NeurogeneticsPub Date : 2024-11-25DOI: 10.1007/s10048-024-00793-5
Vijeta Prakash, Reema Gabrani
{"title":"Epigenetic dysregulation in glioblastoma: potential pathways to precision medicine.","authors":"Vijeta Prakash, Reema Gabrani","doi":"10.1007/s10048-024-00793-5","DOIUrl":"https://doi.org/10.1007/s10048-024-00793-5","url":null,"abstract":"<p><p>The emerging field of epigenetics has been driving glioblastoma multiforme (GBM) development and progression. Various epigenetic alterations involving tumor suppressor genes, oncogenes, and signaling pathways have been identified in GBM. These alterations contribute to the aggressive behavior, therapeutic resistance, and tumor heterogeneity observed in GBM. Furthermore, the identification of specific genetic mutations associated with epigenetic dysregulation in GBM has provided new insights into the molecular subtypes and potential therapeutic targets within GBM. Understanding the complex interplay between genetic and epigenetic alterations in GBM is crucial for the development of effective and personalized therapies for this devastating disease. This review paper provides an overview of the epigenetic changes occurring in GBM and the potential of targeted epigenetic therapies as a promising avenue for GBM treatment, highlighting the challenges and future directions in this field has been deliberated.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"5"},"PeriodicalIF":1.6,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurogeneticsPub Date : 2024-11-25DOI: 10.1007/s10048-024-00794-4
Juan Carlos Castillo Juárez, Alejandro Aguilar Gómez, Adrian Esteban Salatino Díaz, Gabriel Silva Arévalo
{"title":"Understanding pathophysiology in fragile X syndrome: a comprehensive review.","authors":"Juan Carlos Castillo Juárez, Alejandro Aguilar Gómez, Adrian Esteban Salatino Díaz, Gabriel Silva Arévalo","doi":"10.1007/s10048-024-00794-4","DOIUrl":"https://doi.org/10.1007/s10048-024-00794-4","url":null,"abstract":"<p><p>Fragile X syndrome (FXS) is the leading hereditary cause of intellectual disability and the most commonly associated genetic cause of autism. Historically, research into its pathophysiology has focused predominantly on neurons; however, emerging evidence suggests involvement of additional cell types and systems. The objective of this study was to review and synthesize current evidence regarding the pathophysiology of Fragile X syndrome. A comprehensive literature review was conducted using databases such as PubMed and Google Scholar, employing MeSH terms including \"Fragile X Syndrome,\" \"FMR1 gene,\" and \"FMRP.\" Studies on both human and animal models, from inception to 2022, published in recognized journals were included. The evidence supports those neurons, glial cells, stem cells, the immune system, and lipid metabolism pathways contribute to the pathophysiology of Fragile X syndrome. Further research is necessary to explore these fields independently and to elucidate their interactions.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"6"},"PeriodicalIF":1.6,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"DHDDS-related epilepsy with hippocampal atrophy: a case report.","authors":"Álvaro de Oliveira Franco, Matheus Bernardon Morillos, Martim Tobias Bravo Leite, Marino Muxfeldt Bianchin, Carolina Machado Torres","doi":"10.1007/s10048-024-00780-w","DOIUrl":"10.1007/s10048-024-00780-w","url":null,"abstract":"<p><p>Developmental delay and seizures with or without movement abnormalities (DEDSM) is a neurodevelopmental phenotype associated with monoallelic mutations in the DHDDS gene. We report a novel case of DEDSM linked to a DHDDS variant (c.614G > A, p.Arg205Gln) in a 45-year-old Brazilian patient presenting with refractory epilepsy, ataxia, dystonia, parkinsonism, and global developmental delay. This is the first case to associate a DHDDS variant with hippocampal atrophy on neuroimaging. After adjustments in anticonvulsant therapy, seizure control was achieved, and the patient-who was previously unable to walk due to frequent falls attributed to myoclonic jerks-showed significant improvement in gait and mobility.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"3"},"PeriodicalIF":1.6,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurogeneticsPub Date : 2024-11-22DOI: 10.1007/s10048-024-00781-9
Mariia A Parfenenko, Ilya S Dantsev, Sergei V Bochenkov, Rabiat G Kuramagomedova, Natalia V Vinogradova, Mariia P Afanaseva, Olga S Groznova, Victoria Iu Voinova
{"title":"Expansion of phenotypic and genotypic data in autism spectrum disorders due to variants in the CHD8 gene.","authors":"Mariia A Parfenenko, Ilya S Dantsev, Sergei V Bochenkov, Rabiat G Kuramagomedova, Natalia V Vinogradova, Mariia P Afanaseva, Olga S Groznova, Victoria Iu Voinova","doi":"10.1007/s10048-024-00781-9","DOIUrl":"10.1007/s10048-024-00781-9","url":null,"abstract":"<p><p>Autism spectrum disorders are a group of the most common disorders of neuropsychiatric development, characterized by difficulties in social interaction and adherence to stereotypic behavioral patterns. This group of conditions frequently co-occurs with intellectual disability, epilepsy, attention-deficit hyperactivity disorder, connective tissue disorders and others. Among the most common molecular-genetic causes of autism spectrum disorders are pathogenic variants in the CHD8 gene. CHD8 codes for chromodomain-helicase-DNA-binding protein 8 - a chromatin remodeler that regulates cellular proliferation and brain development in embryogenesis. 6 children and 1 adult (mother of 1 of the children) and were found to have clinically significant variants in CHD8 on whole genome sequencing (3 children and 1 adult had likely pathogenic variants, 3 children- variants of unknown significance). Their phenotype consisted of autism spectrum disorders, developmental delay, ataxia, overgrowth and other signs typically observed in patients with pathogenic variants in CHD8, as well as common comorbidities of autism spectrum disorders, such as attention-deficit hyperactivity disorder and connective tissue disorders. Additionally, 4 patients had hepatomegaly and 2- hyperbilirubinemia (1 had both) - clinical features have not been previously associated with pathogenic variants in CHD8. 2 patients also presented with cardiovascular abnormalities, primarily arrythmias and, in 1 case, cardiomyopathy- also uncharacteristic of patients with pathogenic variants in CHD8. Further research is required to determine the mechanisms underlying the abovementioned clinical features, which are likely carried out through complex interactions between CHD8 and other regulatory proteins.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"4"},"PeriodicalIF":1.6,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurogeneticsPub Date : 2024-11-20DOI: 10.1007/s10048-024-00788-2
Lena Sagi-Dain, Annemieke Aartsma-Rus, Moran Echar, Julia Grinshpun-Cohen, Amihood Singer
{"title":"Dystrophinopathy patient data as a guide to interpretation of pregestational female population screening for DMD gene variants.","authors":"Lena Sagi-Dain, Annemieke Aartsma-Rus, Moran Echar, Julia Grinshpun-Cohen, Amihood Singer","doi":"10.1007/s10048-024-00788-2","DOIUrl":"10.1007/s10048-024-00788-2","url":null,"abstract":"<p><p>Pregestational population screening of healthy females for copy number variants in DMD gene has raised numerous challenges regarding the interpretation and disclosure of these findings. Our objective was to analyze data from a local dystrophinopathy patient database, in comparison to population screening results. Utilizing the \"Little steps\" association registry for children with dystrophinopathy, we classified genetic findings (out-of-frame, in-frame, or difficult-to-predict) in 231 DMD and 90 BMD male patients. A comparison was made with a previously published cohort of 162 female carriers identified through population screening. Duplications classified as \"difficult to predict\" were absent in DMD/BMD patients, as opposed to 45.1% of women analyzed in the scope of population screening (p < 0.0001). While the distribution of deletions did not differ between the groups, significantly higher proportion of duplications initiated at the proximal hot spot in the DMD/BMD cohort (87.1%), vs. only 11.7% in women analyzed through population screening (p = 0.0038). Notably, duplications initiating in the dp427c promoter area were noted only in the latter cohort (n = 62). Local databases of dystrophinopathy patients can facilitate analysis and reporting of pregestational female population screening results. These conclusions facilitate future introductions of population screening genetic tests for diseases with variable presentation.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"2"},"PeriodicalIF":1.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurogeneticsPub Date : 2024-11-19DOI: 10.1007/s10048-024-00785-5
Ahoura Nozari, Paria Babaahmadi, Narges Jalilian, Taha Sadeghi, Mahdieh Hasani
{"title":"Introducing a novel TRAPPC10 gene variant as a potential cause of developmental delay and intellectual disability in an Iranian family.","authors":"Ahoura Nozari, Paria Babaahmadi, Narges Jalilian, Taha Sadeghi, Mahdieh Hasani","doi":"10.1007/s10048-024-00785-5","DOIUrl":"10.1007/s10048-024-00785-5","url":null,"abstract":"<p><strong>Background: </strong>TRAPP complexes are crucial components for intracellular transport and cellular organization. Their role in vesicle trafficking, particularly through their involvement in the secretory pathway, make them more important in neurodevelopmental mechanisms. This study aims to identify a novel genetic variant, associated with developmental delay and intellectual disability by analyzing a consanguineous Iranian family.</p><p><strong>Materials and methods: </strong>Here, we performed whole-exome sequencing on an Iranian family, originating from a small population. The patient presented with severe developmental delay, microcephaly, and behavioral abnormalities. Through our analysis, we discovered a new biallelic variant on a previously introduced gene: TRAPPC10 (NM_003274.5): c.3222 C > A; p.(Cys1074Ter) that is a potential cause for these specific clinical characteristics.</p><p><strong>Results: </strong>Previous functional analysis suggest that the mutation causes premature termination of protein translation, likely leading to nonsense-mediated decay because of biallelic loss of functional TRAPPC10 protein which leads to severe developmental delay, microcephaly, and behavioral abnormalities such as aggression and autistic traits.</p><p><strong>Conclusion: </strong>The aim of this research is to discover a novel variant in the TRAPPC10 gene that is responsible for a particular neurodevelopmental condition, dominantly characterized by developmental delay, intellectual disability, and microcephaly. These findings advance the comprehension of TRAPP-related diseases and emphasize the need for further exploration into the impact of TRAPPC10 on the development of the nervous system.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"1"},"PeriodicalIF":1.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurogeneticsPub Date : 2024-10-01Epub Date: 2024-07-18DOI: 10.1007/s10048-024-00767-7
Mark Ainsley Colijn, Stephanie Vrijsen, Ping Yee Billie Au, Rania Abou El Asrar, Marine Houdou, Chris Van den Haute, Justyna Sarna, Greg Montgomery, Peter Vangheluwe
{"title":"Kufor-Rakeb syndrome-associated psychosis: a novel loss-of-function ATP13A2 variant and response to antipsychotic therapy.","authors":"Mark Ainsley Colijn, Stephanie Vrijsen, Ping Yee Billie Au, Rania Abou El Asrar, Marine Houdou, Chris Van den Haute, Justyna Sarna, Greg Montgomery, Peter Vangheluwe","doi":"10.1007/s10048-024-00767-7","DOIUrl":"10.1007/s10048-024-00767-7","url":null,"abstract":"<p><p>Biallelic (autosomal recessive) pathogenic variants in ATP13A2 cause a form of juvenile-onset parkinsonism, termed Kufor-Rakeb syndrome. In addition to motor symptoms, a variety of other neurological and psychiatric symptoms may occur in affected individuals, including supranuclear gaze palsy and cognitive decline. Although psychotic symptoms are often reported, response to antipsychotic therapy is not well described in previous case reports/series. As such, we describe treatment response in an individual with Kufor-Rakeb syndrome-associated psychosis. His disease was caused by a homozygous novel loss-of-function ATP13A2 variant (NM_022089.4, c.1970_1975del) that was characterized in this study. Our patient exhibited a good response to quetiapine monotherapy, which he has so far tolerated well. We also reviewed the literature and summarized all previous descriptions of antipsychotic treatment response. Although its use has infrequently been described in Kufor-Rakeb syndrome, quetiapine is commonly used in other degenerative parkinsonian disorders, given its lower propensity to cause extrapyramidal symptoms. As such, quetiapine should be considered in the treatment of Kufor-Rakeb syndrome-associated psychosis when antipsychotic therapy is deemed necessary.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":" ","pages":"405-415"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141635966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of flexible assertive community treatment model (FACT) on community rehabilitation of schizophrenia in Southern China.","authors":"Yinglin Zhao, Shaoxiong Zheng, Handi Zhang, Yinnan Zhang, Zidong Wang, Qingjun Huang","doi":"10.1007/s10048-024-00778-4","DOIUrl":"10.1007/s10048-024-00778-4","url":null,"abstract":"<p><p>Schizophrenia is a group of severe mental illnesses of unknown etiology, most of which are slow or subacute in young adults. 160 adult schizophrenic patients were randomly divided into an intervention group given FACT and a control group given routine mental health follow-up. The scale includes the Positive and Negative Syndrome Scale (PANSS), Social Disability Screening Schedule Scale (SDSS), and the World Health Organization's multicultural quality of life instrument in its brief form Scale(WHOQOL-BREF) were recorded. The average scores of positive scale, negative scale, general psychopathology scale and total score in PANSS scale before intervention(baseline) of the patients in the intervention group were 24.90 ± 5.43, 17.53 ± 3.84, 38.31 ± 4.09 and 80.54 ± 6.75. After 6 months and 12 months of intervention, positive scale, negative scale, general psychopathology scale and total score of the PANSS scale in the intervention group and the total score of SDSS all decreased significantly. The WHOQOL-BREF total score was significantly improved, and the differences were statistically significant (P < 0.05). The FACT intervention model has a significant effect on the rehabilitation of patients with schizophrenia in the community, improves their social function, and improves their quality of life.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":" ","pages":"481-486"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurogeneticsPub Date : 2024-10-01Epub Date: 2024-08-27DOI: 10.1007/s10048-024-00774-8
P Carballo-Pacoret, A Carracedo, C Rodriguez-Fontenla
{"title":"Unraveling the three-dimensional (3D) genome architecture in Neurodevelopmental Disorders (NDDs).","authors":"P Carballo-Pacoret, A Carracedo, C Rodriguez-Fontenla","doi":"10.1007/s10048-024-00774-8","DOIUrl":"10.1007/s10048-024-00774-8","url":null,"abstract":"<p><p>The human genome, comprising millions of pairs of bases, serves as the blueprint of life, encoding instructions for cellular processes. However, genomes are not merely linear sequences; rather, the complex of DNA and histones, known as chromatin, exhibits complex organization across various levels, which profoundly influence gene expression and cellular function. Central to understanding genome organization is the emerging field of three-dimensional (3D) genome studies. Utilizing advanced techniques such as Hi-C, researchers have unveiled non-random dispositions of genomic elements, highlighting their importance in transcriptional regulation and disease mechanisms. Topologically Associating Domains (TADs), that demarcate regions of chromatin with preferential internal interactions, play crucial roles in gene regulation and are increasingly implicated in various diseases such as cancer and schizophrenia. However, their role in Neurodevelopmental Disorders (NDDs) remains poorly understood. Here, we focus on TADs and 3D conservation across the evolution and between cell types in NDDs. The investigation into genome organization and its impact on disease has led to significant breakthroughs in understanding NDDs etiology such ASD (Autism Spectrum Disorder). By elucidating the wide spectrum of ASD manifestations, researchers aim to uncover the underlying genetic and epigenetic factors contributing to its heterogeneity. Moreover, studies linking TAD disruption to NDDs underscore the importance of spatial genome organization in maintaining proper brain development and function. In summary, this review highlights the intricate interplay between genome organization, transcriptional control, and disease pathology, shedding light on fundamental biological processes and offering insights into the mechanisms underlying NDDs like ASD.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":" ","pages":"293-305"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurogeneticsPub Date : 2024-10-01Epub Date: 2024-07-08DOI: 10.1007/s10048-024-00770-y
Tiyasha De, Pooja Sharma, Bharathram Upilli, A Vivekanand, Shreya Bari, Akhilesh Kumar Sonakar, Achal Kumar Srivastava, Mohammed Faruq
{"title":"Spinocerebellar ataxia type 27B (SCA27B) in India: insights from a large cohort study suggest ancient origin.","authors":"Tiyasha De, Pooja Sharma, Bharathram Upilli, A Vivekanand, Shreya Bari, Akhilesh Kumar Sonakar, Achal Kumar Srivastava, Mohammed Faruq","doi":"10.1007/s10048-024-00770-y","DOIUrl":"10.1007/s10048-024-00770-y","url":null,"abstract":"<p><strong>Background: </strong>The ethnic diversity of India provides a unique opportunity to study the history of the origin of mutations of genetic disorders. Spinocerebellar ataxia type 27B (SCA27B), a recently identified dominantly inherited cerebellar disorder is caused by GAA-repeat expansions in intron 1 of Fibroblast Growth Factor 14 (FGF14). Predominantly reported in the European population, we aimed to screen this mutation and study the founder haplotype of SCA27B in Indian ataxia patients.</p><p><strong>Methods: </strong>We have undertaken screening of GAA repeats in a large Indian cohort of ~ 1400 uncharacterised ataxia patients and kindreds and long-read sequencing-based GAA repeat length assessment. High throughput genotyping-based haplotype analysis was also performed. We utilized ~ 1000 Indian genomes to study the GAA at-risk expansion alleles.</p><p><strong>Findings: </strong>We report a high frequency of 1.83% (n = 23) of SCA27B in the uncharacterized Indian ataxia cohort. We observed several biallelic GAA expansion mutations (n = 5) with younger disease onset. We observed a risk haplotype (AATCCGTGG) flanking the FGF14-GAA locus over a 74 kb region in linkage disequilibrium. We further studied the frequency of this risk haplotype across diverse geographical population groups. The highest prevalence of the risk haplotype was observed in the European population (29.9%) followed by Indians (21.5%). The observed risk haplotype has existed through ~ 1100 generations (~ 22,000 years), assuming a correlated genealogy.</p><p><strong>Interpretation: </strong>This study provides valuable insights into SCA27B and its Upper Paleolithic origin in the Indian subcontinent. The high occurrence of biallelic expansion is probably relevant to the endogamous nature of the Indian population.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":" ","pages":"393-403"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}