Molecular Diagnosis & Therapy最新文献

{"title":"Viral Vector-Based Gene Therapy for Epilepsy: What Does the Future Hold?","authors":"Barbara Bettegazzi, Stefano Cattaneo, Michele Simonato, Silvia Zucchini, Marie Soukupova","doi":"10.1007/s40291-023-00687-6","DOIUrl":"https://doi.org/10.1007/s40291-023-00687-6","url":null,"abstract":"<p>In recent years, many pre-clinical studies have tested gene therapy approaches as possible treatments for epilepsy, following the idea that they may provide an alternative to conventional pharmacological and surgical options. Multiple gene therapy approaches have been developed, including those based on anti-sense oligonucleotides, RNA interference, and viral vectors. In this opinion article, we focus on translational issues related to viral vector-mediated gene therapy for epilepsy. Research has advanced dramatically in addressing issues like viral vector optimization, target identification, strategies of gene expression, editing or regulation, and safety. Some of these pre-clinically validated potential gene therapies are now being tested in clinical trials, in patients with genetic or focal forms of drug-resistant epilepsy. Here, we discuss the ongoing translational research and the advancements that are needed and expected in the near future. We then describe the clinical trials in the pipeline and the further challenges that will need to be addressed at the clinical and economic levels. Our optimistic view is that all these issues and challenges can be overcome, and that gene therapy approaches for epilepsy will soon become a clinical reality.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":"71 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138685728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Novel Internally Controlled HrpB1 Gene-Based Real-Time qPCR Assay for Detection of Burkholderia pseudomallei","authors":"Pranjal Kumar Yadav, Moumita Paul, Suchetna Singh, Sanjay Kumar, S. Ponmariappan, Duraipandian Thavaselvam","doi":"10.1007/s40291-023-00686-7","DOIUrl":"https://doi.org/10.1007/s40291-023-00686-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Melioidosis, caused by category B bioterrorism agent <i>Burkholderia pseudomallei</i>, is a seasonal disease of tropical and subtropical regions with a high mortality rate. An early and culture-independent detection of <i>B. pseudomallei</i> is required for the appropriate disease management and prevention. The present study is designed to identify novel and unique sequences of <i>B. pseudomallei</i> and development of quantitative polymerase chain reaction (qPCR) assay.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>A novel <i>B. pseudomallei</i>-specific target sequence was identified by in silico analysis for the qPCR assay development. The specificity of the developed assay was assessed using purified DNA of 65 different bacterial cultures, and the sensitivity was estimated using a cloned target gene. Further, a type III secretion protein <i>Hrp</i>B1 (<i>Hrp</i>B1) gene-based duplex qPCR assay incorporating suitable extraction and amplification control was developed, and its viability was assessed in different clinical and environmental matrices for the detection of <i>B. pseudomallei</i>.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In this study, an 80-nucleotide-long <i>B. pseudomallei</i>-specific region within the gene <i>Hrp</i>B1 was identified by computational analysis. The developed <i>Hrp</i>B1-based qPCR assay was highly specific for <i>B. pseudomallei</i> detection when evaluated with 65 different bacterial cultures. The sensitivity of the qPCR assay with the <i>Hrp</i>B1-recombinant plasmid was found to be five copies per qPCR reaction. The assay’s detection limit was found to be 5 × 10² CFU/mL for human blood and urine, 5 × 10¹ CFU/mL in river water, and 2 × 10³ CFU/gm in paddy field soil.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The results of the study showed the applicability of a novel <i>Hrp</i>B1-based qPCR assay for sensitive and specific detection of <i>B. pseudomallei</i> in diverse clinical and environmental samples.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":"12 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138573595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Equecabtagene Autoleucel: First Approval.","authors":"Susan J Keam","doi":"10.1007/s40291-023-00673-y","DOIUrl":"10.1007/s40291-023-00673-y","url":null,"abstract":"<p><p>Equecabtagene autoleucel (Fucaso^®), an autologous anti-B cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR)-T cell therapy that uses lentivirus as a gene vector to transfect autologous T cells, is being developed by IASO Biotechnology and Innovent Biologics, Inc. for the treatment of multiple myeloma (MM) and autoimmune diseases of the nervous system, including neuromyelitis optica spectrum disorder (NMOSD). Equecabtagene autoleucel was granted conditional approval in China in June 2023 for the treatment of adults with relapsed or refractory MM (RRMM) who have progressed after ≥ 3 lines of therapy (≥ 1 proteasome inhibitor and an immunomodulator). This article summarizes the milestones in the development of equecabtagene autoleucel leading to this first approval in patients with RRMM who have progressed after multiple lines of therapy.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"781-787"},"PeriodicalIF":4.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10492450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Potential of Expanded Noninvasive Prenatal Testing for Detection of Aneuploidies and Microdeletion/Microduplication Syndromes.","authors":"Chunyan Li, Menghua Xiong, Ying Zhan, Jianfang Zhang, Guyuan Qiao, Jia Li, Hong Yang","doi":"10.1007/s40291-023-00674-x","DOIUrl":"10.1007/s40291-023-00674-x","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to evaluate the clinical performance of expanded noninvasive prenatal testing (NIPT-Plus) for the detection of aneuploidies and microdeletion/microduplication syndromes.</p><p><strong>Methods: </strong>A total of 7177 pregnant women were enrolled in the study from June 2020 to March 2022 at Xijing Hospital, China. Cases with NIPT-Plus-positive results were further confirmed by chromosomal karyotyping and a chromosomal microarray analysis.</p><p><strong>Results: </strong>A total of 112 positive cases (1.56%) were identified by NIPT-Plus, including 60 chromosome aneuploidies and 52 microdeletion/microduplication syndromes. Ninety-five cases were validated by amniocentesis, and 57 were confirmed with true-positive results, comprising 18 trisomy 21, 4 trisomy 18, 1 trisomy 13, 17 sex chromosome aneuploidies, 1 other aneuploidy, and 16 microdeletion/microduplication syndromes. The positive predictive value of total chromosomal abnormalities was 60% (57/95). For trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidies, other aneuploidies and microdeletion/microduplication syndromes, the sensitivity was all 100%, the specificity was 100, 99.986, 100, 99.888, 99.958, and 99.636%, and the positive predictive value was 100, 80, 100, 68, 25, and 38.10%, respectively. For all clinical characteristics, the abnormal maternal serum screening group was found to have the highest prevalence of chromosomal abnormalities (1.54%), and the ultrasound abnormality group presented the highest positive predictive value (73.33%).</p><p><strong>Conclusions: </strong>NIPT-Plus has great potential for the detection of aneuploidies and microdeletion/microduplication syndromes owing to its high sensitivity, safety, and specificity, which greatly reduces unnecessary invasive procedures and the risk of miscarriage and allows informed maternal choice.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"769-779"},"PeriodicalIF":4.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10188752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing CAR-T Therapy for Glioblastoma.","authors":"Oliver Y Tang, Zev A Binder, Donald M O'Rourke, Stephen J Bagley","doi":"10.1007/s40291-023-00671-0","DOIUrl":"10.1007/s40291-023-00671-0","url":null,"abstract":"<p><p>Chimeric antigen receptor T-cell therapies have transformed the management of hematologic malignancies but have not yet demonstrated consistent efficacy in solid tumors. Glioblastoma is the most common primary malignant brain tumor in adults and remains a major unmet medical need. Attempts at harnessing the potential of chimeric antigen receptor T-cell therapy for glioblastoma have resulted in glimpses of promise but have been met with substantial challenges. In this focused review, we discuss current and future strategies being developed to optimize chimeric antigen receptor T cells for efficacy in patients with glioblastoma, including the identification and characterization of new target antigens, reversal of T-cell dysfunction with novel chimeric antigen receptor constructs, regulatable platforms, and gene knockout strategies, and the use of combination therapies to overcome the immune-hostile microenvironment.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"643-660"},"PeriodicalIF":4.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10590221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized Cancer Monitoring Assay for the Detection of ctDNA in Patients with Solid Tumors.","authors":"Jianhua Zhao, Jacquelyn Reuther, Kaylee Scozzaro, Megan Hawley, Emily Metzger, Matthew Emery, Ingrid Chen, Michelle Barbosa, Laura Johnson, Alijah O'Connor, Mike Washburn, Luke Hartje, Erik Reckase, Verity Johnson, Yuhua Zhang, Emily Westheimer, William O'Callaghan, Nirav Malani, Adrian Chesh, Michael Moreau, Robert Daber","doi":"10.1007/s40291-023-00670-1","DOIUrl":"10.1007/s40291-023-00670-1","url":null,"abstract":"<p><strong>Background: </strong>Highly sensitive molecular assays have been developed to detect plasma-based circulating tumor DNA (ctDNA), and emerging evidence suggests their clinical utility for monitoring minimal residual disease and recurrent disease, providing prognostic information, and monitoring therapy responses in patients with solid tumors. The Invitae Personalized Cancer Monitoring^™ assay uses a patient-specific, tumor-informed variant signature identified through whole exome sequencing to detect ctDNA in peripheral blood of patients with solid tumors.</p><p><strong>Methods: </strong>The assay's tumor whole exome sequencing and ctDNA detection components were analytically validated using 250 unique human specimens and nine commercial reference samples that generated 1349 whole exome sequencing and cell-free DNA (cfDNA)-derived libraries. A comparison of tumor and germline whole exome sequencing was used to identify patient-specific tumor variant signatures and generate patient-specific panels, followed by targeted next-generation sequencing of plasma-derived cfDNA using the patient-specific panels with anchored multiplex polymerase chain reaction chemistry leveraging unique molecular identifiers.</p><p><strong>Results: </strong>Whole exome sequencing resulted in overall sensitivity of 99.8% and specificity of > 99.9%. Patient-specific panels were successfully designed for all 63 samples (100%) with ≥ 20% tumor content and 24 (80%) of 30 samples with ≥ 10% tumor content. Limit of blank studies using 30 histologically normal, formalin-fixed paraffin-embedded specimens resulted in 100% expected panel design failure. The ctDNA detection component demonstrated specificity of > 99.9% and sensitivity of 96.3% for a combination of 10 ng of cfDNA input, 0.008% allele frequency, 50 variants on the patient-specific panels, and a baseline threshold. Limit of detection ranged from 0.008% allele frequency when utilizing 60 ng of cfDNA input with 18-50 variants in the patient-specific panels (> 99.9% sensitivity) with a baseline threshold, to 0.05% allele frequency when using 10 ng of cfDNA input with an 18-variant panel with a monitoring threshold (> 99.9% sensitivity).</p><p><strong>Conclusions: </strong>The Invitae Personalized Cancer Monitoring assay, featuring a flexible patient-specific panel design with 18-50 variants, demonstrated high sensitivity and specificity for detecting ctDNA at variant allele frequencies as low as 0.008%. This assay may support patient prognostic stratification, provide real-time data on therapy responses, and enable early detection of residual/recurrent disease.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"753-768"},"PeriodicalIF":4.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/70/5c/40291_2023_Article_670.PMC10590345.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10078589","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":"Cell Therapy of Severe Ischemia in People with Diabetic Foot Ulcers-Do We Have Enough Evidence?","authors":"Michal Dubský, Jitka Husáková, Dominika Sojáková, Vladimíra Fejfarová, Edward B Jude","doi":"10.1007/s40291-023-00667-w","DOIUrl":"10.1007/s40291-023-00667-w","url":null,"abstract":"<p><p>This current opinion article critically evaluates the efficacy of autologous cell therapy (ACT) for chronic limb-threatening ischemia (CLTI), especially in people with diabetes who are not candidates for standard revascularization. This treatment approach has been used in 'no-option' CLTI in the last two decades and more than 1700 patients have received ACT worldwide. Here we analyze the level of published evidence of ACT as well as our experience with this treatment method. Many studies have shown that ACT is safe and an effective method for patients with the most severe lower limb ischemia. However, some trials did not show any benefit of ACT, and there is some heterogeneity in the types of injected cells, route of administration and assessed endpoints. Nevertheless, we believe that ACT plays an important role in a comprehensive treatment of patients with diabetic foot and severe ischemia.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"673-683"},"PeriodicalIF":4.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7f/2a/40291_2023_Article_667.PMC10590286.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41170511","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":"Application of Nanopore Sequencing in the Diagnosis and Treatment of Pulmonary Infections.","authors":"Jie Chen, Feng Xu","doi":"10.1007/s40291-023-00669-8","DOIUrl":"10.1007/s40291-023-00669-8","url":null,"abstract":"<p><p>This review provides an in-depth discussion of the development, principles and utility of nanopore sequencing technology and its diverse applications in the identification of various pulmonary pathogens. We examined the emergence and advancements of nanopore sequencing as a significant player in this field. We illustrate the challenges faced in diagnosing mixed infections and further scrutinize the use of nanopore sequencing in the identification of single pathogens, including viruses (with a focus on its use in epidemiology, outbreak investigation, and viral resistance), bacteria (emphasizing 16S targeted sequencing, rare bacterial lung infections, and antimicrobial resistance studies), fungi (employing internal transcribed spacer sequencing), tuberculosis, and atypical pathogens. Furthermore, we discuss the role of nanopore sequencing in metagenomics and its potential for unbiased detection of all pathogens in a clinical setting, emphasizing its advantages in sequencing genome repeat areas and structural variant regions. We discuss the limitations in dealing with host DNA removal, the inherent high error rate of nanopore sequencing technology, along with the complexity of operation and processing, while acknowledging the possibilities provided by recent technological improvements. We compared nanopore sequencing with the BioFire system, a rapid molecular diagnostic system based on polymerase chain reaction. Although the BioFire system serves well for the rapid screening of known and common pathogens, it falls short in the identification of unknown or rare pathogens and in providing comprehensive genome analysis. As technological advancements continue, it is anticipated that the role of nanopore sequencing technology in diagnosing and treating lung infections will become increasingly significant.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"685-701"},"PeriodicalIF":4.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2a/d1/40291_2023_Article_669.PMC10590290.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10327471","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":"Steps to Improve Precision Medicine in Epilepsy.","authors":"S Balestrini, D Mei, S M Sisodiya, Renzo Guerrini","doi":"10.1007/s40291-023-00676-9","DOIUrl":"10.1007/s40291-023-00676-9","url":null,"abstract":"<p><p>Precision medicine is an old concept, but it is not widely applied across human health conditions as yet. Numerous attempts have been made to apply precision medicine in epilepsy, this has been based on a better understanding of aetiological mechanisms and deconstructing disease into multiple biological subsets. The scope of precision medicine is to provide effective strategies for treating individual patients with specific agent(s) that are likely to work best based on the causal biological make-up. We provide an overview of the main applications of precision medicine in epilepsy, including the current limitations and pitfalls, and propose potential strategies for implementation and to achieve a higher rate of success in patient care. Such strategies include establishing a definition of precision medicine and its outcomes; learning from past experiences, from failures and from other fields (e.g. oncology); using appropriate precision medicine strategies (e.g. drug repurposing versus traditional drug discovery process); and using adequate methods to assess efficacy (e.g. randomised controlled trials versus alternative trial designs). Although the progress of diagnostic techniques now allows comprehensive characterisation of each individual epilepsy condition from a molecular, biological, structural and clinical perspective, there remain challenges in the integration of individual data in clinical practice to achieve effective applications of precision medicine in this domain.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"661-672"},"PeriodicalIF":4.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1b/d8/40291_2023_Article_676.PMC10590329.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41149086","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":"MicroRNAs Function in Dental Stem Cells as a Promising Biomarker and Therapeutic Target for Dental Diseases.","authors":"Kamyar Nasiri, Mohammad Jahri, Shirin Kolahdouz, Milad Soleimani, Ali Makiya, Ravinder S Saini, Muna S Merza, Saman Yasamineh, Morteza Banakar, Mohammad Hossein Yazdanpanah","doi":"10.1007/s40291-023-00675-w","DOIUrl":"10.1007/s40291-023-00675-w","url":null,"abstract":"<p><p>Undifferentiated, highly proliferative, clonogenic, and self-renewing dental stem cells have paved the way for novel approaches to mending cleft palates, rebuilding lost jawbone and periodontal tissue, and, most significantly, recreating lost teeth. New treatment techniques may be guided by a better understanding of these cells and their potential in terms of the specificity of the regenerative response. MicroRNAs have been recognized as an essential component in stem cell biology due to their role as epigenetic regulators of the processes that determine stem cell destiny. MicroRNAs have been proven to be crucial in a wide variety of molecular and biological processes, including apoptosis, cell proliferation, migration, and necrocytosis. MicroRNAs have been recognized to control protein translation, messenger RNA stability, and transcription and have been reported to play essential roles in dental stem cell biology, including the differentiation of dental stem cells, the immunological response, apoptosis, and the inflammation of the dental pulp. Because microRNAs increase dental stem cell differentiation, they may be used in regenerative medicine to either preserve the stem cell phenotype or to aid in the development of tooth tissue. The development of novel biomarkers and therapies for dental illnesses relies heavily on progress made in our knowledge of the roles played by microRNAs in regulating dental stem cells. In this article, we discuss how dental stem cells and their associated microRNAs may be used to cure dental illness.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"703-722"},"PeriodicalIF":4.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41158987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}