Pub Date : 2026-01-01Epub Date: 2025-07-25DOI: 10.1016/j.cca.2025.120510
Franja Dugar, Pedro Lopez-Ayala, Luca Koechlin, Paolo Bima, Jonas Glaeser, Carlos Spagnuolo, Luca Crisanti, Clara Wick, Karin Wildi, Emel Kaplan, Ivo Strebel, Oscar Miro, Francisco Javier Martin-Sanchez, Michael Christ, Beata Morawiec, Maria Rubini Gimenez, Thomas Nestelberger, Jasper Boeddinghaus, Christian Mueller
Background: The possible clinical utility of endocan, a novel inflammatory biomarker involved in the initiation and progression of atherosclerosis, is largely unknown. We aimed to evaluate its diagnostic and prognostic performance in chest pain patients presenting to the emergency department (ED).
Methods: We prospectively enrolled patients presenting with suspected myocardial infarction (MI) to the ED in an international multicenter study. Endocan, high-sensitivity C-reactive protein (hs-CRP), and high-sensitivity cardiac troponin T (hs-cTnT) were measured in blood samples obtained at presentation. Final diagnoses were centrally adjudicated by two independent cardiologists applying the 4th universal definition of MI and current guidelines. Non-ST-elevation MI (NSTEMI) was the diagnostic endpoint and 5-year cardiovascular death was the primary prognostic endpoint.
Results: Among 4728 patients, 843 (17.8 %) had NSTEMI. The diagnostic discrimination of endocan for NSTEMI was low (area under the curve (AUC) 0.585 [95 % CI: 0.563-0.607]. Its combination with hs-cTnT (0.939 [95 % CI: 0.931-0.947]) did not improve the discriminative performance of hs-cTnT alone (0.937 [95 % CI: 0.930-0.950]). Long-term prognostic accuracy of endocan was higher versus hs-CRP, but lower versus hs-cTnT (AUC 0.730 [0.710-0.760] vs 0.650 [0.620-0.680] vs 0.810 [0.790-0.830], respectively). Endocan was associated with an increased 5-year risk for cardiovascular mortality. However, it did not provide relevant incremental prognostic value when added on top of a base model that included SCORE2 risk factors and hs-cTnT.
Conclusion: Endocan has a low diagnostic accuracy for NSTEMI, and moderate long-term prognostic accuracy for cardiovascular death.
{"title":"Diagnostic and prognostic utility of endocan in suspected myocardial infarction: an international cohort study.","authors":"Franja Dugar, Pedro Lopez-Ayala, Luca Koechlin, Paolo Bima, Jonas Glaeser, Carlos Spagnuolo, Luca Crisanti, Clara Wick, Karin Wildi, Emel Kaplan, Ivo Strebel, Oscar Miro, Francisco Javier Martin-Sanchez, Michael Christ, Beata Morawiec, Maria Rubini Gimenez, Thomas Nestelberger, Jasper Boeddinghaus, Christian Mueller","doi":"10.1016/j.cca.2025.120510","DOIUrl":"10.1016/j.cca.2025.120510","url":null,"abstract":"<p><strong>Background: </strong>The possible clinical utility of endocan, a novel inflammatory biomarker involved in the initiation and progression of atherosclerosis, is largely unknown. We aimed to evaluate its diagnostic and prognostic performance in chest pain patients presenting to the emergency department (ED).</p><p><strong>Methods: </strong>We prospectively enrolled patients presenting with suspected myocardial infarction (MI) to the ED in an international multicenter study. Endocan, high-sensitivity C-reactive protein (hs-CRP), and high-sensitivity cardiac troponin T (hs-cTnT) were measured in blood samples obtained at presentation. Final diagnoses were centrally adjudicated by two independent cardiologists applying the 4th universal definition of MI and current guidelines. Non-ST-elevation MI (NSTEMI) was the diagnostic endpoint and 5-year cardiovascular death was the primary prognostic endpoint.</p><p><strong>Results: </strong>Among 4728 patients, 843 (17.8 %) had NSTEMI. The diagnostic discrimination of endocan for NSTEMI was low (area under the curve (AUC) 0.585 [95 % CI: 0.563-0.607]. Its combination with hs-cTnT (0.939 [95 % CI: 0.931-0.947]) did not improve the discriminative performance of hs-cTnT alone (0.937 [95 % CI: 0.930-0.950]). Long-term prognostic accuracy of endocan was higher versus hs-CRP, but lower versus hs-cTnT (AUC 0.730 [0.710-0.760] vs 0.650 [0.620-0.680] vs 0.810 [0.790-0.830], respectively). Endocan was associated with an increased 5-year risk for cardiovascular mortality. However, it did not provide relevant incremental prognostic value when added on top of a base model that included SCORE2 risk factors and hs-cTnT.</p><p><strong>Conclusion: </strong>Endocan has a low diagnostic accuracy for NSTEMI, and moderate long-term prognostic accuracy for cardiovascular death.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov number, NCT00470587, https://clinicaltrials.gov/ct2/show/NCT00470587https://clinicaltrials.gov/ct2/show/NCT00470587.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120510"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728330","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 : 2026-01-01Epub Date: 2025-08-06DOI: 10.1016/j.cca.2025.120536
Hamdi Nsairat, Omer Qutaiba B Allela, Abdulkareem Shareef, S Renuka Jyothi, Priya Priyadarshini Nayak, Ashish Singh Chauhan, Hayder Naji Sameer, Ahmed Yaseen, Zainab H Athab, Mohaned Adil
Breast cancer, a leading cause of cancer-related mortality among women, necessitates the development of sensitive and specific diagnostic tools for early detection and personalized treatment. An aptamer-based biosensor (aptasensor) is a biosensor that utilizes aptamers as its biorecognition element such as single-stranded DNA or RNA molecules that are specifically selected to bind to a target molecule with high affinity. Aptasensors have emerged as promising alternatives to traditional methods, offering advantages such as high affinity, specificity, and ease of synthesis. This review provides an overview of recent advancements in aptasensor technology for breast cancer diagnostics, focusing on the detection of key biomarkers. In this review, first after an overview to different types of aptasensors, we discuss the different type of aptamer immobilization methods on sensor surfaces using covalent, adsorption, and thiol-based self-assembly techniques. Furthermore, we present different aptasensor platforms, including electrochemical and optical approaches, highlighting their design principles, performance characteristics, and clinical applications.
{"title":"Aptamer biosensors in early breast cancer detection.","authors":"Hamdi Nsairat, Omer Qutaiba B Allela, Abdulkareem Shareef, S Renuka Jyothi, Priya Priyadarshini Nayak, Ashish Singh Chauhan, Hayder Naji Sameer, Ahmed Yaseen, Zainab H Athab, Mohaned Adil","doi":"10.1016/j.cca.2025.120536","DOIUrl":"10.1016/j.cca.2025.120536","url":null,"abstract":"<p><p>Breast cancer, a leading cause of cancer-related mortality among women, necessitates the development of sensitive and specific diagnostic tools for early detection and personalized treatment. An aptamer-based biosensor (aptasensor) is a biosensor that utilizes aptamers as its biorecognition element such as single-stranded DNA or RNA molecules that are specifically selected to bind to a target molecule with high affinity. Aptasensors have emerged as promising alternatives to traditional methods, offering advantages such as high affinity, specificity, and ease of synthesis. This review provides an overview of recent advancements in aptasensor technology for breast cancer diagnostics, focusing on the detection of key biomarkers. In this review, first after an overview to different types of aptasensors, we discuss the different type of aptamer immobilization methods on sensor surfaces using covalent, adsorption, and thiol-based self-assembly techniques. Furthermore, we present different aptasensor platforms, including electrochemical and optical approaches, highlighting their design principles, performance characteristics, and clinical applications.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120536"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798323","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 : 2026-01-01Epub Date: 2025-08-06DOI: 10.1016/j.cca.2025.120533
Sultan Ayesh Mohammed Saghir, Amir M Al Hroob, Salah A Alshehade, Sulaiman Alnaimat, Nuha A Al Yousfi, Sarah Ahmad Bahjat Al-Rawashdeh, Mohammad Ahmad Al Rawashdeh, Mohammed Abdullah Alshawsh
Autoimmune diseases (ADs) impact approximately 3% of the global population. It encompasses more than 80 chronic, often debilitating conditions resulting from immune system defects that lead the body to attack its tissues. Although many ADs are rare, their prevalence is rising. Despite advancements, ADs diagnosis and classification still rely heavily on clinical examination combined with conventional laboratory testing and imaging. Emerging proteomic screening, technologies now offer the potential to identify unique biomarkers for more precise diagnosis, classification, and treatment decisions. Protein profiling, an advancing area within proteomics, provides unparalleled insights into biological processes underlying these diseases. Thus, this review highlights recent developments in proteomic and genetic profiling for ADs pathogenesis, diagnosis, and treatment challenges, focusing on the clinical utility of proteomic techniques in prognosis, diagnosis, and therapeutic guidance. Notably, discovering new biomarkers through proteomic screening is crucial for creating robust multi-parameter assays, which enhance diagnostic accuracy and treatment decisions in ADs.
{"title":"Proteomic approaches for biomarker discovery and clinical applications in autoimmune diseases.","authors":"Sultan Ayesh Mohammed Saghir, Amir M Al Hroob, Salah A Alshehade, Sulaiman Alnaimat, Nuha A Al Yousfi, Sarah Ahmad Bahjat Al-Rawashdeh, Mohammad Ahmad Al Rawashdeh, Mohammed Abdullah Alshawsh","doi":"10.1016/j.cca.2025.120533","DOIUrl":"10.1016/j.cca.2025.120533","url":null,"abstract":"<p><p>Autoimmune diseases (ADs) impact approximately 3% of the global population. It encompasses more than 80 chronic, often debilitating conditions resulting from immune system defects that lead the body to attack its tissues. Although many ADs are rare, their prevalence is rising. Despite advancements, ADs diagnosis and classification still rely heavily on clinical examination combined with conventional laboratory testing and imaging. Emerging proteomic screening, technologies now offer the potential to identify unique biomarkers for more precise diagnosis, classification, and treatment decisions. Protein profiling, an advancing area within proteomics, provides unparalleled insights into biological processes underlying these diseases. Thus, this review highlights recent developments in proteomic and genetic profiling for ADs pathogenesis, diagnosis, and treatment challenges, focusing on the clinical utility of proteomic techniques in prognosis, diagnosis, and therapeutic guidance. Notably, discovering new biomarkers through proteomic screening is crucial for creating robust multi-parameter assays, which enhance diagnostic accuracy and treatment decisions in ADs.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120533"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803735","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}
Rheumatoid arthritis (RA) is a chronic autoimmune disease in which early diagnosis and intervention are critical to prevent irreversible joint damage. While rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) remain diagnostic cornerstones, their limitations in sensitivity, particularly in early and seronegative RA, underscore the urgent need for novel biomarkers. This review synthesizes recent advances in the discovery of immunologic, genetic, and heterogeneous biomarkers for RA, evaluating the diagnostic and prognostic potential of a broad spectrum of candidates, including cytokines (e.g., IL-6, IL-17, IL-37), non-coding RNAs (microRNAs, long non-coding RNAs, circular RNAs), epigenetic markers, adipokines, and proteins such as matrix metalloproteinases. Evidence indicates that multi-analyte panels, often incorporating these novel biomarkers, can significantly outperform traditional serological tests. The integration of these innovative biomarkers into clinical practice holds promise for transforming RA management by enabling earlier, more precise diagnosis, improving patient stratification, and facilitating personalized treatment strategies to enhance long-term outcomes.
{"title":"Rheumatoid arthritis: emerging genetic and immunologic biomarkers","authors":"Seyed Moein Mahini , Keihan Salehi , Hamed Irandoost , Reza Sadeghi , Mohammad Samare-Najaf , Mohammad Karim Azadbakht , Navid Jamali","doi":"10.1016/j.cca.2025.120801","DOIUrl":"10.1016/j.cca.2025.120801","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease in which early diagnosis and intervention are critical to prevent irreversible joint damage. While rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) remain diagnostic cornerstones, their limitations in sensitivity, particularly in early and seronegative RA, underscore the urgent need for novel biomarkers. This review synthesizes recent advances in the discovery of immunologic, genetic, and heterogeneous biomarkers for RA, evaluating the diagnostic and prognostic potential of a broad spectrum of candidates, including cytokines (e.g., IL-6, IL-17, IL-37), non-coding RNAs (microRNAs, long non-coding RNAs, circular RNAs), epigenetic markers, adipokines, and proteins such as matrix metalloproteinases. Evidence indicates that multi-analyte panels, often incorporating these novel biomarkers, can significantly outperform traditional serological tests. The integration of these innovative biomarkers into clinical practice holds promise for transforming RA management by enabling earlier, more precise diagnosis, improving patient stratification, and facilitating personalized treatment strategies to enhance long-term outcomes.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120801"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881305","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 : 2026-01-01Epub Date: 2025-08-05DOI: 10.1016/j.cca.2025.120534
Yanan Cao, Mingshu Zhou, Hua Li
The detection of 17β-estradiol (E2), a potent endocrine-disrupting compound, is critical for both environmental monitoring and biomedical diagnostics. Traditional detection methods often suffer from limitations in sensitivity, selectivity, and cost-effectiveness. Aptasensors, which utilize aptamers as biorecognition elements, offer promising alternatives because of their high specificity, stability, and adaptability. This paper explores recent advancements in aptasensor technologies for E2 detection, highlighting optical, electrochemical, and surface-enhanced Raman scattering (SERS)-based platforms. The integration of nanomaterials such as gold nanoparticles, carbon dots, and conductive polymers significantly enhances sensor performance, achieving ultralow detection limits and broad dynamic ranges. By leveraging these innovations, aptasensors provide scalable solutions for real-time monitoring of E2 in environmental, food, and clinical samples, paving the way for improved endocrine regulation and public health safety.
{"title":"Advanced aptasensor technologies for sensitive detection of 17β-Estradiol.","authors":"Yanan Cao, Mingshu Zhou, Hua Li","doi":"10.1016/j.cca.2025.120534","DOIUrl":"10.1016/j.cca.2025.120534","url":null,"abstract":"<p><p>The detection of 17β-estradiol (E2), a potent endocrine-disrupting compound, is critical for both environmental monitoring and biomedical diagnostics. Traditional detection methods often suffer from limitations in sensitivity, selectivity, and cost-effectiveness. Aptasensors, which utilize aptamers as biorecognition elements, offer promising alternatives because of their high specificity, stability, and adaptability. This paper explores recent advancements in aptasensor technologies for E2 detection, highlighting optical, electrochemical, and surface-enhanced Raman scattering (SERS)-based platforms. The integration of nanomaterials such as gold nanoparticles, carbon dots, and conductive polymers significantly enhances sensor performance, achieving ultralow detection limits and broad dynamic ranges. By leveraging these innovations, aptasensors provide scalable solutions for real-time monitoring of E2 in environmental, food, and clinical samples, paving the way for improved endocrine regulation and public health safety.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120534"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798322","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 : 2026-01-01Epub Date: 2025-08-05DOI: 10.1016/j.cca.2025.120528
Renata Paleari, Matteo Vidali, Roberta Rolla, Ferruccio Ceriotti, Massimiliano Ammirabile, Andrea Mosca
Sickle cell disease (SCD) is a severe hereditary hemoglobinopathy with the highest burden in sub-Saharan Africa. Timely diagnosis via newborn screening is critical to enabling low-cost, life-saving interventions, yet its implementation remains inconsistent worldwide. This study assessed the performance and analytical stability of dried blood spot (DBS) samples collected on Guthrie cards for quantifying hemoglobin S (Hb S), using three high-performance liquid chromatography (HPLC) platforms and one capillary electrophoresis system. Simulated neonatal samples at three Hb S concentrations (non-carrier, carrier, and affected) were analyzed at three timepoints (immediate, 1 week, and 2 weeks post-collection). Across all methods, Hb S quantification was highly reproducible, with inter-timepoint variation remaining within the predefined critical threshold for the vast majority of the measurements. While minor discrepancies were observed for fetal hemoglobin (Hb F), all methods correctly classified samples for SCD screening purposes. These findings confirm that Guthrie card-based DBS is a robust and practical matrix for Hb S detection, suitable for transport and delayed analysis-even across different analytical platforms. Limitations include the use of spiked rather than native SCD neonatal samples and ambient-temperature shipping. Nonetheless, the results support broader adoption of DBS in SCD screening programs, particularly in low-resource or decentralized settings, and highlight the need for further standardization of Hb F quantification.
{"title":"Blood collected on dry blood spots is fit for newborn screening of sickle cell disease (SCD) by different analytical systems.","authors":"Renata Paleari, Matteo Vidali, Roberta Rolla, Ferruccio Ceriotti, Massimiliano Ammirabile, Andrea Mosca","doi":"10.1016/j.cca.2025.120528","DOIUrl":"10.1016/j.cca.2025.120528","url":null,"abstract":"<p><p>Sickle cell disease (SCD) is a severe hereditary hemoglobinopathy with the highest burden in sub-Saharan Africa. Timely diagnosis via newborn screening is critical to enabling low-cost, life-saving interventions, yet its implementation remains inconsistent worldwide. This study assessed the performance and analytical stability of dried blood spot (DBS) samples collected on Guthrie cards for quantifying hemoglobin S (Hb S), using three high-performance liquid chromatography (HPLC) platforms and one capillary electrophoresis system. Simulated neonatal samples at three Hb S concentrations (non-carrier, carrier, and affected) were analyzed at three timepoints (immediate, 1 week, and 2 weeks post-collection). Across all methods, Hb S quantification was highly reproducible, with inter-timepoint variation remaining within the predefined critical threshold for the vast majority of the measurements. While minor discrepancies were observed for fetal hemoglobin (Hb F), all methods correctly classified samples for SCD screening purposes. These findings confirm that Guthrie card-based DBS is a robust and practical matrix for Hb S detection, suitable for transport and delayed analysis-even across different analytical platforms. Limitations include the use of spiked rather than native SCD neonatal samples and ambient-temperature shipping. Nonetheless, the results support broader adoption of DBS in SCD screening programs, particularly in low-resource or decentralized settings, and highlight the need for further standardization of Hb F quantification.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120528"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774697","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}
The irreversibility and lethality of Spinal Muscular Atrophy (SMA) underscore the urgency of newborn screening, as diagnostic delay in neonates causes irreversible motor neuron degeneration and poor outcomes. Current SMA detection methods are hindered by high costs, dependence on specialized equipment, and technical complexity, restricting their implementation in primary care setting. Here, we proposed a fast and sensitive SMA-(Recombinase Polymerase Amplification) RPA-Cas12a detection assay based on suboptimal protospacer adjacent motif (sPAM) and 3'-end ssDNA-modified crRNA, named SPSMC. The crRNA is designed based on the sPAM to enhance the specificity of SMN1 gene detection. The competition between RPA and Cas12a digestion for target DNA was resolved by using 3'-end ssDNA-modified crRNA. With ALB as a reference gene, this method can detect DNA at concentrations as low as 1.8 pM within 1 h. The sensitivity and specificity of the proposed method in differentiating SMA patients from non-SMA individuals were both 100 %. This strategy has been used for the detection of the SMN1 gene, which saves time, reduces contamination risks, and offers new possibilities for future point-of-care screening of SMA. In addition, the SPSMC system was successfully adapted to SMA lateral flow assay format and validated using 66 clinical samples, demonstrating 100 % sensitivity and specificity. The method is straightforward to perform, requires no bulky equipment, maintains full portability, and is more suitable for large-scale neonatal screening scenarios compared with traditional methods.
{"title":"Sensitive and visual detection of SMA using RPA-Cas12a one-step assay with ssDNA-modified crRNA.","authors":"Qinyi Huang, Changzhi Xu, Shiqi Liu, Haihong Shi, XiaoBin Zhong, Shumin Zhao, Fengxiang Wei, Lvyuan Fan, Cui Wang, Yuanqing Li, Jia Tang","doi":"10.1016/j.cca.2025.120537","DOIUrl":"10.1016/j.cca.2025.120537","url":null,"abstract":"<p><p>The irreversibility and lethality of Spinal Muscular Atrophy (SMA) underscore the urgency of newborn screening, as diagnostic delay in neonates causes irreversible motor neuron degeneration and poor outcomes. Current SMA detection methods are hindered by high costs, dependence on specialized equipment, and technical complexity, restricting their implementation in primary care setting. Here, we proposed a fast and sensitive SMA-(Recombinase Polymerase Amplification) RPA-Cas12a detection assay based on suboptimal protospacer adjacent motif (sPAM) and 3'-end ssDNA-modified crRNA, named SPSMC. The crRNA is designed based on the sPAM to enhance the specificity of SMN1 gene detection. The competition between RPA and Cas12a digestion for target DNA was resolved by using 3'-end ssDNA-modified crRNA. With ALB as a reference gene, this method can detect DNA at concentrations as low as 1.8 pM within 1 h. The sensitivity and specificity of the proposed method in differentiating SMA patients from non-SMA individuals were both 100 %. This strategy has been used for the detection of the SMN1 gene, which saves time, reduces contamination risks, and offers new possibilities for future point-of-care screening of SMA. In addition, the SPSMC system was successfully adapted to SMA lateral flow assay format and validated using 66 clinical samples, demonstrating 100 % sensitivity and specificity. The method is straightforward to perform, requires no bulky equipment, maintains full portability, and is more suitable for large-scale neonatal screening scenarios compared with traditional methods.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120537"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798326","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}
Background: Biological reference intervals (RIs) are fundamental tools in clinical diagnostics, traditionally derived from geographically and ethnically homogeneous populations, predominantly of Western origin. Such generalized RIs often fail to account for variations arising from genetic, environmental, and lifestyle factors, which can impact clinical decision-making and contribute to health inequities, particularly in countries across Africa, India, and many other Southeast Asian nations. This scoping review investigates ethnicity-based variations in RIs for a range of biomarkers to highlight the importance of population-specific RIs.
Methods: Adhering to the Joanna Briggs Institute (JBI) guidelines, this scoping review examined the literature on ethnicity-based RI variations across multiple biomarkers, including Von Willebrand factor, C-reactive protein, thyroid-stimulating hormone, albumin, creatinine, and more. Studies were identified via searches in MEDLINE (via PubMed), Embase, Scopus, and Web of Science up to December 30, 2024. Eligibility was determined using the Population-Concept-Context (PCC) framework, focusing on observational studies analysing ethnicity-specific differences. Data extraction and charting were performed using CADIMA software, with independent review by two authors to ensure consistency.
Results: Out of 4,514 articles, a total of 15 studies met the inclusion criteria, encompassing multi-ethnic populations. Significant variations in biomarker levels were observed across ethnic groups, highlighting the inadequacy of generalized RIs. Notable differences included variations in lipid profiles, vitamin B12, and anti-Mullerian hormone levels. Regional distribution analysis highlighted gaps in research from underrepresented ethnic populations.
Conclusion: This review emphasizes the critical need for ethnicity-specific RIs to improve diagnostic accuracy and promote equitable healthcare outcomes. Further research should focus on developing robust methodologies for establishing inclusive and representative RIs.
背景:生物参考区间(RIs)是临床诊断的基本工具,传统上来源于地理和种族同质的人群,主要来自西方。这种普遍化的RIs通常无法解释由遗传、环境和生活方式因素引起的变异,这些因素可能影响临床决策并导致卫生不公平,特别是在非洲、印度和许多其他东南亚国家。本综述调查了一系列生物标志物的RIs基于种族的差异,以强调人群特异性RIs的重要性。方法:根据乔安娜布里格斯研究所(JBI)的指导方针,本综述检查了基于种族的RI在多种生物标志物上的变化,包括血管性血淋病因子、c反应蛋白、促甲状腺激素、白蛋白、肌酐等。截至2024年12月30日,通过MEDLINE(通过PubMed)、Embase、Scopus和Web of Science的搜索确定了研究。使用人口-概念-背景(PCC)框架确定资格,重点关注分析种族特异性差异的观察性研究。数据提取和制图使用CADIMA软件,由两位作者独立审查以确保一致性。结果:在4,514篇文章中,共有15项研究符合纳入标准,涵盖了多民族人群。在不同种族的人群中观察到生物标志物水平的显著差异,突出了广义RIs的不足。显著差异包括脂质谱、维生素B12和抗苗勒管激素水平的变化。区域分布分析突出了来自代表性不足的少数民族人口的研究差距。结论:本综述强调了对种族特异性RIs的迫切需要,以提高诊断准确性和促进公平的医疗保健结果。进一步的研究应侧重于发展强有力的方法,以建立包容性和代表性的RIs。
{"title":"Ethnicity-based variations in biological reference interval- A systematic scoping review.","authors":"Sasidharan Sivakumar, Ishika Makhija, Ruchika Bhagat, Saanvi Maurya, Nabendu Sekhar Chatterjee, Savita Bansal, Nilesh Chandra","doi":"10.1016/j.cca.2025.120539","DOIUrl":"10.1016/j.cca.2025.120539","url":null,"abstract":"<p><strong>Background: </strong>Biological reference intervals (RIs) are fundamental tools in clinical diagnostics, traditionally derived from geographically and ethnically homogeneous populations, predominantly of Western origin. Such generalized RIs often fail to account for variations arising from genetic, environmental, and lifestyle factors, which can impact clinical decision-making and contribute to health inequities, particularly in countries across Africa, India, and many other Southeast Asian nations. This scoping review investigates ethnicity-based variations in RIs for a range of biomarkers to highlight the importance of population-specific RIs.</p><p><strong>Methods: </strong>Adhering to the Joanna Briggs Institute (JBI) guidelines, this scoping review examined the literature on ethnicity-based RI variations across multiple biomarkers, including Von Willebrand factor, C-reactive protein, thyroid-stimulating hormone, albumin, creatinine, and more. Studies were identified via searches in MEDLINE (via PubMed), Embase, Scopus, and Web of Science up to December 30, 2024. Eligibility was determined using the Population-Concept-Context (PCC) framework, focusing on observational studies analysing ethnicity-specific differences. Data extraction and charting were performed using CADIMA software, with independent review by two authors to ensure consistency.</p><p><strong>Results: </strong>Out of 4,514 articles, a total of 15 studies met the inclusion criteria, encompassing multi-ethnic populations. Significant variations in biomarker levels were observed across ethnic groups, highlighting the inadequacy of generalized RIs. Notable differences included variations in lipid profiles, vitamin B12, and anti-Mullerian hormone levels. Regional distribution analysis highlighted gaps in research from underrepresented ethnic populations.</p><p><strong>Conclusion: </strong>This review emphasizes the critical need for ethnicity-specific RIs to improve diagnostic accuracy and promote equitable healthcare outcomes. Further research should focus on developing robust methodologies for establishing inclusive and representative RIs.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120539"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811866","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}
Traumatic brain injury (TBI) poses a significant global health challenge, leading to high mortality and morbidity rates. Despite extensive research, effective diagnostic and therapeutic strategies remain limited. This review explores the emerging roles of exosomal non-coding RNAs (ncRNAs) as biomarkers and therapeutic agents in TBI. Exosomes, small extracellular vesicles secreted by various cell types, facilitate intercellular communication and carry diverse ncRNAs that modulate gene expression and cellular functions. The pathogenesis of TBI involves complex inflammatory cascades, in which exosomal ncRNAs play pivotal roles in neuroinflammation, neuronal apoptosis, and secondary injury mechanisms. Key ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been identified as potential biomarkers for diagnosing TBI and predicting outcomes. Additionally, exosomal ncRNAs derived from mesenchymal stem cells (MSCs) show promise in promoting neuroprotection and enhancing recovery through various mechanisms. The review highlights the potential of exosomal ncRNAs in addressing critical unmet needs in TBI management, emphasizing their stability, accessibility, and relevance to disease pathophysiology. However, challenges in standardization, validation, and regulatory pathways must be addressed to facilitate their clinical application. This comprehensive examination underscores the transformative potential of exosomal ncRNAs in TBI diagnosis and treatment, paving the way for future research and clinical innovations.
{"title":"Exosomal non-coding RNA biomarkers in traumatic brain injury.","authors":"Pulatov Sadriddin, Babajanova Umida, Matyakubov Izzat, Urinov Muso, Toxtiyev Jaxongirbek, Akhmedov Shakhboskhan, Narkulova Soxiba, Muradova Emma, Bekchanova Madina, Shodmonov Iskandar, Kasimov Kabil Kasimovich, Matrizayeva Gulnara Djumaniyazovna, Kurbaniyazova Madina Zafajanovna","doi":"10.1016/j.cca.2025.120544","DOIUrl":"10.1016/j.cca.2025.120544","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) poses a significant global health challenge, leading to high mortality and morbidity rates. Despite extensive research, effective diagnostic and therapeutic strategies remain limited. This review explores the emerging roles of exosomal non-coding RNAs (ncRNAs) as biomarkers and therapeutic agents in TBI. Exosomes, small extracellular vesicles secreted by various cell types, facilitate intercellular communication and carry diverse ncRNAs that modulate gene expression and cellular functions. The pathogenesis of TBI involves complex inflammatory cascades, in which exosomal ncRNAs play pivotal roles in neuroinflammation, neuronal apoptosis, and secondary injury mechanisms. Key ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been identified as potential biomarkers for diagnosing TBI and predicting outcomes. Additionally, exosomal ncRNAs derived from mesenchymal stem cells (MSCs) show promise in promoting neuroprotection and enhancing recovery through various mechanisms. The review highlights the potential of exosomal ncRNAs in addressing critical unmet needs in TBI management, emphasizing their stability, accessibility, and relevance to disease pathophysiology. However, challenges in standardization, validation, and regulatory pathways must be addressed to facilitate their clinical application. This comprehensive examination underscores the transformative potential of exosomal ncRNAs in TBI diagnosis and treatment, paving the way for future research and clinical innovations.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120544"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811881","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}