Pub Date : 2025-10-01Epub Date: 2025-08-06DOI: 10.1016/j.clinbiochem.2025.110987
Kevin J Tu, Christina Greever-Wilson
Research funders can play a transformative role in reducing the environmental footprint of science without compromising its quality or productivity. Scientific research is among the most energy- and resource-intensive sectors globally, with its carbon footprint estimated to rival that of the aviation industry-contributing approximately 2 % of global greenhouse gas emissions. Yet the organizations that fund scientific research, particularly in the United States, structurally disincentivize sustainability, often rewarding waste rather than resource efficiency. We highlight how this is beginning to change across Europe, where major funding agencies are leading a growing movement to embed sustainability into research operations-from including environmental impact assessments in grant proposals to supporting green lab certification programs. These policies are on track to accelerate operational efficiency, reduce costs, and align research practices with climate action goals. Finally, we outline specific policy reforms and practical steps that researchers, institutions, and funders everywhere can adopt to build a more sustainable future for science-one where environmental stewardship is a core expectation of research.
{"title":"Rethinking research funding through a sustainability Lens.","authors":"Kevin J Tu, Christina Greever-Wilson","doi":"10.1016/j.clinbiochem.2025.110987","DOIUrl":"10.1016/j.clinbiochem.2025.110987","url":null,"abstract":"<p><p>Research funders can play a transformative role in reducing the environmental footprint of science without compromising its quality or productivity. Scientific research is among the most energy- and resource-intensive sectors globally, with its carbon footprint estimated to rival that of the aviation industry-contributing approximately 2 % of global greenhouse gas emissions. Yet the organizations that fund scientific research, particularly in the United States, structurally disincentivize sustainability, often rewarding waste rather than resource efficiency. We highlight how this is beginning to change across Europe, where major funding agencies are leading a growing movement to embed sustainability into research operations-from including environmental impact assessments in grant proposals to supporting green lab certification programs. These policies are on track to accelerate operational efficiency, reduce costs, and align research practices with climate action goals. Finally, we outline specific policy reforms and practical steps that researchers, institutions, and funders everywhere can adopt to build a more sustainable future for science-one where environmental stewardship is a core expectation of research.</p>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":" ","pages":"110987"},"PeriodicalIF":2.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803720","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}
Pub Date : 2025-10-01Epub Date: 2025-07-31DOI: 10.1016/j.clinbiochem.2025.110980
Pankaj Kumar, Ali Mousavi, Hans Frykman
Dementia is the most common type of neurodegenerative diseases, with Alzheimer's Disease (AD) constituting about two-thirds of these cases. In Canada, an estimated 674,000 individuals may have AD by 2031, nearly doubling from 2011. The total annual economic burden of dementia in Canada was about $40 billion in 2020, with an approximate average of $67,200 per person with dementia and if current trends continue, its annual burden could grow by 275 % over 30 years. AD is a double proteinopathy with its fundamental neuropathologic features defined by amyloid-beta (Aβ) plaques and neurofibrillary tangles with aggregated tau proteins. This supports the potential mechanism-based proteomic biomarkers to be detected in biofluids. Pathophysiologic and topographical biomarkers have significantly improved the diagnosis of typical and atypical phenotypes of AD, helping clinicians recognize and differentiate AD phenotypes from other types of dementia and neurodegenerative diseases. The CSF Aβ42/Aβ40 ratio measurement is a robust biomarker in detecting cerebral Aβ pathology and AD diagnosis. A number of very sensitive assays for measuring AD blood biomarkers including p-tau217, front-runner candidate for AD diagnosis, have been developed during last years. In this review we discus the biological configuration and normal function of involved proteomic in AD including amyloid β and tau protein, particularly tau phosphorylation and biochemistry of tau isoforms and their detection feasibility in plasma using novel technologies. Then, we critically review Blood-Based biomarkers' analytical and clinical validations, focusing more on plasma p-tau217 and their availability and prospects in Canada.
痴呆症是最常见的神经退行性疾病，阿尔茨海默病（AD）约占这些病例的三分之二。在加拿大，到2031年，估计有67.4万人可能患有阿尔茨海默病，比2011年几乎翻了一番。到2020年，加拿大痴呆症的年度经济负担总额约为400亿美元，平均每人约为67,200美元，如果目前的趋势继续下去，其年负担可能在30 年内增长275% %。AD是一种双重蛋白病，其基本的神经病理特征是淀粉样蛋白斑块和聚集tau蛋白的神经原纤维缠结。这支持了在生物体液中检测潜在的基于机制的蛋白质组学生物标志物。病理生理和地形生物标志物显著提高了AD典型和非典型表型的诊断，帮助临床医生识别和区分AD表型与其他类型的痴呆和神经退行性疾病。脑脊液a β42/ a β40比值测定是检测脑a β病理和AD诊断的可靠生物标志物。在过去的几年里，人们开发了许多非常敏感的检测AD血液生物标志物的方法，包括AD诊断的热门候选p-tau217。本文就阿尔茨海默病涉及的蛋白组学包括β淀粉样蛋白和tau蛋白的生物学结构和正常功能，特别是tau磷酸化和tau亚型的生物化学及其在血浆中检测的新技术的可行性进行了综述。然后，我们回顾了基于血液的生物标志物的分析和临床验证，重点关注血浆p-tau217及其在加拿大的可用性和前景。
{"title":"The biological diagnosis of Alzheimer's disease using blood-based biomarkers: A Canadian prospective.","authors":"Pankaj Kumar, Ali Mousavi, Hans Frykman","doi":"10.1016/j.clinbiochem.2025.110980","DOIUrl":"10.1016/j.clinbiochem.2025.110980","url":null,"abstract":"<p><p>Dementia is the most common type of neurodegenerative diseases, with Alzheimer's Disease (AD) constituting about two-thirds of these cases. In Canada, an estimated 674,000 individuals may have AD by 2031, nearly doubling from 2011. The total annual economic burden of dementia in Canada was about $40 billion in 2020, with an approximate average of $67,200 per person with dementia and if current trends continue, its annual burden could grow by 275 % over 30 years. AD is a double proteinopathy with its fundamental neuropathologic features defined by amyloid-beta (Aβ) plaques and neurofibrillary tangles with aggregated tau proteins. This supports the potential mechanism-based proteomic biomarkers to be detected in biofluids. Pathophysiologic and topographical biomarkers have significantly improved the diagnosis of typical and atypical phenotypes of AD, helping clinicians recognize and differentiate AD phenotypes from other types of dementia and neurodegenerative diseases. The CSF Aβ42/Aβ40 ratio measurement is a robust biomarker in detecting cerebral Aβ pathology and AD diagnosis. A number of very sensitive assays for measuring AD blood biomarkers including p-tau217, front-runner candidate for AD diagnosis, have been developed during last years. In this review we discus the biological configuration and normal function of involved proteomic in AD including amyloid β and tau protein, particularly tau phosphorylation and biochemistry of tau isoforms and their detection feasibility in plasma using novel technologies. Then, we critically review Blood-Based biomarkers' analytical and clinical validations, focusing more on plasma p-tau217 and their availability and prospects in Canada.</p>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":" ","pages":"110980"},"PeriodicalIF":2.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768469","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}
Pub Date : 2025-09-30DOI: 10.1016/j.clinbiochem.2025.111017
Meifang Wang , Hongying Bu , Weijia Luo , Xi Zeng , Guodong Chen , Yingchun He , Deliang Cao
{"title":"Corrigendum to “CA19-9, CEA and PIVKA-II as a novel panel of serum markers for diagnosis of pancreatic cancer” [Clin. Biochem. 137 (2025) 110902]","authors":"Meifang Wang , Hongying Bu , Weijia Luo , Xi Zeng , Guodong Chen , Yingchun He , Deliang Cao","doi":"10.1016/j.clinbiochem.2025.111017","DOIUrl":"10.1016/j.clinbiochem.2025.111017","url":null,"abstract":"","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111017"},"PeriodicalIF":2.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205710","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}
Pub Date : 2025-09-29DOI: 10.1016/j.clinbiochem.2025.111015
Pankaj Kumar, Ali Mousavi, Hans Frykman
Dementia is the most common type of neurodegenerative disease, with Alzheimer’s Disease (AD) constituting about two-thirds of these cases. In Canada, an estimated 674,000 individuals may have AD by 2031, nearly doubling from 2011. The total annual economic burden of dementia in Canada was about $40 billion in 2020, with an approximate average of $67,200 per person with dementia and if current trends continue, its annual burden could grow by 275 % over 30 years. AD is a double proteinopathy with its fundamental neuropathologic features defined by amyloid-beta (Aβ) plaques and neurofibrillary tangles with aggregated tau proteins. This supports the potential for mechanism-based proteomic biomarkers to be detected in biofluids. Pathophysiologic and topographical biomarkers have significantly improved the diagnosis of typical and atypical phenotypes of AD, helping clinicians recognize and differentiate AD phenotypes from other types of dementia and neurodegenerative diseases. The cerebrospinal fluid Aβ42/Aβ40 ratio measurement is a robust biomarker in detecting cerebral Aβ pathology and AD diagnosis. A number of very sensitive assays for measuring AD blood biomarkers including p-tau217, front-runner candidate for AD diagnosis, have been developed during last years. In this review we discuss the biological configuration and normal function of involved proteomics in AD including Aβ and tau protein, particularly tau phosphorylation and biochemistry of tau isoforms and their detection feasibility in plasma using novel technologies. Then, we critically review blood-based biomarkers’ analytical and clinical validations, focusing more on plasma p-tau217 and their availability and prospects in Canada.
痴呆症是最常见的神经退行性疾病，阿尔茨海默病（AD）约占这些病例的三分之二。在加拿大，到2031年，估计有67.4万人可能患有阿尔茨海默病，比2011年几乎翻了一番。到2020年，加拿大痴呆症的年度经济负担总额约为400亿美元，平均每人约为67,200美元，如果目前的趋势继续下去，其年度负担可能在30年内增长275%。AD是一种双重蛋白病，其基本的神经病理特征是淀粉样蛋白斑块和聚集tau蛋白的神经原纤维缠结。这支持了在生物流体中检测基于机制的蛋白质组学生物标志物的潜力。病理生理和地形生物标志物显著提高了AD典型和非典型表型的诊断，帮助临床医生识别和区分AD表型与其他类型的痴呆和神经退行性疾病。脑脊液a β42/ a β40比值测定是检测脑a β病理和AD诊断的可靠生物标志物。在过去的几年里，人们开发了许多非常敏感的检测AD血液生物标志物的方法，包括AD诊断的热门候选p-tau217。本文综述了AD相关蛋白质组学的生物学结构和正常功能，包括Aβ和tau蛋白，特别是tau磷酸化和tau亚型的生物化学及其在血浆中检测的新技术的可行性。然后，我们回顾了基于血液的生物标志物的分析和临床验证，重点关注血浆p-tau217及其在加拿大的可用性和前景。
{"title":"The biological diagnosis of Alzheimer’s disease using blood-based biomarkers: a Canadian prospective","authors":"Pankaj Kumar, Ali Mousavi, Hans Frykman","doi":"10.1016/j.clinbiochem.2025.111015","DOIUrl":"10.1016/j.clinbiochem.2025.111015","url":null,"abstract":"<div><div>Dementia is the most common type of neurodegenerative disease, with Alzheimer’s Disease (AD) constituting about two-thirds of these cases. In Canada, an estimated 674,000 individuals may have AD by 2031, nearly doubling from 2011. The total annual economic burden of dementia in Canada was about $40 billion in 2020, with an approximate average of $67,200 per person with dementia and if current trends continue, its annual burden could grow by 275 % over 30 years. AD is a double proteinopathy with its fundamental neuropathologic features defined by amyloid-beta (Aβ) plaques and neurofibrillary tangles with aggregated tau proteins. This supports the potential for mechanism-based proteomic biomarkers to be detected in biofluids. Pathophysiologic and topographical biomarkers have significantly improved the diagnosis of typical and atypical phenotypes of AD, helping clinicians recognize and differentiate AD phenotypes from other types of dementia and neurodegenerative diseases. The cerebrospinal fluid Aβ42/Aβ40 ratio measurement is a robust biomarker in detecting cerebral Aβ pathology and AD diagnosis. A number of very sensitive assays for measuring AD blood biomarkers including p-tau217, front-runner candidate for AD diagnosis, have been developed during last years. In this review we discuss the biological configuration and normal function of involved proteomics in AD including Aβ and tau protein, particularly tau phosphorylation and biochemistry of tau isoforms and their detection feasibility in plasma using novel technologies. Then, we critically review blood-based biomarkers’ analytical and clinical validations, focusing more on plasma p-tau217 and their availability and prospects in Canada.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111015"},"PeriodicalIF":2.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198589","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}
Pub Date : 2025-09-29DOI: 10.1016/j.clinbiochem.2025.111019
Timothy Ming Him Yeung , Elaine Yi Ling Wong , Melody Yee Man Wong , Ching Wan Lam
{"title":"Pregnancy or PEG? Polyethylene glycol causes false positive pregnancy test","authors":"Timothy Ming Him Yeung , Elaine Yi Ling Wong , Melody Yee Man Wong , Ching Wan Lam","doi":"10.1016/j.clinbiochem.2025.111019","DOIUrl":"10.1016/j.clinbiochem.2025.111019","url":null,"abstract":"","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111019"},"PeriodicalIF":2.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205668","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}
Pub Date : 2025-09-29DOI: 10.1016/j.clinbiochem.2025.111020
Katie M. Troike, Adam J. McShane
Background
Iron deficiency (ID) and iron deficiency anemia (IDA) are prevalent and treatable conditions which disproportionately affect women. Serum ferritin is the most sensitive biomarker for ID and IDA, but its utility in clinical decision making is limited by sex-specific reference intervals (RIs) that are frequently lower than evidence-based recommendations. The inclusion of asymptomatic, iron-depleted individuals in RI studies likely accounts for inappropriate ferritin thresholds, and a lower cutoff of 30 µg/L has been proposed by an expert consensus panel to improve sensitivity. In this study, we assessed ferritin RIs for diagnosing ID and IDA in our patient population.
Methods
Patient data, including age, sex assigned at birth, hemoglobin, and iron markers, were extracted from the laboratory information system (LIS). Patients were stratified into iron replete (IR), ID, or IDA groups based on measurements for iron, transferrin saturation, and hemoglobin. Ferritin values from the IR group were used to generate new reference ranges and receiver operator characteristic (ROC) curves were plotted to define optimal ferritin cutoffs for diagnosis of ID and IDA.
Results
Ferritin RIs generated from the IR group had lower limit cutoffs of 16.9 µg/L and 30 µg/L for females and males, respectively. Youden Index analysis of ROC curves identified optimal cutoffs of 45 µg/L and 70 µg/L for ID in females and males, respectively, improving diagnostic sensitivity by 44 % in the female group.
Conclusions
These findings are consistent with recommendations for increasing ferritin cutoffs and demonstrate the need for clinical laboratories to re-examine ferritin RIs, particularly for ID diagnosis in the female patient population.
{"title":"Re-evaluating ferritin thresholds to diagnose iron deficiency","authors":"Katie M. Troike, Adam J. McShane","doi":"10.1016/j.clinbiochem.2025.111020","DOIUrl":"10.1016/j.clinbiochem.2025.111020","url":null,"abstract":"<div><h3>Background</h3><div>Iron deficiency (ID) and iron deficiency anemia (IDA) are prevalent and treatable conditions which disproportionately affect women. Serum ferritin is the most sensitive biomarker for ID and IDA, but its utility in clinical decision making is limited by sex-specific reference intervals (RIs) that are frequently lower than evidence-based recommendations. The inclusion of asymptomatic, iron-depleted individuals in RI studies likely accounts for inappropriate ferritin thresholds, and a lower cutoff of 30 µg/L has been proposed by an expert consensus panel to improve sensitivity.<!--> <!-->In this study, we assessed ferritin RIs for diagnosing ID and IDA in our patient population.</div></div><div><h3>Methods</h3><div>Patient data, including age, sex assigned at birth, hemoglobin, and iron markers, were extracted from the laboratory information system (LIS). Patients were stratified into iron replete (IR), ID, or IDA groups based on measurements for iron, transferrin saturation, and hemoglobin. Ferritin values from the IR group were used to generate new reference ranges and receiver operator characteristic (ROC) curves were plotted to define optimal ferritin cutoffs for diagnosis of ID and IDA.</div></div><div><h3>Results</h3><div>Ferritin RIs generated from the IR group had lower limit cutoffs of 16.9 µg/L and 30 µg/L for females and males, respectively. Youden Index analysis of ROC curves identified optimal cutoffs of 45 µg/L and 70 µg/L for ID in females and males, respectively, improving diagnostic sensitivity by 44 % in the female group.</div></div><div><h3>Conclusions</h3><div>These findings are consistent with recommendations for increasing ferritin cutoffs and demonstrate the need for clinical laboratories to re-examine ferritin RIs, particularly for ID diagnosis in the female patient population.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111020"},"PeriodicalIF":2.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205646","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}
Pub Date : 2025-09-29DOI: 10.1016/j.clinbiochem.2025.111021
Yun Huang , Brendan Ly
Objectives
The use of point-of-care (POC) glucose meters and effectiveness of glycemic control should be monitored as part of quality assurance practices. This study is the first to establish indicators to evaluate the utilization of glucose meters in our academic hospital.
Methods
Patient results from glucose meters located in emergency department (ED), intensive care units (ICUs), general wards, and neonatal units were extracted from the data management system for the months of October to December from 2021 to 2023. Six indicators were developed and compared across clinical units, including: glucose test number per meter, daily frequency of patient glucose testing 1–4 times (%), ratio of POC to core lab glucose testing, and percentages of patient glucose results within target ranges, below critical level 2.5 mmol/L, or above 25.0 mmol/L.
Results
The six indicators varied greatly between clinical units due to the differences in patient populations, clinical scenarios, and clinical guidelines. About 90 % of patients in general wards, ED and neonatal units were tested glucose 1–4 times/day, while 27.1 % patients in ICUs were tested glucose 5–10 times/day or more. The average POC/core lab glucose testing ratio in neonatal units, general wards, ICUs, and ED was 17.6, 14.9, 2.2, and 0.3, respectively. Overall, 69.6 % of patient glucose results in all clinical units fell within the target ranges. Percentages of patient glucose results below 2.5 mmol/L or above 25.0 mmol/L were both under 0.6 % across clinical units.
Conclusions
In this study, the indicators were able to assess the use of POC glucose meters and the effectiveness of glycemic control and to identify opportunities for quality improvement. The approach can be readily applied in other hospitals.
{"title":"Establishing indicators to monitor the utilization of POC glucose meters in glycemic control","authors":"Yun Huang , Brendan Ly","doi":"10.1016/j.clinbiochem.2025.111021","DOIUrl":"10.1016/j.clinbiochem.2025.111021","url":null,"abstract":"<div><h3>Objectives</h3><div>The use of point-of-care (POC) glucose meters and effectiveness of glycemic control should be monitored as part of quality assurance practices. This study is the first to establish indicators to evaluate the utilization of glucose meters in our academic hospital.</div></div><div><h3>Methods</h3><div>Patient results from glucose meters located in emergency department (ED), intensive care units (ICUs), general wards, and neonatal units were extracted from the data management system for the months of October to December from 2021 to 2023. Six indicators were developed and compared across clinical units, including: glucose test number per meter, daily frequency of patient glucose testing 1–4 times (%), ratio of POC to core lab glucose testing, and percentages of patient glucose results within target ranges, below critical level 2.5 mmol/L, or above 25.0 mmol/L.</div></div><div><h3>Results</h3><div>The six indicators varied greatly between clinical units due to the differences in patient populations, clinical scenarios, and clinical guidelines. About 90 % of patients in general wards, ED and neonatal units were tested glucose 1–4 times/day, while 27.1 % patients in ICUs were tested glucose 5–10 times/day or more. The average POC/core lab glucose testing ratio in neonatal units, general wards, ICUs, and ED was 17.6, 14.9, 2.2, and 0.3, respectively. Overall, 69.6 % of patient glucose results in all clinical units fell within the target ranges. Percentages of patient glucose results below 2.5 mmol/L or above 25.0 mmol/L were both under 0.6 % across clinical units.</div></div><div><h3>Conclusions</h3><div>In this study, the indicators were able to assess the use of POC glucose meters and the effectiveness of glycemic control and to identify opportunities for quality improvement. The approach can be readily applied in other hospitals.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111021"},"PeriodicalIF":2.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205702","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}
Pub Date : 2025-09-24DOI: 10.1016/j.clinbiochem.2025.111018
Thanyatorn Chantivas , Prin Vathesatogkit , Anchalee Chittamma , Nisakron Thongmung , Martin H Kroll , Pornpen Srisawasdi
Objectives
Calculated, small dense low-density lipoprotein cholesterol (CsdLDL-C), derived using the Sampson equation, has been proposed as a screening tool for atherosclerotic cardiovascular disease risk. The current study investigated the utility of CsdLDL-C and calculated large buoyant low-density lipoprotein cholesterol (ClbLDL-C) for coronary artery disease (CAD) risk assessment in a Thai population.
Methods
This study included 6448 participants without prior CAD from the Electricity Generating Authority of Thailand (EGAT) prospective cohort (2007–2009). CsdLDL-C and ClbLDL-C were estimated from standard lipid panel measurements. Associations with CAD risk were evaluated using Kaplan–Meier survival analysis and Cox proportional hazards models.
Results
Over a mean follow-up period of 10.24 ± 1.01 years, 262 (4.06 %) participants experienced CAD events. At the optimal cutoffs, high CsdLDL-C [>1.08 mmol/L (41.85 mg/dL)] was significantly associated with incident CAD events (HR = 1.57; 95 % CI = 1.22–2.02), whereas high ClbLDL-C [>2.52 mmol/L (97.59 mg/dL)] was inversely associated with incident CAD events (HR = 0.72; 95 % CI = 0.56-0.92). The CsdLDL-C/ClbLDL-C ratio exhibited the strongest association (HR = 2.02; 95 % CI = 1.58–2.60) among all lipid parameters. When individually added to the pooled cohort risk equation, CsdLDL-C and the CsdLDL-C/ClbLDL-C ratio remained significant predictors of new-onset CAD. They also demonstrated good discriminatory power (P < 0.004).
Conclusion
CsdLDL-C and ClbLDL-C, derived using the Sampson equation, were significantly associated with CAD risk in the opposite direction. Their ratio had greater predictive effectiveness. Incorporating CsdLDL-C and the CsdLDL-C/ClbLDL-C ratio into cardiovascular risk assessment models may improve early identification of at-risk individuals.
{"title":"Calculated small-dense and large-buoyant low-density lipoprotein-cholesterol and their ratio in predicting coronary artery disease risk: A cohort study in Thailand","authors":"Thanyatorn Chantivas , Prin Vathesatogkit , Anchalee Chittamma , Nisakron Thongmung , Martin H Kroll , Pornpen Srisawasdi","doi":"10.1016/j.clinbiochem.2025.111018","DOIUrl":"10.1016/j.clinbiochem.2025.111018","url":null,"abstract":"<div><h3>Objectives</h3><div>Calculated, small dense low-density lipoprotein cholesterol (CsdLDL-C), derived using the Sampson equation, has been proposed as a screening tool for atherosclerotic cardiovascular disease risk. The current study investigated the utility of CsdLDL-C and calculated large buoyant low-density lipoprotein cholesterol (ClbLDL-C) for coronary artery disease (CAD) risk assessment in a Thai population.</div></div><div><h3>Methods</h3><div>This study included 6448 participants without prior CAD from the Electricity Generating Authority of Thailand (EGAT) prospective cohort (2007–2009). CsdLDL-C and ClbLDL-C were estimated from standard lipid panel measurements. Associations with CAD risk were evaluated using Kaplan–Meier survival analysis and Cox proportional hazards models.</div></div><div><h3>Results</h3><div>Over a mean follow-up period of 10.24 ± 1.01 years, 262 (4.06 %) participants experienced CAD events. At the optimal cutoffs, high CsdLDL-C [>1.08 mmol/L (41.85 mg/dL)] was significantly associated with incident CAD events (HR = 1.57; 95 % CI = 1.22–2.02), whereas high ClbLDL-C [>2.52 mmol/L (97.59 mg/dL)] was inversely associated with incident CAD events (HR = 0.72; 95 % CI = 0.56-0.92). The CsdLDL-C/ClbLDL-C ratio exhibited the strongest association (HR = 2.02; 95 % CI = 1.58–2.60) among all lipid parameters. When individually added to the pooled cohort risk equation, CsdLDL-C and the CsdLDL-C/ClbLDL-C ratio remained significant predictors of new-onset CAD. They also demonstrated good discriminatory power (<em>P</em> < 0.004).</div></div><div><h3>Conclusion</h3><div>CsdLDL-C and ClbLDL-C, derived using the Sampson equation, were significantly associated with CAD risk in the opposite direction. Their ratio had greater predictive effectiveness. Incorporating CsdLDL-C and the CsdLDL-C/ClbLDL-C ratio into cardiovascular risk assessment models may improve early identification of at-risk individuals.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111018"},"PeriodicalIF":2.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155145","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}
Pub Date : 2025-09-20DOI: 10.1016/j.clinbiochem.2025.111016
Siarhei A. Dabravolski , Alexander L. Golovyuk , Olga N. Maltseva , Aleksandra S. Utkina , Alikhan Z. Asoyan , Alexander N. Orekhov
Modified low-density lipoproteins (LDL) play a pivotal role in the pathogenesis of atherosclerosis, contributing to plaque formation and vascular inflammation. This review explores how a diverse array of forms of modified LDL, including carbamylated LDL, nitrated LDL, and desialylated LDL, along with various enzymatic modifications, contribute to disease progression. We discuss how these alterations promote the formation of a heterogeneous, highly atherogenic pool of particles known as electronegative LDL (LDL(−)). Mechanistic insights highlight pathways involving upregulated scavenger receptors, foam cell formation, and chronic inflammatory responses. The diagnostic and prognostic implications of LDL(−), including its association with autoimmune conditions like rheumatoid arthritis and chronic conditions such as type 2 diabetes, underscore its potential as a biomarker for cardiovascular risk. Emerging therapies targeting LDL(−), such as nanoformulations of single-chain fragment variable antibodies, demonstrate promising efficacy in reducing lesion size and inflammation without adverse systemic effects. Despite these advances, a critical barrier to clinical translation is the lack of standardised, high-throughput assays suitable for routine laboratory use. Future research must therefore prioritise the development and validation of robust clinical assays to quantify these atherogenic particles, a crucial step for establishing their role in advanced risk stratification and for guiding novel therapeutic strategies..
{"title":"Modified LDL variants in atherosclerosis: molecular pathways, diagnostic potential, and therapeutic perspectives","authors":"Siarhei A. Dabravolski , Alexander L. Golovyuk , Olga N. Maltseva , Aleksandra S. Utkina , Alikhan Z. Asoyan , Alexander N. Orekhov","doi":"10.1016/j.clinbiochem.2025.111016","DOIUrl":"10.1016/j.clinbiochem.2025.111016","url":null,"abstract":"<div><div>Modified low-density lipoproteins (LDL) play a pivotal role in the pathogenesis of atherosclerosis, contributing to plaque formation and vascular inflammation. This review explores how a diverse array of forms of modified LDL, including carbamylated LDL, nitrated LDL, and desialylated LDL, along with various enzymatic modifications, contribute to disease progression. We discuss how these alterations promote the formation of a heterogeneous, highly atherogenic pool of particles known as electronegative LDL (LDL(−)). Mechanistic insights highlight pathways involving upregulated scavenger receptors, foam cell formation, and chronic inflammatory responses. The diagnostic and prognostic implications of LDL(−), including its association with autoimmune conditions like rheumatoid arthritis and chronic conditions such as type 2 diabetes, underscore its potential as a biomarker for cardiovascular risk. Emerging therapies targeting LDL(−), such as nanoformulations of single-chain fragment variable antibodies, demonstrate promising efficacy in reducing lesion size and inflammation without adverse systemic effects. Despite these advances, a critical barrier to clinical translation is the lack of standardised, high-throughput assays suitable for routine laboratory use. Future research must therefore prioritise the development and validation of robust clinical assays to quantify these atherogenic particles, a crucial step for establishing their role in advanced risk stratification and for guiding novel therapeutic strategies..</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111016"},"PeriodicalIF":2.1,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118121","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}
Pub Date : 2025-09-13DOI: 10.1016/j.clinbiochem.2025.111013
Chunyan Zhang , Nan Bai , Yanling Yang , Yuxuan Cheng , Xiyu He , Meng Wang , Honghui Zhou , Yaping Tian
Objectives
Metabolic disorders in newborns can cause significant morbidity and mortality if not diagnosed and managed early. In this study, we developed and validated a reliable LC-MS/MS method to simultaneously quantify methylmalonic acid, methylcitric acid, malonic acid, ethylmalonic acid, and total homocysteine associated with metabolic disorders.
Design and methods
According to Clinical Laboratory Standards Institute (CLSI) guidelines, various analytical performances (i.e., precision, linearity, accuracy and reference intervals) were rigorously evaluated. Meanwhile, sample preparation, chromatographic separation and mass spectrometric detection and incorporating stable isotope-labeled internal standards were optimized. Furthermore, calibrators and quality controls were developed to ensure standardization and traceability.
Results
The coefficient of variations for precision were less than 10.0 %. Meanwhile, the results showed high accuracy (recoveries: 94.57 %–109.60 %) and robust linearity (R2 > 0.9935) over clinically relevant ranges. The limits of detection and limits of quantification for all analytes were established, enabling sensitive detection of pathological elevations. Reference intervals for pediatric populations (ages 0–1 month and 2 months to 18 years) were determined, providing essential baselines for clinical interpretation.
Conclusions
The newly developed method demonstrated good analytical performance and offers a standardized, high-throughput solution for clinical laboratories to improve early diagnosis and personalized management of metabolic diseases.
{"title":"Reliable LC-MS/MS method development and validation for the determination of methylmalonic acid, methylcitric acid, malonic acid, ethylmalonic acid, and total homocysteine in dried blood spots","authors":"Chunyan Zhang , Nan Bai , Yanling Yang , Yuxuan Cheng , Xiyu He , Meng Wang , Honghui Zhou , Yaping Tian","doi":"10.1016/j.clinbiochem.2025.111013","DOIUrl":"10.1016/j.clinbiochem.2025.111013","url":null,"abstract":"<div><h3>Objectives</h3><div>Metabolic disorders in newborns can cause significant morbidity and mortality if not diagnosed and managed early. In this study, we developed and validated a reliable LC-MS/MS method to simultaneously quantify methylmalonic acid, methylcitric acid, malonic acid, ethylmalonic acid, and total homocysteine associated with metabolic disorders.</div></div><div><h3>Design and methods</h3><div>According to Clinical Laboratory Standards Institute (CLSI) guidelines, various analytical performances (i.e., precision, linearity, accuracy and reference intervals) were rigorously evaluated. Meanwhile, sample preparation, chromatographic separation and mass spectrometric detection and incorporating stable isotope-labeled internal standards were optimized. Furthermore, calibrators and quality controls were developed to ensure standardization and traceability.</div></div><div><h3>Results</h3><div>The coefficient of variations for precision were less than 10.0 %. Meanwhile, the results showed high accuracy (recoveries: 94.57 %–109.60 %) and robust linearity (R<sup>2</sup> > 0.9935) over clinically relevant ranges. The limits of detection and limits of quantification for all analytes were established, enabling sensitive detection of pathological elevations. Reference intervals for pediatric populations (ages 0–1 month and 2 months to 18 years) were determined, providing essential baselines for clinical interpretation.</div></div><div><h3>Conclusions</h3><div>The newly developed method demonstrated good analytical performance and offers a standardized, high-throughput solution for clinical laboratories to improve early diagnosis and personalized management of metabolic diseases.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111013"},"PeriodicalIF":2.1,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057325","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}
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