeR) and conjunctional false discovery rate (conjFDR), to non-overlapping genome-wide association studies of brainstem volumes (n = 27,034) and blood pressure (n = 321,843) in the UK Biobank cohort. We observed negative associations between the whole brainstem and medulla oblongata volumes and systolic blood and pulse pressure, and positive relationships between midbrain and pons volumes and blood pressure traits when adjusting for the whole brainstem volume (all partial correlation coefficients ∣r∣ effects between 0.03 and 0.05, p ≤ 0.0042). We observed the largest genetic overlap for the whole brainstem, sharing 77% of its trait-influencing variants with blood pressure. We identified 65 shared loci between brainstem volumes and blood pressure traits and mapped these to 71 genes, implicating molecular pathways linked to sympathetic nervous system development, metal ion transport, and vascular homeostasis. The present findings support a link between brainstem structures and blood pressure and provide insights into their shared genetic underpinnings. The overlapping genetic architectures and mapped genes offer mechanistic information about the roles of brainstem regions in hypertension.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100392"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814453","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":"Chronic overlapping pain conditions and nociplastic pain.","authors":"Keira J A Johnston, Rebecca Signer, Laura M Huckins","doi":"10.1016/j.xhgg.2024.100381","DOIUrl":"10.1016/j.xhgg.2024.100381","url":null,"abstract":"<p><p>Chronic overlapping pain conditions (COPCs) are a subset of chronic pain conditions commonly comorbid with one another and more prevalent in women and individuals assigned female at birth (AFAB). Pain experience in these conditions may better fit with a new mechanistic pain descriptor, nociplastic pain, and nociplastic pain may represent a shared underlying factor among COPCs. We applied GenomicSEM common-factor genome-wide association study (GWAS) and multivariate transcriptome-wide association (TWAS) analyses to existing GWAS output for six COPCs in order to find genetic variation associated with nociplastic pain, followed by genetic correlation (linkage disequilibrium score regression), gene set, and tissue enrichment analyses. We found 24 independent single nucleotide polymorphisms (SNPs), and 127 unique genes significantly associated with nociplastic pain, and showed nociplastic pain to be a polygenic trait with significant SNP heritability. We found significant genetic overlap between multisite chronic pain and nociplastic pain, and to a smaller extent with rheumatoid arthritis and a neuropathic pain phenotype. Tissue enrichment analyses highlighted cardiac and thyroid tissue, and gene set enrichment analyses emphasized potential shared mechanisms in cognitive, personality, and metabolic traits and nociplastic pain along with distinct pathology in migraine and headache. We used a well-powered network approach to investigate nociplastic pain using existing COPC GWAS output, and show nociplastic pain to be a complex, heritable trait, in addition to contributing to understanding of potential mechanisms in development of nociplastic pain.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100381"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142577061","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 phenome-wide association study of polygenic scores for selected childhood cancer: Results from the UK Biobank.","authors":"Eun Mi Jung, Andrew R Raduski, Lauren J Mills, Logan G Spector","doi":"10.1016/j.xhgg.2024.100356","DOIUrl":"10.1016/j.xhgg.2024.100356","url":null,"abstract":"<p><p>The aim of this study was to scan phenotypes in adulthood associated with polygenic risk scores (PRS) for childhood cancers with well-articulated genetic architectures-acute lymphoblastic leukemia (ALL), Ewing sarcoma, and neuroblastoma-to examine genetic pleiotropy. Furthermore, we aimed to determine which SNPs could drive associations. Per-SNP summary statistics were extracted for PRS calculation. Participants with white British ancestry were exclusively included for analyses. SNPs were queried from the UK Biobank genotype imputation data. Records from the cancer registry, death registry, and inpatient diagnoses were abstracted for phenome-wide scans. Firth logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) alongside corresponding p values, adjusting for age at recruitment and sex. A total of 244,332 unrelated white British participants were included. We observed a significant association between ALL-PRS and ALL (OR: 1.20e+24, 95% CI: 9.08e+14-1.60e+33). In addition, we observed a significant association between high-risk neuroblastoma PRS and nonrheumatic aortic valve disorders (OR: 43.9, 95% CI: 7.42-260). There were no significant phenotype associations with Ewing sarcoma and neuroblastoma PRS. Regarding individual SNPs, rs17607816 increased the risk of ALL (OR: 6.40, 95% CI: 3.26-12.57). For high-risk neuroblastoma, rs80059929 elevated the risk of atrioventricular block (OR: 3.04, 95% CI: 1.85-4.99). Our findings suggest that individuals with genetic susceptibility to ALL may face a lifelong risk for developing ALL, along with a genetic pleiotropic association between high-risk neuroblastoma and circulatory diseases.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100356"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355561","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":"HCV- and HBV-mediated liver cancer converge on similar transcriptomic landscapes and immune profiles.","authors":"Elizabeth S Borden, Annika Jorgensen, Heini M Natri, Karen Taraszka Hastings, Kenneth H Buetow, Melissa A Wilson","doi":"10.1016/j.xhgg.2024.100373","DOIUrl":"10.1016/j.xhgg.2024.100373","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide, and a large proportion is attributable to viral causes, including hepatitis B (HBV) and C viruses (HCV). The pathogenesis of viral-mediated HCC can differ between HBV and HCV, but it is unclear how much these differences influence the tumors' final molecular and immune profiles. Additionally, there are known sex differences in the molecular etiology of HCC, but sex differences have not been explored in the context of viral-mediated HCC. To determine the extent to which the viral status and sex impact the molecular and immune profiles of HCC, we performed differential expression and immune cell deconvolution analyses. We identified a large number of differentially expressed genes unique to the HBV or HCV tumor:tumor-adjacent comparison. Pathway enrichment analyses demonstrated that changes unique to the HCV tumor:tumor-adjacent tissue were dominated by changes in immune pathways. Immune cell deconvolution demonstrated that HCV tumor-adjacent tissue had the largest immune cell infiltrate, with no difference in the immune profiles within HBV and HCV tumor samples. Overall, this work demonstrates the convergence of HBV- and HCV-mediated HCC on a similar transcriptomic landscape and immune profile despite differences in the surrounding tissue.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100373"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476455","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":"Differential inclusion of NEB exons 143 and 144 provides insight into NEB-related myopathy variant interpretation and disease manifestation.","authors":"Sarah Silverstein, Rotem Orbach, Safoora Syeda, A Reghan Foley, Svetlana Gorokhova, Katherine G Meilleur, Meganne E Leach, Prech Uapinyoying, Katherine R Chao, Sandra Donkervoort, Carsten G Bönnemann","doi":"10.1016/j.xhgg.2024.100354","DOIUrl":"10.1016/j.xhgg.2024.100354","url":null,"abstract":"<p><p>Biallelic pathogenic variants in the gene encoding nebulin (NEB) are a known cause of congenital myopathy. We present two brothers with congenital myopathy and compound heterozygous variants (NC_000002.12:g.151692086G>T; NM_001271208.2: c.2079C>A; p.(Cys693Ter) and NC_000002.12:g.151533439T>C; NM_001271208.2:c.21522+3A>G) in NEB. Transcriptomic sequencing on affected individual muscles revealed that the extended splice variant c.21522+3A>G causes exon 144 skipping. Nebulin isoforms containing exon 144 are known to be mutually exclusive with isoforms containing exon 143, and these isoforms are differentially expressed during development and in adult skeletal muscles. Affected individuals' MRI patterns of muscle involvement were compared with the known pattern of relative abundance of these two isoforms in muscle. We propose that the pattern of muscle involvement in these affected individuals better fits the distribution of exon 144-containing isoforms in muscle than with previously published MRI findings in NEB-related disease due to other variants. Our report introduces disease pathogenesis and manifestation as a result of alteration of isoform distributions in muscle.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100354"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355563","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":"Polygenic scores and social determinants of health: Their correlations and potential biases.","authors":"Daniel J Schaid, Shannon K McDonnell, Farida S Akhtari, Jason P Sinnwell, Anthony Batzler, Ewan K Cobran, Alison Motsinger-Reif","doi":"10.1016/j.xhgg.2024.100389","DOIUrl":"10.1016/j.xhgg.2024.100389","url":null,"abstract":"<p><p>The use of polygenic scores (PGS) for personalized medicine has gained momentum, along with caution to avoid accentuating health disparities. Greater ancestral diversity in genetic studies is needed, as well as close attention to the social determinants of health (SDoH).We measured the correlations between 3,030 PGS from the PGS Catalog and SDoH among participants in the Personalized Environment and Genes Study (PEGS). Correlations mainly ranged from -0.05 to 0.05, yet there was a heterogeneity of correlations across SDoH themes, with the largest amount of heterogeneity for PGS predicting body measures and smoking, as well as some common diseases. We also quantify the expected bias of PGS effect size on disease risk when strong predictors, such as SDoH, are omitted from models, emphasizing the importance of including SDoH with PGS to avoid biased estimates of PGS risk and to achieve equitable precision medicine.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100389"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740654","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":"RLIM-specific activity reporters define variant pathogenicity in Tonne-Kalscheuer syndrome.","authors":"Venkateshwarlu Bandi, Martin Rennie, Intisar Koch, Polly Gill, Oscar D Pacheco, Aaron D Berg, Hong Cui, D Isum Ward, Francisco Bustos","doi":"10.1016/j.xhgg.2024.100378","DOIUrl":"10.1016/j.xhgg.2024.100378","url":null,"abstract":"<p><p>Tonne-Kalscheuer syndrome (TOKAS; MIM: 300978) is an X-linked recessive disorder with devastating consequences for patients, such as intellectual disability, developmental delay, and multiple congenital abnormalities. TOKAS is associated with hemizygous variants in the RLIM gene, which encodes a RING-type E3 ubiquitin ligase. The current sustained increase in reported RLIM variants of uncertain significance creates an urgent need to develop assays that can screen these variants and experimentally determine their pathogenicity and disease association. Here, we engineered flow cytometry-based RLIM-specific reporters to measure RLIM activity in TOKAS. This paper describes the design and use of RLIM-specific reporters to determine the pathogenicity of a TOKAS RLIM gene variant. Our data demonstrate that RLIM-specific flow cytometry reporters based on either the full length or a degron region of the substrate REX1 measure RLIM activity in cells. Further, we describe the TOKAS variant RLIM p.Asn581Lys and, using reporter assays, determine that it disrupts RLIM catalytic activity. These data reveal how the p.Asn581Lys variant impairs RLIM function and suggests pathogenic mechanisms. The use of RLIM-specific reporters will greatly accelerate the resolution of variants of uncertain significance and disease association in TOKAS.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100378"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558997","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":"Advancements in genetic research by the Hispanic Community Health Study/Study of Latinos: A 10-year retrospective review.","authors":"Hridya Rao, Margaret C Weiss, Jee Young Moon, Krista M Perreira, Martha L Daviglus, Robert Kaplan, Kari E North, Maria Argos, Lindsay Fernández-Rhodes, Tamar Sofer","doi":"10.1016/j.xhgg.2024.100376","DOIUrl":"10.1016/j.xhgg.2024.100376","url":null,"abstract":"<p><p>The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a multicenter, longitudinal cohort study designed to evaluate environmental, lifestyle, and genetic risk factors as they relate to cardiometabolic and other chronic diseases among Hispanic/Latino populations in the United States. Since the study's inception in 2008, as a result of the study's robust genetic measures, HCHS/SOL has facilitated major contributions to the field of genetic research. This 10-year retrospective review highlights the major findings for genotype-phenotype relationships and advancements in statistical methods owing to the HCHS/SOL. Furthermore, we discuss the ethical and societal challenges of genetic research, especially among Hispanic/Latino adults in the United States. Continued genetic research, ancillary study expansion, and consortia collaboration through HCHS/SOL will further drive knowledge and advancements in human genetics research.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100376"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547996","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":"Functional characterization of QT interval associated SCN5A enhancer variants identify combined additive effects.","authors":"Lavanya Gunamalai, Parul Singh, Brian Berg, Leilei Shi, Ernesto Sanchez, Alexa Smith, Ghislain Breton, Mark T Bedford, Darius Balciunas, Ashish Kapoor","doi":"10.1016/j.xhgg.2024.100358","DOIUrl":"10.1016/j.xhgg.2024.100358","url":null,"abstract":"<p><p>Several empirical and theoretical studies suggest the presence of multiple enhancers per gene that collectively regulate gene expression, and that common sequence variation impacting on the activities of these enhancers is a major source of inter-individual gene expression variability. However, for the vast majority of genes, enhancers and the underlying regulatory variation remains unknown. Even for the genes with well-characterized enhancers, the nature of the combined effects from multiple enhancers and their variants, when known, on gene expression regulation remains unexplored. Here, we have evaluated the combined effects from five SCN5A enhancers and their regulatory variants that are known to collectively correlate with SCN5A cardiac expression and underlie QT interval association in the general population. Using small deletions centered at the regulatory variants in episomal reporter assays in a mouse cardiomyocyte cell line, we demonstrate that the variants and their flanking sequences play critical role in individual enhancer activities, likely being a transcription factor (TF) binding site. By oligonucleotide-based pulldown assays on predicted TFs, we identify the TFs likely driving allele-specific enhancer activities. Using all 32 possible allelic synthetic constructs in reporter assays, representing the five bi-allelic enhancers, we demonstrate combined additive effects on overall enhancer activities. Using transient enhancer assays in zebrafish embryos we demonstrate that four elements act as enhancers in vivo. Together, these studies uncover the TFs driving the enhancer activities of QT interval associated SCN5A regulatory variants, reveal the additive effects from allelic combinations of these regulatory variants, and prove their potential to act as enhancers in vivo.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100358"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362213","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}