HGG Advances最新文献

{"title":"Missense variants weakening a SOX9 phosphodegron linked to odontogenesis defects, scoliosis, and other skeletal features.","authors":"Imane Ettaki, Abdul Haseeb, Anirudha Karvande, Ghita Amalou, Asmae Saih, Imane AitRaise, Salsabil Hamdi, Lahcen Wakrim, Abdelhamid Barakat, Hassan Fellah, Mustapha El Alloussi, Véronique Lefebvre","doi":"10.1016/j.xhgg.2025.100404","DOIUrl":"10.1016/j.xhgg.2025.100404","url":null,"abstract":"<p><p>SOX9 encodes an SRY-related transcription factor critical for chondrogenesis and sex determination among other processes. Loss-of-function variants cause campomelic dysplasia and Pierre Robin sequence, while both gain- and loss-of-function variants cause disorders of sex development. SOX9 has also been linked to scoliosis and cancers, but variants are undetermined. It is highly expressed in tooth progenitor cells, but its odontogenic roles remain elusive, and tooth defects are unreported in SOX9-related conditions. Here, we performed whole-exome sequencing for nine unrelated children with tooth eruption delay and no known syndromes and identified a 7-year-old girl heterozygous for a SOX9 p.Thr239Pro variant and a 10-year-old boy heterozygous for presumably adjacent p.Thr239Pro and p.Thr240Pro variants. These variants were de novo and rare in control populations. Both cases had primary tooth eruption delay. Additionally, the boy had mesiodens blocking permanent central upper incisor eruption, severe scoliosis, and mild craniofacial and appendicular skeleton abnormalities. p.Thr239 and p.Thr240 occupy variable and obligatory positions, respectively, in a cell division control protein 4 (Cdc4)/FBXW7-targeted phosphodegron motif (CPD) fully conserved in SOX9 vertebrate orthologs and SOX8 and SOX10 paralogs, but functionally uncharacterized in vivo. Structural modeling predicted p.Thr240Pro and p.Thr239Pro/p.Thr240Pro but not p.Thr239Pro to strongly reduce SOX9/FBXW7 interaction. Accordingly, p.Thr240Pro and p.Thr239Pro/p.Thr240Pro but not p.Thr239Pro blocked FBXW7-induced SOX9 degradation in cultured cells. All variants increased SOX9-mediated reporter activation independently of protein stabilization, suggesting that CPD may also modulate the transactivation function of SOX9. Altogether, these findings concur that CPD has critical functions, that SOX9 decisively controls odontogenesis, and that gain-of-function variants may markedly perturb both this process and skeletogenesis.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100404"},"PeriodicalIF":3.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967213","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 recurrent variant in PPP2R5C identified in individuals with macrocephaly, intellectual disability, and seizures.","authors":"Alison M Muir, Adi Reich, Fanggeng Zou, Deanna Alexis Carere, Sue Moyer Harasink, Lily Tran, Bobbi McGivern","doi":"10.1016/j.xhgg.2024.100394","DOIUrl":"10.1016/j.xhgg.2024.100394","url":null,"abstract":"<p><p>PPP2R5C encodes a B-type regulatory subunit of protein phosphatase 2A (PP2A). This protein serine/threonine phosphatase is a component of multiple signaling pathways and is an established negative regulator of cell division, growth, and proliferation. De novo variants in other subunits of PP2A are associated with neurodevelopment disorders and intellectual disability (ID). We report two unrelated affected individuals with a recurrent variant in PPP2R5C (c.457G>A: p.(Glu153Lys)). Core features in affected individuals include macrocephaly, ID, hypotonia, and seizures. The Glu153 residue is part of a highly conserved acidic loop and directly interacts with the PP2A catalytic subunit. Our results support heterozygous PPP2R5C missense variants as a potential cause of macrocephaly and neurodevelopmental disorder.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100394"},"PeriodicalIF":3.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855740","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":"Genome-wide maps of highly-similar intrachromosomal repeats that can mediate ectopic recombination in three human genome assemblies.","authors":"Luis Fernandez-Luna, Carlos Aguilar-Perez, Christopher M Grochowski, Michele G Mehaffey, Claudia M B Carvalho, Claudia Gonzaga-Jauregui","doi":"10.1016/j.xhgg.2024.100396","DOIUrl":"10.1016/j.xhgg.2024.100396","url":null,"abstract":"<p><p>Repeated sequences spread throughout the genome play important roles in shaping the structure of chromosomes and facilitating the generation of new genomic variation through structural rearrangements. Several mechanisms of structural variation formation use shared nucleotide similarity between repeated sequences as substrate for ectopic recombination. We performed genome-wide analyses of direct and inverted intrachromosomal repeated sequence pairs with 200 bp or more and 80% or greater sequence identity in three human genome assemblies, GRCh37, GRCh38, and T2T-CHM13. Overall, the composition and distribution of direct and inverted repeated sequences identified was similar among the three assemblies involving 13%-15% of the haploid genome, with an increased, albeit not significant, number of repeated sequences in T2T-CHM13. Interestingly, the majority of repeated sequences are below 1 kb in length with a median of 84.2% identity, highlighting the potential relevance of smaller, less identical repeats, such as Alu-Alu pairs, for ectopic recombination. We cross-referenced the identified repeated sequences with protein-coding genes to identify those at risk for being involved in genomic rearrangements. Olfactory receptors and immune response genes were enriched among those impacted.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100396"},"PeriodicalIF":3.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898716","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 proposed role for CDO1 in CNS development: Three children with rare missense variants and a neurological phenotype.","authors":"Leah Rowe, Sureni V Mullegama, Rachel Lombardo, Caitlin Barnes, Shelley Towner, Matthew T Snyder, Alexis Heidlebaugh, Heather Riordan, Amber Begtrup, Amy Crunk, Hong Cui, Amy E Dameron, Leandra Folk, Maria J Guillen Sacoto, Jane Juusola, Olivia L Redlich, Adi Reich, Bobbi McGivern","doi":"10.1016/j.xhgg.2025.100417","DOIUrl":"10.1016/j.xhgg.2025.100417","url":null,"abstract":"<p><p>Cysteine dioxygenase type 1 (CDO1) encodes a non-heme iron dioxygenase, which is involved in cysteine metabolism. While CDO1 has been proposed to be involved in multiple physiological processes, an association with congenital disease has yet to be well defined. This study presents detailed clinical and molecular information on three individuals with overlapping neurological features. All three individuals were found to have rare, conserved, de novo variants clustered in a conserved region of the CDO1 gene with no alternative genetic etiology identified. Features present in all three individuals included electroencephalogram abnormality or seizure, movement abnormalities, hypertonia, encephalopathy, severe microcephaly (-4 SD below mean), growth failure, feeding difficulty, and abnormal brain morphology. Other common features included global developmental delay, sleep disturbance, contractures, cerebral palsy, hyper-reflexia, hearing loss, and hypoxic respiratory failure. This study provides evidence supporting an association between de novo CDO1 missense variants and human neurological disease.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100417"},"PeriodicalIF":3.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415416","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":"Unraveling the genetic landscape of susceptibility to multiple primary cancers.","authors":"Pooja Middha, Linda Kachuri, Jovia L Nierenberg, Rebecca E Graff, Taylor B Cavazos, Thomas J Hoffmann, Jie Zhang, Stacey Alexeeff, Laurel Habel, Douglas A Corley, Stephen Van Den Eeden, Lawrence H Kushi, Elad Ziv, Lori C Sakoda, John S Witte","doi":"10.1016/j.xhgg.2025.100413","DOIUrl":"10.1016/j.xhgg.2025.100413","url":null,"abstract":"<p><p>With advances in cancer screening and treatment, there is a growing population of cancer survivors who may develop subsequent primary cancers. While hereditary cancer syndromes account for only a portion of multiple cancer cases, we sought to explore the role of common genetic variation in susceptibility to multiple primary tumors. We conducted a cross-ancestry genome-wide association study (GWAS) and transcriptome-wide association study (TWAS) of 10,983 individuals with multiple primary cancers, 84,475 individuals with single cancer, and 420,944 cancer-free controls from two large-scale studies. Our GWAS identified six lead variants across five genomic regions that were significantly associated (p < 5 × 10^-8) with the risk of developing multiple primary tumors (overall and invasive) relative to cancer-free controls (at 3q26, 8q24, 10q24, 11q13.3, and 17p13). We also found one variant significantly associated with multiple cancers when compared with single cancer cases (at 22q13.1). Multi-tissue TWAS detected associations with genes involved in telomere maintenance in two of these regions (ACTRT3 in 3q26 and SLK and STN1 in 10q24) and the development of multiple cancers. Additionally, the TWAS also identified several novel genes associated with multiple cancers, including two immune-related genes, IRF4 and TNFRSF6B. Telomere maintenance and immune dysregulation emerge as central, common pathways influencing susceptibility to multiple cancers. These findings underscore the importance of exploring shared mechanisms in carcinogenesis, offering insights for targeted prevention and intervention strategies.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100413"},"PeriodicalIF":3.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256912","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":"De novo missense variants in the RPEL3 domain of PHACTR4 in individuals with overlapping congenital anomalies.","authors":"Erin Torti, Sureni V Mullegama, Isabelle De Bie, Angelique Mercier, Deanna Alexis Carere, Leandra Folk, Jane Juusola, Kristin G Monaghan, Ingrid M Wentzensen, Olivia L Redlich, Adi Reich, Bobbi McGivern","doi":"10.1016/j.xhgg.2025.100421","DOIUrl":"10.1016/j.xhgg.2025.100421","url":null,"abstract":"<p><p>PHACTR4 is proposed to play a role in embryonic development but has yet to be associated with human disease. Here, we report the detailed clinical features of two individuals for whom molecular diagnostic testing was undertaken at a large diagnostic laboratory and who were found to harbor rare, damaging de novo missense variants in the conserved RPEL3 domain of PHACTR4. We also present aggregate information on additional individuals in whom missense variants in the same PHACTR4 gene region were detected. All presented with overlapping phenotypes. Features present in at least half of these individuals included cleft palate, ophthalmologic abnormalities, hearing impairment, dysmorphic facial features, digital anomalies, renal/urinary anomalies, growth delay, microcephaly, abnormal brain imaging, and neurodevelopmental abnormalities; some individuals had additional unique findings as well. The proposed cellular function of PHACTR4 and information from related genes with variants in an RPEL domain suggest that PHACTR4 is a promising candidate gene for human disease. We hope that this report will promote additional research interest in the PHACTR4 gene and lead to the publication of additional cases, to potentially establish a causative relationship and to further delineate the phenotypic and variant spectrum of a PHACTR4-related disorder.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100421"},"PeriodicalIF":3.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516824","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":"Caution when using network partners for target identification in drug discovery.","authors":"Dandan Tan, Yiheng Chen, Yann Ilboudo, Kevin Y H Liang, Guillaume Butler-Laporte, J Brent Richards","doi":"10.1016/j.xhgg.2025.100409","DOIUrl":"10.1016/j.xhgg.2025.100409","url":null,"abstract":"<p><p>Identifying novel, high-yield drug targets is challenging and often results in a high failure rate. However, recent data indicate that leveraging human genetic evidence to identify and validate these targets significantly increases the likelihood of success in drug development. Two recent papers from Open Targets claimed that around half of US Food and Drug Administration-approved drugs had targets with direct human genetic evidence. By expanding target identification to include protein network partners-molecules in physical contact-the proportion of drug targets with genetic evidence support increased to two-thirds. However, the efficacy of using these network partners for target identification was not formally tested. To address this, we tested the approach on a list of robust positive control genes. We used the IntAct database to find physically interacting proteins of genes identified by exome-wide association studies (ExWASs), genome-wide association studies (GWASs) combined with a locus-to-gene mapping algorithm called the Effector Index, and Genetic Priority Score (GPS), which integrated eight genetic features with drug indications from the Open Targets and SIDER databases. We assessed how accurately including interacting genes with the ExWAS-, Effector Index-, and GPS-selected genes identified positive controls, focusing on precision, sensitivity, and specificity. Our results indicated that although molecular interactions led to higher sensitivity in identifying positive control genes, their practical application is limited by low precision. Expanding genetically identified targets to include network partners using IntAct did not increase the likelihood of identifying drug targets across the 412 tested traits, suggesting that such results should be interpreted with caution.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100409"},"PeriodicalIF":3.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042160","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":"Transcriptome-wide analyses delineate the genetic architecture of expression variation in atopic dermatitis.","authors":"Charalabos Antonatos, Dimitra Mitsoudi, Alexandros Pontikas, Adam Akritidis, Panagiotis Xiropotamos, Georgios K Georgakilas, Sophia Georgiou, Aikaterini Tsiogka, Stamatis Gregoriou, Katerina Grafanaki, Yiannis Vasilopoulos","doi":"10.1016/j.xhgg.2025.100422","DOIUrl":"10.1016/j.xhgg.2025.100422","url":null,"abstract":"<p><p>Genome-wide association studies (GWASs) for atopic dermatitis (AD) have uncovered 81 risk loci in European participants; however, translating these findings into functional and therapeutic insights remains challenging. We conducted a transcriptome-wide association study (TWAS) in AD leveraging cis-eQTL data from sun exposed (n = 517), non-sun exposed skin (n = 602) and whole blood (n = 670) tissues and the latest GWAS of AD in Europeans (n = 864982). We implemented the OTTERS pipeline that combines polygenic risk score (PRS) techniques accommodating diverse assumptions in the architecture of gene regulation. We also used differential expression meta-analysis and co-expression networks (n = 186) to characterize the transcriptomic landscape of AD. We identified 176 gene-tissue associations covering 126 unique genes (53 previously unreported). Most TWAS risk genes were identified by adaptive PRS frameworks, with non-significant differences compared with clumping and thresholding approaches. TWAS risk genes were enriched in allergic reactions (e.g., AQP7, AFF4), skin barrier integrity (e.g., ACER3), and inflammatory pathways (e.g., TAPBPL). By integrating co-expression networks of lesional AD skin, we identified 16 hub genes previously identified as TWAS risk genes (six previously unreported) that orchestrate inflammatory responses (e.g., HSPA4) and keratinization (e.g., LCE3E, LCE3D), serving as potential drug targets through drug-gene interactions. Consistent associations between all analyses were reported for FOSL1 and RORC. Collectively, our findings provide additional risk genes for AD with potential implications in therapeutic approaches.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100422"},"PeriodicalIF":3.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524639","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":"Unbiased causal inference with Mendelian randomization and covariate-adjusted GWAS data.","authors":"Peiyao Wang, Zhaotong Lin, Wei Pan","doi":"10.1016/j.xhgg.2025.100412","DOIUrl":"10.1016/j.xhgg.2025.100412","url":null,"abstract":"<p><p>Mendelian randomization (MR) facilitates causal inference with observational data using publicly available genome-wide association study (GWAS) results. In a GWAS, one or more heritable covariates may be adjusted for to estimate the direct effects of SNPs on a focal trait or to improve statistical power, which may introduce collider bias in SNP-trait association estimates, thus affecting downstream MR analyses. Numerical studies suggested that using covariate-adjusted GWAS summary data might introduce bias in univariable Mendelian randomization (UVMR), which can be mitigated by multivariable Mendelian randomization (MVMR). However, it remains unclear and even mysterious why/how MVMR works; a rigorous theory is needed to explain and substantiate the above empirical observation. In this paper, we derive some analytical results when multiple covariates are adjusted for in the GWAS of exposure and/or the GWAS of outcome, thus supporting and explaining the empirical results. Our analytical results offer insights to how bias arises in UVMR and how it is avoided in MVMR, regardless of whether collider bias is present. We also consider applying UVMR or MVMR methods after collider-bias correction. We conducted extensive simulations to demonstrate that with covariate-adjusted GWAS summary data, MVMR had an advantage over UVMR by producing nearly unbiased causal estimates; however, in some situations it is advantageous to apply UVMR after bias correction. In real data analyses of the GWAS data with body mass index (BMI) being adjusted for metabolomic principal components, we examined the causal effect of BMI on blood pressure, confirming the above points.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100412"},"PeriodicalIF":3.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075715","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":"Togaram1 is expressed in the neural tube and its absence causes neural tube closure defects.","authors":"Yanyan Wang, Nadine Kraemer, Joanna Schneider, Olaf Ninnemann, Kai Weng, Michael Hildebrand, Joshua Reid, Na Li, Hao Hu, Shyamala Mani, Angela M Kaindl","doi":"10.1016/j.xhgg.2024.100363","DOIUrl":"10.1016/j.xhgg.2024.100363","url":null,"abstract":"<p><p>Neural tube closure defect pathomechanisms in human embryonic development are poorly understood. Here we identified spina bifida patients expressing novel variants of the TOGARAM gene family. TOGARAM1 has been associated with the ciliopathy Joubert syndrome, but its connection to spina bifida and role in neural development is unknown. We show that Togaram1 is expressed in the neural tube and Togaram1 knockout mice have abnormal cilia, reduced sonic hedgehog (Shh) signaling, abnormal neural tube patterning, and display neural tube closure defects. Neural stem cells from Togaram1 knockout embryos showed reduced cilia and defects in Shh signaling. Overexpression in IMCD3 and HEK293 cells of TOGARAM1 carrying the variant found in the spina bifida patient resulted in cilia defect along with reduced pericentriolar material one (PCM1), a critical constituent of centriolar satellites involved in transporting proteins toward the centrosome and primary cilia. Our results demonstrate the role of TOGARAM1 in regulating Shh signaling during early neural development that is critical for neural tube closure and elucidates potential mechanisms whereby the ciliopathy-associated gene TOGARAM1 gives rise to spina bifida aperta in humans.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100363"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393898","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}