Human molecular genetics最新文献

{"title":"Differential expression of a disease-associated MRE11 variant reveals distinct phenotypic outcomes.","authors":"McKenna B DeFoer, Ahmed M Mostafa, Andrea J Hartlerode, Steven K Orban, Keegan McDonough, Sophie Quirk, Brianna K L Ferguson, David O Ferguson, JoAnn M Sekiguchi","doi":"10.1093/hmg/ddaf154","DOIUrl":"10.1093/hmg/ddaf154","url":null,"abstract":"<p><p>The MRE11 DNA nuclease plays central roles in the repair of DNA double-strand breaks (DSBs) as a core component of the MRE11-RAD50-NBS1 (MRN) complex. MRN localizes to chromosomal DSBs and recruits and activates the DSB repair protein kinase, ATM, which phosphorylates downstream substrates to elicit cellular DNA damage responses. Pathogenic variants in MRE11 cause the genome instability disorder ataxia-telangiectasia-like disorder (ATLD). The first ATLD patient allele identified, ATLD1, is a nonsense mutation that deletes 76 residues from the MRE11 C-terminus and markedly reduces levels of MRE11-ATLD1 and the entire MRN complex. The MRE11 C-terminus has been demonstrated to function in DNA binding, mediate protein interactions, and undergo post-translational modifications that regulate the MRE11 nuclease. We previously demonstrated that transgenic mice expressing reduced wildtype MRN levels exhibit severe phenotypes, including small body size, anemia, and DNA DSB repair defects. Thus, it is currently unknown whether low MRE11-ATLD1 levels, loss of the C-terminus, or both cause disease-associated phenotypes. In this study, we generated transgenic mouse models that express near endogenous or significantly reduced levels of MRE11-ATLD1 to determine the in vivo importance of the MRE11 C-terminus. We observe that low MRE11-ATLD1 expression leads to anemia, bone marrow failure, extramedullary hematopoiesis, and impaired lymphocyte development, similar to mice expressing low wildtype MRE11. In contrast, higher MRE11-ATLD1 expression results in a subset of moderate phenotypes, indicating that loss of the C-terminus has limited impact on MRN functions in vivo. These findings provide a foundation for predicting the clinical presentation and severity of ATLD patient phenotypes.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic variants associated with gout identified through a genome-wide study in the UK biobank (N = 150 542).","authors":"Yiwen Tao, Tengda Cai, Qi Pan, Luning Yang, Sen Lin, Mainul Haque, Tania Dottorini, Abhishek Abhishek, Weihua Meng","doi":"10.1093/hmg/ddaf151","DOIUrl":"https://doi.org/10.1093/hmg/ddaf151","url":null,"abstract":"<p><p>Gout is a prevalent and painful form of inflammatory arthritis associated with hyperuricemia, which leads to monosodium urate crystal deposition in joints and surrounding tissues, triggering acute inflammatory responses. This disease is also closely linked to serious comorbidities, including cardiovascular diseases, chronic kidney diseases, diabetes, and increased mortality risk, significantly impacting global health. In this study, we conducted a comprehensive genome-wide association study (GWAS) based on the UK Biobank pain questionnaire 2019, comprising 10 474 gout cases and 140 068 controls, identifying 13 loci associated with gout. These findings were further explored in the FinnGen cohort, with 10 loci being replicated significantly. Sex-stratified analyses revealed notable differences, with 16 loci identified in males and two loci identified in females, reflecting both shared and sex -stratified genetic influences on gout susceptibility. In addition, genetic correlation analyses demonstrated strong associations between gout and traits related to urate levels, specific medication use, and metabolic functions. Transcriptome-wide association studies highlighted several genes, such as SLC16A9 and ASAH2B, which showed significant expression patterns across various tissues, implicating metabolic and immune pathways in gout. Phenome-wide association studies of significant single nucleotide polymorphisms revealed links to metabolic, immunological, and skeletal traits, underscoring the multi-faceted nature of gout. These results contribute valuable insights into the genetic architecture and biological mechanisms underlying gout, suggesting potential avenues for tailored interventions.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic heterogeneity and homogeneity among orofacial cleft subtypes: genome-wide association studies in the cleft collective.","authors":"Kyle Dack, Kerstin U Ludwig, Evie Stergiakouli, Jonathan Sandy, Sethlina Aryee, George Davey Smith, Amy Davies, Yvonne Wren, Gemma C Sharp, Kerry Humphries, Elisabeth Mangold, Lucy Goudswaard, Karen Ho, Tom Dudding, Sarah J Lewis","doi":"10.1093/hmg/ddaf131","DOIUrl":"https://doi.org/10.1093/hmg/ddaf131","url":null,"abstract":"<p><p>Several genome wide association studies (GWASs) of orofacial cleft have been conducted. However only a few such studies to date have combined all cleft cases, focused on subtypes other than non-syndromic cleft lip with/without cleft palate, or investigated subtype heterogeneity. We conducted a GWAS of orofacial clefts within 2268 cases from the Cleft Collective and 7913 population-based controls; we performed analyses of all orofacial clefts, plus 7 subgroups. We replicated our findings in a meta-analysis of independent samples and investigated patterns of correlation across subgroups. We identified 27 regions at genome-wide significance, 8 of which were novel. We also conducted the first GWAS of Pierre Robin Sequence, despite the small sample size (n cases = 237), we found one genome wide significant SNP (P < 5 × 10-8), and another 21 suggestive associations (P < 10-5). Novel loci include those mapping to LHX8 and TSBP1 (combined clefts), ARHGEF18 and ARHGEF19 (cleft lip with/without palate), FBN2 (cleft lip only), SLC35B3 (cleft palate only), CASC20 (Pierre Robin Sequence) and CHRM2 (non-syndromic cleft palate only). Several novel hits were in regions previously associated with facial morphology in GWAS or were in regions involved in key developmental processes, including neural crest cell migration and craniofacial development. We identified genetic loci with similar effects across all subgroups and some loci which were subtype specific, we also identified 3 loci with opposing effects on cleft lip and Pierre Robin sequence. Our findings highlight the merit of including all orofacial cleft subtypes in GWAS studies and investigating heterogeneity of effects across subtypes.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determining off-target effects of splice-switching antisense oligonucleotides using short read RNAseq in neuronally differentiated human induced pluripotent stem cells.","authors":"Elsa C Kuijper, Linda van der Graaf, Barry A Pepers, Mariana Guimarães Ramos, Sylvia Korhorn, Lodewijk J A Toonen, Davy Cats, Ronald A M Buijsen, Eleni Mina, Hailiang Mei, Willeke M C van Roon-Mom","doi":"10.1093/hmg/ddaf153","DOIUrl":"https://doi.org/10.1093/hmg/ddaf153","url":null,"abstract":"<p><p>Antisense oligonucleotides (AONs) are small pieces of chemically modified DNA or RNA that bind to RNA in a sequence-specific manner based on Watson-Crick base-pairing. Splice-switching AONs are designed to modulate pre-mRNA splicing, thereby for instance restoring protein expression or modifying the eventual protein to restore its function or reduce its toxicity. Given the current lack of in silico methods that adequately predict off-target splicing events, assessment of off-target effects of AONs in human cells using RNAseq could be a promising approach. The identification and prioritization of potential off-target effects for validation and further investigation into the biological relevance would contribute to the development of safe and effective AONs. In this study, we used three different splice-switching AONs targeting three different human transcripts to study their transcriptome-wide, hybridization-dependent off-target effects with short read RNAseq. Using the computational tools rMATS and Whippet, we identified differential splicing events of which only a minority could be explained by hybridization, illustrating the difficulty of predicting off-target effects based on sequence homology. The main splicing events could all be validated with RT-PCR. Furthermore, from the three AONs studied, one AON induced considerably more changes in gene expression and splicing compared to the two other AONs assessed, which was confirmed in a validation experiment. Our study demonstrates that interpretation of short read RNAseq data to determine off-target effects is challenging. Nonetheless, valuable results can be obtained as it allows the comparison of toxicity between different AONs within an experiment and identification of AON-specific off-target profiles.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic structural equation Modeling analysis of glaucoma Endophenotypes: investigating genetic architecture and non-intraocular pressure mechanisms.","authors":"Maryam Marzban, Santiago Diaz-Torres, Jackson Thorp, Jue Sheng Ong, Anthony P Khawaja, Christopher J Hammond, Pirro G Hysi, Louis R Pasquale, Peter Kraft, Jae H Kang, Alex W Hewitt, David A Mackey, Jamie E Craig, Janey L Wiggs, Stuart MacGregor, Puya Gharahkhani","doi":"10.1093/hmg/ddae191","DOIUrl":"https://doi.org/10.1093/hmg/ddae191","url":null,"abstract":"<p><p>To explore the genetic underpinnings of glaucoma endophenotypes influenced by mechanisms other than intraocular pressure (IOP), this study employs genomic structural equation modelling (GenomicSEM) and utilises summary statistics from Genome-Wide Association Studies (GWAS) to examine endophenotypes associated with non-IOP mechanisms. We investigated the genetic relationships among primary open-angle glaucoma (POAG) and key endophenotypes: IOP, normal tension glaucoma (NTG), vertical cup disc ratio (VCDR), total macular thickness, ganglion cell-inner plexiform layer (GCIPL), and retinal nerve fiber layer (RNFL), through exploratory factorial analysis (EFA) and confirmatory factorial analyses (CFA). GWAS-by-subtraction approach was employed to explore the genetic architecture of non-IOP components. Post-GWAS analyses implemented in Functional Mapping and Annotation (FUMA) and Multi-marker Analysis of Genomic Annotation (MAGMA) were conducted to identify non-IOP genes and pathways. The EFA revealed that 60% of the cumulative variance was explained by two latent factors (F1, F2). F1 included VCDR, POAG, NTG, and IOP, while F2 comprised RNFL, GCIPL, macular thickness, and VCDR. Significant associations between F2 and macular thickness and RNFL persisted after subtracting IOP. MAGMA analysis identified IOP-independent pathways for macular thickness and VCDR, primarily involving nerve and vascular pathways. Despite lower IOP levels in NTG patients, GWAS-by-subtraction revealed both significant IOP and non-IOP components for NTG. This research highlights the significance of non-IOP mechanisms in the development of glaucoma. Targeting these mechanisms could pave the way for developing novel treatments that extend beyond conventional IOP-based therapies. Further research is needed to explore non-IOP pathways in NTG and validate these findings across diverse populations.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atypical phenotypic characteristics, mutation analysis and treatment in a family of riboflavin transporter deficiency caused by SLC52A3 variants.","authors":"Peipei Li, Ting Zhang, Hongen Xu, Mengwei Zhao, Yingying Wang, Ziwen Zhao, Mengli Zhang, Xingle Zhao, Bei Chen","doi":"10.1093/hmg/ddaf155","DOIUrl":"https://doi.org/10.1093/hmg/ddaf155","url":null,"abstract":"<p><p>Variants in the SLC52A3 gene have been associated with riboflavin transporter deficiency type 3 (RTD3), a severe neurodegenerative disorder, typically inherited in an autosomal recessive manner. In this study, two SLC52A3 variants (NM_033409.4: c.62A > G [p.Asn21Ser] and c.161G > A [p.Gly54Glu]) were identified in a family with hereditary hearing loss through whole-exome sequencing. The compound heterozygous proband exhibited only late-onset, progressive, and symmetric sensorineural hearing loss over 23 yr, along with unilateral facial muscle spasm. A heterozygous carrier of the c.62A > G variant also exhibited optic nerve dysfunction, while no other neurological abnormalities were observed in the family. Although the proband's decreased serum riboflavin level has been improved through supplementation, no significant clinical improvement was observed. These findings further support the phenotypic variability, incomplete penetrance, and a potential autosomal dominant inheritance pattern of RTD3. We also underscore the importance of early genetic testing, timely and sustained riboflavin supplementation, and long-term follow-up in affected individuals.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human and pathogen-encoded circular RNAs in viral infections: insights into functions and therapeutic opportunities.","authors":"Noah L Mueller, Adela Dujsikova, Amrita Singh, Y Grace Chen","doi":"10.1093/hmg/ddaf031","DOIUrl":"10.1093/hmg/ddaf031","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are emerging as important regulatory molecules in both host and viral systems, acting as microRNA sponges, protein decoys or scaffolds, and templates for protein translation. Host-derived circRNAs are increasingly recognized for their roles in immune responses, while virus-encoded circRNAs, especially those from DNA viruses, have been shown to modulate host cellular machinery to favor viral replication and immune evasion. Recently, RNA virus-encoded circRNAs were also discovered, but evidence suggests that they might be generated using a different mechanism compared to the circRNAs produced from the host and DNA viruses. This review highlights recent advances in our understanding of both host and virus-derived circRNAs, with a focus on their biological roles and contributions to pathogenesis. Furthermore, we discuss the potential of circRNAs as biomarkers and their application as therapeutic targets or scaffolds for RNA-based therapies. Understanding the roles of circRNAs in host-virus interactions offers novel insights into RNA biology and opens new avenues for therapeutic strategies against viral diseases and associated cancers.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"R54-R67"},"PeriodicalIF":3.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional downregulation of rhodopsin is associated with desensitization of rods to light-induced damage in a murine model of retinitis pigmentosa.","authors":"Shimpei Takita, Hemavathy Harikrishnan, Masaru Miyagi, Yoshikazu Imanishi","doi":"10.1093/hmg/ddaf146","DOIUrl":"10.1093/hmg/ddaf146","url":null,"abstract":"<p><p>Class I rhodopsin mutations are known for some of the most severe forms of vision impairments in dominantly inherited rhodopsin retinitis pigmentosa. They disrupt the VxPx transport signal, which is required for the proper localization of rhodopsin to the outer segments. While various studies have focused on the light-dependent toxicity of mutant rhodopsin, it remains unclear whether and how these mutations exert dominant-negative effects. Using the class I RhoQ344X rhodopsin knock-in mouse model, we characterized the expression of rhodopsin and other genes by RNA sequencing and qPCR. Those studies indicated that rhodopsin is the most prominently downregulated photoreceptor-specific gene in RhoQ344X/+ mice. Rhodopsin mRNA is downregulated significantly prior to the onset of rod degeneration, whereas mRNA downregulation of other phototransduction components, transducinα, and Pde6α, occurs after the onset and correlate with the degree of rod cell loss. Those studies indicated that the mutant rhodopsin gene causes downregulation of wild-type rhodopsin, imposing a transcript-level dominant-negative effect. Moreover, it causes downregulation of the mutant mRNA itself, mitigating the toxicity. The transcript-level dominant effect was also observed in the major class II rhodopsin mutant model, RhoP23H/+ mice, in which mutant rhodopsin is prone to misfold. Potentially due to mitigated toxicity by reduced rhodopsin expression, RhoQ344X/+ mice did not exhibit light-dependent exacerbation of rod degeneration, even after continuous exposure of mice for 5 days at 3000 lux. Thus, this study describes a novel form of dominant-negative effect in inherited neurodegenerative disorders.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STING: a multifaced player in cellular homeostasis.","authors":"Kun Song, Lyu Heng, Nan Yan","doi":"10.1093/hmg/ddae175","DOIUrl":"10.1093/hmg/ddae175","url":null,"abstract":"<p><p>The stimulator of interferon gene (STING) is an important innate immune mediator of the cytoplasmic DNA sensing pathway. As a mediator known for its role in the immune response to infections, STING is also surprisingly at the center of a variety of non-infectious human diseases, including cancer, autoimmune diseases and neurodegenerative diseases. Recent studies have shown that STING has many signaling activities, including type I interferon (IFN-I) and other IFN-independent activities, many of which are poorly understood. STING also has the unique property of being continuous transported from the ER to the Golgi then to the lysosome. Mutations of STING or trafficking cofactors are associated with human diseases affecting multiple immune and non-immune organs. Here, we review recent advances in STING trafficking and signaling mechanisms based in part on studies of STING-associated monogenic inborn error diseases.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"R68-R74"},"PeriodicalIF":3.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inborn errors of canonical autophagy in neurodegenerative diseases.","authors":"Dennis Freisem, Helene Hoenigsperger, Alberto Catanese, Konstantin M J Sparrer","doi":"10.1093/hmg/ddae179","DOIUrl":"10.1093/hmg/ddae179","url":null,"abstract":"<p><p>Neurodegenerative disorders (NDDs), characterized by a progressive loss of neurons and cognitive function, are a severe burden to human health and mental fitness worldwide. A hallmark of NDDs such as Alzheimer's disease, Huntington's disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and prion diseases is disturbed cellular proteostasis, resulting in pathogenic deposition of aggregated protein species. Autophagy is a major cellular process maintaining proteostasis and integral to innate immune defenses that mediates lysosomal protein turnover. Defects in autophagy are thus frequently associated with NDDs. In this review, we discuss the interplay between NDDs associated proteins and autophagy and provide an overview over recent discoveries in inborn errors in canonical autophagy proteins that are associated with NDDs. While mutations in autophagy receptors seems to be associated mainly with the development of ALS, errors in mitophagy are mainly found to promote PD. Finally, we argue whether autophagy may impact progress and onset of the disease, as well as the potential of targeting autophagy as a therapeutic approach. Concludingly, understanding disorders due to inborn errors in autophagy-\"autophagopathies\"-will help to unravel underlying NDD pathomechanisms and provide unique insights into the neuroprotective role of autophagy, thus potentially paving the way for novel therapeutic interventions.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"R23-R34"},"PeriodicalIF":3.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}