Pub Date : 2026-02-01DOI: 10.1016/j.cca.2026.120879
Qamar Abuhassan , Mutaz Jamal Al-khreisat , R. Roopashree , Maitreyee Panda , T. Sudhakar , Vipasha Sharma , Ashish Singh Chauhan , Guzal Klebleeva
Melanoma remains one of the most aggressive forms of skin cancer, with an increasing incidence and limited therapeutic success in advanced stages. Early detection and precise prognostic assessment are critical for improving patient outcomes, yet conventional biomarkers often lack sensitivity and specificity. In recent years, noncoding RNAs (ncRNAs), including microRNAs, long noncoding RNAs, and circular RNAs, have emerged as pivotal regulators of melanoma biology. These molecules modulate key pathways involved in tumor initiation, progression, metastasis, and therapeutic resistance while also demonstrating remarkable stability in biofluids, making them attractive candidates for minimally invasive diagnostics. This narrative review synthesizes current evidence on the role of ncRNAs as emerging biomarkers in melanoma, highlighting their potential utility in early detection, prognostic stratification, and prediction of therapeutic response. Furthermore, we discuss methodological advances in ncRNA profiling, translational challenges, and future directions for integrating ncRNA-based assays into clinical practice. By consolidating mechanistic insights and clinical relevance, this review underscores the promise of ncRNAs as transformative tools in precision oncology for melanoma management.
{"title":"Non-coding RNAs as emerging biomarkers in melanoma","authors":"Qamar Abuhassan , Mutaz Jamal Al-khreisat , R. Roopashree , Maitreyee Panda , T. Sudhakar , Vipasha Sharma , Ashish Singh Chauhan , Guzal Klebleeva","doi":"10.1016/j.cca.2026.120879","DOIUrl":"10.1016/j.cca.2026.120879","url":null,"abstract":"<div><div>Melanoma remains one of the most aggressive forms of skin cancer, with an increasing incidence and limited therapeutic success in advanced stages. Early detection and precise prognostic assessment are critical for improving patient outcomes, yet conventional biomarkers often lack sensitivity and specificity. In recent years, noncoding RNAs (ncRNAs), including microRNAs, long noncoding RNAs, and circular RNAs, have emerged as pivotal regulators of melanoma biology. These molecules modulate key pathways involved in tumor initiation, progression, metastasis, and therapeutic resistance while also demonstrating remarkable stability in biofluids, making them attractive candidates for minimally invasive diagnostics. This narrative review synthesizes current evidence on the role of ncRNAs as emerging biomarkers in melanoma, highlighting their potential utility in early detection, prognostic stratification, and prediction of therapeutic response. Furthermore, we discuss methodological advances in ncRNA profiling, translational challenges, and future directions for integrating ncRNA-based assays into clinical practice. By consolidating mechanistic insights and clinical relevance, this review underscores the promise of ncRNAs as transformative tools in precision oncology for melanoma management.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"585 ","pages":"Article 120879"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112461","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 : 2026-01-31DOI: 10.1016/j.cca.2026.120881
Jonas Schmidt , Sarina Weiß , Frithjof Blessing , Josef Blessing , Peter Schierack , Stefan Rödiger , Rico Hiemann , Dirk Roggenbuck
Objectives
Detection of antinuclear antibody (ANA) via indirect immunofluorescence (IIF) on HEp-2 cells is a screening test for the serological diagnosis of systemic autoimmune rheumatic diseases. Automated interpretation of ANA classification by novel artificial intelligence (AI)-aided pattern recognition was compared with expert reading under routine conditions.
Methods
Consecutive serum samples of 2671 individuals referred to a routine laboratory were analysed for ANA titers and patterns using the automated interpretation system akironNeo. AI-based ANA detection was compared with independent classification by two experienced immunologists according to the international consensus on ANA patterns (ICAP) competence level.
Results
Overall, a good agreement (κ > 0.60) between the different evaluators both for positive/negative classification of ANA fluorescence images as well as for the pattern classification of positive samples with a titer ≥ 1:320 was observed. Positive/negative differentiation at different cut-offs revealed κ values from 0.584 to 0.760 whereas corresponding pattern recognition for interphase, metaphase and cytoplasmic patterns demonstrated κ values from 0.560 to 0.736 for samples scored as positive by all three evaluators.
Conclusions
The AI-based software showed a similar performance compared to human observers. AI-aided ANA image analysis can facilitate the diagnostic workflow of ANA IIF assays and reduce subjectivity during image classification.
{"title":"Comparison of manual with artificial intelligence-aided interpretation of ANA HEp-2 IIF assay patterns in a clinical diagnostics lab","authors":"Jonas Schmidt , Sarina Weiß , Frithjof Blessing , Josef Blessing , Peter Schierack , Stefan Rödiger , Rico Hiemann , Dirk Roggenbuck","doi":"10.1016/j.cca.2026.120881","DOIUrl":"10.1016/j.cca.2026.120881","url":null,"abstract":"<div><h3>Objectives</h3><div>Detection of antinuclear antibody (ANA) via indirect immunofluorescence (IIF) on HEp-2 cells is a screening test for the serological diagnosis of systemic autoimmune rheumatic diseases. Automated interpretation of ANA classification by novel artificial intelligence (AI)-aided pattern recognition was compared with expert reading under routine conditions.</div></div><div><h3>Methods</h3><div>Consecutive serum samples of 2671 individuals referred to a routine laboratory were analysed for ANA titers and patterns using the automated interpretation system akironNeo. AI-based ANA detection was compared with independent classification by two experienced immunologists according to the international consensus on ANA patterns (ICAP) competence level.</div></div><div><h3>Results</h3><div>Overall, a good agreement (κ > 0.60) between the different evaluators both for positive/negative classification of ANA fluorescence images as well as for the pattern classification of positive samples with a titer ≥ 1:320 was observed. Positive/negative differentiation at different cut-offs revealed κ values from 0.584 to 0.760 whereas corresponding pattern recognition for interphase, metaphase and cytoplasmic patterns demonstrated κ values from 0.560 to 0.736 for samples scored as positive by all three evaluators.</div></div><div><h3>Conclusions</h3><div>The AI-based software showed a similar performance compared to human observers. AI-aided ANA image analysis can facilitate the diagnostic workflow of ANA IIF assays and reduce subjectivity during image classification.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"584 ","pages":"Article 120881"},"PeriodicalIF":2.9,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146104394","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 : 2026-01-31DOI: 10.1016/j.cca.2026.120876
Arthur M. Chiwaya , Shima M. Abdulgader , Patricia Manjate , James Sserubiri , Bayanda Mdoda , Loide N.N. Shipingana , Dinis Nguenha , Derrick Semugenze , Marc Bañuls , Vinzeigh N. Leukes , Adam Penn-Nicholson , Achilles Katamba , Moses Joloba , Willy Ssengooba , Alberto L. García-Basteiro , Frank Cobelens , Grant Theron
Background
C-reactive protein (CRP) is recommended to screen people living with HIV (PLWH) for tuberculosis (TB). LumiraDx is a portable platform that uses fingerprick blood. How CRP compares in fingerprick blood and serum is unknown.
Methods
CRP was measured in 1034 consecutively recruited contacts of people with TB using fresh fingerprick blood (LumiraDx at point-of-care) and stored (−80 °C) serum [LumiraDx and cobas C-Reactive Protein (Latex) High Sensitive (CRPHS) in laboratories]. Agreement was assessed using Lin's concordance correlation coefficient (CCC), Passing-Bablok (PB) regression, and Bland-Altman (BA) plots. Sensitivity and specificity for TB were evaluated in 156 contacts with microbiological reference standard information, namely culture, Xpert MTB/RIF Ultra, or both.
Results
Strong agreement [CCC = 0.85, PB slope −0.27 (95% confidence interval −0.82, 0.2), BA mean difference 1 (−1,3)] was observed between LumiraDx on fingerprick blood and serum. Similar agreement occurred for serum CRPHS vs. LumiraDx on serum [0.79; 1.1 (−1.1, 2.3); 11 (9, 14)] or fingerprick blood [0.75; 1.3 (−0.6, 2.5); 10 (8, 13)]. Areas under the receiver operating characteristic curves (AUROCs) were 0.747 (0.595, 0.899) for fingerprick LumiraDx, 0.761 (0.628, 0.893) for serum LumiraDx and 0.775 (0.636, 0.914) for serum CRPHS. At >5 mg/L, all tests showed identical sensitivity [77% (70, 83)]. Specificities were 60% (53, 68), 64% (57, 72) and 50% (43, 58), respectively. Serum storage duration did not affect performance.
Conclusions
LumiraDx CRP readouts on fingerprick blood and serum correlate closely. Stored serum can be used for LumiraDx CRP measurement. High sensitivity methods increase the proportion of people who screen false-positive.
{"title":"Bioequivalence of C-reactive protein in fingerprick blood and serum measured using the point-of-care LumiraDx test for tuberculosis diagnosis in exposed contacts","authors":"Arthur M. Chiwaya , Shima M. Abdulgader , Patricia Manjate , James Sserubiri , Bayanda Mdoda , Loide N.N. Shipingana , Dinis Nguenha , Derrick Semugenze , Marc Bañuls , Vinzeigh N. Leukes , Adam Penn-Nicholson , Achilles Katamba , Moses Joloba , Willy Ssengooba , Alberto L. García-Basteiro , Frank Cobelens , Grant Theron","doi":"10.1016/j.cca.2026.120876","DOIUrl":"10.1016/j.cca.2026.120876","url":null,"abstract":"<div><h3>Background</h3><div>C-reactive protein (CRP) is recommended to screen people living with HIV (PLWH) for tuberculosis (TB). LumiraDx is a portable platform that uses fingerprick blood. How CRP compares in fingerprick blood and serum is unknown.</div></div><div><h3>Methods</h3><div>CRP was measured in 1034 consecutively recruited contacts of people with TB using fresh fingerprick blood (LumiraDx at point-of-care) and stored (−80 °C) serum [LumiraDx and cobas C-Reactive Protein (Latex) High Sensitive (CRPHS) in laboratories]. Agreement was assessed using Lin's concordance correlation coefficient (CCC), Passing-Bablok (PB) regression, and Bland-Altman (BA) plots. Sensitivity and specificity for TB were evaluated in 156 contacts with microbiological reference standard information, namely culture, Xpert MTB/RIF Ultra, or both.</div></div><div><h3>Results</h3><div>Strong agreement [CCC = 0.85, PB slope −0.27 (95% confidence interval −0.82, 0.2), BA mean difference 1 (−1,3)] was observed between LumiraDx on fingerprick blood and serum. Similar agreement occurred for serum CRPHS vs. LumiraDx on serum [0.79; 1.1 (−1.1, 2.3); 11 (9, 14)] or fingerprick blood [0.75; 1.3 (−0.6, 2.5); 10 (8, 13)]. Areas under the receiver operating characteristic curves (AUROCs) were 0.747 (0.595, 0.899) for fingerprick LumiraDx, 0.761 (0.628, 0.893) for serum LumiraDx and 0.775 (0.636, 0.914) for serum CRPHS. At >5 mg/L, all tests showed identical sensitivity [77% (70, 83)]. Specificities were 60% (53, 68), 64% (57, 72) and 50% (43, 58), respectively. Serum storage duration did not affect performance.</div></div><div><h3>Conclusions</h3><div>LumiraDx CRP readouts on fingerprick blood and serum correlate closely. Stored serum can be used for LumiraDx CRP measurement. High sensitivity methods increase the proportion of people who screen false-positive.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"584 ","pages":"Article 120876"},"PeriodicalIF":2.9,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146104397","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 : 2026-01-30DOI: 10.1016/j.cca.2026.120878
Tahir S. Pillay , Barbara S. van Deventer , Siphokazi Gwiliza , Evette L. Subramoney , Chantal van Niekerk
Clinical laboratories face stringent privacy constraints, limited datasets for rare conditions, and rising demands to validate AI algorithms and workflows safely. Synthetic data—artificially generated data that preserve the statistical characteristics of real clinical data without exposing patient identities—has emerged as a powerful tool to address these challenges. This review provides a comprehensive overview of synthetic data in the context of laboratory medicine. We begin by defining synthetic data and describing the main generation methods, from rule-based simulations to modern generative models (including generative adversarial networks, variational autoencoders, and diffusion models) with examples of their use in healthcare. We then delve into key applications in the clinical laboratory: quality control and method validation, education and training, machine learning development, test utilization and workflow simulation, and external quality assessment. Advantages of synthetic data—such as enhanced privacy, scalability, flexibility in simulating rare events, and cost-effectiveness—are discussed with illustrative case studies. We also examine challenges and limitations, including concerns about data fidelity, bias amplification, risks of model overfitting or re-identification attacks, and the cautious stance of regulators that still require real patient data for approvals. Finally, we outline future directions for synthetic data in laboratory medicine, from hybrid real–synthetic datasets and privacy-enhancing techniques to evolving regulatory frameworks and the potential to democratize data access globally. While synthetic data cannot entirely replace real clinical data—especially for regulatory validation—it can significantly augment what laboratories can design, test, and achieve, provided it is used with careful validation and ethical safeguards.
{"title":"Synthetic data in the clinical laboratory: methods, applications, and future prospects","authors":"Tahir S. Pillay , Barbara S. van Deventer , Siphokazi Gwiliza , Evette L. Subramoney , Chantal van Niekerk","doi":"10.1016/j.cca.2026.120878","DOIUrl":"10.1016/j.cca.2026.120878","url":null,"abstract":"<div><div>Clinical laboratories face stringent privacy constraints, limited datasets for rare conditions, and rising demands to validate AI algorithms and workflows safely. Synthetic data—artificially generated data that preserve the statistical characteristics of real clinical data without exposing patient identities—has emerged as a powerful tool to address these challenges. This review provides a comprehensive overview of synthetic data in the context of laboratory medicine. We begin by defining synthetic data and describing the main generation methods, from rule-based simulations to modern generative models (including generative adversarial networks, variational autoencoders, and diffusion models) with examples of their use in healthcare. We then delve into key applications in the clinical laboratory: quality control and method validation, education and training, machine learning development, test utilization and workflow simulation, and external quality assessment. Advantages of synthetic data—such as enhanced privacy, scalability, flexibility in simulating rare events, and cost-effectiveness—are discussed with illustrative case studies. We also examine challenges and limitations, including concerns about data fidelity, bias amplification, risks of model overfitting or re-identification attacks, and the cautious stance of regulators that still require real patient data for approvals. Finally, we outline future directions for synthetic data in laboratory medicine, from hybrid real–synthetic datasets and privacy-enhancing techniques to evolving regulatory frameworks and the potential to democratize data access globally. While synthetic data cannot entirely replace real clinical data—especially for regulatory validation—it can significantly augment what laboratories can design, test, and achieve, provided it is used with careful validation and ethical safeguards.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"585 ","pages":"Article 120878"},"PeriodicalIF":2.9,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099677","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 : 2026-01-29DOI: 10.1016/j.cca.2026.120874
Ye Liu , Lijia Zhang , Qian Wang , Xinyue Li , Xiaoling Feng
Ovarian cancer remains one of the most lethal gynecologic malignancies, largely because of late-stage diagnosis, extensive intratumoral heterogeneity, and the dynamic complexity of the tumor microenvironment (TME). Emerging evidence highlights the TME as a central orchestrator of immune evasion, angiogenic remodeling, and therapeutic resistance, which are three mechanistic pillars that critically shape disease progression and treatment outcomes. This narrative review synthesizes current mechanistic insights into how stromal, immune, and vascular components interact to promote tumor survival and metastasis. We examine the roles of immunosuppressive cell populations, cytokine networks, and checkpoint pathways in facilitating immune escape; delineate angiogenic drivers and endothelial–tumor crosstalk that sustain aberrant vascularization; and explore TME-mediated mechanisms that underlie chemoresistance, targeted therapy failure, and limited immunotherapy responsiveness. Furthermore, we evaluate recent advances in biomarker discovery, including the identification of circulating ncRNAs, exosomal signatures, spatial immune profiles, and TME-derived molecular indicators, which hold promise for improving early detection, prognostication, and therapeutic stratification. By integrating mechanistic biology with translational biomarker innovation, this review outlines a forward-looking framework for leveraging TME-informed diagnostics and therapeutics to enhance precision oncology in ovarian cancer.
{"title":"Tumor microenvironment and biomarker innovation in ovarian cancer: mechanistic insights into immune evasion, angiogenesis, and therapeutic resistance","authors":"Ye Liu , Lijia Zhang , Qian Wang , Xinyue Li , Xiaoling Feng","doi":"10.1016/j.cca.2026.120874","DOIUrl":"10.1016/j.cca.2026.120874","url":null,"abstract":"<div><div>Ovarian cancer remains one of the most lethal gynecologic malignancies, largely because of late-stage diagnosis, extensive intratumoral heterogeneity, and the dynamic complexity of the tumor microenvironment (TME). Emerging evidence highlights the TME as a central orchestrator of immune evasion, angiogenic remodeling, and therapeutic resistance, which are three mechanistic pillars that critically shape disease progression and treatment outcomes. This narrative review synthesizes current mechanistic insights into how stromal, immune, and vascular components interact to promote tumor survival and metastasis. We examine the roles of immunosuppressive cell populations, cytokine networks, and checkpoint pathways in facilitating immune escape; delineate angiogenic drivers and endothelial–tumor crosstalk that sustain aberrant vascularization; and explore TME-mediated mechanisms that underlie chemoresistance, targeted therapy failure, and limited immunotherapy responsiveness. Furthermore, we evaluate recent advances in biomarker discovery, including the identification of circulating ncRNAs, exosomal signatures, spatial immune profiles, and TME-derived molecular indicators, which hold promise for improving early detection, prognostication, and therapeutic stratification. By integrating mechanistic biology with translational biomarker innovation, this review outlines a forward-looking framework for leveraging TME-informed diagnostics and therapeutics to enhance precision oncology in ovarian cancer.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"584 ","pages":"Article 120874"},"PeriodicalIF":2.9,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096640","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 : 2026-01-29DOI: 10.1016/j.cca.2026.120877
Mugdha Gautam , Prashant Sharma , Arnab Pal , Pulkit Rastogi , Praveen Sharma , Alka Rani Khadwal , Manu Jamwal , Minakshi Gupta , Reena Das
Introduction
Iron deficiency (ID) is the most common micronutrient deficiency globally, often underdiagnosed due to nonspecific symptoms and limitations of standard laboratory tests. Reticulocyte-derived indices from modern hematology analyzers offer enhanced early detection of iron-restricted erythropoiesis.
Methods
We studied 103 self-reported asymptomatic healthy adults who underwent complete blood counts and reticulocyte analysis on XN-2000 analyzers (Sysmex Corp., Kobe, Japan). Detailed biochemical iron profile and vitamin B12/folate testing were done. Diagnostic performance of hematologic parameters was assessed and combinatorial logistic regression models and discriminant indices were developed.
Results
Participants' median age was 28 years (range 22–79); 69.9% (n = 72) were women. 54.4% (n = 56) had ID and 21.4% (n = 22) were anemic. Latent ID was detected in 34.9% (36/103). B12 and folate deficiencies were present in 41% and 40%, respectively - extensively overlapping with ID. Key individual indices for ID included RET-He, RET-Y, and RET-RBC-Y, each with area under the ROC curve (AUC) >85%. A comprehensive 21-variable logistic regression model yielded AUC 93.7% (95% C.I. 88.9–98.5), sensitivity 89.1%, and specificity 70.2%. A pared-down 3-variable model achieved AUC 90.1% (95% C.I. 84.1–96.1), sensitivity 87.5%, and specificity 70.9%. Of the two heuristic composite indices tested, one – [RDW-CV × PLT × 105] / [RET-He × RET-RBC-Y × IRF-Y × RET-Y] - showed AUC 89.8% (95% C.I. 83.7–95.9), sensitivity 87%, and specificity 72.3%.
Conclusion
In a cohort with high rates of nutritional deficiency, cost-effective equations combining conventional and advanced reticulocyte indices demonstrated strong diagnostic utility for screening ID, with potential for broader application in resource-limited settings.
{"title":"Combining conventional hemogram and reticulocyte metrics enhances iron deficiency detection in asymptomatic individuals","authors":"Mugdha Gautam , Prashant Sharma , Arnab Pal , Pulkit Rastogi , Praveen Sharma , Alka Rani Khadwal , Manu Jamwal , Minakshi Gupta , Reena Das","doi":"10.1016/j.cca.2026.120877","DOIUrl":"10.1016/j.cca.2026.120877","url":null,"abstract":"<div><h3>Introduction</h3><div>Iron deficiency (ID) is the most common micronutrient deficiency globally, often underdiagnosed due to nonspecific symptoms and limitations of standard laboratory tests. Reticulocyte-derived indices from modern hematology analyzers offer enhanced early detection of iron-restricted erythropoiesis.</div></div><div><h3>Methods</h3><div>We studied 103 self-reported asymptomatic healthy adults who underwent complete blood counts and reticulocyte analysis on XN-2000 analyzers (Sysmex Corp., Kobe, Japan). Detailed biochemical iron profile and vitamin B12/folate testing were done. Diagnostic performance of hematologic parameters was assessed and combinatorial logistic regression models and discriminant indices were developed.</div></div><div><h3>Results</h3><div>Participants' median age was 28 years (range 22–79); 69.9% (<em>n</em> = 72) were women. 54.4% (<em>n</em> = 56) had ID and 21.4% (<em>n</em> = 22) were anemic. Latent ID was detected in 34.9% (36/103). B12 and folate deficiencies were present in 41% and 40%, respectively - extensively overlapping with ID. Key individual indices for ID included RET-He, RET-Y, and RET-RBC-Y, each with area under the ROC curve (AUC) >85%. A comprehensive 21-variable logistic regression model yielded AUC 93.7% (95% C.I. 88.9–98.5), sensitivity 89.1%, and specificity 70.2%. A pared-down 3-variable model achieved AUC 90.1% (95% C.I. 84.1–96.1), sensitivity 87.5%, and specificity 70.9%. Of the two heuristic composite indices tested, one – [RDW-CV × PLT × 10<sup>5</sup>] / [RET-He × RET-RBC-Y × IRF-Y × RET-Y] - showed AUC 89.8% (95% C.I. 83.7–95.9), sensitivity 87%, and specificity 72.3%.</div></div><div><h3>Conclusion</h3><div>In a cohort with high rates of nutritional deficiency, cost-effective equations combining conventional and advanced reticulocyte indices demonstrated strong diagnostic utility for screening ID, with potential for broader application in resource-limited settings.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"584 ","pages":"Article 120877"},"PeriodicalIF":2.9,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096651","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 : 2026-01-29DOI: 10.1016/j.cca.2026.120875
Wasim Shah , Mujahid Hussain , Ayesha Serwat , Muhammad Bilal , Yousaf Raza , Abu Mansoor , Ahmad Faraz
Reproductive failure affects millions of couples worldwide and frequently arises from genetic defects that impair gametogenesis, fertilization, or early embryonic development. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome-editing technology has emerged as a powerful experimental platform for dissecting infertility-associated genes and, in principle, correcting pathogenic variants in germline cells or preimplantation embryos. This review critically examines current applications of CRISPR/Cas9 in reproductive biology, including disease modeling in animal systems, editing of spermatogonial stem cells (SSCs), manipulation of oocytes and zygotes, and proof-of-concept studies in human embryos.
Particular emphasis is placed on the major technical barriers that currently preclude clinical translation, including off-target mutagenesis, embryo mosaicism, and the low efficiency of homology-directed repair relative to non-homologous end joining. Limitations related to delivery strategies, DNA damage responses, chromosomal rearrangements, and the genetic heterogeneity of infertility are also evaluated. Comparative discussion highlights how germline editing differs fundamentally from somatic CRISPR therapies that have already reached clinical application in hematologic disorders.
The review further analyzes ethical and regulatory challenges associated with heritable genome modification, including long-term safety, consent across generations, international governance disparities, and the continued reliance on assisted reproductive technologies combined with preimplantation genetic testing as safer clinical alternatives. Collectively, current evidence indicates that CRISPR/Cas9 remains primarily a research tool for elucidating reproductive biology rather than an imminent therapeutic option for human infertility. Continued technological refinement, rigorous preclinical validation, and globally harmonized oversight will be essential before germline applications can be ethically or clinically justified.
{"title":"CRISPR/Cas9 and reproductive failure: applications, ethical challenges, and future perspectives in human germline genome editing","authors":"Wasim Shah , Mujahid Hussain , Ayesha Serwat , Muhammad Bilal , Yousaf Raza , Abu Mansoor , Ahmad Faraz","doi":"10.1016/j.cca.2026.120875","DOIUrl":"10.1016/j.cca.2026.120875","url":null,"abstract":"<div><div>Reproductive failure affects millions of couples worldwide and frequently arises from genetic defects that impair gametogenesis, fertilization, or early embryonic development. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome-editing technology has emerged as a powerful experimental platform for dissecting infertility-associated genes and, in principle, correcting pathogenic variants in germline cells or preimplantation embryos. This review critically examines current applications of CRISPR/Cas9 in reproductive biology, including disease modeling in animal systems, editing of spermatogonial stem cells (SSCs), manipulation of oocytes and zygotes, and proof-of-concept studies in human embryos.</div><div>Particular emphasis is placed on the major technical barriers that currently preclude clinical translation, including off-target mutagenesis, embryo mosaicism, and the low efficiency of homology-directed repair relative to non-homologous end joining. Limitations related to delivery strategies, DNA damage responses, chromosomal rearrangements, and the genetic heterogeneity of infertility are also evaluated. Comparative discussion highlights how germline editing differs fundamentally from somatic CRISPR therapies that have already reached clinical application in hematologic disorders.</div><div>The review further analyzes ethical and regulatory challenges associated with heritable genome modification, including long-term safety, consent across generations, international governance disparities, and the continued reliance on assisted reproductive technologies combined with preimplantation genetic testing as safer clinical alternatives. Collectively, current evidence indicates that CRISPR/Cas9 remains primarily a research tool for elucidating reproductive biology rather than an imminent therapeutic option for human infertility. Continued technological refinement, rigorous preclinical validation, and globally harmonized oversight will be essential before germline applications can be ethically or clinically justified.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"584 ","pages":"Article 120875"},"PeriodicalIF":2.9,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075483","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}
To investigate genetic and metabolic profiles in primary carnitine deficiency (PCD) patients from Ganzhou.
Methods
Newborns screened in Ganzhou were included. Free carnitine (C0) and acylcarnitines were quantified using tandem mass spectrometry (MS/MS). Positive cases underwent SLC22A5 gene analysis using next-generation and sanger sequencing. Clinical data, genetic results, and amino acid/acylcarnitine levels were collected for confirmed PCD patients. Regional PCD variant frequencies were analyzed. Metabolic profiles of normal infants and PCD patients were compared to identify disease features. Homozygous and compound heterozygous PCD groups were analyzed.
Results
Screening 392,389 newborns identified 43 PCD cases (1:9125). Five maternal PCD cases were also identified. Of 48 PCD patients, 10 were homozygous and 38 heterozygous. Nineteen SLC22A5 mutations were found; the most common were c.51C > G (32.30%), c.1400C > G (26.00%), and c.428C > T (10.40%). In newborn PCD patients, C0 and multiple acylcarnitines including acetylcarnitine (C2), propionylcarnitine (C3), butyrylcarnitine (C4), isovalerylcarnitine (C5), hexanoylcarnitine (C6), octanoylcarnitine (C8), decanoylcarnitine (C10), dodecanoylcarnitine (C12), tetradecanoylcarnitine (C14), hexadecanoylcarnitine (C16), and octadecanoylcarnitine (C18) were significantly lower compared to controls (P < 0.05). Additionally, levels of glycine (GLY), ornithine (ORN), phenylalanine (PHE), tyrosine (TYR), and proline (PRO) were reduced(all P < 0.05), whereas arginine (ARG) was found to be elevated in PCD patients (P = 0.002). Furthermore, homozygous PCD patients exhibited lower C0 levels than heterozygous PCD patients (P = 0.049).
Conclusion
PCD incidence is high in Ganzhou Area. The most common mutations are c.51C > G, followed by c.1400C > G and c.428C > T. Multiple acylcarnitine reductions are a hallmark of PCD. Homozygous mutations correlate with lower C0 levels compared to heterozygous ones.
{"title":"Analysis of genetic mutation distribution and metabolic characteristics in patients with primary carnitine deficiency from the Ganzhou area, China","authors":"Xiangwen Tu , Feng Zhang , Junkun Chen , Chunlian Xie","doi":"10.1016/j.cca.2026.120873","DOIUrl":"10.1016/j.cca.2026.120873","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate genetic and metabolic profiles in primary carnitine deficiency (PCD) patients from Ganzhou.</div></div><div><h3>Methods</h3><div>Newborns screened in Ganzhou were included. Free carnitine (C0) and acylcarnitines were quantified using tandem mass spectrometry (MS/MS). Positive cases underwent <em>SLC22A5</em> gene analysis using next-generation and sanger sequencing. Clinical data, genetic results, and amino acid/acylcarnitine levels were collected for confirmed PCD patients. Regional PCD variant frequencies were analyzed. Metabolic profiles of normal infants and PCD patients were compared to identify disease features. Homozygous and compound heterozygous PCD groups were analyzed.</div></div><div><h3>Results</h3><div>Screening 392,389 newborns identified 43 PCD cases (1:9125). Five maternal PCD cases were also identified. Of 48 PCD patients, 10 were homozygous and 38 heterozygous. Nineteen <em>SLC22A5</em> mutations were found; the most common were c.51C > G (32.30%), c.1400C > G (26.00%), and c.428C > T (10.40%). In newborn PCD patients, C0 and multiple acylcarnitines including acetylcarnitine (C2), propionylcarnitine (C3), butyrylcarnitine (C4), isovalerylcarnitine (C5), hexanoylcarnitine (C6), octanoylcarnitine (C8), decanoylcarnitine (C10), dodecanoylcarnitine (C12), tetradecanoylcarnitine (C14), hexadecanoylcarnitine (C16), and octadecanoylcarnitine (C18) were significantly lower compared to controls (<em>P</em> < 0.05). Additionally, levels of glycine (GLY), ornithine (ORN), phenylalanine (PHE), tyrosine (TYR), and proline (PRO) were reduced(all <em>P</em> < 0.05), whereas arginine (ARG) was found to be elevated in PCD patients (<em>P</em> = 0.002). Furthermore, homozygous PCD patients exhibited lower C0 levels than heterozygous PCD patients (<em>P</em> = 0.049).</div></div><div><h3>Conclusion</h3><div>PCD incidence is high in Ganzhou Area. The most common mutations are c.51C > G, followed by c.1400C > G and c.428C > T. Multiple acylcarnitine reductions are a hallmark of PCD. Homozygous mutations correlate with lower C0 levels compared to heterozygous ones.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"584 ","pages":"Article 120873"},"PeriodicalIF":2.9,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096993","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}
Prostate cancer remains one of the most frequently diagnosed malignancies among men and continues to be a major cause of cancer-related deaths worldwide. Early and accurate detection is crucial for improving patient survival and enabling timely and appropriate treatment. Although the prostate-specific antigen (PSA) test is widely used for screening, its limited specificity—particularly within the diagnostic “gray zone”—often results in unnecessary biopsies, overdiagnosis, and missed detection of early-stage disease. Consequently, growing attention has turned to novel biomarkers with greater sensitivity and specificity that can complement or even replace PSA in clinical settings. Recent advances in biosensor technology have facilitated the development of rapid, cost-effective, and portable diagnostic tools. Among them, paper-based biosensors have emerged as a promising platform due to their low fabrication cost, simplicity, biodegradability, and compatibility with point-of-care (POC) testing. These devices enable highly sensitive and quantitative detection, where performance largely depends on the selection and engineering of sensing materials. The integration of nanomaterials and surface modification strategies has further enhanced target recognition, signal transduction efficiency, and sensor stability. This review provides an overview of recent progress in biosensor platforms for prostate cancer detection. It emphasizes the potential of advanced materials to improve analytical performance, highlights promising biomarkers beyond PSA, and discusses the major challenges impeding clinical translation. Addressing these barriers will be crucial for enabling paper-based biosensors to transition from research prototypes to reliable, field-ready tools for early prostate cancer diagnosis and monitoring.
{"title":"Advancing Prostate Cancer Diagnostics: The Potential of Paper-Based Biosensors for Point-of-Care Testing","authors":"Wei Yin Lim , Wee Jian Chin , Gopinath Packirisamy , Pavai Sthaneshwar , Narayanan Ramakrishnan , Choon-Hian Goh","doi":"10.1016/j.cca.2026.120872","DOIUrl":"10.1016/j.cca.2026.120872","url":null,"abstract":"<div><div>Prostate cancer remains one of the most frequently diagnosed malignancies among men and continues to be a major cause of cancer-related deaths worldwide. Early and accurate detection is crucial for improving patient survival and enabling timely and appropriate treatment. Although the prostate-specific antigen (PSA) test is widely used for screening, its limited specificity—particularly within the diagnostic “gray zone”—often results in unnecessary biopsies, overdiagnosis, and missed detection of early-stage disease. Consequently, growing attention has turned to novel biomarkers with greater sensitivity and specificity that can complement or even replace PSA in clinical settings. Recent advances in biosensor technology have facilitated the development of rapid, cost-effective, and portable diagnostic tools. Among them, paper-based biosensors have emerged as a promising platform due to their low fabrication cost, simplicity, biodegradability, and compatibility with point-of-care (POC) testing. These devices enable highly sensitive and quantitative detection, where performance largely depends on the selection and engineering of sensing materials. The integration of nanomaterials and surface modification strategies has further enhanced target recognition, signal transduction efficiency, and sensor stability. This review provides an overview of recent progress in biosensor platforms for prostate cancer detection. It emphasizes the potential of advanced materials to improve analytical performance, highlights promising biomarkers beyond PSA, and discusses the major challenges impeding clinical translation. Addressing these barriers will be crucial for enabling paper-based biosensors to transition from research prototypes to reliable, field-ready tools for early prostate cancer diagnosis and monitoring.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"584 ","pages":"Article 120872"},"PeriodicalIF":2.9,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146084353","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 : 2026-01-27DOI: 10.1016/j.cca.2026.120871
Qiang Zou , Niu Niu , Leilei Sun , Xiaoyan Xu , Yu Wang , Hong Qin
Diabetic retinopathy (DR) remains a leading cause of blindness, with oxidative stress as a central pathogenic driver. However, the translation of this mechanistic knowledge into clinical diagnostics and targeted therapies has been hampered by inconsistent biomarkers and a simplistic view of redox balance. This critical review moves beyond cataloging oxidative markers to evaluate their biological specificity, analytical robustness, and compartmentalization between systemic circulation and the ocular microenvironment. We dissect the technical challenges of direct reactive species measurement and appraise established markers of macromolecular damage, lipid peroxidation adducts, protein carbonyls, and oxidized nucleic acids, emphasizing that analytical rigor is paramount for interpretability. Furthermore, we explore integrative pathways linking glycoxidation, inflammation, and VEGF in a feed-forward loop. A key translational hurdle is the poor correlation between systemic biomarkers and intraretinal oxidative events. We propose a future roadmap featuring a tiered “DR oxidative stress profile” that combines scalable systemic screening with pathway-specific panels and advanced ocular imaging. This refined approach aims to enable precision phenotyping, enriching clinical trials for mechanism-targeted therapies and ultimately paving the way for personalized antioxidant strategies tailored to the dominant oxidative axis in individual patients.
{"title":"Oxidative stress in diabetic retinopathy","authors":"Qiang Zou , Niu Niu , Leilei Sun , Xiaoyan Xu , Yu Wang , Hong Qin","doi":"10.1016/j.cca.2026.120871","DOIUrl":"10.1016/j.cca.2026.120871","url":null,"abstract":"<div><div>Diabetic retinopathy (DR) remains a leading cause of blindness, with oxidative stress as a central pathogenic driver. However, the translation of this mechanistic knowledge into clinical diagnostics and targeted therapies has been hampered by inconsistent biomarkers and a simplistic view of redox balance. This critical review moves beyond cataloging oxidative markers to evaluate their biological specificity, analytical robustness, and compartmentalization between systemic circulation and the ocular microenvironment. We dissect the technical challenges of direct reactive species measurement and appraise established markers of macromolecular damage, lipid peroxidation adducts, protein carbonyls, and oxidized nucleic acids, emphasizing that analytical rigor is paramount for interpretability. Furthermore, we explore integrative pathways linking glycoxidation, inflammation, and VEGF in a feed-forward loop. A key translational hurdle is the poor correlation between systemic biomarkers and intraretinal oxidative events. We propose a future roadmap featuring a tiered “DR oxidative stress profile” that combines scalable systemic screening with pathway-specific panels and advanced ocular imaging. This refined approach aims to enable precision phenotyping, enriching clinical trials for mechanism-targeted therapies and ultimately paving the way for personalized antioxidant strategies tailored to the dominant oxidative axis in individual patients.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"584 ","pages":"Article 120871"},"PeriodicalIF":2.9,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075484","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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