HGG Advances最新文献

{"title":"Phasing millions of samples achieves near perfect accuracy, enabling parent-of-origin analyses.","authors":"Cole M Williams, Jared O'Connell, Ethan Jewett, William A Freyman, Christopher R Gignoux, Sohini Ramachandran, Amy L Williams","doi":"10.1016/j.xhgg.2025.100479","DOIUrl":"https://doi.org/10.1016/j.xhgg.2025.100479","url":null,"abstract":"<p><p>Haplotype phasing, the process of determining which genetic variants are physically located on the same chromosome, is crucial for genetic analyses. Here, we benchmark SHAPEIT and Beagle, two state-of-the-art phasing methods, on two large datasets: >8 million research-consented 23andMe, Inc. customers and the UK Biobank (UKB). Remarkably, both methods' median switch error rate (SER) (after excluding single SNP switches, which we call 'blips') is 0.00% across all tested 23andMe trio children and 0.026% in British samples from UKB. Across UKB samples, switch errors predominantly occur in regions lacking identity-by-descent (IBD) coverage. SHAPEIT and Beagle excel at intra-chromosomal phasing, but lack the ability to phase across chromosomes, motivating us to develop HAPTiC (HAPlotype Tiling and Clustering), an inter-chromosomal phasing method that assigns paternal and maternal variants genome-wide. Our approach uses IBD segments to phase blocks of variants on different chromosomes. HAPTiC represents the segments a focal individual shares with their relatives as nodes in a signed graph and performs spectral clustering. We test HAPTiC on 1022 UKB trios, yielding a median per-site phase error of 0.13% in regions covered by IBD segments (45.1% of sites). We also ran HAPTiC in the 23andMe database and found a median phase error rate of 0.49% in Europeans (100% of sites) and 0.16% in admixed Africans (99.8% of sites). HAPTiC enables analyses that require the parent-of-origin of variants, such as association studies and ancestry inference of untyped parents.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100479"},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics predicting reduced penetrance variants in the high-risk cancer predisposition gene TP53.","authors":"Cristina Fortuno, Marcy E Richardson, Tina Pesaran, Kelly McGoldrick, Paul A James, Amanda B Spurdle","doi":"10.1016/j.xhgg.2025.100484","DOIUrl":"https://doi.org/10.1016/j.xhgg.2025.100484","url":null,"abstract":"<p><p>Disease-causing variants with penetrance that is lower than the average expected for a given gene complicate classification, even when using gene-specific guidelines. For TP53, a gene associated with some of the highest cancer risks, even reduced penetrance disease-predisposition variants remain clinically actionable. We conducted a review of ClinVar submissions to identify TP53 variants flagged as having reduced penetrance by genetic testing laboratories and analyzed functional, bioinformatic, immunogenicity, frequency, and clinical features of these variants compared to standard pathogenic and benign variants. Our findings show that reported reduced penetrance TP53 variants are more likely to exhibit intermediate functional activity in multiple assays and are predicted as deleterious with bioinformatic tools, though with lower scores than pathogenic variants. These variants also have a higher population frequency than pathogenic variants, and heterozygotes tend to manifest disease later in life, suggesting a need for refined clinical criteria to better capture attenuated Li-Fraumeni syndrome phenotypes. Finally, by applying a random forest prediction model to all TP53 uncertain or conflicting variants in ClinVar, we identified 106 additional variants with potential reduced penetrance.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100484"},"PeriodicalIF":3.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical syndromes linked to biallelic germline variants in MCM8 and MCM9.","authors":"Noah C Helderman, Ting Yang, Claire Palles, Diantha Terlouw, Hailiang Mei, Ruben H P Vorderman, Davy Cats, Marcos Díaz Gay, Marjolijn C J Jongmans, Ashwin Ramdien, Irma van de Beek, Thomas F Eleveld, Andrew Green, Frederik J Hes, Marry M van den Heuvel-Eibrink, Annelore Van Der Kelen, Sabine Kliesch, Roland P Kuiper, Inge M M Lakeman, Lisa E E L O Lashley, Leendert H J Looijenga, Manon S Oud, Johanna Steingröver, Yardena Tenenbaum-Rakover, Carli M Tops, Frank Tüttelmann, Richarda M de Voer, Dineke Westra, Margot J Wyrwoll, Mariano Golubicki, Marina Antelo, Laia Bonjoch, Mariona Terradas, Laura Valle, Ludmil B Alexandrov, Hans Morreau, Tom van Wezel, Sergi Castellví-Bel, Yael Goldberg, Maartje Nielsen","doi":"10.1016/j.xhgg.2025.100480","DOIUrl":"https://doi.org/10.1016/j.xhgg.2025.100480","url":null,"abstract":"<p><p>MCM8 and MCM9 are newly proposed cancer predisposition genes, linked to polyposis and early-onset cancer, in addition to their previously established association with hypogonadism. Given the uncertain range of phenotypic manifestations and unclear cancer risk estimates, this study aimed to delineate the molecular and clinical characteristics of biallelic germline MCM8/MCM9 variant carriers. We found significant enrichment of biallelic MCM9 variants in individuals with colonic polyps (OR 6.51, 95% CI 1.24-34.11; P=0.03), rectal polyps (OR 8.40, 95% CI 1.28-55.35; P=0.03), and gastric cancer (OR 27.03, 95% CI 2.93-248.5; P=0.004) in data from the 100K Genomes Project, compared to controls. No similar enrichment was found for biallelic MCM8 variants or in the 200K UK Biobank. Likewise, in our case series, which included 26 MCM8 and 28 MCM9 variant carriers, we documented polyposis, gastric cancer, and early-onset colorectal cancer in MCM9 carriers, but not in MCM8 carriers. Moreover, our case series indicates that, beyond hypogonadism, biallelic MCM8 and MCM9 variants are associated with early-onset germ cell tumors (occurring before age 15). Tumors from MCM8/MCM9 variant carriers predominantly displayed clock-like mutational processes, without evidence of DNA repair deficiency-associated signatures. Collectively, our data indicates that biallelic MCM9 variants are associated with polyposis, gastric cancer, and early-onset CRC, while both biallelic MCM8 and MCM9 variants are linked to hypogonadism and the early development of germ cell tumors. These findings underscore the importance of including MCM8/MCM9 in diagnostic gene panels for certain clinical contexts and suggest that biallelic carriers may benefit from cancer surveillance.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100480"},"PeriodicalIF":3.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging Global Genetics Resources to Enhance Polygenic Prediction Across Ancestrally Diverse Populations.","authors":"Oliver Pain","doi":"10.1016/j.xhgg.2025.100482","DOIUrl":"https://doi.org/10.1016/j.xhgg.2025.100482","url":null,"abstract":"<p><p>Genome-wide association studies (GWAS) from multiple ancestral populations are increasingly available, offering opportunities to improve the accuracy and equity of polygenic scores (PGS). Several methods now aim to leverage multiple GWAS sources, but predictive performance and computational efficiency remain unclear, particularly when individual-level tuning data are unavailable. This study evaluates a comprehensive set of PGS methods across African (AFR), East Asian (EAS), and European (EUR) ancestries for 10 complex traits, using summary statistics from the Ugandan Genome Resource, Biobank Japan, UK Biobank, and the Million Veteran Program. Single-source PGS were derived using methods including DBSLMM, lassosum, LDpred2, MegaPRS, pT+clump, PRS-CS, QuickPRS, and SBayesRC. Multi-source approaches included PRS-CSx, TL-PRS, X-Wing, and combinations of independently optimised single-source scores. All methods were restricted to HapMap3 variants and used linkage disequilibrium reference panels matching the GWAS super population. A key contribution is a novel application of the LEOPARD method to estimate optimal linear combinations of population-specific PGS using only summary statistics. Analyses were implemented using the open-source GenoPred pipeline. In AFR and EAS populations, PGS combining ancestry-aligned and European GWAS outperformed single-source models. Linear combinations of independently optimised scores consistently outperformed current jointly optimised multi-source methods, while being substantially more computationally efficient. The LEOPARD extension offered a practical solution for tuning these combinations when only summary statistics were available, achieving performance comparable to tuning with individual-level data. These findings highlight a flexible and generalisable framework for multi-source PGS construction. The GenoPred pipeline supports more equitable, accurate, and accessible polygenic prediction.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100482"},"PeriodicalIF":3.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotypic, functional, and phenotypic characterization in CTNNB1 neurodevelopmental syndrome.","authors":"Nina Žakelj, David Gosar, Špela Miroševič, Stephan J Sanders, Alicia Ljungdhal, Sayeh Kohani, Shouhe Huang, Lok I Leong, Ying An, Miou-Jing Teo, Fiona Moultrie, Roman Jerala, Duško Lainšček, Vida Forstnerič, Petra Sušjan, Leszek Lisowski, Andrea Perez-Iturralde, Jasna Oražem Mrak, Ho Yin Edwin Chan, Damjan Osredkar","doi":"10.1016/j.xhgg.2025.100483","DOIUrl":"https://doi.org/10.1016/j.xhgg.2025.100483","url":null,"abstract":"<p><p>CTNNB1 neurodevelopmental syndrome is a rare disorder caused by de novo heterozygous variants in the CTNNB1 gene encoding β-catenin. This study aims to characterize genetic variants in individuals with CTNNB1 neurodevelopmental syndrome, systematically assess the spectrum of clinical phenotypes using standardized measures and explore potential genotype-phenotype correlations. In this cross-sectional cohort study, individuals diagnosed with CTNNB1 neurodevelopmental syndrome underwent structured interviews using standardized scales to evaluate motor skills, speech, communication, feeding abilities, visual function, neurodevelopment, and psychopathology. Genetic variants were analyzed, and in a subset of cases, the impact of β-catenin variants on the Wnt/β-catenin signaling pathway was assessed. Across the 127 included participants (mean age: 70 months; range: 7-242 months) from 20 countries, we identified 88 different variants of the CTNNB1 gene, 87 of which were predicted to lead to loss of CTNNB1 function. Functional assays demonstrated reduced Wnt signaling activity, including 11 variants that also exhibited a dominant-negative effect. One missense variant demonstrated a gain-of-function effect. Dominant-negative variants were not clearly associated with a distinct phenotype, however, those with missense variants presented a milder phenotype, including earlier achievement of independent walking, fewer motor impairments, better conceptual and social skills, improved communication, and fewer feeding difficulties. This study describes genetic, functional, and phenotypic characteristics in individuals with CTNNB1 neurodevelopmental syndrome. Further investigation into the genotypic and phenotypic characteristics of this syndrome and their interrelationships is essential to deepen our understanding of the disorder and inform the development of targeted therapies.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100483"},"PeriodicalIF":3.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Genotype-Phenotype Analysis in POLR3-Related Disorders.","authors":"Mackenzie A Michell-Robinson, Stefanie Perrier, Samuel Gauthier, Alexa Derksen, Quentin Sabbagh, Mathias Girbig, Agata D Misiaszek, Amy M Pizzino, Deborah L Renaud, Danilo De Assis Pereira, Paola Okuda, Luciana Maestri Karoleska, Stephanie Keller, Karen Chong, Laurence Gauquelin, Bernard Brais, Barbara Leube, Tiffany Grider, Michael E Shy, Rebecca Schüle, Martina Minnerop, Enrico Bertini, Francesco Nicita, Davide Tonduti, Christoph W Müller, Adeline Vanderver, Nicole I Wolf, Geneviève Bernard","doi":"10.1016/j.xhgg.2025.100481","DOIUrl":"https://doi.org/10.1016/j.xhgg.2025.100481","url":null,"abstract":"<p><p>RNA Polymerase III (POLR3)-related disorders (POLR3-RD) are a group of clinical entities characterized by causal variants in genes encoding Pol III subunits, including POLR3A, POLR3B, POLR1C, POLR1D, POLR3D, POLR3E, POLR3F, POLR3GL, POLR3H, and POLR3K. These typically cause developmental phenotypes affecting the central nervous system, the eyes, connective tissues including bones, teeth, endocrine axes, and the reproductive system. Similar phenotypes can be caused by variants in separate subunit genes (multigenic). In contrast, variants in the same gene can cause different phenotypes (pleiotropy), making genotype-phenotype correlation challenging. POLR3-RD, though individually rare, have never been analyzed collectively. To bridge this gap, we developed an extensive database encompassing all published and unpublished cases of POLR3-RD and conducted the first comprehensive genotype-phenotype correlation study across their entire spectrum. This work contributed new cases, representing 13% of all documented cases in the literature, along with 31 novel variants, accounting for 8% of all identified variants. This database was constructed by systematically reviewing the literature and integrating data from patients under the care of our international network of collaborators. The dataset includes genotype curation, bioinformatics, prior publications, and individual patient outcome information. By leveraging this comprehensive data, we were able to establish clear genotype-phenotype correlations for some pathogenic variants, which will help provide optimal clinical care, genetic counseling (including insights into disease phenotypes and progression), and offer valuable guidance for future clinical trial design and patient stratification.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100481"},"PeriodicalIF":3.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of de novo variants in KCTD10 as a proposed cause for multiple congenital anomalies.","authors":"Michelle M Morrow, Erin Torti, Bobbi McGivern, Ryan Gates, Mir Reza Bekheirnia, Nasim Bekheirnia, Leandra Folk, Shannon Holtrop, Timothy Blake Palculict, Olivia L Redlich, Adi Reich, Maria J Guillen Sacoto, Lisong Shi, Ingrid M Wentzensen, Kirsty McWalter","doi":"10.1016/j.xhgg.2025.100426","DOIUrl":"10.1016/j.xhgg.2025.100426","url":null,"abstract":"<p><p>To date, the KCTD10 gene (MIM: 608726) has not been definitively associated with a human disease, although studies in animal models suggest that it plays a role in embryonic development. We have identified multiple unrelated individuals with de novo missense variants and overlapping phenotypes, including congenital heart anomalies and congenital anomalies in other organ systems, in our internal database. This report includes a detailed description of the genotype and phenotype for two consented individuals and aggregate data of additional individuals who were not available for case-specific publication. Based on the data presented here, we propose that damaging de novo missense KCTD10 variants are associated with an autosomal dominant phenotype that includes cardiac and other congenital anomalies. We encourage additional studies to further characterize this condition and identify a mechanism for disease.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100426"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693620","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":"Multi-tissue transcriptome-wide association study identifies novel candidate genes and pleiotropy effects across four abdominal hernia subtypes.","authors":"Dima L Chaar, Chen Jiang, Brandon Cowan, Sahil Patel, Mark Kvale, Jie Yin, Rouzbeh Mostaedi, Nadav Ahituv, Eric Jorgenson, Thomas J Hoffmann, Hélène Choquet","doi":"10.1016/j.xhgg.2025.100436","DOIUrl":"10.1016/j.xhgg.2025.100436","url":null,"abstract":"<p><p>Abdominal hernias are caused by the protrusion of an organ or tissue through a weakened abdominal wall. Genome-wide association studies (GWASs) have identified 81 genetic susceptibility loci for different hernia subtypes, with 26 loci associated with more than one hernia type; however, additional work is needed to prioritize causal genes at known GWAS loci, identify novel ones, and characterize shared genetic effects across hernia subtypes. We conduct transcriptome-wide association study (TWAS) analyses of four hernia subtypes (i.e., inguinal, umbilical, ventral, femoral) using GWAS summary statistics from up to 57,291 hernia cases and 436,717 controls of European ancestry. Our TWAS, which leveraged imputed gene expression from 54 tissues, identifies 211 unique genes, of which 85 did not overlap with known hernia-associated loci. We also investigate patterns of pleiotropy and identify four genes (LYPLAL1-AS1, RIMKLBP2, AL513283.1, and EFEMP1) associated with all four hernia subtypes. Our findings enhance understanding of transcriptomic mechanisms through which hernias develop.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":"6 3","pages":"100436"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12050004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988280","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":"Targeted sequencing for hereditary breast and ovarian cancer in BRCA1/2-negative families reveals complex genetic architecture and phenocopies.","authors":"Jocelyn N Plowman, Evanjalina J Matoy, Lavanya V Uppala, Samantha B Draves, Cynthia J Watson, Bridget A Sefranek, Mark L Stacey, Samuel P Anderson, Michael A Belshan, Elizabeth E Blue, Chad D Huff, Yusi Fu, Holly A F Stessman","doi":"10.1016/j.xhgg.2025.100453","DOIUrl":"10.1016/j.xhgg.2025.100453","url":null,"abstract":"","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":"6 3","pages":"100453"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136418","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":"Transcriptomic signatures of rare variant impacts across sex and the X chromosome.","authors":"Rachel A Ungar, Taibo Li, Nikolai G Vetr, Nicole Ersaro, Alexis Battle, Stephen B Montgomery","doi":"10.1016/j.xhgg.2025.100463","DOIUrl":"10.1016/j.xhgg.2025.100463","url":null,"abstract":"<p><p>The human X chromosome contains hundreds of genes and has well-established impacts on sex differences and traits. However, the X chromosome is often excluded from many genetic analyses, limiting broader understanding of variant effects. In particular, the functional impact of rare variants on the X chromosome is understudied. To investigate functional rare variants on the X chromosome, we use observations of outlier gene expression from Genotype Tissue Expression consortium data. We show that outlier genes are enriched for having nearby rare variants on the X chromosome, and this enrichment is stronger for males. Using the RIVER model, we identified 733 rare variants in 450 genes predicted to have functional differences between males and females. We examined the pharmacogenetic implications of these variants and observed that 25% of drugs with a known sex difference in adverse drug reactions were connected to genes that contained a sex-biased rare variant. We further identify that sex-biased rare variants preferentially impact transcription factors with predicted sex-differential binding, such as the XIST-modulated SIX1. Overall, we observed more within-sex variation than between-sex variation. Combined, our study investigates functional rare variants on the X chromosome, and further details how sex stratification of variant effect prediction improves identification of rare variants with predicted sex-biased effects, transcription factor biology, and pharmacogenomic impacts.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100463"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200159","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}