Journal of Molecular Diagnostics最新文献

{"title":"Integrating Formalin-Fixed, Paraffin-Embedded–Derived Whole-Genome Sequencing into Routine Molecular Pathology","authors":"Cassandra Litchfield ,&nbsp;Ronny Nienhold ,&nbsp;Andreas Wicki ,&nbsp;Michael Schmid ,&nbsp;Domingo Aguilera-Garcia ,&nbsp;Viktor Hendrik Koelzer","doi":"10.1016/j.jmoldx.2025.04.011","DOIUrl":"10.1016/j.jmoldx.2025.04.011","url":null,"abstract":"<div><div>Formalin-fixed, paraffin-embedded (FFPE) tumor tissue is the standard in pathology due to logistical and quality constraints of fresh-frozen samples. Although whole-genome sequencing (WGS) offers diagnostic promise, its validity and utility in FFPE samples remain underexplored. This study bridges the gap by comparing FFPE-derived tumor WGS with next-generation sequencing results from FoundationOneCDx (F1CDx) and a melanoma-specific panel (MelArray) in 78 metastatic melanoma samples from the Swiss Tumor Profiler Study. A diagnostic pipeline was developed for quality control, variant annotation, and clinical actionability using public and commercial databases. FFPE-derived WGS displayed robust analytical validity, detecting 95% of somatic single nucleotide variants, 98% of multinucleotide variants, 90% of insertions/deletions, 76% of amplifications, and 96% of homozygous deletions identified by F1CDx. Tumor mutational burden strongly correlated with F1CDx (<em>R</em> = 0.98), particularly at the clinical threshold of ≥10 mutations per megabase, crucial for treatment decisions. WGS detected complex biomarkers such as UV-associated mutational signatures and genome-wide copy number alterations, aiding melanoma subtype distinction. Clinically, WGS suggested treatments or trials for all cases, identifying additional markers in 38% and 71% compared with F1CDx and MelArray, respectively. Novel therapeutic opportunities were found in 18% and 56% of cases. FFPE-derived WGS closely matches targeted panels in performance while providing comprehensive insights, enhancing therapeutic options. With decreasing costs, WGS could become a powerful routine diagnostic tool.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 8","pages":"Pages 722-735"},"PeriodicalIF":3.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703032","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":"Informatics Powering Data to Shape the Future of Molecular Pathology","authors":"Andrea Sboner ,&nbsp;Jamal Benhamida ,&nbsp;Julie W. Hirschhorn ,&nbsp;Robyn L. Temple-Smolkin ,&nbsp;Weiwei Zhang ,&nbsp;Annette Leon ,&nbsp;Association for Molecular Pathology Informatics Subdivision Leadership","doi":"10.1016/j.jmoldx.2025.03.005","DOIUrl":"10.1016/j.jmoldx.2025.03.005","url":null,"abstract":"","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 8","pages":"Pages 671-673"},"PeriodicalIF":3.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703114","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 Implementation of Matched Tumor/Germline Sequencing Improves Accuracy of Tumor Genomic Profiling and Therapeutic Recommendations.","authors":"Danielle K Manning, Guruprasad Ananda, Cheryl Eifert, Vanesa Rojas-Rudilla, William Swanton, Shawn Keefe, Elizabeth P Garcia, Michael D'Eletto, Erica Holdmore, Satyakam Mishra, Kirill Borziak, Pieter Lukasse, Phani Davineni, Monica Devi Manam, Priyanka Shivdasani, Arezou A Ghazani, Ai Ling Wang, Murat Bastepe, Himisha Beltran, Katherine A Janeway, Alanna Church, Alicia Pollaci, Anuradha B Chittenden, Diane R Koeller, Alison Schwartz Levine, Judy E Garber, Bruce E Johnson, Neal I Lindeman, Jonathan A Nowak, Lynette M Sholl, Laura E MacConaill","doi":"10.1016/j.jmoldx.2025.06.005","DOIUrl":"https://doi.org/10.1016/j.jmoldx.2025.06.005","url":null,"abstract":"<p><p>Genomic profiling of cancers informs diagnostic and prognostic classification and aids in selection of targeted therapeutics. Targeted, next-generation sequencing of cancer-specific genes is clinically feasible and enables comprehensive somatic reporting; without a matched germline specimen, germline alterations can confound analyses of the somatic profile and create uncertainty in interpretation. We report the validation and implementation of optional matched tumor/germline sequencing in our precision cancer medicine program. Sixty-three cases were selected for technical validation. DNA was analyzed using OncoPanel, a hybrid capture-based sequencing assay of 461 cancer genes. Three analytical pipelines were implemented: tumor-only, matched tumor/germline, and germline-only. For matched tumor/germline, we \"rescued\" germline alterations in 19 genes with actionable/therapeutic implications. We retrospectively analyzed the first 1600 matched cases to determine the potential clinical utility of this approach. Limit of detection for point mutations/indels was 3% allele fraction; reproducibility was >98%. Matched tumor/germline concordance across 938 somatic calls was 100%. The average TMB was ∼4 mutations/Mb lower than tumor-only sequencing. TMB-high patients were accurately reclassified as TMB-low in 14% of cases. 25% of validation cases (14% post-launch) had a pathogenic or likely pathogenic germline variant conferring cancer susceptibility; 14% of validation cases (7% post-launch) harbored a germline variant of therapeutic significance. Matched tumor/germline sequencing is more accurate than tumor-only sequencing, while still encompassing all genomic findings that inform targeted therapy selection.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709677","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":"Survey of Demographics, Training, Duties, and Professional Development for Variant Scientists in Genomic Medicine.","authors":"Alexa Dickson, Kelsey R Cone, Barbara K Fortini, Jennifer Goldstein, Michelle L Thompson, Matheus V M B Wilke, Anna C E Hurst, Molly C Schroeder, Katarzyna Polonis, Kevin M Bowling","doi":"10.1016/j.jmoldx.2025.06.004","DOIUrl":"https://doi.org/10.1016/j.jmoldx.2025.06.004","url":null,"abstract":"<p><p>Genomic testing has proven utility in disease diagnostics, guiding clinical management and improving outcomes. Use of high throughput sequencing by clinical laboratories has generated opportunities and challenges in data analysis resulting in the emergence of a laboratory role termed Variant Scientist. The aim of this study was to characterize this laboratory role. We developed a thirty-item survey to collect information describing the current demographic landscape, salary ranges, work environments, training options, and professional development of Variant Scientists. The survey was disseminated to individuals conducting variant analysis in the United States from November 6, 2023, to March 15, 2024. Survey responders (n=87) are predominantly female (78%), age 40 or less (64%), hold advanced degrees (38% master's, 47% doctoral), and report four or more years of experience (75%). Responders report involvement in a diverse set of laboratory tasks and received relevant training on the job (78%). This workforce is satisfied with their career path (70%) and reports adequate support from employers but perceive that resources and recognition from professional organizations are currently lacking. Characterization of this workforce will be of interest to individuals working as Variant Scientists, individuals interested in careers in variant science, and laboratory directors looking to Variant Scientists for assistance with maintaining efficient and growing clinical laboratory operations.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709678","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":"A Systematic, Evidence-Based Workflow for Classifying KMT2A Fusions in AML.","authors":"Lauren M Petersen, Rachana Sainger, Paulina Sanchez, Jillian Burke, Joshua D Wemmer, Bradley Patay, Jeffrey E Miller","doi":"10.1016/j.jmoldx.2025.06.007","DOIUrl":"https://doi.org/10.1016/j.jmoldx.2025.06.007","url":null,"abstract":"<p><p>KMT2A fusions are a critical oncogenic driver in 5-10% of acute myeloid leukemia (AML) patients and are associated with poor prognosis. Currently, there are no published somatic guidelines for fusions in AML and developing methods to accurately classify fusions, especially those involving KMT2A, is essential for patient care. Therefore, the LabPMM KMT2A Fusions Workflow was developed to address this need. This workflow was designed based on the somatic guidelines by Horak et al., where classification of oncogenicity is based on points awarded for varying types of evidence. Fusions previously detected by LabPMM's CAP/CLIA-certified MyAML and MyMRD gene panels were used to test this workflow. A total of 100 KMT2A fusions were reassessed and 97 of these had a breakpoint in the major breakpoint cluster region (BCR1). There were 20 distinct partner genes for KMT2A with various functions and the most common partners were MLLT3, ELL, AFDN, MLLT10, and AFF1. Five KMT2A fusions had a novel partner (MYB, RC3H1, SNAPC3, STPG1, and HPSE2). Breakpoints in the partner genes were assessed to better understand their potential role in driving leukemogenesis. Out of the 100 fusions reassessed, 9 had a classification change. This LabPMM KMT2A Fusions Workflow provides a points-based system for curation that allows for standardization and clarity both within and among genetic diagnostic laboratories reporting on KMT2A fusions in AML.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709676","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":"Cost-Effectiveness Analysis of Comprehensive Genomic Profiling in Patients with Advanced Non-Small-Cell Lung Cancer Using Real-World Data.","authors":"Scott Spencer, Weicheng Ye, Siyang Peng, Denise Zou","doi":"10.1016/j.jmoldx.2025.05.011","DOIUrl":"10.1016/j.jmoldx.2025.05.011","url":null,"abstract":"<p><p>Cancer treatment costs pose a significant global economic burden. By facilitating treatment plans tailored to the genomic profile of patients' cancer, genomic testing has the potential to reduce health care costs. Using real-world evidence, this study compared the cost-effectiveness of comprehensive genomic profiling (CGP) versus small panel (SP) testing in patients with advanced non-small-cell lung cancer in the United States and Germany. A partitioned survival model was developed to estimate the life years and drug acquisition costs associated with CGP and SP testing in patients receiving matched targeted therapy, matched immunotherapy, or no matched therapy/untreated. Key model parameters were informed by real-world data derived from the Syapse study. Scenario and sensitivity analyses were conducted. CGP improved the average overall survival by 0.10 years compared with SP. CGP was associated with higher health care costs because of a higher percentage of patients receiving targeted therapies. The estimated incremental cost-effectiveness ratio (ICER) of CGP versus SP was $174,782 and $63,158 per life-year gained in the United States and Germany, respectively. Increasing the number of patients receiving treatment decreased the ICERs ($86,826 in the United States and $29,235 in Germany), while switching from immunotherapy plus chemotherapy to chemotherapy alone increased the ICERs ($223,226 in the United States and $83,333 in Germany). Altogether, CGP has the potential to improve patient outcomes and is more cost-effective than SP.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700229","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 Multiplex Real-Time PCR Assay for the Rapid Detection of the Asian-Type DEL.","authors":"Min Young Park, Kang-Hee Lee, Yong-Jin Yang, Ji Young Seo, Jong Kwon Lee, Ja-Hyun Jang, Yong-Hak Sohn, Kyou-Sup Han, Duck Cho","doi":"10.1016/j.jmoldx.2025.05.010","DOIUrl":"10.1016/j.jmoldx.2025.05.010","url":null,"abstract":"<p><p>Asian-type DEL (RHD, c.1227G>A) is relatively prevalent in East Asians and is essential to detect in serologic rhesus (Rh) D-negative individuals. Despite the recognized importance of identifying Asian-type DEL, traditional detection methods, such as adsorption-elution and Sanger sequencing, are complex and time-consuming. A reliable method is required for the rapid and precise detection of Asian-type DEL. A novel multiplex real-time PCR assay using allele-specific TaqMan hydrolysis probes was developed to target the Asian-type DEL variant. Analytical specificity and sensitivity were evaluated using RHD or RHCE synthetic DNAs with 1227G or 1227A. The assay was tested on 315 clinical samples, and the results were compared with Sanger sequencing to assess diagnostic performance. Analytical specificity evaluations confirmed that the assay selectively amplified RHD, 1227A, or 1227G without cross-reactivity to RHCE. Additionally, clinical sample tests showed the assay maintained high specificity and sensitivity even at high nucleic acid concentrations. The Asian-type DEL multiplex real-time PCR assay demonstrated 100% sensitivity and specificity, with complete concordance across all samples compared with reference methods. Compared with Sanger sequencing, the multiplex real-time PCR assay had a shorter analysis time. The assay developed in this study offers a fast, reliable, and accurate approach for detecting Asian-type DEL. This method significantly improves efficiency over conventional techniques and provides a valuable tool for managing transfusion safety and RhD alloimmunization risks in RhD-negative populations.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660930","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":"Age-Stratified Epidemiology of Respiratory Pathogens and the Value of Customizable Syndromic Testing Using the LIAISON PLEX Respiratory Flex Assay.","authors":"Kaisha Gonzalez, Giulia Amicarelli","doi":"10.1016/j.jmoldx.2025.05.009","DOIUrl":"10.1016/j.jmoldx.2025.05.009","url":null,"abstract":"<p><p>Molecular syndromic assays have improved respiratory diagnostics by enabling the simultaneous detection of multiple pathogens from a single sample. However, fixed-panel designs may not align with age-specific prevalence patterns or evolving epidemiologic trends, limiting clinical utility and reimbursement viability. In this study, 1520 positive nasopharyngeal swabs from symptomatic individuals collected during the 2022 to 2023 respiratory season were analyzed by using the LIAISON PLEX Respiratory Flex Assay to evaluate the benefits of customizable, tiered testing strategies. Diagnostic yields from a standard-of-care panel were compared with tiered (core-plus-reflex) frameworks across pediatric (age ≤21 years), adult (age 22 to 64 years), and elderly (age ≥65 years) cohorts. Weighted analyses revealed that 99.8% of cases were viral, while bacterial pathogens accounted for <1%. The most commonly detected viruses included severe acute respiratory syndrome coronavirus 2 (28.2%), human enterovirus/rhinovirus (17.1%), influenza A (11.9%), and human coronavirus (7.4%). Age-related differences were observed, with human enterovirus/rhinovirus and adenovirus more common in pediatric patients, whereas severe acute respiratory syndrome coronavirus 2 and influenza A predominated in adults and the elderly. Standard-of-care panels captured only 58% of infections overall and 33% in pediatric patients; the tiered testing approach identified ≥99% of infections using flexible core-plus-reflex panels. Moreover, core panel targets alone accounted for >76% of all detections. These findings underscore the diagnostic, clinical, operational, and cost management value of age-informed, customizable testing frameworks to improve detection, reduce unnecessary testing, and support stewardship.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530805","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 an End-to-End Total RNA Sequencing Quality Control Framework for Blood-Based Biomarker Discovery.","authors":"Cheryl L Sesler, Guzel I Shaginurova, Lukasz S Wylezinski, Elena V Grigorenko, Franklin R Cockerill, Charles F Spurlock","doi":"10.1016/j.jmoldx.2025.05.008","DOIUrl":"10.1016/j.jmoldx.2025.05.008","url":null,"abstract":"<p><p>Next-generation RNA sequencing (RNA-seq) enables comprehensive transcriptomic profiling for disease characterization, biomarker discovery, and precision medicine. Despite its potential, RNA-seq has not yet been widely adopted for clinical applications, and a key barrier to its adoption is the variability introduced during processing and analysis. Quality controls (QCs) must be considered through all stages of biomarker discovery. This study describes a comprehensive QC framework for effective RNA-seq biomarker discovery. Multilayered quality metrics were established across preanalytical, analytical, and postanalytical processes. Total RNA-seq was performed by using RNA isolated from whole blood (PAXgene Blood RNA tubes). Bulk RNA controls were incorporated to monitor sequencing batches. This framework was applied to a catalog of prospectively collected or biobanked clinical specimens spanning multiple disease indications. Among all QCs, preanalytical metrics (specimen collection, RNA integrity, and genomic DNA contamination) exhibited the highest failure rates and resulted in the addition of a secondary DNase treatment, which reduced genomic DNA levels. The additional DNase treatment significantly lowered intergenic read alignment and provided sufficient RNA for downstream sequencing and analysis. This end-to-end QC framework for RNA-seq biomarker discovery was developed and implemented to enhance the confidence and reliability of results. To advance the clinical adoption of RNA-seq, developing and implementing standards will improve reliability, accelerate biomarker discovery, and facilitate its translation into clinically actionable diagnostics and therapeutics.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512714","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":"Cell-Free DNA, Tumor Molecular Concordance, and Clinical Correlates of Patients with Cancer Treated in a Large Community Health Care Network.","authors":"William A LaFramboise, Patti Petrosko, Phillip H Gallo, Louis Gil, Tuong L Lam, Robin M Barr, Philip E Schumacher, Harmeet K Kharoud, Katherine M Taylor, Emily Dalton, Bella Bapat, Sefali Patel, John Nakayama, Christie J Hilton, Lisa B Ercolano, Ali H Zaidi, Casey J Allen, Thomas Rachman, Oana Carja, Russell Schwartz, Patrick L Wagner, David L Bartlett","doi":"10.1016/j.jmoldx.2025.05.007","DOIUrl":"10.1016/j.jmoldx.2025.05.007","url":null,"abstract":"<p><p>Blood collection, plasma processing, and cell-free DNA (cfDNA) purification were optimized to capture circulating tumor DNA without blood cell background DNA among 874 patients with cancer. cfDNA comprised predominantly mononucleosomal fragments [n = 874; mean (x¯) ± SD = 166 ± 5 bp] that generated comparably sized sequencing reads (x¯ ± SD = 162 ± 25 bp). Despite a vast range of cfDNA concentrations (0.50 to 1132.9 ng/mL) across 21 tumor types, matched tumor and blood specimens (n = 430 patients) revealed high concordance for coding (median = 97%) and clinical oncogenic mutations (median = 88% concordance). Therapeutically actionable mutations were identified in 233 patients by both assays, whereas 126 patients had oncogenic mutations without an established pharmacotherapeutic agent. An additional 48 patients (11%) had actionable mutations detected only in cfDNA assays, whereas 23 patients (5%) had mutations in tumor only. Concordance was high in both prevalent (lung, breast, and colon) and rare tumors (appendiceal, sarcoma). Cell-free DNA levels from diagnostic blood specimens were a strong indicator of patient survival duration independent of age, sex, tumor type, and stage, demonstrative of a potentially important role as a prognostic biomarker. Mutations in established oncogenes and tumor suppressors were readily detectable across all tumor types in circulating tumor DNA, indicating a diagnostic role for cfDNA from blood extending beyond the identification of companion therapeutics to patient screening and monitoring.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512713","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}