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Determinants of Cardiac Myosin Binding Protein C in the General Population.
IF 7.1 2区 医学
Clinical chemistry Pub Date : 2025-03-20 DOI: 10.1093/clinchem/hvaf013
Michael F Paus, Magnus N Lyngbakken, Arnljot Tveit, Kjetil Steine, Trygve Berge, Julia B Skranes, Erika N Aagaard, Brede Kvisvik, Jon Brynildsen, Siri L Heck, Thakshani Wimalanathan, Kristin M Aakre, Helge Røsjø, Torbjørn Omland
{"title":"Determinants of Cardiac Myosin Binding Protein C in the General Population.","authors":"Michael F Paus, Magnus N Lyngbakken, Arnljot Tveit, Kjetil Steine, Trygve Berge, Julia B Skranes, Erika N Aagaard, Brede Kvisvik, Jon Brynildsen, Siri L Heck, Thakshani Wimalanathan, Kristin M Aakre, Helge Røsjø, Torbjørn Omland","doi":"10.1093/clinchem/hvaf013","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf013","url":null,"abstract":"<p><strong>Background: </strong>Cardiac myosin binding protein C (cMyC) is a novel, cardiac-specific biomarker with an early release profile after acute ischemic myocardial injury. Whether cMyC reflects chronic myocardial injury and left ventricular remodelling in the general population is unknown. The aims of the study were to test the hypotheses that cMyC concentrations are associated with cardiovascular risk factors, biomarkers of chronic myocardial injury, and imaging biomarkers of cardiac anatomy, function, and fibrosis.</p><p><strong>Methods: </strong>Circulating cMyC and cardiac troponin I and T concentrations were measured in 3672 individuals from the general population, born in 1950, who underwent echocardiography. One-hundred-ninety-nine participants with measured cMyC completed a cardiovascular magnetic resonance (CMR) examination for assessment of myocardial fibrosis.</p><p><strong>Results: </strong>Circulating cMyC was measurable in 99.6% of study participants and in 99.0% of CMR substudy participants. cMyC was positively associated with left ventricular mass and left atrial volume and inversely associated with renal function and indices of left ventricular systolic and diastolic function. In participants with available late gadolinium enhancement images for the assessment of focal fibrosis (n = 197), cMyC was positively associated with indices of focal myocardial fibrosis.</p><p><strong>Conclusions: </strong>In the general population, circulating cMyC concentrations are associated with cardiovascular risk factors, reflect left ventricular remodelling, including focal myocardial fibrosis, and systolic and diastolic dysfunction independently of traditional risk factors.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662948","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}
引用次数: 0
Pediatric Vaccine-Induced Antibody Thresholds: Rethinking Pre-Immunosuppression Serologic Testing and Revaccination Implications
IF 9.3 2区 医学
Clinical chemistry Pub Date : 2025-03-19 DOI: 10.1093/clinchem/hvaf020
Megan Culler Freeman, Adam Sinder, Grace Conway, Sarah Chamseddine, Mariam Faiz Nassar, Bradley J Wheeler, Adam Anderson, Sarah E Wheeler
{"title":"Pediatric Vaccine-Induced Antibody Thresholds: Rethinking Pre-Immunosuppression Serologic Testing and Revaccination Implications","authors":"Megan Culler Freeman, Adam Sinder, Grace Conway, Sarah Chamseddine, Mariam Faiz Nassar, Bradley J Wheeler, Adam Anderson, Sarah E Wheeler","doi":"10.1093/clinchem/hvaf020","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf020","url":null,"abstract":"Background Immune response to vaccination is assessed when adequate vaccine protection is in question or immunosuppression is imminent through measurement of antibody levels, which wane as time from vaccination increases. The serologic cutoff value for adequate response is based on thresholds derived from studies in adults, and age-appropriate thresholds for children have not been established. We sought to investigate age-specific differences in antibody levels in healthy children to guide determination of vaccine immunity status when clinically indicated. Methods This cross-sectional study assessed clinical serology for measles, mumps, rubella (MMR), varicella, and hepatitis B (HepB) in an age-stratified cohort of 471 healthy children who were up to date for vaccination (1 to 18 years). Remnant specimens with sufficient volume were collected from July 23, 2019, to November 17, 2020, as convenience samples and chart reviewed for inclusion. Results While children of all ages had detectable titers to MMR, median titers for HepB and varicella waned by ages 11 to 12 and 9 to 10 years, respectively. Children had titers above adult thresholds for MMR at all measured timepoints, retrospectively resulting in 24.6% (95% CI, 21.6%–27.8%) of children having an inappropriate MMR classification when adult instead of pediatric thresholds were used. Current use of HepB and varicella serology may be inappropriate due to the rapid waning of titers. The adequacy of an individual’s response to one vaccine component did not infer adequate responses to other components. Conclusions Application of age-appropriate reference intervals for vaccine serologic tests will provide a foundation for improved treatment recommendations and standards of care.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"90 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653457","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}
引用次数: 0
Carbamylated Albumin, Heart Failure, and Mortality in Patients Undergoing Coronary Angiography.
IF 7.1 2区 医学
Clinical chemistry Pub Date : 2025-03-19 DOI: 10.1093/clinchem/hvaf021
Babak Yazdani, Graciela E Delgado, Anders H Berg, Christoph Wanner, Bernhard K Krämer, Winfried März, Marcus E Kleber, Christiane Drechsler
{"title":"Carbamylated Albumin, Heart Failure, and Mortality in Patients Undergoing Coronary Angiography.","authors":"Babak Yazdani, Graciela E Delgado, Anders H Berg, Christoph Wanner, Bernhard K Krämer, Winfried März, Marcus E Kleber, Christiane Drechsler","doi":"10.1093/clinchem/hvaf021","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf021","url":null,"abstract":"<p><strong>Background: </strong>Urea is elevated in chronic kidney disease (CKD) and end-stage renal disease (ESRD), and promotes the carbamylation of proteins, including human albumin, on multiple lysine side chains. Higher proportions of carbamylated albumin (C-Alb) have been associated with increased mortality risk in patients with ESRD. Whether C-Alb predicts mortality in patients with no or mild impairment of kidney function is unknown.</p><p><strong>Methods: </strong>We measured C-Alb in 3197 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study who had been referred to coronary angiography and followed-up for 10 years. Association of baseline C-Alb with all-cause and cause-specific mortality was investigated using Cox proportional hazards regression.</p><p><strong>Results: </strong>Higher quartiles of C-Alb were associated with a significantly increased risk of death from any cause, with hazard ratios (HRs, 95%CI) of 1.53 (1.26-1.85) and 2.52 (2.11-3.01) in the third and fourth quartiles, respectively. After adjustment for cardiovascular (CV) risk factors, including estimate glomerular filtration rate (eGFR), the association with mortality was attenuated with a HR of 1.25 (1.02-1.53) for the fourth quartile as compared to the first quartile. We observed the strongest association with death due to congestive heart failure (HF) with a HR of 7.19 (4.57-11.3) and 3.99 (2.40-6.63) per 1-unit increase of log-transformed C-Alb in unadjusted and multivariate adjusted analyses, respectively.</p><p><strong>Conclusions: </strong>We observed a strong association of C-Alb with CV risk in patients with no or mild CKD. This association was independent of traditional CV risk factors including eGFR and particularly strong regarding death due to congestive HF.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662930","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}
引用次数: 0
Oropouche Virus: The Next (Re)Emerging Arboviral Threat?
IF 7.1 2区 医学
Clinical chemistry Pub Date : 2025-03-12 DOI: 10.1093/clinchem/hvaf017
Portia Mira, Elitza S Theel
{"title":"Oropouche Virus: The Next (Re)Emerging Arboviral Threat?","authors":"Portia Mira, Elitza S Theel","doi":"10.1093/clinchem/hvaf017","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf017","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604190","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}
引用次数: 0
The Impact of Climate Change on Laboratory Medicine: A Global Health Perspective.
IF 7.1 2区 医学
Clinical chemistry Pub Date : 2025-03-11 DOI: 10.1093/clinchem/hvaf012
Melissa Richard-Greenblatt, Catherine L Omosule, Bernard Owusu Agyare, Saswati Das, Carol Devine, Margaret Mokomane, Sheri Scott, Manivanh Vongsouvath
{"title":"The Impact of Climate Change on Laboratory Medicine: A Global Health Perspective.","authors":"Melissa Richard-Greenblatt, Catherine L Omosule, Bernard Owusu Agyare, Saswati Das, Carol Devine, Margaret Mokomane, Sheri Scott, Manivanh Vongsouvath","doi":"10.1093/clinchem/hvaf012","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf012","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604240","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}
引用次数: 0
Enrichment of Microbial DNA in Plasma to Improve Pathogen Detection in Sepsis: A Pilot Study
IF 9.3 2区 医学
Clinical chemistry Pub Date : 2025-03-11 DOI: 10.1093/clinchem/hvaf011
Eddie G Dominguez, Bradon R McDonald, Haikun Zhang, Michelle D Stephens, Elise C Dietmann, Megan Nedden, Nicole Byington, Sydney Thompson, Mary Junak, Caitlin S Pepperell, Mehreen T Kisat
{"title":"Enrichment of Microbial DNA in Plasma to Improve Pathogen Detection in Sepsis: A Pilot Study","authors":"Eddie G Dominguez, Bradon R McDonald, Haikun Zhang, Michelle D Stephens, Elise C Dietmann, Megan Nedden, Nicole Byington, Sydney Thompson, Mary Junak, Caitlin S Pepperell, Mehreen T Kisat","doi":"10.1093/clinchem/hvaf011","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf011","url":null,"abstract":"Background Diagnosis of sepsis and timely identification of pathogens in critically ill patients remains challenging. Plasma metagenomic sequencing to detect microbial cell-free DNA (mDNA) has shown promise, but low abundance of mDNA in plasma limits sensitivity and necessitates high sequencing depth. mDNA is shorter and more fragmented than human cell-free DNA. Here, we evaluated whether combining single-stranded DNA (ssDNA) sequencing library preparation and size selection can enrich mDNA and improve pathogen detection. Methods We prospectively enrolled 48 trauma patients and collected daily blood samples during the first 10 days of intensive care unit (ICU) admission. For patients with culture-proven infections, we extracted plasma DNA, prepared double-stranded DNA (dsDNA) and ssDNA sequencing libraries, and applied size selection to exclude fragments &amp;gt;110 bp. Following sequencing, we performed taxonomic classification, and evaluated differences in mDNA fractions and in sensitivity for pathogen detection (compared to background noise). Results We analyzed 46 plasma samples from 5 patients who developed culture-proven infections, including 17 samples coincident with positive microbial cultures. Size-selected ssDNA libraries showed the total mDNA fraction 204-fold higher on average than conventional dsDNA libraries (P &amp;lt; 0.0001). However, for pathogen-specific DNA (at the genus level), the highest sensitivity was observed in size-selected dsDNA (82%), compared to dsDNA (41%), ssDNA (71%), and size-selected ssDNA (35%) library preparations. Conclusions Our results demonstrate that combining ssDNA library preparation together with fragment size selection improves mDNA yield, potentially reducing sequencing requirements. However, at the genus level, this combination also increases background noise, which limits sensitivity for pathogen detection.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"213 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599830","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}
引用次数: 0
Comprehensive Annotation of Complete ABO Alleles and Resolution of ABO Variants by an Improved Full-Length ABO Haplotype Sequencing
IF 9.3 2区 医学
Clinical chemistry Pub Date : 2025-03-06 DOI: 10.1093/clinchem/hvaf015
Yanling Ying, Jingjing Zhang, Xiaozhen Hong, Wenjing Yuan, Kairong Ma, Xinyu Huang, Xianguo Xu, Faming Zhu
{"title":"Comprehensive Annotation of Complete ABO Alleles and Resolution of ABO Variants by an Improved Full-Length ABO Haplotype Sequencing","authors":"Yanling Ying, Jingjing Zhang, Xiaozhen Hong, Wenjing Yuan, Kairong Ma, Xinyu Huang, Xianguo Xu, Faming Zhu","doi":"10.1093/clinchem/hvaf015","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf015","url":null,"abstract":"Background Full-length ABO haplotype sequencing is crucial for accurate genotyping, reference gene annotation, and molecular mechanism analysis of its variants. However, there is currently a deficiency of comprehensive annotation for full-length ABO haplotypes, spanning from the 5′ untranslated region (UTR) to the 3′ UTR. Methods Two sets of specimens (79 random blood donors and 47 ABO variants) were tested. The full-length ABO gene spanning the 5′ UTR to the 3′ UTR was amplified using an improved one-step ultra-long-range PCR with a pair of PCR suppression primers. A single-molecule real-time library was constructed, and ABO haplotype sequencing was performed. Data analysis including basecalling, aligning, variant calling, clustering, and variant annotation were performed. Results The amplicon measured 26.1 kb without splicing, representing the most complete ABO gene reported to date. The complete ABO haplotype sequence was obtained via long-read sequencing. The comprehensive ABO reference alleles were obtained and the ABO sequence patterns within each allele in a Chinese population were further classified. The full-length ABO gene haplotype analysis technique effectively resolved ABO variants with structural variations (SVs), including large fragment deletions, inversions, recombination, and chimeras. Conclusions Full-length ABO haplotype sequencing filled a gap that was missing with respect to the 3′ UTR sequences of ABO alleles and can advance blood group genomic analysis, aiding in ABO gene function analysis, evolutionary studies, and the resolution of ABO variants.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"18 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143570438","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}
引用次数: 0
Commentary on A Pulmonary Nodule with an Unexpected Mutation Profile.
IF 7.1 2区 医学
Clinical chemistry Pub Date : 2025-03-03 DOI: 10.1093/clinchem/hvae204
Viral Patel, Sheena Bhalla
{"title":"Commentary on A Pulmonary Nodule with an Unexpected Mutation Profile.","authors":"Viral Patel, Sheena Bhalla","doi":"10.1093/clinchem/hvae204","DOIUrl":"https://doi.org/10.1093/clinchem/hvae204","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"71 3","pages":"356-357"},"PeriodicalIF":7.1,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556120","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}
引用次数: 0
Advances in Cardiac Troponin Composition Assays: A Step Closer to the Clinic? 心肌肌钙蛋白组成测定的进展:离临床又近了一步?
IF 7.1 2区 医学
Clinical chemistry Pub Date : 2025-03-03 DOI: 10.1093/clinchem/hvae206
Xander M R van Wijk, Sander A J Damen
{"title":"Advances in Cardiac Troponin Composition Assays: A Step Closer to the Clinic?","authors":"Xander M R van Wijk, Sander A J Damen","doi":"10.1093/clinchem/hvae206","DOIUrl":"10.1093/clinchem/hvae206","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"342-344"},"PeriodicalIF":7.1,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853462","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}
引用次数: 0
An AI Model (LORIS) to Predict Immune Checkpoint Blockade Response in Cancer: A Clinical Data Science Perspective. 预测癌症免疫检查点阻断反应的人工智能模型(LORIS):临床数据科学视角。
IF 7.1 2区 医学
Clinical chemistry Pub Date : 2025-03-03 DOI: 10.1093/clinchem/hvae196
Thomas E Tavolara, Wenchao Han, David S McClintock
{"title":"An AI Model (LORIS) to Predict Immune Checkpoint Blockade Response in Cancer: A Clinical Data Science Perspective.","authors":"Thomas E Tavolara, Wenchao Han, David S McClintock","doi":"10.1093/clinchem/hvae196","DOIUrl":"10.1093/clinchem/hvae196","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"345-347"},"PeriodicalIF":7.1,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834420","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}
引用次数: 0
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