Human Genomics最新文献

{"title":"Correction: Shared genetics between breast cancer and predisposing diseases identifies novel breast cancer treatment candidates.","authors":"Panagiotis N Lalagkas, Rachel D Melamed","doi":"10.1186/s40246-024-00707-4","DOIUrl":"10.1186/s40246-024-00707-4","url":null,"abstract":"","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"6"},"PeriodicalIF":3.8,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The GeoTox Package: open-source software for connecting spatiotemporal exposure to individual and population-level risk.","authors":"Kyle P Messier, David M Reif, Skylar W Marvel","doi":"10.1186/s40246-024-00711-8","DOIUrl":"10.1186/s40246-024-00711-8","url":null,"abstract":"<p><strong>Background: </strong>Comprehensive environmental risk characterization, encompassing physical, chemical, social, ecological, and lifestyle stressors, necessitates innovative approaches to handle the escalating complexity. This is especially true when considering individual and population-level diversity, where the myriad combinations of real-world exposures magnify the combinatoric challenges. The GeoTox framework offers a tractable solution by integrating geospatial exposure data from source-to-outcome in a series of modular, interconnected steps.</p><p><strong>Results: </strong>Here, we introduce the GeoTox open-source R software package for characterizing the risk of perturbing molecular targets involved in adverse human health outcomes based on exposure to spatially-referenced stressor mixtures. We demonstrate its usage in building computational workflows that incorporate individual and population-level diversity. Our results demonstrate the applicability of GeoTox for individual and population-level risk assessment, highlighting its capacity to capture the complex interplay of environmental stressors on human health.</p><p><strong>Conclusions: </strong>The GeoTox package represents a significant advancement in environmental risk characterization, providing modular software to facilitate the application and further development of the GeoTox framework for quantifying the relationship between environmental exposures and health outcomes. By integrating geospatial methods with cutting-edge exposure and toxicological frameworks, GeoTox offers a robust tool for assessing individual and population-level risks from environmental stressors. GeoTox is freely available at https://niehs.github.io/GeoTox/ .</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"5"},"PeriodicalIF":3.8,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The interplay of sex and genotype in disease associations: a comprehensive network analysis in the UK Biobank.","authors":"Vivek Sriram, Jakob Woerner, Yong-Yeol Ahn, Dokyoon Kim","doi":"10.1186/s40246-024-00710-9","DOIUrl":"10.1186/s40246-024-00710-9","url":null,"abstract":"<p><strong>Background: </strong>Disease comorbidities and longer-term complications, arising from biologically related associations across phenotypes, can lead to increased risk of severe health outcomes. Given that many diseases exhibit sex-specific differences in their genetics, our objective was to determine whether genotype-by-sex (GxS) interactions similarly influence cross-phenotype associations. Through comparison of sex-stratified disease-disease networks (DDNs)-where nodes represent diseases and edges represent their relationships-we investigate sex differences in patterns of polygenicity and pleiotropy between diseases.</p><p><strong>Results: </strong>Using UK Biobank summary statistics, we built male- and female-specific DDNs for 103 diseases. This revealed that male and female diseasomes have similar topology and central diseases (e.g., hypertensive, chronic respiratory, and thyroid-based disorders), yet some phenotypes exhibit sex-specific influence in cross-phenotype associations. Multiple sclerosis and osteoarthritis are central only in the female DDN, while cardiometabolic diseases and skin cancer are more prominent in the male DDN. Edge comparison indicated similar shared genetics between the two graphs relative to a random model of disease association, though notable discrepancies in embedding distances and clustering patterns imply a more expansive genetic influence on multimorbidity risk for females than males. Analysis of pleiotropic contributions of two sexually-dimorphic single-nucleotide polymorphisms related to thyroid disorders further validated a distinct genetic architecture across sexes that influences associations, confirmed through examination of corresponding gene expression profiles from the GTEx Portal.</p><p><strong>Conclusions: </strong>Our analysis affirms the presence of GxS interactions in cross-phenotype associations, emphasizing the need to investigate the role of sex in disease onset and its importance in biomedical discovery and precision medicine research.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"4"},"PeriodicalIF":3.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High clinical utility of long-read sequencing for precise diagnosis of congenital adrenal hyperplasia in 322 probands.","authors":"Yunpeng Wang, Gaohui Zhu, Danhua Li, Yu Pan, Rong Li, Ting Zhou, Aiping Mao, Libao Chen, Jing Zhu, Min Zhu","doi":"10.1186/s40246-024-00696-4","DOIUrl":"https://doi.org/10.1186/s40246-024-00696-4","url":null,"abstract":"<p><strong>Background: </strong>The molecular genetic diagnosis of congenital adrenal hyperplasia (CAH) is very challenging due to the high homology between the CYP21A2 gene and its pseudogene CYP21A1P.</p><p><strong>Methodology: </strong>This study aims to assess the clinical efficacy of targeted long-read sequencing (T-LRS) by comparing it with a control method based on the combined assay (NGS, Multiplex ligation-dependent probe amplification and Sanger sequencing) and to introduce T-LRS as a first-tier diagnostic test for suspected CAH patients to improve the precise diagnosis of CAH.</p><p><strong>Results: </strong>A large cohort of 562 participants including 322 probands and 240 family members was enrolled for the perspective (96 probands) and prospective study (226 probands). The comparison analysis of T-LRS and control method have been performed. In the perspective study, 96 probands were identified using both the control method and T-LRS. Concordant results were detected in 85.42% (82/96) of probands. T-LRS performed more precise diagnosis in 14.58% (14/96) of probands. Among these, a novel 4141 kb deletion involving CYP21A2 and TNXB was established. A new diagnosis was improved by T-LRS. The duplications were also precisely identified to clarify the misdiagnosis by MLPA. In the prospective study, Variants were identified not only in CYP21A2 but also in HSD3B2 and CYP11B1 in 226 probands. Expand to 322 probands, the actual frequency of duplication haplotype (1.55%) could be calculated due to the accurate genotyping. Moreover, 75.47% of alleles with SNVs/indels, 22.20% of alleles with deletion chimeras.</p><p><strong>Conclusion: </strong>T-LRS has higher resolution and reduced cost than control method with accurate diagnosis. The clinical utility of L-LRS could help to provide precision therapy to CAH patients, advance the life-long management of this complex disease and promote our understanding of CAH.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"3"},"PeriodicalIF":3.8,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the role of splicing in TP53 variant pathogenicity through predictions and minigene assays.","authors":"Cristina Fortuno, Inés Llinares-Burguet, Daffodil M Canson, Miguel de la Hoya, Elena Bueno-Martínez, Lara Sanoguera-Miralles, Sonsoles Caldes, Paul A James, Eladio A Velasco-Sampedro, Amanda B Spurdle","doi":"10.1186/s40246-024-00714-5","DOIUrl":"10.1186/s40246-024-00714-5","url":null,"abstract":"<p><strong>Background: </strong>TP53 variant classification benefits from the availability of large-scale functional data for missense variants generated using cDNA-based assays. However, absence of comprehensive splicing assay data for TP53 confounds the classification of the subset of predicted missense and synonymous variants that are also predicted to alter splicing. Our study aimed to generate and apply splicing assay data for a prioritised group of 59 TP53 predicted missense or synonymous variants that are also predicted to affect splicing by either SpliceAI or MaxEntScan.</p><p><strong>Methods: </strong>We conducted splicing analyses using a minigene construct containing TP53 exons 2 to 9 transfected into human breast cancer SKBR3 cells, and compared results against different splice prediction methods, including correlation with the SpliceAI-10k calculator. We additionally applied the splicing results for TP53 variant classification using an approach consistent with the ClinGen Sequence Variant Interpretation Splicing Subgroup recommendations.</p><p><strong>Results: </strong>Aberrant transcript profile consistent with loss of function, and for which a PVS1 (RNA) code would be assigned, was observed for 42 (71%) of prioritised variants, of which aberrant transcript expression was over 50% for 26 variants, and over 80% for 15 variants. Data supported the use of SpliceAI ≥ 0.2 cutoff for predicted splicing impact of TP53 variants. Prediction of aberration types using SpliceAI-10k calculator generally aligned with the corresponding assay results, though maximum SpliceAI score did not accurately predict level of aberrant expression. Application of the observed splicing results was used to reclassify 27/59 (46%) test variants as (likely) pathogenic or (likely) benign.</p><p><strong>Conclusions: </strong>In conclusion, this study enhances the integration of splicing predictions and provides splicing assay data for exonic variants to support TP53 germline classification.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"2"},"PeriodicalIF":3.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11715486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scrutinizing neurodegenerative diseases: decoding the complex genetic architectures through a multi-omics lens.","authors":"Relu Cocoș, Bogdan Ovidiu Popescu","doi":"10.1186/s40246-024-00704-7","DOIUrl":"10.1186/s40246-024-00704-7","url":null,"abstract":"<p><p>Neurodegenerative diseases present complex genetic architectures, reflecting a continuum from monogenic to oligogenic and polygenic models. Recent advances in multi-omics data, coupled with systems genetics, have significantly refined our understanding of how these data impact neurodegenerative disease mechanisms. To contextualize these genetic discoveries, we provide a comprehensive critical overview of genetic architecture concepts, from Mendelian inheritance to the latest insights from oligogenic and omnigenic models. We explore the roles of common and rare genetic variants, gene-gene and gene-environment interactions, and epigenetic influences in shaping disease phenotypes. Additionally, we emphasize the importance of multi-omics layers including genomic, transcriptomic, proteomic, epigenetic, and metabolomic data in elucidating the molecular mechanisms underlying neurodegeneration. Special attention is given to missing heritability and the contribution of rare variants, particularly in the context of pleiotropy and network pleiotropy. We examine the application of single-cell omics technologies, transcriptome-wide association studies, and epigenome-wide association studies as key approaches for dissecting disease mechanisms at tissue- and cell-type levels. Our review introduces the OmicPeak Disease Trajectory Model, a conceptual framework for understanding the genetic architecture of neurodegenerative disease progression, which integrates multi-omics data across biological layers and time points. This review highlights the critical importance of adopting a systems genetics approach to unravel the complex genetic architecture of neurodegenerative diseases. Finally, this emerging holistic understanding of multi-omics data and the exploration of the intricate genetic landscape aim to provide a foundation for establishing more refined genetic architectures of these diseases, enhancing diagnostic precision, predicting disease progression, elucidating pathogenic mechanisms, and refining therapeutic strategies for neurodegenerative conditions.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"18 1","pages":"141"},"PeriodicalIF":3.8,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating single-cell RNA-seq and bulk RNA-seq to construct a neutrophil prognostic model for predicting prognosis and immune response in oral squamous cell carcinoma.","authors":"Jinhang Wang, Zifeng Cui, Qiwen Song, Kaicheng Yang, Yanping Chen, Shixiong Peng","doi":"10.1186/s40246-024-00712-7","DOIUrl":"10.1186/s40246-024-00712-7","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) is an aggressive malignancy with poor prognosis. Neutrophil infiltration has been associated with unfavorable outcomes in OSCC, but the underlying molecular mechanisms remain unclear.</p><p><strong>Methods: </strong>This study integrated single-cell transcriptomics (scRNA-seq) with bulk RNA-seq data to analyze neutrophil infiltration patterns in OSCC and identify key gene modules using weighted gene co-expression network analysis (hdWGCNA). A prognostic model was developed based on univariate and Lasso-Cox regression analyses, stratifying patients into high- and low-risk groups. Immune landscape and drug sensitivity analyses were conducted to explore group-specific differences. Additionally, Mendelian randomization analysis was employed to identify genes causally related to OSCC progression.</p><p><strong>Results: </strong>Several key pathways associated with neutrophil interactions in OSCC progression were identified, leading to the construction of a prognostic model based on significant module genes. The model demonstrated strong predictive performance in distinguishing survival rates between high- and low-risk groups. Immune landscape analysis revealed significant differences in cell infiltration patterns and TIDE scores between the groups. Drug sensitivity analysis highlighted differences in drug responsiveness between high- and low-risk groups.</p><p><strong>Conclusion: </strong>This study elucidates the critical role of neutrophils and their associated gene modules in OSCC progression. The prognostic model provides a novel reference for patient stratification and targeted therapy. These findings offer potential new targets for OSCC diagnosis, prognosis, and immunotherapy.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"18 1","pages":"140"},"PeriodicalIF":3.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying PTAFR as a hub gene in atherosclerosis: implications for NETosis and disease progression.","authors":"Chaowen Ye, Yunli Zhao, Wei Yu, Rongzhong Huang, Tianyang Hu","doi":"10.1186/s40246-024-00708-3","DOIUrl":"10.1186/s40246-024-00708-3","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis (AS) is a major cause of cardiovascular diseases and neutrophil extracellular traps (NETs) may be actively involved in the development of atherosclerosis. Identifying key biomarkers in this process is essential for developing targeted treatments for AS.</p><p><strong>Methods: </strong>We performed bioinformatics analysis using a NETosis-related gene (NRGs) set and three AS datasets (GSE100927, GSE21545, and GSE159677). Differential expression analysis and machine learning techniques (random forest and SVM-RFE) were used to screen for key NRGs. Functional enrichment analysis was conducted using GO and KEGG pathways. The expression and role of PTAFR and NETs in the mouse AS model were validated through histology, immunofluorescence, flow cytometry, and Western blot analysis. The regulatory relationship between PTAFR and NETs was confirmed by siRNA and antagonist intervention targeting PTAFR.</p><p><strong>Results: </strong>We identified 24 differentially expressed NRGs in AS. Random Forest and SVM-RFE analyses highlighted PTAFR as a key gene. Prognostic analysis revealed PTAFR significantly impacts ischemic events in AS patients. WB and immunofluorescence confirmed increased levels of NETs and PTAFR in the mouse AS model. Single-cell analysis, flow cytometry, and immunofluorescence revealed that PTAFR is primarily distributed in macrophages and neutrophils. Cellular experiments further confirmed that PTAFR regulates NETs formation.</p><p><strong>Conclusion: </strong>PTAFR is an important regulatory factor for NET formation in AS, influencing the progression and prognosis of atherosclerosis. Targeting PTAFR may provide new therapeutic strategies for AS.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"18 1","pages":"139"},"PeriodicalIF":3.8,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two recurrent pathogenic/likely pathogenic variants in PALB2 account for half of PALB2 positive families in Slovenia.","authors":"Vita Andreja Mesarič, Ana Blatnik, Kristina Drusany Starič, Ksenija Strojnik, Vida Stegel, Simona Hotujec, Vita Šetrajčič Dragoš, Petra Škerl, Srdjan Novaković, Mateja Krajc","doi":"10.1186/s40246-024-00706-5","DOIUrl":"10.1186/s40246-024-00706-5","url":null,"abstract":"","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"18 1","pages":"137"},"PeriodicalIF":3.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nationwide survey on awareness of consanguinity and genetic diseases in Saudi Arabia: challenges and potential solutions to reduce the national healthcare burden.","authors":"Nura A Yousef, Ashraf A ElHarouni, Noor Ahmad Shaik, Babajan Banaganapalli, Asayil Faisal Al Ghamdi, Amani H Galal, Turki Saad Alahmadi, Taghreed Shuaib, Deema Aljeaid, Dalal S Alshaer, Mahmoud Almutadares, Ramu Elango","doi":"10.1186/s40246-024-00700-x","DOIUrl":"10.1186/s40246-024-00700-x","url":null,"abstract":"<p><strong>Background: </strong>Consanguineous marriage is a major contributing factor for many genetic diseases and a burden to the healthcare system and national economy due to costly long-term care. Earlier studies highlighted the significantly limited awareness of the higher prevalence of genetic disease due to consanguinity even among the educated Arabs. In Saudi Arabia, more than 50% of marriages are between first cousins. This national study aims to gauge the level of the public awareness regarding the consanguinity and its impact on prevalence of genetic diseases across the Saudi Arabia.</p><p><strong>Methods: </strong>A cross-sectional bilingual online survey was conducted across Saudi Arabia, distributed through a variety of social media platforms for all residents. Pooled summary data was used from the participants.</p><p><strong>Results: </strong>Majority of the 9191 participants are < 30 years of age (72.85%), single (61.35%), women (74.12%) and college educated (77.16%). Consanguineous marriages are common in the extended family of 61.24% of participants. Though majority of them (85.45%) recognise the higher genetic disease risk associated with consanguinity, low awareness among men was observed (76.61 vs 88.53%). Sickle cell anaemia and thalassemia were not considered as genetic diseases by 60.68% of males and 48.39% of females, though they are the most common genetic diseases in Saudi Arabia. More women are aware of the carrier screening tests than men (42.62 vs 34.56%). Only 6.87% know the rationale behind the national mandatory premarital screening tests and the diseases screened. Although almost all (99.18%) are active users of the social media, 47.77% of men and 57.17% of women use them to search for health-related information.</p><p><strong>Conclusion: </strong>The present study, one of the largest national surveys in highly consanguineous society, highlights that even the young and college-educated participants have low awareness of the genetic disease burden, which is strikingly high in all corners of the country. Social media platforms can be used by genetic professionals and national organizations to disseminate the reliable educational material to the public to reduce the national healthcare and economic burden in the future.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"18 1","pages":"138"},"PeriodicalIF":3.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}