Journal of Molecular Diagnostics最新文献

{"title":"Association of Mitochondrial DNA Copy Number in Peripheral Blood with Risk and Prognosis in Acute Aortic Syndrome","authors":"Chun Yin ,&nbsp;Ying Wang ,&nbsp;Hao Yang ,&nbsp;Gaoshan Li ,&nbsp;Zhichun Gao ,&nbsp;Kunyan Li ,&nbsp;Guiquan Zhou ,&nbsp;Xuan Zhang ,&nbsp;Xiangzheng Xu ,&nbsp;Hu Tan ,&nbsp;Jun Jin","doi":"10.1016/j.jmoldx.2024.12.009","DOIUrl":"10.1016/j.jmoldx.2024.12.009","url":null,"abstract":"<div><div>Previous studies have reported that mitochondrial DNA copy number (mtDNA-CN) of blood was associated with a series of aging-related diseases. However, it remains unknown whether mtDNA-CN can be a potential biomarker of acute aortic syndromes (AASs). The mtDNA-CN in blood of 190 male patients with AAS and 207 healthy controls were detected by standardized real-time quantitative PCR–based assay. The mtDNA sequencing data of blood and myocardial muscle in 134 individuals were used to analyze mtDNA somatic mutations in blood. mtDNA-CN in peripheral blood was negatively correlated with age of individuals. Further analysis based on next-generation sequencing data demonstrated numbers and heteroplasmy of mtDNA mutations were positively correlated with age. Remarkably, mtDNA-CN of patients with AAS was lower than that of healthy controls. Logistic regression also showed that mtDNA-CN was independently associated with risk of AAS. During follow-up, patients with the lowest mtDNA-CN quartile had a hazard ratio of 2.543 for all-cause-mortality and 1.964 for composite end points compared with the other patients. Moreover, multivariate Cox regression indicated that lowest mtDNA-CN quartile was independently associated with all-cause mortality in patients with AAS. Our study demonstrated a negative correlation between mtDNA-CN and age. Moreover, lower mtDNA-CN in peripheral blood was significantly associated with higher risk and worse prognosis of AAS. It provided crucial evidence supporting the potential of mtDNA-CN as a novel biomarker of AAS.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 4","pages":"Pages 270-281"},"PeriodicalIF":3.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043157","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":"Distribution of BCR::ABL1 Transcript Types and Response to Therapy in Pediatric Patients with Chronic Myeloid Leukemia","authors":"Esra Seiser ,&nbsp;Yvonne L. Behrens ,&nbsp;Sabine Lukat ,&nbsp;Stephanie Sembill ,&nbsp;Axel Karow ,&nbsp;Meinolf Suttorp ,&nbsp;Markus Metzler ,&nbsp;Manuela Krumbholz","doi":"10.1016/j.jmoldx.2024.12.010","DOIUrl":"10.1016/j.jmoldx.2024.12.010","url":null,"abstract":"<div><div>Achieving a stable deep molecular response with the option to discontinue tyrosine kinase inhibitor treatment is the new therapeutic goal for patients with chronic myeloid leukemia (CML). Several studies have shown that individuals expressing the BCR::ABL1 e14a2 transcript achieve a major molecular response more rapidly than those with the e13a2 transcript. However, technical issues may have confounded these observations, and data for pediatric patients are limited. This study analyzed the distribution of BCR::ABL1 transcript types and their association with baseline hematologic parameters and tyrosine kinase inhibitor treatment response in 102 pediatric patients with CML. Subgroups were compared on the basis of results from routine multiplex PCR and droplet digital PCR (ddPCR). The dynamics of the transcript types under therapy were evaluated in detail in patients and a CML cell line co-expressing e13a2 + e14a2. ddPCR has identified significantly more patients co-expressing e13a2 + e14a2 than classified on the basis of routine diagnostics. This has implications for the categorization of individual subgroups. Comparing transcript dynamics in individuals or a cell line expressing both variants simultaneously revealed no differences in treatment response. When analyzing clinical data based on the transcript classification of patients, it is important to use methods that detect both variants with equal sensitivity. In ddPCR, the transcript variants' ratio is accurately shown because there is no competitive template amplification, as seen in multiplex and quantitative real-time PCR.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 4","pages":"Pages 282-291"},"PeriodicalIF":3.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043163","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":"Optimization of Pre-Analytical Handling to Maintain DNA Integrity in Diagnostic Papanicolaou Tests","authors":"Sara Schumacher ,&nbsp;Jacob Malchau Lauesgaard ,&nbsp;Therese Carlsson ,&nbsp;Anna Linder ,&nbsp;Karin Sundfeldt","doi":"10.1016/j.jmoldx.2024.12.008","DOIUrl":"10.1016/j.jmoldx.2024.12.008","url":null,"abstract":"<div><div>Cell-free DNA (cfDNA) of ovarian carcinoma origin can be detected in samples from the gynecologic tract. This study aims to evaluate how pre-analytical handling affects DNA profile and integrity in Papanicolaou (Pap) tests, to optimize their potential for detection of ovarian cancers (OCs). Analysis of archived Pap tests from patients with OC, kept at room temperature for 48 hours and stored at −80°C, was complemented by <em>in vitro</em> experiments. Temperature-associated effects on DNA fragmentation were evaluated in samples stored at 4°C, −20°C, or −80°C. Time-dependent DNA degradation at room temperature was evaluated in comparison to storage at 4°C. Results were validated in prospectively collected Pap tests. The DNA integrity was assessed by fragment analysis. Accumulation of short DNA fragments was observed in archived Pap tests from patients with OC<em>. In vitro</em>, fragments of 100 to 350 bp increased 11.5-fold within 48 hours at room temperature compared with 1.7-fold when stored at 4°C. Consistent with the <em>in vitro</em> findings, prospectively collected samples showed reduced fragmentation when stored at 4°C compared with room temperature (<em>P</em> = 0.007). Long-term storage at 4°C had a significant negative effect on DNA stability (<em>P</em> = 0.013), whereas freezing slowed down fragmentation. Immediate storage at 4°C after sampling markedly reduces DNA degradation, suggesting a simple way to optimize pre-analytical handling and decrease unwanted fragmentation for cfDNA analysis in Pap tests.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 3","pages":"Pages 199-208"},"PeriodicalIF":3.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015341","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":"A Software Tool for Reagent Design to Expand Access to Single-Nucleotide Variant Detection by the Oligonucleotide Ligation Assay","authors":"Dalton J. Nelson ,&nbsp;Kunal Chugh ,&nbsp;Heather H. Pua ,&nbsp;Frederick R. Haselton","doi":"10.1016/j.jmoldx.2024.12.007","DOIUrl":"10.1016/j.jmoldx.2024.12.007","url":null,"abstract":"<div><div>Single-nucleotide variants (SNVs) and polymorphisms are characteristic biomarkers in various biological contexts, including pathogen drug resistances and human diseases. Tools that lower the implementation barrier of molecular SNV detection methods would provide greater leverage of the expanding single-nucleotide polymorphism/SNV database. The oligonucleotide ligation assay (OLA) is a highly specific means for detection of known SNVs and is especially powerful when coupled with PCR. Yet, the OLA design process remains intensive, and criteria for success are uncertain. To assist in the design process, this study describes OLAgen, an open-source tool to automate development of OLAs and their coupled PCR assays. The software facilitates alignment of sequences surrounding SNVs and generates ligation probes while screening for dimerization potential. OLAgen successfully produced ligation probes that closely matched previously validated designs for HIV-1, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and <em>KRAS</em>, confirming its reliability and potential for clinical applications. The tool was used to generate new assays targeting <em>Mycobacterium tuberculosis</em> drug resistance and variants in the human <em>JAK2</em>, <em>BRAF</em>, and factor V genes, all of which demonstrated 100% sensitivity and specificity in controlled laboratory experiments. The OLAgen predicted assay designs detected mutant frequencies as low as 1% to 5% in wild-type backgrounds in proof-of-concept laboratory studies. OLAgen represents a significant advancement in accessible assay design, promoting the broader application of OLA technology in clinical and research settings.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 3","pages":"Pages 184-198"},"PeriodicalIF":3.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015339","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":"Analytical Validation of the Labcorp Plasma Complete Test, a Cell-Free DNA Comprehensive Genomic Profiling Tool for Precision Oncology","authors":"Ellen L. Verner ,&nbsp;Jennifer B. Jackson ,&nbsp;Cynthia Maddox ,&nbsp;Kenneth C. Valkenburg ,&nbsp;James R. White ,&nbsp;James Occean ,&nbsp;Laine Morris ,&nbsp;Aanavi Karandikar ,&nbsp;Kelly M.R. Gerding ,&nbsp;Mark Sausen ,&nbsp;Faezeh Koohestani ,&nbsp;Eric A. Severson ,&nbsp;Taylor J. Jensen ,&nbsp;Brian J. Caveney ,&nbsp;Marcia Eisenberg ,&nbsp;Shakti H. Ramkissoon ,&nbsp;Amy E. Greer","doi":"10.1016/j.jmoldx.2024.12.006","DOIUrl":"10.1016/j.jmoldx.2024.12.006","url":null,"abstract":"<div><div>To help guide treatment decisions and trial matching, tumor genomic profiling is an essential precision oncology tool. Liquid biopsy, a complementary approach to tissue testing, can assess tumor-specific DNA alterations circulating in the blood. Labcorp Plasma Complete is a next-generation sequencing, cell-free DNA comprehensive genomic profiling test that identifies clinically relevant somatic variants across 521 genes in advanced and metastatic solid cancers. Over 800 unique sequencing libraries across 27 cancer types were evaluated to establish analytical sensitivity, specificity, accuracy, and precision, reproducibility, and repeatability (PRR). Sensitivity was verified for each variant type, with a median variant allele frequency (VAF) of 1.25% and 1.27% for panel-wide single nucleotide variants (SNVs) and insertions/deletions (indels) (sequence mutations), respectively, with &lt;1% VAF sensitivity observed for clinically actionable variants, 1.72-fold for copy number amplifications (CNAs), 0.48% fusion read fraction for translocations, and 0.47% sequence mutation VAF for microsatellite instability-high (MSI-H). Specificity was 99.9999% for SNVs and 100% for other variant types. PRR resulted in 94.9% average positive agreement (APA) and 99.9% average negative agreement (ANA) for sequence mutations and 100% APA and ANA for CNAs, translocations, and MSI-H. Orthogonal assays were utilized to assess accuracy, demonstrating concordance of 97.4% positive percent agreement and &gt;99.99997% negative percent agreement across all variants. Overall, the test demonstrates high sensitivity, specificity, accuracy, and robustness to enable informed clinical decision-making.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 3","pages":"Pages 216-231"},"PeriodicalIF":3.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015335","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":"Concordance of Whole-Genome Long-Read Sequencing with Standard Clinical Testing for Prader-Willi and Angelman Syndromes","authors":"Cate R. Paschal ,&nbsp;Miranda P.G. Zalusky ,&nbsp;Anita E. Beck ,&nbsp;Madelyn A. Gillentine ,&nbsp;Jaya Narayanan ,&nbsp;Nikhita Damaraju ,&nbsp;Joy Goffena ,&nbsp;Sophie H.R. Storz ,&nbsp;Danny E. Miller","doi":"10.1016/j.jmoldx.2024.12.003","DOIUrl":"10.1016/j.jmoldx.2024.12.003","url":null,"abstract":"<div><div>Current clinical testing approaches for individuals with suspected imprinting disorders are complex, often requiring multiple tests performed in a stepwise manner to make a precise molecular diagnosis. We investigated whether whole-genome long-read sequencing could be used as a single data source to simultaneously evaluate copy number variants, single-nucleotide variants, structural variants, and differences in methylation in a cohort of individuals known to have either Prader-Willi or Angelman syndrome. Twenty-five individuals sequenced to an average depth of coverage of 36× on an Oxford Nanopore Technologies PromethION were evaluated. A custom one-page report was generated that could be used to assess copy number, single-nucleotide variants, and methylation patterns at select CpG sites within the 15q11.2-q13.1 region and prioritize candidate pathogenic variants in <em>UBE3A</em>. After training with three positive controls, three analysts blinded to the known clinical diagnosis arrived at the correct molecular diagnosis for 22 of 22 cases (20 true positive, 2 negative controls). Our findings demonstrate the utility of long-read sequencing as a single, comprehensive data source for complex clinical testing, offering potential benefits, such as reduced testing costs, increased diagnostic yield, and shorter turnaround times, in the clinical laboratory.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 3","pages":"Pages 166-176"},"PeriodicalIF":3.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933413","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":"Celebrating 30 Years at the Heart of Precision Medicine","authors":"Maria E. Arcila ,&nbsp;Aaron D. Bossler ,&nbsp;Jane Gibson ,&nbsp;Laura J. Tafe","doi":"10.1016/j.jmoldx.2024.11.001","DOIUrl":"10.1016/j.jmoldx.2024.11.001","url":null,"abstract":"","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 1","pages":"Pages 1-5"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898922","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 Clinical Laboratory Improvement Amendments/College of American Pathologists–Compliant Noninvasive Laboratory-Developed Test for Early Detection of Pancreatic Ductal Adenocarcinoma","authors":"Jian Tajbakhsh ,&nbsp;Silvana Debernardi ,&nbsp;Oleg Blyuss ,&nbsp;Jianhao Bai ,&nbsp;Ruifen Weng ,&nbsp;Simon Lo ,&nbsp;Stephen J. Pandol ,&nbsp;Tatjana Crnogorac-Jurcevic ,&nbsp;Nirdesh K. Gupta","doi":"10.1016/j.jmoldx.2024.10.001","DOIUrl":"10.1016/j.jmoldx.2024.10.001","url":null,"abstract":"<div><div>A noninvasive test for earlier detection of pancreatic cancer in individuals at higher risk is currently unavailable. We devised PancSure, a laboratory-developed test based on the protein biomarkers lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) and regenerating family member 1 β (REG1B), measured in urine by enzyme-linked immunosorbent assay, and commonly used serum/plasma carbohydrate antigen 19.9 (CA19.9), with an updated PancRISK algorithm for data interpretation. The test was validated in 565 patients: 117 asymptomatic patients without any known pancreatic condition or malignancies (21%), 242 symptomatic patients with benign pancreatic diseases (43%), and 206 patients with confirmed cancers (36%); 161 (77.5%) had stage I to II disease, and 45 (22.5%) had stage III to IV disease. PancSure passed all specifications during analytical validation and distinguishes early-stage resectable cancer from asymptomatic individuals with area under the receiver operating characteristic curve (AUC) of 0.93 (95% CI, 0.89–0.97) and 85% to 90% sensitivity (SN) and 78% to 87% specificity (SP); from symptomatic patients with AUC of 0.86 (95% CI, 0.81–0.91) and 83% to 85% SN and 72% to 83% SP; and from all noncancer patients (pooled controls) with AUC of 0.89 (95% CI, 0.84–0.93) and 83% to 85% SN and 78% to 87% SP. PancSure is a noninvasive clinical-grade test with a 48-hour turnover, ready for implementation, providing a viable solution for the earlier detection of pancreatic cancer in at-risk groups for improved patient care.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 1","pages":"Pages 54-61"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631478","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":"Considerations for Severe Acute Respiratory Syndrome Coronavirus 2 Genomic Surveillance","authors":"Julie W. Hirschhorn ,&nbsp;N. Esther Babady ,&nbsp;Allen Bateman ,&nbsp;Heather M. Blankenship ,&nbsp;Jennifer Dien Bard ,&nbsp;Kelsey Florek ,&nbsp;Paige M.K. Larkin ,&nbsp;Marie-Claire Rowlinson ,&nbsp;Kelly Wroblewski ,&nbsp;Donna M. Wolk","doi":"10.1016/j.jmoldx.2024.09.005","DOIUrl":"10.1016/j.jmoldx.2024.09.005","url":null,"abstract":"<div><div>Next-generation sequencing (NGS) has applications in research, epidemiology, oncology, and infectious disease diagnostics. Wide variability exists in NGS wet laboratory techniques and dry laboratory analytical considerations. Thus, many questions remain unanswered when NGS methods are implemented in laboratories for infectious disease testing. Although this review is not intended to answer all questions, the most pressing questions from a public health and clinical hospital-based laboratory perspective will be addressed. The authors of this review are laboratory professionals who perform and interpret severe acute respiratory syndrome coronavirus 2 NGS results. Considerations for pre-analytical, analytical, and postanalytical NGS will be explored. This review highlights challenges for molecular laboratory professionals considering adopting or expanding NGS methods.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 1","pages":"Pages 12-24"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512117","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":"Analysis of Molecular Testing for Suspected Myeloproliferative Neoplasm at a Hybrid Community-Academic Health System","authors":"Andrew B. Stone ,&nbsp;Ryan J. Martinez ,&nbsp;Cade Arries ,&nbsp;Andrew C. Nelson ,&nbsp;Bharat Thyagarajan ,&nbsp;Sophia Yohe ,&nbsp;Pawel Mroz","doi":"10.1016/j.jmoldx.2024.10.003","DOIUrl":"10.1016/j.jmoldx.2024.10.003","url":null,"abstract":"<div><div>Testing for somatic mutations in <em>JAK2</em>, <em>MPL</em>, and <em>CALR</em> genes is critical in the diagnosis of myeloproliferative neoplasms (MPNs). However, this testing may have inadvertently led to increased requests to rule out MPN, including clinical situations with low pretest probability. This article examines <em>JAK2</em>, <em>MPL</em>, and <em>CALR</em> testing by next-generation sequencing (NGS) with the goal of formulating practical guidelines to make test use more efficient and effective. NGS results from 1482 patients tested between 2015 and March 2022 were retrieved, along with corresponding bone marrow biopsies and complete blood cell count results performed within 90 days before NGS, and 245 cases (16.5%) were positive for pathogenic variants in <em>JAK2</em>, <em>MPL</em>, or <em>CALR</em> genes. The findings showed an increase in the proportion of positive cases with patient age, and a statistically significant difference in red blood cell counts and platelet counts among patients with positive versus negative results. Using these factors, simple algorithms were constructed to predict positive results with a maximum sensitivity of 91%, while potentially eliminating 28% of negative test results. However, these models still failed to identify approximately 9% of patients with MPNs. Among these missed patients, many had either primary myelofibrosis or myelodysplastic syndrome/MPN. Considering a simple triage model to help guide MPN testing could represent a more cost-effective approach, particularly if missed patients could be further reduced.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 1","pages":"Pages 42-53"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631496","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}