Pub Date : 2025-02-01DOI: 10.1016/j.cca.2024.120120
Paul J. Dunn , Neven Maksemous , Robert A. Smith , Heidi G. Sutherland , Larisa M. Haupt , Lyn R. Griffiths
Background and aims
Cerebral small vessel diseases (CSVDs) are a set of conditions that affect the small blood vessels in the brain and can cause severe neurological pathologies such as stroke and vascular dementia. The most common monogenic CSVD is cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) which is caused by mutations in NOTCH3. However, only 15–20% of CADASIL cases referred for genetic testing have pathogenic mutations in NOTCH3. We hypothesise that other monogenic causes of CSVD may be causing a CADASIL-like CSVD phenotype.
Methods
To test this, we performed whole exome sequencing for 50 individuals suspected of having CADASIL, but did not exhibit a disease-causing mutation in NOTCH3, and applied targeted analysis of all monogenic forms of CSVD.
Results
This analysis identified three mutations affecting the Collagen type IV genes in three individuals likely to be causative of CSVD.
Conclusions
This suggests that screening for all monogenic forms of CSVD when one monogenic form is clinically suspected may improve diagnosis in clinically suspected monogenic CSVD. However, despite these findings, the majority of NOTCH3 negative CSVD cases did not have candidate mutations in known CSVD genes, suggesting that additional genetic factors contributing to the disease are yet to be identified.
{"title":"Targeted exonic sequencing identifies novel variants in a cerebral small vessel disease cohort","authors":"Paul J. Dunn , Neven Maksemous , Robert A. Smith , Heidi G. Sutherland , Larisa M. Haupt , Lyn R. Griffiths","doi":"10.1016/j.cca.2024.120120","DOIUrl":"10.1016/j.cca.2024.120120","url":null,"abstract":"<div><h3>Background and aims</h3><div>Cerebral small vessel diseases (CSVDs) are a set of conditions that affect the small blood vessels in the brain and can cause severe neurological pathologies such as stroke and vascular dementia. The most common monogenic CSVD is cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) which is caused by mutations in <em>NOTCH3.</em> However, only 15–20% of CADASIL cases referred for genetic testing have pathogenic mutations in <em>NOTCH3</em>. We hypothesise that other monogenic causes of CSVD may be causing a CADASIL-like CSVD phenotype.</div></div><div><h3>Methods</h3><div>To test this, we performed whole exome sequencing for 50 individuals suspected of having CADASIL, but did not exhibit a disease-causing mutation in <em>NOTCH3,</em> and applied targeted analysis of all monogenic forms of CSVD.</div></div><div><h3>Results</h3><div>This analysis identified three mutations affecting the Collagen type IV genes in three individuals likely to be causative of CSVD.</div></div><div><h3>Conclusions</h3><div>This suggests that screening for all monogenic forms of CSVD when one monogenic form is clinically suspected may improve diagnosis in clinically suspected monogenic CSVD. However, despite these findings, the majority of <em>NOTCH3</em> negative CSVD cases did not have candidate mutations in known CSVD genes, suggesting that additional genetic factors contributing to the disease are yet to be identified.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"567 ","pages":"Article 120120"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.cca.2024.120121
Samad Rastmanesh , Ilghar Zeinaly , Vahid Alivirdiloo , Ahmad Mobed , Mohammad Darvishi
The emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) bacteria poses a significant threat to global public health, complicating the management of infectious diseases and increasing morbidity and mortality rates. Rapid and sensitive detection of these resistant pathogens is crucial for effective treatment and infection control. This manuscript provides a comprehensive overview of various biosensor technologies developed for the rapid identification and quantification of MDR and XDR bacteria. We discuss the principles of operation, sensitivity, specificity, and practical applications of different biosensing platforms, including electrochemical, optical, and piezoelectric sensors. Additionally, we explore recent advancements in nanomaterials and microfluidics that enhance biosensor performance and enable point-of-care testing. The manuscript also addresses the challenges faced in the implementation of these technologies in clinical settings, such as regulatory hurdles and the need for standardization. A systematic literature review was conducted to identify relevant studies. Databases utilized include PubMed and Scopus, covering the time frame from 2015 to 2024. The literature screening criteria focused on the inclusion of only clinically validated studies to ensure the reliability and applicability of the findings. By highlighting the potential of biosensors to revolutionize the detection of drug-resistant bacteria, this work aims to inform researchers, clinicians, and policymakers about the critical role of innovative diagnostic tools in combating antibiotic resistance and improving patient outcomes.
{"title":"Biosensing for rapid detection of MDR, XDR and PDR bacteria","authors":"Samad Rastmanesh , Ilghar Zeinaly , Vahid Alivirdiloo , Ahmad Mobed , Mohammad Darvishi","doi":"10.1016/j.cca.2024.120121","DOIUrl":"10.1016/j.cca.2024.120121","url":null,"abstract":"<div><div>The emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) bacteria poses a significant threat to global public health, complicating the management of infectious diseases and increasing morbidity and mortality rates. Rapid and sensitive detection of these resistant pathogens is crucial for effective treatment and infection control. This manuscript provides a comprehensive overview of various biosensor technologies developed for the rapid identification and quantification of MDR and XDR bacteria. We discuss the principles of operation, sensitivity, specificity, and practical applications of different biosensing platforms, including electrochemical, optical, and piezoelectric sensors. Additionally, we explore recent advancements in nanomaterials and microfluidics that enhance biosensor performance and enable point-of-care testing. The manuscript also addresses the challenges faced in the implementation of these technologies in clinical settings, such as regulatory hurdles and the need for standardization. A systematic literature review was conducted to identify relevant studies. Databases utilized include PubMed and Scopus, covering the time frame from 2015 to 2024. The literature screening criteria focused on the inclusion of only clinically validated studies to ensure the reliability and applicability of the findings. By highlighting the potential of biosensors to revolutionize the detection of drug-resistant bacteria, this work aims to inform researchers, clinicians, and policymakers about the critical role of innovative diagnostic tools in combating antibiotic resistance and improving patient outcomes.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"567 ","pages":"Article 120121"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920756","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 : 2025-02-01DOI: 10.1016/j.cca.2025.120179
Arzoo Saini , Neeraj Dilbaghi , Neelam Yadav
Cancer remains one of the leading causes of morbidity and mortality globally, necessitating need for advancements of technologies for early therapeutics. Conventional detection methodologies often lag behind in terms of sensitivity, specificity, and cost-effectiveness, leading to delayed diagnosis and inadequate treatment. The need of advanced diagnostic techniques has considerably increased and led to the development of biosensors. Biosensing technologies offer several advantages over conventional methods hence, overcome limitations and improve diagnostic accuracy. Biosensors, particularly CRISPR-Cas based biosensors have emerged as a revolutionary technology for oncology diagnostics due to their high precision and adaptability. CRISPR-based biosensors provide remarkable precision, sensitivity, multiplexing capabilities, specificity, and rapidness for developing a cost-effective and portable point of care diagnostic device for cancer detection. In this review, we have discussed cancer pathogenicity, assessed the traditional detection techniques, and explored the advancements and advantages of biosensors, particularly CRISPR-based biosensors, in the detection of some major cancer types, namely lung, liver, colorectal, prostate, and cervical cancers. CRISPR-based biosensors represent a significant potential in cancer diagnostics, offering precise, cost-effective, and rapid detection of cancer biomarkers. The integration of CRISPR technology with biosensors holds substantial promise for enhancing early detection and improving patient outcomes in cancer diagnostics.
{"title":"CRISPR integrated biosensors: A new paradigm for cancer detection","authors":"Arzoo Saini , Neeraj Dilbaghi , Neelam Yadav","doi":"10.1016/j.cca.2025.120179","DOIUrl":"10.1016/j.cca.2025.120179","url":null,"abstract":"<div><div>Cancer remains one of the leading causes of morbidity and mortality globally, necessitating need for advancements of technologies for early therapeutics. Conventional detection methodologies often lag behind in terms of sensitivity, specificity, and cost-effectiveness, leading to delayed diagnosis and inadequate treatment. The need of advanced diagnostic techniques has considerably increased and led to the development of biosensors. Biosensing technologies offer several advantages over conventional methods hence, overcome limitations and improve diagnostic accuracy. Biosensors, particularly CRISPR-Cas based biosensors have emerged as a revolutionary technology for oncology diagnostics due to their high precision and adaptability. CRISPR-based biosensors provide remarkable precision, sensitivity, multiplexing capabilities, specificity, and rapidness for developing a cost-effective and portable point of care diagnostic device for cancer detection. In this review, we have discussed cancer pathogenicity, assessed the traditional detection techniques, and explored the advancements and advantages of biosensors, particularly CRISPR-based biosensors, in the detection of some major cancer types, namely lung, liver, colorectal, prostate, and cervical cancers. CRISPR-based biosensors represent a significant potential in cancer diagnostics, offering precise, cost-effective, and rapid detection of cancer biomarkers. The integration of CRISPR technology with biosensors holds substantial promise for enhancing early detection and improving patient outcomes in cancer diagnostics.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"569 ","pages":"Article 120179"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078762","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 : 2025-02-01DOI: 10.1016/j.cca.2024.120099
Anouk Olthof , Vera H. de Kleijne , Anita Boelen , Annemieke C. Heijboer
Background
An important aspect of the shift towards dried blood spots (DBS) as a sample matrix for laboratory measurements, is the availability of robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods that can reliably quantify analyte concentrations in DBS. The development and validation of these LC-MS/MS methods, however, concerns an extensive process, for which large amounts of DBS samples are required. DBS are usually obtained from capillary blood samples, but they can also be prepared from venous (residual) blood samples, which are widely available in clinical laboratories. Therefore, we aimed to determine whether DBS prepared from (residual) venous blood samples, collected in EDTA blood tubes, can be used for future development and validation of LC-MS/MS methods to quantify steroid hormones in DBS.
Methods
Capillary DBS and venous blood samples (EDTA tube and tube without additives) were collected from twenty healthy volunteers (12F/8M). From both venous blood samples, DBS were prepared volumetrically. Samples were analyzed using in-house developed LC-MS/MS methods for testosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), cortisol, cortisone, corticosterone, and for dehydroepiandrosterone sulfate (DHEA-S).
Results
DBS made from venous blood collected in EDTA tubes compared with capillary blood showed a correlation coefficient of ≥ 0.89 for all steroid hormones except corticosterone (0.67). DBS made from venous blood collected in tubes without additives showed a strong correlation with both DBS made from venous blood collected in EDTA tubes (≥0.97 for all steroid hormones) and capillary DBS (>0.90) except corticosterone (0.64).
Conclusion
DBS prepared from (residual) venous blood collected in EDTA blood tubes can be used for future development and validation of LC-MS/MS methods to quantify steroid hormones, except for corticosterone, in capillary DBS.
{"title":"Steroid hormone concentrations in dried blood spots: A comparison between capillary and venous blood samples","authors":"Anouk Olthof , Vera H. de Kleijne , Anita Boelen , Annemieke C. Heijboer","doi":"10.1016/j.cca.2024.120099","DOIUrl":"10.1016/j.cca.2024.120099","url":null,"abstract":"<div><h3>Background</h3><div>An important aspect of the shift towards dried blood spots (DBS) as a sample matrix for laboratory measurements, is the availability of robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods that can reliably quantify analyte concentrations in DBS. The development and validation of these LC-MS/MS methods, however, concerns an extensive process, for which large amounts of DBS samples are required. DBS are usually obtained from capillary blood samples, but they can also be prepared from venous (residual) blood samples, which are widely available in clinical laboratories. Therefore, we aimed to determine whether DBS prepared from (residual) venous blood samples, collected in EDTA blood tubes, can be used for future development and validation of LC-MS/MS methods to quantify steroid hormones in DBS.</div></div><div><h3>Methods</h3><div>Capillary DBS and venous blood samples (EDTA tube and tube without additives) were collected from twenty healthy volunteers (12F/8M). From both venous blood samples, DBS were prepared volumetrically. Samples were analyzed using in-house developed LC-MS/MS methods for testosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), cortisol, cortisone, corticosterone, and for dehydroepiandrosterone sulfate (DHEA-S).</div></div><div><h3>Results</h3><div>DBS made from venous blood collected in EDTA tubes compared with capillary blood showed a correlation coefficient of ≥ 0.89 for all steroid hormones except corticosterone (0.67). DBS made from venous blood collected in tubes without additives showed a strong correlation with both DBS made from venous blood collected in EDTA tubes (≥0.97 for all steroid hormones) and capillary DBS (>0.90) except corticosterone (0.64).</div></div><div><h3>Conclusion</h3><div>DBS prepared from (residual) venous blood collected in EDTA blood tubes can be used for future development and validation of LC-MS/MS methods to quantify steroid hormones, except for corticosterone, in capillary DBS.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"567 ","pages":"Article 120099"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.cca.2024.120110
Qiong Wu , Yumeng Gao , Xinyuan Zhang , Wenbo Cui , Shumin Li , Chunyu Luo , Dianjun Mo , Xinqi Cheng
Background
To explore the underlying causes of significant fluctuations in creatinine levels within three days due to transient and severe uric acid elevation, and to provide evidence for the interpretation of abnormal test results and clinical diagnosis and management.
Methods
The issues were resolved by retesting the samples, comparing results across different detection platforms, and analyzing the reaction curve. We comprehensively reviewed patients’ general conditions, imaging examinations, and treatments. Additionally, we compared pre- and post-admission changes in laboratory indices and performed an extensive literature search for comprehensive analysis.
Results
At the patient’s first visit, the levels of uric acid (UA), creatinine (CR), and urea (UREA) were measured at 891 umol/L, 211 umol/L, and 7.8 mmol/L, respectively using a Roche full-automatic biochemical analyzer and its corresponding reagents. Subsequent testing yielded 917 umol/L, 211 umol/L, and 8.3 mmol/L for UA, CR, and UREA. After retesting with the Beckman automatic biochemical analyzer and its corresponding reagents, the results for UA, CR, and UREA were 1013 umol/L, 221 umol/L, and 7.75 mmol/L, respectively. The results of the two detection systems were in agreement. A supplementary measurement of Cystatin C (CYSC) at 1.69 mg/L indicates renal dysfunction, consistent with the observed increase in CR levels and ruling out false elevation due to assay-related issues. At 48 h post-admission, untreated, the levels of blood UA, CR, and UREA decreased to 567umol/L, 77umol/L, and 5.1 mmol/L, respectively. Through literature review and analysis, it was determined that the transient abnormal increase in the patient’s creatinine level may be attributed to a substantial accumulation of uric acid crystals obstructing the renal tubules, leading to an impediment in renal tubular excretion which subsequently resolves spontaneously.
Conclusion
Severe hyperuricemia may result in a transient increase in blood CR levels and could potentially lead to the development of acute uric acid nephropathy. When a clinical laboratory encounters test results inconsistent with the clinical manifestations, it is essential to not only address any potential detection issues but also proactively investigate the underlying reasons for abnormal test results through comprehensive literature reviews and other rigorous methodologies.
{"title":"A case of transient elevation of creatinine caused by severe hyperuricemia","authors":"Qiong Wu , Yumeng Gao , Xinyuan Zhang , Wenbo Cui , Shumin Li , Chunyu Luo , Dianjun Mo , Xinqi Cheng","doi":"10.1016/j.cca.2024.120110","DOIUrl":"10.1016/j.cca.2024.120110","url":null,"abstract":"<div><h3>Background</h3><div>To explore the underlying causes of significant fluctuations in creatinine levels within three days due to transient and severe uric acid elevation, and to provide evidence for the interpretation of abnormal test results and clinical diagnosis and management.</div></div><div><h3>Methods</h3><div>The issues were resolved by retesting the samples, comparing results across different detection platforms, and analyzing the reaction curve. We comprehensively reviewed patients’ general conditions, imaging examinations, and treatments. Additionally, we compared pre- and post-admission changes in laboratory indices and performed an extensive literature search for comprehensive analysis.</div></div><div><h3>Results</h3><div>At the patient’s first visit, the levels of uric acid (UA), creatinine (CR), and urea (UREA) were measured at 891 umol/L, 211 umol/L, and 7.8 mmol/L, respectively using a Roche full-automatic biochemical analyzer and its corresponding reagents. Subsequent testing yielded 917 umol/L, 211 umol/L, and 8.3 mmol/L for UA, CR, and UREA. After retesting with the Beckman automatic biochemical analyzer and its corresponding reagents, the results for UA, CR, and UREA were 1013 umol/L, 221 umol/L, and 7.75 mmol/L, respectively. The results of the two detection systems were in agreement. A supplementary measurement of Cystatin C (CYSC) at 1.69 mg/L indicates renal dysfunction, consistent with the observed increase in CR levels and ruling out false elevation due to assay-related issues. At 48 h post-admission, untreated, the levels of blood UA, CR, and UREA decreased to 567umol/L, 77umol/L, and 5.1 mmol/L, respectively. Through literature review and analysis, it was determined that the transient abnormal increase in the patient’s creatinine level may be attributed to a substantial accumulation of uric acid crystals obstructing the renal tubules, leading to an impediment in renal tubular excretion which subsequently resolves spontaneously.</div></div><div><h3>Conclusion</h3><div>Severe hyperuricemia may result in a transient increase in blood CR levels and could potentially lead to the development of acute uric acid nephropathy. When a clinical laboratory encounters test results inconsistent with the clinical manifestations, it is essential to not only address any potential detection issues but also proactively investigate the underlying reasons for abnormal test results through comprehensive literature reviews and other rigorous methodologies.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"567 ","pages":"Article 120110"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902679","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 : 2025-02-01DOI: 10.1016/j.cca.2024.120115
Ergin Çam , Deniz İ. Topcu , Alev Kural
Introduction
To perform simulation studies on patient-based real-time quality control (PBRTQC) for aspartate aminotransferase (AST), iron (Fe), potassium (K), and thyrotropin (thyroid stimulating hormone, TSH) analytes, focusing on optimizing systematic error detection while minimizing data loss.
Methods
Clinical laboratory data for the four analytes were analyzed using various truncation methods. Among these methods, truncation limits corresponding to fixed percentiles (e.g., 1st–99th percentiles), reference change value based on between-individual biological variation (RCVg), and truncation limits derived from ± 3 standard deviations from the mean were included. These exclusion methods were applied using trimming or winsorization techniques, and transformation methods (logarithmic, square root, and Yeo–Johnson transformations) were employed to fit the data to a normal or near-normal distribution. Moving average techniques, such as exponentially weighted moving average (EWMA), were used with various block sizes to evaluate systematic error detection performance.
Results
Truncation based on RCVg improved performance for analytes with lower individuality indices—AST, potassium, and TSH—by enabling faster error detection. In contrast, methods either without truncation or with winsorization applied proved to be more effective for Fe. Among the moving average methods, EWMA with smaller block sizes (20 and 30) generally showed superior performance by detecting systematic errors more quickly.
Conclusion
RCVg-based truncation improves error detection for analytes with low individuality when combined with PBRTQC methods like EWMA, minimizing data loss. Tailored strategies considering analyte-specific individuality and distribution are essential for optimal error monitoring, warranting further validation in diverse clinical settings.
{"title":"Evaluation of current patient-based real-time quality control in clinical chemistry testing","authors":"Ergin Çam , Deniz İ. Topcu , Alev Kural","doi":"10.1016/j.cca.2024.120115","DOIUrl":"10.1016/j.cca.2024.120115","url":null,"abstract":"<div><h3>Introduction</h3><div>To perform simulation studies on patient-based real-time quality control (PBRTQC) for aspartate aminotransferase (AST), iron (Fe), potassium (K), and thyrotropin (thyroid stimulating hormone, TSH) analytes, focusing on optimizing systematic error detection while minimizing data loss.</div></div><div><h3>Methods</h3><div>Clinical laboratory data for the four analytes were analyzed using various truncation methods. Among these methods, truncation limits corresponding to fixed percentiles (e.g., 1st–99th percentiles), reference change value based on between-individual biological variation (RCVg), and truncation limits derived from ± 3 standard deviations from the mean were included. These exclusion methods were applied using trimming or winsorization techniques, and transformation methods (logarithmic, square root, and Yeo–Johnson transformations) were employed to fit the data to a normal or near-normal distribution. Moving average techniques, such as exponentially weighted moving average (EWMA), were used with various block sizes to evaluate systematic error detection performance.</div></div><div><h3>Results</h3><div>Truncation based on RCVg improved performance for analytes with lower individuality indices—AST, potassium, and TSH—by enabling faster error detection. In contrast, methods either without truncation or with winsorization applied proved to be more effective for Fe. Among the moving average methods, EWMA with smaller block sizes (20 and 30) generally showed superior performance by detecting systematic errors more quickly.</div></div><div><h3>Conclusion</h3><div>RCVg-based truncation improves error detection for analytes with low individuality when combined with PBRTQC methods like EWMA, minimizing data loss. Tailored strategies considering analyte-specific individuality and distribution are essential for optimal error monitoring, warranting further validation in diverse clinical settings.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"567 ","pages":"Article 120115"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913788","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}
Urinary bladder cancer (UBC) is a prominent malignancy with high morbidity and mortality worldwide. Addressing this public health challenge requires the development of effective diagnostic and prognostic indicators. MicroRNAs (miRNAs) are short, non-coding sequences of nucleic acid that modulate gene expression. Due to their high stability in biofluids such as serum, blood and urine, they have become a viable source for non-invasive diagnosis of pathologic processes in general and UBC specifically. This review comprehensively explores the role of urinary miRNAs, both free and exosomal, in the diagnosis, progression, staging, grading, metastasis, recurrence, survival, and treatment of UBC that includes chemo and immunotherapy. Specific miRNAs such as miR-21, miR-126, miR-143, and miR-145 have shown potential as diagnostic markers, whereas others like miR-200 family, miR-34a, miR-125b, and miR-221 are valuable for prognostic and predictive assessment. The review also discusses mechanistic insights into miRNA function and addresses the challenges of translating these findings into clinical practice. It aims to bridge the knowledge gap between academicians, researchers, and medical practitioners by providing a platform to understand, exchange, research, and infer information that could lead to novel therapeutic strategies for UBC. Integration of urinary miRNAs into routine clinical practice could significantly enhance the management of UBC, offering a pathway to personalized medicine and improved patient outcomes, particularly in India, where UBC incidence is increasing.
{"title":"Urinary miRNAs in bladder cancer","authors":"Amrit Chattopadhaya , Sukhad Kural , Ashish Verma , Priyamvada Gupta , Harshita Tiwari , Swati Singh , Anuja Thakur , Rajiv Kumar , Satya Narayan Sankhwar , Santosh Kumar Singh , Sakshi Agarwal , Sanjana Mehrotra , Vibhav Gautam , Lalit Kumar","doi":"10.1016/j.cca.2024.120113","DOIUrl":"10.1016/j.cca.2024.120113","url":null,"abstract":"<div><div>Urinary bladder cancer (UBC) is a prominent malignancy with high morbidity and mortality worldwide. Addressing this public health challenge requires the development of effective diagnostic and prognostic indicators. MicroRNAs (miRNAs) are short, non-coding sequences of nucleic acid that modulate gene expression. Due to their high stability in biofluids such as serum, blood and urine, they have become a viable source for non-invasive diagnosis of pathologic processes in general and UBC specifically. This review comprehensively explores the role of urinary miRNAs, both free and exosomal, in the diagnosis, progression, staging, grading, metastasis, recurrence, survival, and treatment of UBC that includes chemo and immunotherapy. Specific miRNAs such as miR-21, miR-126, miR-143, and miR-145 have shown potential as diagnostic markers, whereas others like miR-200 family, miR-34a, miR-125b, and miR-221 are valuable for prognostic and predictive assessment. The review also discusses mechanistic insights into miRNA function and addresses the challenges of translating these findings into clinical practice. It aims to bridge the knowledge gap between academicians, researchers, and medical practitioners by providing a platform to understand, exchange, research, and infer information that could lead to novel therapeutic strategies for UBC. Integration of urinary miRNAs into routine clinical practice could significantly enhance the management of UBC, offering a pathway to personalized medicine and improved patient outcomes, particularly in India, where UBC incidence is increasing.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"567 ","pages":"Article 120113"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143173819","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 : 2025-02-01DOI: 10.1016/j.cca.2024.120066
Yi Li , Liangqiong Zhou , Kangyi Wang , Xiaoge Luo , Liqun Zhang , Kaiyong Cai
Marginal zone lymphoma (MZL) of the lung is an indolent B-cell lymphoma. The peripheral blood of most patients with pulmonary MZL contains low or undetectable monoclonal immunoglobulin (M protein) levels. In this case, the clinical laboratory discovered that the pulmonary MZL patient not only associated with high concentration of monoclonal IgG-type protein but also exhibited obvious gel formation characteristics that interfered with clinical biochemistry tests. Thus, the role of M protein in total bilirubin determination was examined in this study. Total bilirubin detection curve difference comparison between monoclonal IgG protein and polyclonal immunoglobulin, interference experiments, and dilution elimination experiments were conducted. These experiments revealed not only a positive correlation between M protein interference in bilirubin detection with its concentration, but also M protein-specific interference distinct from polyclonal immunoglobulin. We employed the R and EmpowerStat statistical systems to evaluate the correlation between serum monoclonal protein and total bilirubin absorbance curve data. Multivariate analysis revealed a nonlinear correlation between with globulin (GLB) and square root transformed curve optical density (OD) data. The receiver operating characteristic (ROC) curve analysis indicated an area under the curve (AUC) of 0.852 for the GLB ≥ 31.9 g/L subgroup using combined curve indicators. Our findings can enhance clinical M protein screening and scientific assessment of the populations requiring serum protein electrophoresis testing, thereby reducing the rate of missed diagnoses in the M protein population.
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Pub Date : 2025-02-01DOI: 10.1016/j.cca.2024.120094
Mohamed J. Saadh , Faris Anad Muhammad , Rafid Jihad Albadr , Ashok Kumar Bishoyi , Suhas Ballal , Lakshay Bareja , K.Satyam Naidu , Jasur Rizaev , Waam Mohammed Taher , Mariem Alwan , Mahmood Jasem Jawad , Ali M. Ali Al-Nuaimi
Early detection and management of cardiovascular diseases (CVDs) are crucial for patient survival and long-term health. CVD biomarkers such as cardiac Troponin-I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase MB (CK-MB), Galectin-3 (Gal-3), etc are released into the circulation following heart muscle injury, ie, acute myocardial infarction (AMI). Biosensor technology including the use of nanoparticles can be designed to target specific biomarkers associated with CVD, enabling early detection and more rapid intervention to decrease morbidity and mortality. To date, with the combination of developed nanoparticles, several optical and electrochemical-based biosensors have successfully been used detection of CVD biomarkers. Nanomaterials, when introduced as the modifiers of sensor surfaces like electrodes and gold chips, can result in the more comprehensive and more effective immobilization of capture molecules, ie, antibodies, aptamers and other ligands, due to their large surface area. In recent years, inorganic nanoparticles have regularly been used in the production of biosensors mostly due to their excellent response intensification, adaptable functionalization chemistry, shape control, good biocompatibility, and great stability. In this review, we discuss the application of different kinds of nanoparticles for the sensitive and specific detection of CVD biomarkers.
心血管疾病（cvd）的早期发现和管理对患者的生存和长期健康至关重要。心血管疾病的生物标志物如心肌肌钙蛋白- i （cTnI）、n端前脑利钠肽（NT-proBNP）、肌酸激酶MB （CK-MB）、半乳糖凝集素-3 （Gal-3）等在心肌损伤即急性心肌梗死（AMI）后释放到循环中。包括使用纳米颗粒在内的生物传感器技术可以设计成针对与心血管疾病相关的特定生物标志物，从而实现早期检测和更快速的干预，以降低发病率和死亡率。到目前为止，随着纳米颗粒的结合，一些基于光学和电化学的生物传感器已经成功地用于CVD生物标志物的检测。纳米材料作为电极和金芯片等传感器表面的修饰剂，由于其较大的表面积，可以更全面、更有效地固定捕获分子，即抗体、适体和其他配体。近年来，无机纳米颗粒由于其优异的响应强化、适应性强的功能化化学、形状控制、良好的生物相容性和良好的稳定性而被广泛应用于生物传感器的生产中。本文综述了不同类型纳米颗粒在心血管疾病生物标志物检测中的应用。
{"title":"Nanoparticle biosensors for cardiovascular disease detection","authors":"Mohamed J. Saadh , Faris Anad Muhammad , Rafid Jihad Albadr , Ashok Kumar Bishoyi , Suhas Ballal , Lakshay Bareja , K.Satyam Naidu , Jasur Rizaev , Waam Mohammed Taher , Mariem Alwan , Mahmood Jasem Jawad , Ali M. Ali Al-Nuaimi","doi":"10.1016/j.cca.2024.120094","DOIUrl":"10.1016/j.cca.2024.120094","url":null,"abstract":"<div><div>Early detection and management of cardiovascular diseases (CVDs) are crucial for patient survival and long-term health. CVD biomarkers such as cardiac Troponin-I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase MB (CK-MB), Galectin-3 (Gal-3), etc are released into the circulation following heart muscle injury, ie, acute myocardial infarction (AMI). Biosensor technology including the use of nanoparticles can be designed to target specific biomarkers associated with CVD, enabling early detection and more rapid intervention to decrease morbidity and mortality. To date, with the combination of developed nanoparticles, several optical and electrochemical-based biosensors have successfully been used detection of CVD biomarkers. Nanomaterials, when introduced as the modifiers of sensor surfaces like electrodes and gold chips, can result in the more comprehensive and more effective immobilization of capture molecules, ie, antibodies, aptamers and other ligands, due to their large surface area. In recent years, inorganic nanoparticles have regularly been used in the production of biosensors mostly due to their excellent response intensification, adaptable functionalization chemistry, shape control, good biocompatibility, and great stability. In this review, we discuss the application of different kinds of nanoparticles for the sensitive and specific detection of CVD biomarkers.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"567 ","pages":"Article 120094"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834163","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 : 2025-02-01DOI: 10.1016/j.cca.2024.120095
Yuemeng Li , Wenxiu He , Yu Zhou , Haotian Chen , Pengyue You , Danni Mu , Yichen Ma , Yumeng Gao , Kaiduo Xu , Haitao Dong , Xinqi Cheng
Sjogren’s disease (SjD) in children is a rare chronic autoimmune disease not fully recognized due to clinical manifestations different from adults. As such, new objective indicators are needed to supplement existing markers and assist in diagnosis. This review summarizes pathogenesis of SjD in children, current diagnostic criteria and research progress in laboratory diagnosis including serologic testing, saliva and tear analysis, histopathological examination as well as emerging markers of interest.
{"title":"Advances in laboratory diagnosis of Sjogren’s disease in children","authors":"Yuemeng Li , Wenxiu He , Yu Zhou , Haotian Chen , Pengyue You , Danni Mu , Yichen Ma , Yumeng Gao , Kaiduo Xu , Haitao Dong , Xinqi Cheng","doi":"10.1016/j.cca.2024.120095","DOIUrl":"10.1016/j.cca.2024.120095","url":null,"abstract":"<div><div>Sjogren’s disease (SjD) in children is a rare chronic autoimmune disease not fully recognized due to clinical manifestations different from adults. As such, new objective indicators are needed to supplement existing markers and assist in diagnosis. This review summarizes pathogenesis of SjD in children, current diagnostic criteria and research progress in laboratory diagnosis including serologic testing, saliva and tear analysis, histopathological examination as well as emerging markers of interest.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"567 ","pages":"Article 120095"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833800","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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