Veronica Buia, Martina Bonacini, Cecilia Catellani, Alessandro Rossi, Francesco Muratore, Carlo Salvarani, Alessandro Zerbini, Stefania Croci
Background
Soluble immune checkpoints (sICs) are emerging as possible serum and plasma biomarkers in cancer and immune-mediated diseases, but little is known about the impact of the matrix type in sIC detection. This study aimed to assess whether sIC measurements are comparable between serum and EDTA-plasma samples.
Methods
A cohort of 38 healthy subjects was enrolled. A multiplex bead-based assay was used to evaluate a panel of 17 sICs (CD137, 4-1BBL, CD27, CTLA4/CD152, CD80, CD40, CD40L, GITR, GITRL, ICOSL, IDO, LAG3, PD-1, PD-L1, PD-L2, TIM3, and VISTA) in paired serum and plasma-EDTA samples. The detection frequencies, concentrations, and correlations of each sIC were analyzed by comparing the two matrices.
Results
Soluble CD137, CD152, CD40, and LAG3 were detected more frequently in plasma, while soluble CD40L was detected predominantly in serum. The concentrations of soluble 4-1BBL, CD27, PD-1, VISTA were higher in plasma, while the concentrations of soluble PD-L2 were higher in serum. The concentrations of soluble CD80, GITR, GITRL, ICOSL, IDO, and TIM3 were comparable between serum and plasma. Soluble CD27, CD80, GITRL showed a significant positive, slight correlation between plasmatic and serum concentrations.
Conclusion
Except for soluble CD80, the detection of the other sICs by the bead-based assay was influenced by the matrix type. The evaluation of the best matrix for sICs should be considered before starting clinical studies.
{"title":"Matrix Type Influences the Levels of Soluble Immune Checkpoints","authors":"Veronica Buia, Martina Bonacini, Cecilia Catellani, Alessandro Rossi, Francesco Muratore, Carlo Salvarani, Alessandro Zerbini, Stefania Croci","doi":"10.1002/jcla.70153","DOIUrl":"10.1002/jcla.70153","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Soluble immune checkpoints (sICs) are emerging as possible serum and plasma biomarkers in cancer and immune-mediated diseases, but little is known about the impact of the matrix type in sIC detection. This study aimed to assess whether sIC measurements are comparable between serum and EDTA-plasma samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cohort of 38 healthy subjects was enrolled. A multiplex bead-based assay was used to evaluate a panel of 17 sICs (CD137, 4-1BBL, CD27, CTLA4/CD152, CD80, CD40, CD40L, GITR, GITRL, ICOSL, IDO, LAG3, PD-1, PD-L1, PD-L2, TIM3, and VISTA) in paired serum and plasma-EDTA samples. The detection frequencies, concentrations, and correlations of each sIC were analyzed by comparing the two matrices.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Soluble CD137, CD152, CD40, and LAG3 were detected more frequently in plasma, while soluble CD40L was detected predominantly in serum. The concentrations of soluble 4-1BBL, CD27, PD-1, VISTA were higher in plasma, while the concentrations of soluble PD-L2 were higher in serum. The concentrations of soluble CD80, GITR, GITRL, ICOSL, IDO, and TIM3 were comparable between serum and plasma. Soluble CD27, CD80, GITRL showed a significant positive, slight correlation between plasmatic and serum concentrations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Except for soluble CD80, the detection of the other sICs by the bead-based assay was influenced by the matrix type. The evaluation of the best matrix for sICs should be considered before starting clinical studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.70153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145855911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elizabeth Huamanyalli-Villar, Julia Moya-Naranjo, Billy Sanchez-Jacinto, Julio Espíritu-Antezano, Jaime Rosales-Rimache
Introduction
Flow cytometry (FC) enables rapid identification of cell lineages based on their fluorescent and light-scattering properties, playing a critical role in diagnosing and monitoring oncohematological diseases. Standardization of procedures in spectral FC is essential for method validation studies.
Methods
We designed a comparative study using 21 blood samples from healthy donors. Three commercial lysing solutions used in spectral FC immunophenotyping were evaluated. Samples were stained with a panel of eight antibody-conjugated fluorochromes and aliquoted for assessment with each lysing solution (Excellyse I, Excellyse Easy, and Tombo RBC Lysis Buffer), following the manufacturers' protocols. Data acquisition was performed using a full-spectrum flow cytometer.
Results
An average cell loss of 31.4% was observed, with no statistically significant differences between lysing solutions, although Excellyse I showed lower cell loss under the no-wash protocol. This reagent also achieved superior resolution in distinguishing lymphocytes from debris. It demonstrated the lowest coefficients of variation in both scatter and fluorescence parameters of leukocyte populations, highlighting its ability to preserve the optical characteristics of stained cells. RBC-T performed well in specific channels such as APC and PE-Cy7, whereas Excellyse Easy produced a resolution comparable to Excellyse I, albeit with greater signal dispersion.
Conclusion
Excellyse I demonstrated the best overall performance, with greater cell preservation, clearer population resolution, and lower variability in scatter and fluorescence. Nonetheless, Excellyse Easy may still be considered a viable alternative.
{"title":"Analytical Comparison of Three Commercial Lysing Reagents for Full-Spectrum Flow Cytometric Immunophenotyping","authors":"Elizabeth Huamanyalli-Villar, Julia Moya-Naranjo, Billy Sanchez-Jacinto, Julio Espíritu-Antezano, Jaime Rosales-Rimache","doi":"10.1002/jcla.70140","DOIUrl":"10.1002/jcla.70140","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Flow cytometry (FC) enables rapid identification of cell lineages based on their fluorescent and light-scattering properties, playing a critical role in diagnosing and monitoring oncohematological diseases. Standardization of procedures in spectral FC is essential for method validation studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We designed a comparative study using 21 blood samples from healthy donors. Three commercial lysing solutions used in spectral FC immunophenotyping were evaluated. Samples were stained with a panel of eight antibody-conjugated fluorochromes and aliquoted for assessment with each lysing solution (Excellyse I, Excellyse Easy, and Tombo RBC Lysis Buffer), following the manufacturers' protocols. Data acquisition was performed using a full-spectrum flow cytometer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>An average cell loss of 31.4% was observed, with no statistically significant differences between lysing solutions, although Excellyse I showed lower cell loss under the no-wash protocol. This reagent also achieved superior resolution in distinguishing lymphocytes from debris. It demonstrated the lowest coefficients of variation in both scatter and fluorescence parameters of leukocyte populations, highlighting its ability to preserve the optical characteristics of stained cells. RBC-T performed well in specific channels such as APC and PE-Cy7, whereas Excellyse Easy produced a resolution comparable to Excellyse I, albeit with greater signal dispersion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Excellyse I demonstrated the best overall performance, with greater cell preservation, clearer population resolution, and lower variability in scatter and fluorescence. Nonetheless, Excellyse Easy may still be considered a viable alternative.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bronchiectasis, a leading chronic airway disease, often worsens due to infections, making rapid pathogen detection crucial. This study aims to evaluate the diagnostic value of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) in identifying pathogens in moderate-to-severe bronchiectasis and compare its advantages to conventional methods.
Methods
Fifty-two hospitalized patients initially diagnosed with moderate-to-severe bronchiectasis at Foshan Hospital of Traditional Chinese Medicine from May 2022 to March 2024 were enrolled. Clinical data and BALF samples were collected and subjected to both mNGS and conventional pathogen detection methods. The differences and concordance in pathogen distribution between mNGS and conventional methods, as well as their diagnostic performance, were compared.
Results
The positive detection rate of pathogens by mNGS was significantly higher than that by conventional methods (p < 0.01). Both methods predominantly identified bacterial pathogens, with Pseudomonas aeruginosa being the most common bacterium and Aspergillus fumigatus the most frequent fungus. However, mNGS detected a broader range of pathogens and demonstrated superior sensitivity in identifying mixed infections (p < 0.01). The sensitivity of mNGS was 66% higher than that of conventional methods (p < 0.01), and the complete concordance rate between the two methods in double-positive cases was 41.18%. Additionally, mNGS-guided anti-infection treatment significantly improves patient symptoms, reduces hospital stays, and lowers costs (p < 0.05).
Conclusions
Compared with conventional methods, BALF mNGS demonstrates higher sensitivity, a greater positive detection rate, superior capability in identifying mixed infections, improved diagnostic performance, and a better guiding effect on anti-infection treatment in moderate-to-severe bronchiectasis.
{"title":"The Application Value of Bronchoalveolar Lavage Fluid Metagenomic Next-Generation Sequencing in Moderate-to-Severe Bronchiectasis","authors":"Jiachun Li, Qiuping Quan, Junshan Chen, Xiaoyun Jian, Weijie Zhan, Jingmin Wang, Rongbin Jiang","doi":"10.1002/jcla.70156","DOIUrl":"10.1002/jcla.70156","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bronchiectasis, a leading chronic airway disease, often worsens due to infections, making rapid pathogen detection crucial. This study aims to evaluate the diagnostic value of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) in identifying pathogens in moderate-to-severe bronchiectasis and compare its advantages to conventional methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fifty-two hospitalized patients initially diagnosed with moderate-to-severe bronchiectasis at Foshan Hospital of Traditional Chinese Medicine from May 2022 to March 2024 were enrolled. Clinical data and BALF samples were collected and subjected to both mNGS and conventional pathogen detection methods. The differences and concordance in pathogen distribution between mNGS and conventional methods, as well as their diagnostic performance, were compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The positive detection rate of pathogens by mNGS was significantly higher than that by conventional methods (<i>p</i> < 0.01). Both methods predominantly identified bacterial pathogens, with <i>Pseudomonas aeruginosa</i> being the most common bacterium and <i>Aspergillus fumigatus</i> the most frequent fungus. However, mNGS detected a broader range of pathogens and demonstrated superior sensitivity in identifying mixed infections (<i>p</i> < 0.01). The sensitivity of mNGS was 66% higher than that of conventional methods (<i>p</i> < 0.01), and the complete concordance rate between the two methods in double-positive cases was 41.18%. Additionally, mNGS-guided anti-infection treatment significantly improves patient symptoms, reduces hospital stays, and lowers costs (<i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Compared with conventional methods, BALF mNGS demonstrates higher sensitivity, a greater positive detection rate, superior capability in identifying mixed infections, improved diagnostic performance, and a better guiding effect on anti-infection treatment in moderate-to-severe bronchiectasis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Accurate hematological analysis relies heavily on the integrity of blood samples, which can be compromised by pre-analytical errors such as hemolysis and clotting. This study aimed to determine the frequency and associated factors of clotted and hemolyzed samples in selected hospitals in South Gonder, Ethiopia.
Methods
This institutionally based cross-sectional study was conducted from September to December 2023 in northwestern Ethiopia at the medical hematology laboratories of selected South Gonder Zone hospitals. Debre Tabor's specialized referral hospital was selected. Addis Zemen and Nefas Mewcha primary hospitals were chosen at random.
Results
Among the 2331 test samples, 829 (35.6%) were clotted, and 269 (11.5%) were hemolyzed. We found a significant association of clotting with contamination, inadequate sample volume, puncture site other than the median cubital region, more than three attempts to collect blood, and the use of a partially filled collection tube when attempting another vein puncture.
Conclusion
On the basis of our observations, the findings presented here have a significant impact on patient diagnosis and treatment, leading to delayed or inaccurate diagnoses, inappropriate treatment decisions, increased risk of adverse events, and increased healthcare costs.
{"title":"Frequency and Associated Factors of Clotted and Hemolyzed Samples in South Gonder Hospitals, Ethiopia: A Multicenter Cross-Sectional Study, 2023","authors":"Birhanemaskal Malkamu, Getaneh Atikilt Yemata, Andargachew Almaw, Ayenew Assefa, Birhanu Getie, Teklehaimanot Kiros, Mulat Erkihun, Shewaneh Damtie, Tegenaw Tiruneh, Berhanu Abebaw Mekonnen, Meron Asmamaw Alemayehu, Abraham Teym, Abathun Temesgen, Gashaw Melkie Bayeh, Almaw Genet Yeshiwas, Rahel Mulatie Anteneh, Melkamu Aderajew Zemene, Tesfaneh Shimels, Chalachew Yenew, Wolde Melese Ayele, Ahmed Fentaw Ahmed, Assefa Andargie Kassa, Tilahun Degu Tsega, Chalachew Abiyu Ayalew, Sintayehu Simie Tsega, Zeamanuel Anteneh Yigzaw, Amare Genetu Ejigu, Wondimnew Desalegn Addis, Getasew Yirdaw, Kalaab Esubalew Sharew, Daniel Adane, Samuel Berihun Dagnew, Gebyaw Arega, Habitamu Mekonen","doi":"10.1002/jcla.70148","DOIUrl":"10.1002/jcla.70148","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Accurate hematological analysis relies heavily on the integrity of blood samples, which can be compromised by pre-analytical errors such as hemolysis and clotting. This study aimed to determine the frequency and associated factors of clotted and hemolyzed samples in selected hospitals in South Gonder, Ethiopia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This institutionally based cross-sectional study was conducted from September to December 2023 in northwestern Ethiopia at the medical hematology laboratories of selected South Gonder Zone hospitals. Debre Tabor's specialized referral hospital was selected. Addis Zemen and Nefas Mewcha primary hospitals were chosen at random.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 2331 test samples, 829 (35.6%) were clotted, and 269 (11.5%) were hemolyzed. We found a significant association of clotting with contamination, inadequate sample volume, puncture site other than the median cubital region, more than three attempts to collect blood, and the use of a partially filled collection tube when attempting another vein puncture.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>On the basis of our observations, the findings presented here have a significant impact on patient diagnosis and treatment, leading to delayed or inaccurate diagnoses, inappropriate treatment decisions, increased risk of adverse events, and increased healthcare costs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bo Liu, Zhaodong Sun, Kaiyong Chen, Na Wang, Jibao Qin, Dengli Feng, Fumeng Yang, Jiaping Wang, Huiyi Wu, Ming Hu
Background
Quality control (QC) is critical for ensuring the accuracy and reliability of hematology testing. Traditional QC strategies, however, are often limited in their ability to provide timely detection of analytical errors and to adapt to complex, real-world laboratory conditions.
Methods
In this multicenter study, we applied the Six Sigma quality management framework to systematically evaluate the performance of five hematology parameters (Hb, WBC, RBC, HCT, and PLT). To enhance QC monitoring, we established a dynamic quality control strategy that integrates moving average (MA) monitoring with a long short-term memory (LSTM) predictive model. Patient sample data were incorporated alongside routine QC data to validate clinical adaptability.
Results
Sigma metrics revealed marked performance differences among the parameters, with Hb and WBC achieving world-class or excellent performance (σ ≥ 6), while PLT showed relatively lower stability. The combined MA–LSTM approach significantly improved sensitivity for error detection while reducing false positives compared with conventional rule-based QC. The dynamic model demonstrated robust predictive ability, enabling real-time QC monitoring across multiple laboratory sites.
Conclusion
By combining Six Sigma evaluation, MA monitoring, and LSTM modeling, we propose a dynamic QC strategy that overcomes key limitations of conventional quality control methods. This approach provides laboratories with an intelligent, proactive, and clinically adaptable solution for improving the reliability of hematology testing and ensuring higher quality patient care.
{"title":"Evaluation of a Six Sigma-Based Dynamic Quality Control Strategy for Hematology Analysis: A Multicenter Study","authors":"Bo Liu, Zhaodong Sun, Kaiyong Chen, Na Wang, Jibao Qin, Dengli Feng, Fumeng Yang, Jiaping Wang, Huiyi Wu, Ming Hu","doi":"10.1002/jcla.70138","DOIUrl":"10.1002/jcla.70138","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Quality control (QC) is critical for ensuring the accuracy and reliability of hematology testing. Traditional QC strategies, however, are often limited in their ability to provide timely detection of analytical errors and to adapt to complex, real-world laboratory conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this multicenter study, we applied the Six Sigma quality management framework to systematically evaluate the performance of five hematology parameters (Hb, WBC, RBC, HCT, and PLT). To enhance QC monitoring, we established a dynamic quality control strategy that integrates moving average (MA) monitoring with a long short-term memory (LSTM) predictive model. Patient sample data were incorporated alongside routine QC data to validate clinical adaptability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sigma metrics revealed marked performance differences among the parameters, with Hb and WBC achieving world-class or excellent performance (<i>σ</i> ≥ 6), while PLT showed relatively lower stability. The combined MA–LSTM approach significantly improved sensitivity for error detection while reducing false positives compared with conventional rule-based QC. The dynamic model demonstrated robust predictive ability, enabling real-time QC monitoring across multiple laboratory sites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>By combining Six Sigma evaluation, MA monitoring, and LSTM modeling, we propose a dynamic QC strategy that overcomes key limitations of conventional quality control methods. This approach provides laboratories with an intelligent, proactive, and clinically adaptable solution for improving the reliability of hematology testing and ensuring higher quality patient care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Calcium (Ca), inorganic phosphorus (IP), and zinc (Zn) are essential minerals in human milk for infant growth and health. Current methods for determining minerals in human milk, including inductively coupled plasma atomic emission spectroscopy (ICP-AES), are time-consuming and laborious. This study aimed to measure Ca, IP, and Zn in human milk by a rapid, simple, and accurate method using clinical laboratory reagents based on a colorimetric assay.
Methods
71 pooled donor human milk (DHM) samples were collected after Holder pasteurization. The only pretreatment required was dilution, and samples were diluted 5-fold. Ca, IP, and Zn concentrations were measured by colorimetric assay using an automated analyzer. The results were validated in terms of repeatability, recovery, and comparison with ICP-AES.
Results
The coefficients of variation for intra-assay precision were 0.7%–1.9% for Ca, 1.5%–2.1% for IP, and 0.8%–7.4% for Zn. The recovery rates ranged from 104.1% to 104.9% for Ca, 96.3%–103.4% for IP, and 94.5%–103.2% for Zn with high, medium, and low concentrations. There were significant correlations between Ca, IP, and Zn levels determined by colorimetric assay and Ca, total P, and Zn levels determined by ICP-AES (Ca: r = 0.944, IP: r = 0.463, and Zn: r = 0.949, p < 0.001, n = 58).
Conclusion
These results confirm the precision and accuracy of the colorimetric assay using clinical laboratory reagents for determining Ca, IP, and Zn levels in human milk. Its use may contribute to the rapid and easy provision of appropriate DHM to preterm infants.
背景：钙（Ca）、无机磷（IP）和锌（Zn）是母乳中对婴儿生长和健康至关重要的矿物质。目前测定母乳中矿物质的方法，包括电感耦合等离子体原子发射光谱（ICP-AES），耗时且费力。本研究旨在利用临床实验室试剂基于比色法快速、简单、准确地测定人乳中的钙、IP和锌。方法：收集71份经霍尔德巴氏消毒后的供乳样本。唯一需要的预处理是稀释，样品被稀释5倍。Ca， IP和Zn浓度采用自动分析仪比色法测定。结果在重复性、回收率以及与ICP-AES的比较方面得到了验证。结果：Ca、IP、Zn的测定内精密度变异系数分别为0.7% ~ 1.9%、1.5% ~ 2.1%和0.8% ~ 7.4%。在高、中、低浓度条件下，Ca回收率为104.1% ~ 104.9%，IP回收率为96.3% ~ 103.4%，Zn回收率为94.5% ~ 103.2%。比色法测定的Ca、IP、Zn含量与ICP-AES测定的Ca、总P、Zn含量存在显著相关性（Ca: r = 0.944, IP: r = 0.463, Zn: r = 0.949， P）。结论：采用临床实验室试剂进行比色法测定人乳中Ca、IP、Zn含量具有较好的精密度和准确性。它的使用可能有助于快速和容易地提供适当的DHM给早产儿。
{"title":"A Rapid Colorimetric Method for Determining Calcium, Inorganic Phosphorus, and Zinc in Human Milk Using Clinical Laboratory Reagents","authors":"Miori Tanaka, Misaki Mochida, Midori Date, Katsumi Mizuno","doi":"10.1002/jcla.70146","DOIUrl":"10.1002/jcla.70146","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Calcium (Ca), inorganic phosphorus (IP), and zinc (Zn) are essential minerals in human milk for infant growth and health. Current methods for determining minerals in human milk, including inductively coupled plasma atomic emission spectroscopy (ICP-AES), are time-consuming and laborious. This study aimed to measure Ca, IP, and Zn in human milk by a rapid, simple, and accurate method using clinical laboratory reagents based on a colorimetric assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>71 pooled donor human milk (DHM) samples were collected after Holder pasteurization. The only pretreatment required was dilution, and samples were diluted 5-fold. Ca, IP, and Zn concentrations were measured by colorimetric assay using an automated analyzer. The results were validated in terms of repeatability, recovery, and comparison with ICP-AES.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The coefficients of variation for intra-assay precision were 0.7%–1.9% for Ca, 1.5%–2.1% for IP, and 0.8%–7.4% for Zn. The recovery rates ranged from 104.1% to 104.9% for Ca, 96.3%–103.4% for IP, and 94.5%–103.2% for Zn with high, medium, and low concentrations. There were significant correlations between Ca, IP, and Zn levels determined by colorimetric assay and Ca, total P, and Zn levels determined by ICP-AES (Ca: <i>r</i> = 0.944, IP: <i>r</i> = 0.463, and Zn: <i>r</i> = 0.949, <i>p</i> < 0.001, <i>n</i> = 58).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results confirm the precision and accuracy of the colorimetric assay using clinical laboratory reagents for determining Ca, IP, and Zn levels in human milk. Its use may contribute to the rapid and easy provision of appropriate DHM to preterm infants.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Youn-Ji Hong, Misun Yang, Hyeon Jeong Kwon, Jooyoung Cha, Ja-Hyun Jang, Sung Eun Wang, Eun Sun Lee, Mi-Ae Jang
Background
Schaaf–Yang syndrome (SYS) is a rare genetic disorder caused by pathogenic variants in MAGEL2, a paternally expressed and maternally imprinted gene on 15q11.2. Genetic diagnosis of SYS is challenging due to clinical features that overlap with those of other rare syndromic disorders and limited clinician awareness regarding the diagnosis of imprinting disorders.
Methods
We present a neonate presenting with respiratory distress and joint contractures, diagnosed with SYS through comprehensive genetic testing. Whole-exome sequencing identified a heterozygous de novo nonsense variant in MAGEL2 c.2092G>T [p.(Gly698Ter)]. To confirm the paternal origin of this variant, methylation-sensitive restriction enzyme digestion followed by long-range PCR, nested PCR, and Sanger sequencing was performed.
Results
The MAGEL2 c.2092G>T was absent in both parents, indicating a de novo mutation. Methylation analysis confirmed that the variant resided on the paternal allele, establishing its pathogenicity. A proband diagnostic approach integrating sequence analysis, parental testing, and methylation assays effectively delineates MAGEL2 variants and their inheritance patterns.
Conclusion
Our study underscores the importance of combining genomic sequencing with methylation assay to accurately diagnose SYS, especially for de novo variants. The proposed diagnostic workflow facilitates reliable identification of pathogenic MAGEL2 mutations and their parental origin, improving diagnostic precision in clinical settings. Further research is needed to elucidate the molecular mechanisms underlying MAGEL2-related disorders and develop targeted therapies.
{"title":"Identification of a De Novo MAGEL2 Pathogenic Variant in Schaaf–Yang Syndrome and the Importance of Paternal Allele Confirmation","authors":"Youn-Ji Hong, Misun Yang, Hyeon Jeong Kwon, Jooyoung Cha, Ja-Hyun Jang, Sung Eun Wang, Eun Sun Lee, Mi-Ae Jang","doi":"10.1002/jcla.70152","DOIUrl":"10.1002/jcla.70152","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Schaaf–Yang syndrome (SYS) is a rare genetic disorder caused by pathogenic variants in <i>MAGEL2</i>, a paternally expressed and maternally imprinted gene on 15q11.2. Genetic diagnosis of SYS is challenging due to clinical features that overlap with those of other rare syndromic disorders and limited clinician awareness regarding the diagnosis of imprinting disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We present a neonate presenting with respiratory distress and joint contractures, diagnosed with SYS through comprehensive genetic testing. Whole-exome sequencing identified a heterozygous <i>de novo</i> nonsense variant in <i>MAGEL2</i> c.2092G>T [p.(Gly698Ter)]. To confirm the paternal origin of this variant, methylation-sensitive restriction enzyme digestion followed by long-range PCR, nested PCR, and Sanger sequencing was performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The <i>MAGEL2</i> c.2092G>T was absent in both parents, indicating a <i>de novo</i> mutation. Methylation analysis confirmed that the variant resided on the paternal allele, establishing its pathogenicity. A proband diagnostic approach integrating sequence analysis, parental testing, and methylation assays effectively delineates <i>MAGEL2</i> variants and their inheritance patterns.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study underscores the importance of combining genomic sequencing with methylation assay to accurately diagnose SYS, especially for <i>de novo</i> variants. The proposed diagnostic workflow facilitates reliable identification of pathogenic <i>MAGEL2</i> mutations and their parental origin, improving diagnostic precision in clinical settings. Further research is needed to elucidate the molecular mechanisms underlying <i>MAGEL2</i>-related disorders and develop targeted therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12888762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cryptosporidium spp. is an important pathogen responsible for severe diarrheal illness, especially in children, and is transmitted by various modes. The present work is aimed at categorizing Cryptosporidium spp. infection and determining associated risk factors by ML on a known dataset of diarrhea among children.
Materials and Methods
For classification, we used random forest and bagging CART trees. Model discrimination was measured by accuracy, balanced accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1-score. Then, a 5-fold cross-validation method was used to verify the reliability of the model. Importance values were also calculated to identify the most important risk factors for infection.
Results
The bagged CART model emerged as the best among the models applied, with slightly better classification. For this model, performance metrics were: accuracy (87.2%), balanced accuracy (56.3%), sensitivity (97.2%), specificity (15.4%), positive predictive value (89.3%), negative predictive value (42.9%), F1-score (93.0%). As shown by the variable importance analysis, the strongest risk factor was the number of people in the household (people ≥ 5), which represented a higher risk of infection in crowded housings. Sources of water also came up as an important environmental factor; plain tap water and pipe-line water appeared to be major causes of transmission.
Conclusion
Such results indicate that waterborne transmission is the main route of Cryptosporidium spp. infection. These findings underscore the importance of water quality improvements, including efforts to address water disinfection, particularly in areas with household crowding and inadequate sanitation access.
{"title":"Modeling Factors Associated With Diarrhea Caused by Cryptosporidium Species Using Machine Learning Methods","authors":"Türkan Mutlu Yar, Zeynep Küçükakçali, Ülkü Karaman","doi":"10.1002/jcla.70150","DOIUrl":"10.1002/jcla.70150","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p><i>Cryptosporidium</i> spp. is an important pathogen responsible for severe diarrheal illness, especially in children, and is transmitted by various modes. The present work is aimed at categorizing <i>Cryptosporidium</i> spp. infection and determining associated risk factors by ML on a known dataset of diarrhea among children.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>For classification, we used random forest and bagging CART trees. Model discrimination was measured by accuracy, balanced accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1-score. Then, a 5-fold cross-validation method was used to verify the reliability of the model. Importance values were also calculated to identify the most important risk factors for infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The bagged CART model emerged as the best among the models applied, with slightly better classification. For this model, performance metrics were: accuracy (87.2%), balanced accuracy (56.3%), sensitivity (97.2%), specificity (15.4%), positive predictive value (89.3%), negative predictive value (42.9%), F1-score (93.0%). As shown by the variable importance analysis, the strongest risk factor was the number of people in the household (people ≥ 5), which represented a higher risk of infection in crowded housings. Sources of water also came up as an important environmental factor; plain tap water and pipe-line water appeared to be major causes of transmission.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Such results indicate that waterborne transmission is the main route of <i>Cryptosporidium</i> spp. infection. These findings underscore the importance of water quality improvements, including efforts to address water disinfection, particularly in areas with household crowding and inadequate sanitation access.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.70150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Collince Odiwuor Ogolla, Lucy W. Karani, Stanslaus Musyoki, Phidelis Maruti
Background
Chronic kidney disease is a progressive disorder of the body with high morbidity. Hematological biomarkers can predict CKD progression.
Objective
This study examined the predictive role of hematological parameters among adult CKD patients.
Methods
The records of 120 adult patients with CKD were retrieved. CKD staging was according to KDIGO guidelines. Hematological parameters were hemoglobin, WBC, percentages of neutrophils and lymphocytes, NLR, platelet count, MCV, and RDW. Data were analyzed to assess associations between hematological markers and disease stage.
Results
Mean age was 56.4 ± 13.2 years, with 56.7% being male. Prevalence was 65.0% for hypertension and 38.3% for diabetes mellitus. There was a significant decrease in hemoglobin with CKD stage (13.4 ± 1.1 g/dL in Stage 1 to 8.5 ± 1.7 g/dL in Stage 5, p < 0.001), while NLR and RDW increased progressively with CKD stage (NLR: 1.55 ± 0.48 to 4.12 ± 1.02; RDW: 13.1% ± 0.8% to 16.0% ± 1.6%, both p < 0.001). Anemia and raised NLR were more frequent in the advanced stages of CKD. Logistic regression analysis identified hemoglobin (OR = 0.69, 95% CI: 0.58–0.82, p < 0.001), RDW (OR = 1.78, 95% CI: 1.33–2.39, p = 0.002), and NLR (OR = 1.91, 95% CI: 1.35–2.72, p = 0.001) as independent predictors of advanced CKD. These simple and inexpensive biomarkers are particularly valuable in resource-limited settings.
Conclusion
Hematological biomarkers, especially hemoglobin, NLR, and RDW, were effectively used to predict the progression of CKD.
{"title":"Predictive Role of Hematological Biomarkers in Chronic Kidney Disease Progression","authors":"Collince Odiwuor Ogolla, Lucy W. Karani, Stanslaus Musyoki, Phidelis Maruti","doi":"10.1002/jcla.70142","DOIUrl":"10.1002/jcla.70142","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic kidney disease is a progressive disorder of the body with high morbidity. Hematological biomarkers can predict CKD progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study examined the predictive role of hematological parameters among adult CKD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The records of 120 adult patients with CKD were retrieved. CKD staging was according to KDIGO guidelines. Hematological parameters were hemoglobin, WBC, percentages of neutrophils and lymphocytes, NLR, platelet count, MCV, and RDW. Data were analyzed to assess associations between hematological markers and disease stage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mean age was 56.4 ± 13.2 years, with 56.7% being male. Prevalence was 65.0% for hypertension and 38.3% for diabetes mellitus. There was a significant decrease in hemoglobin with CKD stage (13.4 ± 1.1 g/dL in Stage 1 to 8.5 ± 1.7 g/dL in Stage 5, <i>p</i> < 0.001), while NLR and RDW increased progressively with CKD stage (NLR: 1.55 ± 0.48 to 4.12 ± 1.02; RDW: 13.1% ± 0.8% to 16.0% ± 1.6%, both <i>p</i> < 0.001). Anemia and raised NLR were more frequent in the advanced stages of CKD. Logistic regression analysis identified hemoglobin (OR = 0.69, 95% CI: 0.58–0.82, <i>p</i> < 0.001), RDW (OR = 1.78, 95% CI: 1.33–2.39, <i>p</i> = 0.002), and NLR (OR = 1.91, 95% CI: 1.35–2.72, <i>p</i> = 0.001) as independent predictors of advanced CKD. These simple and inexpensive biomarkers are particularly valuable in resource-limited settings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Hematological biomarkers, especially hemoglobin, NLR, and RDW, were effectively used to predict the progression of CKD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manal Ibrahim-Kosta, Gaïa Zirka, Karine Carriere, Philippe Ohlmann, Marie-Christine Alessi
Aim
This study aims to investigate the nature and extent of hemolyzed, icteric, or lipemic (HIL) interference on platelet aggregation (PA) using the TA-8 V aggregometer (Diagnostica Stago, Asnière sur Seine) equipped with a near infrared light source outside the typical absorbance range of HIL.
Methods
Platelet-Rich-Plasma (PRP) samples were spiked with substances mimicking HIL interference: red blood cell hemolysate (RBCH; 0.3–20 g/L of hemoglobin), bilirubin (15–400 mg/L), and a fat emulsion (Intralipid 20%: 0.5–3 g/L). Maximal intensity (MaxInt) and velocity (Vel) were recorded in the basal state and in response to ADP 5 μmol/L and collagen 2 μg/mL. RBCH solution was treated with apyrase 0.1 U/mL.
Results
Spontaneous aggregation appeared above 0.6 g/L RBCH and significantly intensified with increased RBCH concentrations. The addition of apyrase to RBCH prevented spontaneous aggregation regardless of the RBCH concentration and led to reduced interindividual variability. In response to ADP and collagen, MaxInt and Vel significantly decreased as apyrase-treated RBCH concentrations increased. MaxInt and Vel in response to ADP or collagen were not affected by increasing concentrations of bilirubin. The presence of lipids significantly increases MaxInt in response to ADP or collagen starting at 0.5 g/L.
Conclusion
Our findings suggest that PA testing using the TA-8 V instrument is not significantly impacted by icterus and hyperlipidemia within the specified ranges in healthy individuals. However, it is crucial to reject grossly hemolysed samples (exceeding 0.6 g/L) to avoid interference with ADP released from red blood cells. Further research is needed to confirm these results in patients with platelet dysfunction.
{"title":"Effects of Spectral Interfering Substances on Light Transmission Platelet Aggregation Using Infrared Based Aggregometer","authors":"Manal Ibrahim-Kosta, Gaïa Zirka, Karine Carriere, Philippe Ohlmann, Marie-Christine Alessi","doi":"10.1002/jcla.70151","DOIUrl":"10.1002/jcla.70151","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study aims to investigate the nature and extent of hemolyzed, icteric, or lipemic (HIL) interference on platelet aggregation (PA) using the TA-8 V aggregometer (Diagnostica Stago, Asnière sur Seine) equipped with a near infrared light source outside the typical absorbance range of HIL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Platelet-Rich-Plasma (PRP) samples were spiked with substances mimicking HIL interference: red blood cell hemolysate (RBCH; 0.3–20 g/L of hemoglobin), bilirubin (15–400 mg/L), and a fat emulsion (Intralipid 20%: 0.5–3 g/L). Maximal intensity (MaxInt) and velocity (Vel) were recorded in the basal state and in response to ADP 5 μmol/L and collagen 2 μg/mL. RBCH solution was treated with apyrase 0.1 U/mL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Spontaneous aggregation appeared above 0.6 g/L RBCH and significantly intensified with increased RBCH concentrations. The addition of apyrase to RBCH prevented spontaneous aggregation regardless of the RBCH concentration and led to reduced interindividual variability. In response to ADP and collagen, MaxInt and Vel significantly decreased as apyrase-treated RBCH concentrations increased. MaxInt and Vel in response to ADP or collagen were not affected by increasing concentrations of bilirubin. The presence of lipids significantly increases MaxInt in response to ADP or collagen starting at 0.5 g/L.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that PA testing using the TA-8 V instrument is not significantly impacted by icterus and hyperlipidemia within the specified ranges in healthy individuals. However, it is crucial to reject grossly hemolysed samples (exceeding 0.6 g/L) to avoid interference with ADP released from red blood cells. Further research is needed to confirm these results in patients with platelet dysfunction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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