Molecular Diagnosis & Therapy最新文献

{"title":"Identification of Plasmatic MicroRNA-206 as New Predictor of Early Recurrence of Atrial Fibrillation After Catheter Ablation Using Next-generation Sequencing.","authors":"Filip Šustr, Táňa Macháčková, Martin Pešl, Jana Svačinova, Karolína Trachtová, Zdeněk Stárek, Bohuslav Kianička, Ondřej Slabý, Jan Novák","doi":"10.1007/s40291-024-00698-x","DOIUrl":"10.1007/s40291-024-00698-x","url":null,"abstract":"<p><strong>Background: </strong>Catheter ablation (CA) of atrial fibrillation (AF) is indicated in patients with recurrent and symptomatic AF episodes. Despite the strict inclusion/exclusion criteria, AF recurrence after CA remains high. Identification of a novel biomarker that would predict AF recurrence would help to stratify the patients. The aim of the study was to seek novel biomarkers among the plasmatic microRNAs (miRNAs, miRs).</p><p><strong>Methods: </strong>A prospective monocentric study was conducted. A total of 49 consecutive AF patients indicated for CA were included. Blood sampling was performed prior to CA. RNA was isolated from plasma using commercial kits. In the exploration phase, small RNA sequencing was performed in ten AF patients (five with and five without AF recurrence) using Illumina instrument. In the validation phase, levels of selected miRNAs were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in all participants.</p><p><strong>Results: </strong>Altogether, 22 miRNAs were identified as altered between the groups by next-generation sequencing (using the DESeq2 algorithm). Using qRT-PCR, levels of the five most altered miRNAs (miR-190b/206/326/505-5p/1296-5p) were verified in the whole cohort. Plasma levels of hsa-miR-206 were significantly higher in patients with early (within 6 months) AF recurrence and showed an increase of risk recurrence,2.65 times by every increase in its level by 1 unit in the binary logistic regression.</p><p><strong>Conclusion: </strong>We have identified a set of 22 plasmatic miRNAs that differ between the patients with and without AF recurrence after CA and confirmed hsa-miR-206 as a novel miRNA associated with early AF recurrence. Results shall be verified in a larger independent cohort.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"301-310"},"PeriodicalIF":4.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11068688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140066129","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":"Unwinding Helicase MCM Functionality for Diagnosis and Therapeutics of Replication Abnormalities Associated with Cancer: A Review.","authors":"Arathi Radhakrishnan, Ritwik Gangopadhyay, Chandresh Sharma, Raj Kishor Kapardar, Nilesh Kumar Sharma, Rajpal Srivastav","doi":"10.1007/s40291-024-00701-5","DOIUrl":"10.1007/s40291-024-00701-5","url":null,"abstract":"<p><p>The minichromosome maintenance (MCM) protein is a component of an active helicase that is essential for the initiation of DNA replication. Dysregulation of MCM functions contribute to abnormal cell proliferation and genomic instability. The interactions of MCM with cellular factors, including Cdc45 and GINS, determine the formation of active helicase and functioning of helicase. The functioning of MCM determines the fate of DNA replication and, thus, genomic integrity. This complex is upregulated in precancerous cells and can act as an important tool for diagnostic applications. The MCM protein complex can be an important broad-spectrum therapeutic target in various cancers. Investigations have supported the potential and applications of MCM in cancer diagnosis and its therapeutics. In this article, we discuss the physiological roles of MCM and its associated factors in DNA replication and cancer pathogenesis.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"249-264"},"PeriodicalIF":4.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295124","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":"Advances in Radioligand Theranostics in Oncology.","authors":"Ismaheel O Lawal, Sofiullah O Abubakar, Honest Ndlovu, Kgomotso M G Mokoala, Stuart S More, Mike M Sathekge","doi":"10.1007/s40291-024-00702-4","DOIUrl":"10.1007/s40291-024-00702-4","url":null,"abstract":"<p><p>Theranostics with radioligands (radiotheranostics) has played a pivotal role in oncology. Radiotheranostics explores the molecular targets expressed on tumor cells to target them for imaging and therapy. In this way, radiotheranostics entails non-invasive demonstration of the in vivo expression of a molecular target of interest through imaging followed by the administration of therapeutic radioligand targeting the tumor-expressed molecular target. Therefore, radiotheranostics ensures that only patients with a high likelihood of response are treated with a particular radiotheranostic agent, ensuring the delivery of personalized care to cancer patients. Within the last decades, a couple of radiotheranostics agents, including Lutetium-177 DOTATATE (¹⁷⁷Lu-DOTATATE) and Lutetium-177 prostate-specific membrane antigen (¹⁷⁷Lu-PSMA), were shown to prolong the survival of cancer patients compared to the current standard of care leading to the regulatory approval of these agents for routine use in oncology care. This recent string of successful approvals has broadened the interest in the development of different radiotheranostic agents and their investigation for clinical translation. In this work, we present an updated appraisal of the literature, reviewing the recent advances in the use of established radiotheranostic agents such as radioiodine for differentiated thyroid carcinoma and Iodine-131-labeled meta-iodobenzylguanidine therapy of tumors of the sympathoadrenal axis as well as the recently approved ¹⁷⁷Lu-DOTATATE and ¹⁷⁷Lu-PSMA for differentiated neuroendocrine tumors and advanced prostate cancer, respectively. We also discuss the radiotheranostic agents that have been comprehensively characterized in preclinical studies and have shown some clinical evidence supporting their safety and efficacy, especially those targeting fibroblast activation protein (FAP) and chemokine receptor 4 (CXCR4) and those still being investigated in preclinical studies such as those targeting poly (ADP-ribose) polymerase (PARP) and epidermal growth factor receptor 2.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"265-289"},"PeriodicalIF":4.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330271","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":"Inflammatory Gene Panel Guiding the Study of Genetics in Inflammatory Bowel Disease","authors":"Ryan Xin","doi":"10.1007/s40291-024-00709-x","DOIUrl":"https://doi.org/10.1007/s40291-024-00709-x","url":null,"abstract":"<p>Inflammatory bowel disease (IBD) is a complex disease that develops through a sequence of molecular events that are still poorly defined. This process is driven by a multitude of context-dependent genes that play different roles based on their environment. The complexity and multi-faceted nature of these genes make it difficult to study the genetic basis of IBD. The goal of this article is to review the key genes in the pathophysiology of IBD and highlight new technology that can be used in further research. This paper examines Nanostring RNA probe technology, which uses tissue analyzed without the use of enzymes, transcription, or amplification. Nanostring offers several panels of genes to test, including an inflammation panel of 234 genes. This article analyzes this panel and reviews the literature for each gene’s effect in IBD for use as a framework to review the pathophysiology of the disease. The panel was narrowed to 26 genes with significant evidence of mechanistic potential in IBD, which were then categorized into specific areas of pathogenesis. These include gut barrier breakdown, inappropriate recognition of commensal bacteria, immune cell activation, proinflammatory cytokine release, and subsequent impairment of the anti-inflammatory response. The eventual goal of this paper is the creation of a customized panel of IBD genes that can be used to better understand the genetic mechanism of IBD and aid in the development of future therapies in IBD.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":"1 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140623625","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":"Lifileucel: First Approval","authors":"Susan J. Keam","doi":"10.1007/s40291-024-00708-y","DOIUrl":"https://doi.org/10.1007/s40291-024-00708-y","url":null,"abstract":"<p>Lifileucel (AMTAGVI™), a one-time autologous T cell therapy derived and expanded from tumour-infiltrating lymphocytes (TIL) from a patient’s own tumour, is being developed by Iovance Biotherapeutics, Inc. for the treatment of cancer. Lifileucel was granted accelerated approval based on objective response rate (ORR) in February 2024 in the USA for use in adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if <i>BRAF</i> V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. This article summarizes the milestones in the development of lifileucel leading to this first approval for the treatment of patients with unresectable or metastatic melanoma who have progressed on or after prior anti-PD-1/L1 therapy and targeted therapy.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":"41 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597556","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":"Estimating the Prognostic Value of the NTRK Fusion Biomarker for Comparative Effectiveness Research in The Netherlands","authors":"Irene Santi, Heleen Vellekoop, Matthijs M Versteegh, Simone A Huygens, Winand N. M. Dinjens, Maureen Rutten-van Mölken","doi":"10.1007/s40291-024-00704-2","DOIUrl":"https://doi.org/10.1007/s40291-024-00704-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>We evaluated the prognostic value of the neurotrophic tyrosine receptor kinase (<i>NTRK</i>) gene fusions by comparing the survival of patients with <i>NTRK+ </i>tumours with patients without <i>NTRK+</i> tumours.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We used genomic and clinical registry data from the Center for Personalized Cancer Treatment (CPCT-02) study containing a cohort of cancer patients who were treated in Dutch clinical practice between 2012 and 2020. We performed a propensity score matching analysis, where <i>NTRK+</i> patients were matched to <i>NTRK−</i> patients in a 1:4 ratio. We subsequently analysed the survival of the matched sample of <i>NTRK+</i> and <i>NTRK−</i> patients using the Kaplan–Meier method and Cox regression, and performed an analysis of credibility to evaluate the plausibility of our result.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Among 3556 patients from the CPCT-02 study with known tumour location, 24 <i>NTRK</i>+ patients were identified. <i>NTRK+</i> patients were distributed across nine different tumour types: bone/soft tissue, breast, colorectal, head and neck, lung, pancreas, prostate, skin and urinary tract. <i>NTRK</i> fusions involving the <i>NTRK3</i> gene (46%) and <i>NTRK1</i> gene (33%) were most common. The survival analysis rendered a hazard ratio (HR) of 1.44 (95% CI 0.81–2.55) for <i>NTRK+</i> patients. Using the point estimates of three prior studies on the prognostic value of <i>NTRK</i> fusions, our finding that the HR is &gt; 1 was deemed plausible.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p><i>NTRK+</i> patients may have an increased risk of death compared with <i>NTRK−</i> patients. When using historic control data to assess the comparative effectiveness of TRK inhibitors, the prognostic value of the <i>NTRK</i> fusion biomarker should therefore be accounted for.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":"48 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597553","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":"Molecular Dynamic Simulations to Determine Individualized Therapy: Tetrabenazine for the GNAO1 Encephalopathy E246K Variant","authors":"","doi":"10.1007/s40291-024-00706-0","DOIUrl":"https://doi.org/10.1007/s40291-024-00706-0","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Introduction</h3> <p>GNAO1 encephalopathy is characterized by severe hypotonia, psychomotor retardation, epilepsy, and movement disorders. Genetic variations in <em>GNAO1</em> have been linked to neurological symptoms including movement disorders like dystonia. The correlation between the E246K mutation in the Gα subunit and aberrant signal transduction of G proteins has been established but no data are reported regarding the efficacy of medical treatment with tetrabenazine.</p> </span> <span> <h3>Methods</h3> <p>Molecular modeling studies were performed to elucidate the molecular mechanisms underlying this mutation. We developed drug efficacy models using molecular dynamic simulations that replicated the behavior of wild-type and mutated proteins in the presence or absence of ligands.</p> </span> <span> <h3>Results and discussion</h3> <p>We demonstrated that the absence of the mutation leads to normal signal transduction upon receptor activation by the endogenous ligand, but not in the presence of tetrabenazine. In contrast, the presence of the mutation resulted in abnormal signal transduction in the presence of the endogenous ligand, which was corrected by the drug tetrabenazine. Tetrabenazine was identified as a promising therapeutic option for pediatric patients suffering from encephalopathy due to an E246K mutation in the GNAO1 gene validated through molecular dynamics. This is a potential first example of the use of this technique in a rare neurological pediatric disease.</p> </span>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":"298 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597482","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":"Diagnostic Approaches to Investigate JAK2-Unmutated Erythrocytosis Based on a Single Tertiary Center Experience","authors":"Youngeun Lee, Soo Hyun Seo, Jinho Kim, Sang-A Kim, Ji Yun Lee, Jeong-Ok Lee, Soo-Mee Bang, Kyoung Un Park, Sang Mee Hwang","doi":"10.1007/s40291-024-00703-3","DOIUrl":"https://doi.org/10.1007/s40291-024-00703-3","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Erythrocytosis is attributed to various clinical and molecular factors. Many cases of <i>JAK2</i>-unmutated erythrocytosis remain undiagnosed. We investigated the characteristics and causes of <i>JAK2</i>-unmutated erythrocytosis.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We assessed the clinical and laboratory results of patients with erythrocytosis without <i>JAK2</i> mutations and performed targeted next-generation sequencing (NGS) panels for somatic and germline mutations.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In total, 117 patients with <i>JAK2</i>-unmutated erythrocytosis were included. The median hemoglobin and hematocrit levels were 17.9 g/dL and 53.4%, respectively. Erythropoietin levels were not below the reference range. Thrombotic events were reported in 17 patients (14.5%). Among <i>JAK2</i>-unmutated patients, 44 had undergone targeted panel sequencing consisting of myeloid neoplasm-related genes, and 16 had one or more reportable variants in <i>ASXL1</i> (5/44), <i>TET2</i>, <i>CALR</i>, <i>FLT3</i>, and <i>SH2B3</i> (2/44). Additional testing for germline causes revealed eight variants in seven genes in eight patients, including <i>NF1</i>, <i>BPGM</i>, <i>EPAS1</i>, <i>PIEZO1</i>, <i>RHAG</i>, <i>SH2B3</i>, and <i>VHL</i> genes. One <i>NF1</i> pathogenic, one <i>BPGM</i> likely pathogenic, and six variants of undetermined significance were detected.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Somatic and germline mutations were identified in 36.4% and 33.3 % of the <i>JAK2</i>-unmutated group; most variants had unknown clinical significance. Not all genetic causes have been identified; comprehensive diagnostic approaches are crucial for identifying the cause of erythrocytosis.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":"1 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597484","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":"Personalizing Oncolytic Immunovirotherapy Approaches.","authors":"Georgios M Stergiopoulos, Ianko Iankov, Evanthia Galanis","doi":"10.1007/s40291-023-00689-4","DOIUrl":"10.1007/s40291-023-00689-4","url":null,"abstract":"<p><p>Development of successful cancer therapeutics requires exploration of the differences in genetics, metabolism, and interactions with the immune system among malignant and normal cells. The clinical observation of spontaneous tumor regression following natural infection with microorganism has created the premise of their use as cancer therapeutics. Oncolytic viruses (OVs) originate from viruses with attenuated virulence in humans, well-characterized vaccine strains of known human pathogens, or engineered replication-deficient viral vectors. Their selectivity is based on receptor expression level and post entry restriction factors that favor replication in the tumor, while keeping the normal cells unharmed. Clinical trials have demonstrated a wide range of patient responses to virotherapy, with subgroups of patients significantly benefiting from OV administration. Tumor-specific gene signatures, including antiviral interferon-stimulated gene (ISG) expression profile, have demonstrated a strong correlation with tumor permissiveness to infection. Furthermore, the combination of OVs with immunotherapeutics, including anticancer vaccines and immune checkpoint inhibitors [ICIs, such as anti-PD-1/PD-L1 or anti-CTLA-4 and chimeric antigen receptor (CAR)-T or CAR-NK cells], could synergistically improve the therapeutic outcome. Creating response prediction algorithms represents an important step for the transition to individualized immunovirotherapy approaches in the clinic. Integrative predictors could include tumor mutational burden (TMB), inflammatory gene signature, phenotype of tumor-infiltrating lymphocytes, tumor microenvironment (TME), and immune checkpoint receptor expression on both immune and target cells. Additionally, the gut microbiota has recently been recognized as a systemic immunomodulatory factor and could further be used in the optimization of individualized immunovirotherapy algorithms.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"153-168"},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139040797","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":"Exagamglogene Autotemcel: First Approval.","authors":"Sheridan M Hoy","doi":"10.1007/s40291-024-00696-z","DOIUrl":"10.1007/s40291-024-00696-z","url":null,"abstract":"<p><p>Exagamglogene autotemcel (Casgevy™) is a genetically modified autologous CD34⁺ cell enriched population. It contains human haematopoietic stem and progenitor cells edited ex vivo by CRISPR/Cas9 (a DNA double strand break-inducing nuclease system) to differentiate into erythroid cells that produce high levels of foetal hemoglobin. Developed by Vertex Pharmaceuticals and CRISPR Therapeutics, exagamglogene autotemcel received its first approval on 16 November 2023 in the UK for the treatment of transfusion-dependent β-thalassemia (TDT) in patients aged ≥ 12 years for whom haematopoietic stem cell (HSC) transplantation is appropriate and a human leukocyte antigen matched related HSC donor is not available. On the same day, it was also approved in the UK for the treatment of sickle cell disease (SCD) in patients aged ≥ 12 years with recurrent vasoocclusive crises (VOCs) who have the β^S/β^S, β^S/β⁺ or β^S/β⁰ genotype for whom HSC transplantation is appropriate and a human leukocyte antigen matched related HSC donor is not available. Subsequently, exagamglogene autotemcel was approved in the USA on 8 December 2023 for the treatment of SCD in patients aged ≥ 12 years with recurrent VOCs and received a positive opinion in the EU on 14 December 2023 for the treatment of TDT and SCD. A regulatory assessment of exagamglogene autotemcel is currently underway for the treatment of TDT in the USA. This article summarizes the milestones in the development of exagamglogene autotemcel leading to these first approvals.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"133-139"},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139479432","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}