Clinical chemistry最新文献

{"title":"Characterization of STRC Gene Conversions by Nanopore Sequencing.","authors":"Chiara Rigon, Ugo Sorrentino, Sara Volta, Francesco Prevedello, Eva Trevisson, Leonardo Salviati, Carlo Viscomi, Matteo Cassina","doi":"10.1093/clinchem/hvag004","DOIUrl":"10.1093/clinchem/hvag004","url":null,"abstract":"<p><strong>Background: </strong>Biallelic loss-of-function variants of STRC are a frequent cause of mild to moderate nonsyndromic hearing loss. The high (>98%) sequence homology between STRC and its pseudogene STRCP1 poses a significant challenge for accurate interpretation of STRC variants using standard methods. Although STRC-STRCP1 gene conversions have frequently been inferred from next-generation sequencing and copy number variant analysis data, their structure remains poorly delineated. We employed long-read sequencing to characterize the breakpoints of STRC-STRCP1 gene conversions.</p><p><strong>Methods: </strong>Three specimens with suspected STRC-STRCP1 gene conversions were analyzed by Nanopore sequencing. Long-range PCR was employed to selectively amplify the rearranged alleles, using 2 different primer pairs based on the predicted gene-conversion structures.</p><p><strong>Results: </strong>Nanopore sequencing data confirmed that segments of the wild-type STRC gene were replaced by the corresponding STRCP1 regions in the amplified alleles, consistent with a gene-conversion mechanism in all 3 specimens. Detailed analysis of mismatch patterns, obtained by aligning long reads to reference sequences, further clarified the extent of these conversions. One specimen showed replacement of STRC exons 12 to 23 by STRCP1 sequences, while the other 2 revealed gene conversions involving the terminal STRC exons extending into the adjacent CKMT1B gene. Breakpoints were mapped with variable resolution depending on the rearrangement characteristics.</p><p><strong>Conclusions: </strong>Our approach successfully overcomes the resolution limitations of conventional techniques, providing the molecular characterization of STRC-STRCP1 gene conversions. These findings underscore the clinical relevance of such events and highlight the diagnostic potential of Nanopore sequencing in genetic testing.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"583-590"},"PeriodicalIF":6.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146200375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Large-Language Models for Structured Feature Extraction of Anatomic and Clinical Pathology Reports.","authors":"Brody H Foy, Kelly D Smith, Olivia L Vargas, Michael Keebaugh, Liang Lu, Aanand A Patel, Shreeram Akilesh, Noah G Hoffman","doi":"10.1093/clinchem/hvag006","DOIUrl":"10.1093/clinchem/hvag006","url":null,"abstract":"<p><strong>Background: </strong>Feature extraction via manual chart review is often used for both patient care and research, but it is time-intensive and costly. Recent improvements in natural language processing present novel opportunities to perform high-throughput automated feature extraction. Here, we assessed the accuracy of large language models (LLMs) for structured feature extraction from clinical and anatomic pathology notes.</p><p><strong>Methods: </strong>We assessed the accuracy of feature extraction by the OpenAI GPT-4o and GPT-5 models across 3 pathology data sets: cardiac transplant pathology reports, hemoglobin variant test interpretations, and urine drug test interpretations. For each case, model-derived features were compared to manual labels from expert clinicians. We also developed a novel web application to enable rapid development and prototyping of structured function calls to common LLM models.</p><p><strong>Results: </strong>We first developed a \"toolbuilder\" application to design structured feature extractions from clinical text. Using this application, current LLMs had high accuracy with error rates near 5% for simple cases and 10% for more complex use cases. Performance was strongly influenced by model type but was not drastically improved by prompt engineering or other input adaptations. Across a range of features, expert-LLM concordance was extremely high (κ>0.9), and only slightly below inter-expert concordance. Model errors were most commonly due to mistakes between negative and indeterminate findings, suggesting overconfidence of the models in the presence of reduced information.</p><p><strong>Conclusion: </strong>These findings suggest that LLM tools can provide significant value in automating time- and cost-intensive clinical note feature extraction and annotation.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"591-600"},"PeriodicalIF":6.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Diagnostic Value of Serum p-tau217 in Alzheimer Disease: Equal to Plasma in Levels and Clinical Utility?","authors":"","doi":"10.1093/clinchem/hvag015","DOIUrl":"10.1093/clinchem/hvag015","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"615"},"PeriodicalIF":6.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147303093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Creatinine Measurement in Pediatrics: Is There Still a Role for the Compensated Jaffe Method?","authors":"","doi":"10.1093/clinchem/hvag040","DOIUrl":"https://doi.org/10.1093/clinchem/hvag040","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Saliva vs Plasma in Liquid Biopsy Sampling for Head and Neck Cancer: A Comparative Study.","authors":"Mouadh Barbirou,Amanda Miller,David Baek,Allison Hameier,Ashley Wetzel,Julia Fiedor,Claire Yang,Alban Linnenbach,Kathryn Nunes,Pablo Llerena,Hani Samarah,Voichita Bar-Ad,Adam Luginbuhl,Bingshan Li,Guojun Li,Andrew Yampolsky,Lifang Hou,Joseph Curry,Chun Wang,Hushan Yang","doi":"10.1093/clinchem/hvag035","DOIUrl":"https://doi.org/10.1093/clinchem/hvag035","url":null,"abstract":"BACKGROUNDHead and neck squamous cell carcinoma (HNSCC) presents significant diagnostic and therapeutic challenges due to its rising incidence and poor prognosis. Liquid biopsy, utilizing biofluids such as blood and saliva, offers a noninvasive approach to detect circulating tumor DNA (ctDNA), circulating tumor RNA (ctRNA), and small extracellular vesicles (sEVs) containing DNA (sEV-DNA) and RNA (sEV-RNA), which reflect tumor biology. However, comprehensive comparisons of these liquid biopsy markers are limited.METHODSPaired plasma and saliva samples were collected from HNSCC patients and healthy controls. We analyzed ctDNA and sEV-DNA from both plasma and saliva for tumor fraction (TF), copy number variations (CNVs), and methylation patterns. Additionally, we profiled small RNAs from saliva-derived ctRNA and sEV-RNA to explore their potential as biomarkers for disease monitoring.RESULTSSaliva sEV-DNA exhibited significantly higher TF compared to plasma sEV-DNA in HNSCC patients (mean, 0.0744 vs 0.0253, P < 0.001), suggesting superior tumor DNA capture in saliva. CNV analysis revealed shared and distinct genomic alterations across different sample types. Aberrant methylation patterns were observed more frequently in sEV-DNA than in ctDNA across both saliva and plasma samples. Small RNA profiling demonstrated broader coverage of differentially expressed genes in saliva sEV-RNA, enhancing its biomarker potential.CONCLUSIONSOur findings suggest that saliva-derived sEVs hold promise as noninvasive biomarkers for HNSCC. Saliva-based liquid biopsies, particularly sEV-DNA and sEV-RNA, provide a comprehensive molecular portrait of HNSCC that may facilitate the development of personalized medicine strategies.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"6 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poor Performance of LDL-Cholesterol Equations versus Beta Quantification in a Very Large Cohort of Patients with Dyslipidemia.","authors":"Martine Paquette,George Thanassoulis,Mark H Sherman,David W Blank,Alexis Baass","doi":"10.1093/clinchem/hvag038","DOIUrl":"https://doi.org/10.1093/clinchem/hvag038","url":null,"abstract":"BACKGROUNDAccurate estimations of low-density lipoprotein cholesterol (LDL-C) is important to guide clinical decisions concerning lipid-lowering treatment. The Friedewald formula has been used for the past 50 years, but its limitations compared to the reference β-quantification method have led to the development of several newer equations. The objective of this study was to evaluate and compare the performance of calculated LDL-C equations using a real-world β-quantification dataset from a very large cohort of dyslipidemic patients.METHODSA total of 32 533 LDL-C results from β-quantification were available for this study. The β-quantification procedure was performed by qualified technicians according to the NIH reference method. LDL-C was calculated using the following equations: Modified Sampson, Enhanced Sampson, Extended Martin-Hopkins, Sampson, Martin-Hopkins, and Friedewald.RESULTSIn patients with triglycerides (TG) concentrations between 401 and 800 mg/dL, the proportion of values outside the National Cholesterol Education Program total allowable error limit of 12% was >49% for every equation, whereas it was >79% for every equation in patients with TG concentration >800 mg/dL. In patients with TG concentrations ≤400 mg/dL, the Enhanced Sampson equation had the lowest proportion of values outside the error limit (8.5%), followed by the Friedewald equation (11.6%).CONCLUSIONSIn patients with TG <400 mg/dL (≤4.52 mmol/L), the Friedewald equation performed well and was not inferior to the Sampson or the Martin-Hopkins equations. However, in patients with TG >400 mg/dL none of the formulas performed adequately and LDL-C should not be calculated in these patients.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"46 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Rapid Phenotypic Susceptibility Testing Techniques That Enhance Antimicrobial Stewardship and Clinical Decision-Making.","authors":"Janiece S Glover,Romney Humphries","doi":"10.1093/clinchem/hvag033","DOIUrl":"https://doi.org/10.1093/clinchem/hvag033","url":null,"abstract":"BACKGROUNDAntimicrobial resistance (AMR) is a critical global health challenge, underscoring the need for diagnostic innovations that enable timely, and targeted therapy. Rapid phenotypic antimicrobial susceptibility testing (AST) offers a transformative approach by delivering actionable susceptibility results significantly earlier than conventional methods. This accelerated turnaround is vital for optimizing antibiotic therapy and improving outcomes in severe infections, such as sepsis, where delays in effective treatment increase morbidity and mortality. Despite these advantages, implementation faces challenges, including variability in test performance, lack of standardized protocols, and cost-benefit considerations.CONTENTThis review provides an overview of emerging rapid phenotypic AST technologies, focusing on their clinical relevance and operational implications. We outline the fundamentals of the phenotypic approach, highlight growth-based methods, and summarize evidence, demonstrating the impact of rapid phenotypic AST on reducing time to effective therapy and supporting antimicrobial stewardship.SUMMARYRapid phenotypic AST represents a pivotal advancement in combating AMR, offering the potential to bridge diagnostic gaps and enhance patient outcomes through timely, evidence-based antimicrobial therapy.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"18 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147735195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transferability and Between Laboratory Imprecision of an LC-MS/MS-Based Reference Measurement Procedure for Apolipoproteins.","authors":"L Renee Ruhaak,Zsuzsanna Kuklenyik,Julia Dittrich,Eline Dantuma,Fred Romijn,Nina M Diederiks,Liesbet Deprez,Andrew N Hoofnagle,Hubert Vesper,Uta Ceglarek,Christa M Cobbaert, ","doi":"10.1093/clinchem/hvag020","DOIUrl":"https://doi.org/10.1093/clinchem/hvag020","url":null,"abstract":"BACKGROUNDApolipoprotein standardization in multiple calibration laboratories requires equivalent results to value assign matrix-based reference and external quality assurance materials. A multiplexed LC-MS/MS-based reference measurement procedure (RMP) has been developed for serum apolipoproteins apo(a), apoA-I, apoB, apoC-I, apoC-II, apoC-III, and apoE. This study evaluates the transferability of the RMP between 3 calibration labs and determines the between-laboratory imprecision.METHODSSix periodic ring trial surveys were held. The study protocol, calibrators, internal standards, quality controls (QCs), and clinical samples (CSs) were shared among the laboratories. Intra-laboratory imprecision and inter-peptide comparisons evaluated intra-laboratory performance, while inter-laboratory imprecision evaluated equivalence between the calibration labs. Precision of the common bilevel QC monitored the level of harmonization over time.RESULTSIntra-laboratory imprecision fulfilled predefined analytical performance, defined as repeatability <50% of the maximum allowable uncertainty (MAU) at minimal criteria. Median interlaboratory variation (CVbl) was 3.71%, 3.33%, 7.38%, 6.74%, 3.88%, and 3.90% for apoA-I, apoB, apoC-I, apoC-II, apoC-III, and apoE, respectively. For apo(a), CVbl was concentration (x) dependent following 206.32×x-0.899%. In QC samples, the average imprecision for all apolipoproteins decreased from 6.0% and 18.1% for QC1 and QC2, to 5.2% and 9.5%, indicating improvement of analytical performance of the network over time.CONCLUSIONSThis study shows the feasibility of transferring the multiplex apo LC-MS/MS-based RMP between laboratories. Predefined performance specifications were fulfilled for all seven apolipoproteins. Ongoing round-robin studies will ensure stable performance of the calibration labs required to accomplish an accurate value-base for apolipoprotein certification of commercial reagents.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"10 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147702195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Point of Concern for Troponin Testing with High-Sensitivity Assays in the Near Patient Setting.","authors":"Peter A Kavsak","doi":"10.1093/clinchem/hvag034","DOIUrl":"https://doi.org/10.1093/clinchem/hvag034","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"3 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whose Role Is It, Anyway? Ensuring Correct Genomic Variant Nomenclature in Published Literature.","authors":"Sadeem Qdaisat,Birgit Funke,Heather Mason-Suares","doi":"10.1093/clinchem/hvag031","DOIUrl":"https://doi.org/10.1093/clinchem/hvag031","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"55 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147666645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}