Journal of Clinical Laboratory Analysis最新文献

{"title":"Prospective Head-To-Head Comparison of a 10-Color Single-Tube Flow Cytometry and EuroFlow Next-Generation Flow in Multiple Myeloma Minimal Residual Disease","authors":"Go Eun Bae,&nbsp;Dae Jin Lim,&nbsp;Sung Hoan Bang,&nbsp;Suhng-Wook Kim,&nbsp;Ari Ahn,&nbsp;Hee-Jin Kim,&nbsp;Jun Ho Yi,&nbsp;Kihyun Kim,&nbsp;Duck Cho,&nbsp;Hyun-Young Kim","doi":"10.1002/jcla.70332","DOIUrl":"10.1002/jcla.70332","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Minimal residual disease (MRD) assessment by next-generation flow cytometry (NGF) is an important prognostic tool in multiple myeloma (MM). Although the EuroFlow NGF assay provides highly standardized and sensitive MRD detection, its dual-tube workflow requires larger sample volumes and longer processing time, potentially limiting efficiency in routine clinical practice. This prospective study evaluated a 10-color single-tube (ST-10C) MRD assay by directly comparing its analytical and clinical performance with the EuroFlow NGF assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MRD analysis was performed in 40 patients with MM, of whom 39 who achieved very good partial response or complete response were included in the final analysis. Each sample was analyzed in parallel using both assays. Analytical sensitivity, qualitative and quantitative agreement, and progression-free survival (PFS) were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both assays achieved analytical sensitivity below 10⁻⁵. MRD was detected in 48.7% of samples by the ST-10C assay and in 38.5% by the EuroFlow NGF assay, with substantial agreement (κ = 0.79). Concordance remained high using the clinical MRD cutoff (≥ 0.001%) (κ = 0.84). Quantitative MRD levels showed strong correlation between the assays (ρ = 0.964) without significant systematic bias. MRD-positive patients showed a trend toward inferior PFS compared with MRD-negative patients by both assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The ST-10C assay demonstrated analytical performance comparable to the EuroFlow NGF assay, supporting its adoption as a more efficient and streamlined alternative for routine MRD assessment in MM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 18","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13458865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706508","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}

{"title":"A Practical and Efficient Multiplex qPCR Assay for Simultaneous Detection of HLA Cross-Reactive Groups and Human Platelet Antigens","authors":"Huimin Ji,&nbsp;Kaihao Feng,&nbsp;Yunping Xu,&nbsp;Le Chang,&nbsp;Ying Yan,&nbsp;Jie Ma,&nbsp;Yi Liu,&nbsp;Jinfeng Zeng,&nbsp;Huizhen Sun,&nbsp;Lunan Wang","doi":"10.1002/jcla.70326","DOIUrl":"10.1002/jcla.70326","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Immune-mediated platelet transfusion refractoriness (IPTR) remains a major clinical challenge, with immune alloimmunization against HLA and HPA as the predominant causes. Although HLA cross-reactive groups (CREGs) provide a practical alternative to allele-level matching, methods for simultaneous HLA-CREG and HPA genotyping remain limited despite their potential to improve platelet matching.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Specific U-anchoring primers (UAPs) and amplification refractory mutation system (ARMS) primers were designed and optimized based on one or more SNPs within HLA-CREG subgroups and HPA alleles. Reaction conditions were optimized, and analytical performance was evaluated. A total of 200 donor DNA samples were tested and compared with NGS and a commercial HPA sequencing kit, with discrepant results verified by Sanger sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We developed and optimized a novel multiplex real-time quantitative PCR (qPCR) assay integrating UAPs and ARMS primers for simultaneous detection of HLA-A/B CREGs and major HPA alleles in 12 reaction tubes. The assay demonstrated an overall limit of detection (LOD) of 0.838 ng/μL and the intra-/inter-assay coefficients of variation were both below 5%, indicating high reproducibility. HLA-CREG typing results were 100% concordant with next-generation sequencing. Sixteen discrepant HPA genotyping results were identified compared with the commercial kit, all of which were confirmed by Sanger sequencing and were consistent with the multiplex qPCR assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This multiplex qPCR assay enables rapid, accurate, and cost-effective simultaneous detection of HLA-CREGs and HPA alleles, providing a practical tool for comprehensive platelet compatibility assessment and improved transfusion matching.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 18","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13470767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148725744","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}

{"title":"Whole Exome Sequencing Identified a Novel Mutation in the LOXHD1 Gene in Consanguineous Iranian Families With Hearing Loss","authors":"Solmaz Hassani Fard Katiraei,&nbsp;Milad Gholami,&nbsp;Mohsen Soosanabadi,&nbsp;Mona Entezam,&nbsp;Seyed Alireza Dastgheib","doi":"10.1002/jcla.70327","DOIUrl":"10.1002/jcla.70327","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hearing loss is one of the most common sensory disorders caused by genetic and environmental factors. Autosomal recessive non-syndromic hearing loss (ARNSHL) is extremely heterogeneous, with over 100 genes known to be involved. Hearing loss can result from mutations in the LOXHD1 gene, which codes a highly conserved protein known as lipoxygenase and is located at 18q21.1. Despite the association between LOXHD1 mutations and ARNSHL, there are still few documented cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We examined a case of non-syndromic hearing loss in an Iranian family with a history of consanguinity and several affected siblings. Next-generation sequencing (NGS) was conducted on the proband to discover causal genetic alterations. Sanger sequencing was employed to confirm the identified variation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A novel likely pathogenic variant in the LOXHD1 gene, c.3713dupA (p.Asp1238Glufs*10), was identified. Sanger sequencing was used to confirm that the affected family members had this frameshift mutation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings broaden the mutational range of LOXHD1 linked to ARNSHL. This unique variant enhances the comprehension of the genetic underpinnings of hearing loss and may aid in molecular diagnostics and genetic counseling for impacted families.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 18","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793918","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}

{"title":"Verification of False Reactivity in HIV Rapid Diagnostic Tests and Its Translation Into the Three Tests Algorithm in Cameroon","authors":"Rogers Ajeh Awoh,&nbsp;Désiré Takou,&nbsp;Isidore Oscar Bienvenu Etogo Ondigui,&nbsp;Roger Onana,&nbsp;Etienne Kembou,&nbsp;Collins Chenwi,&nbsp;Daniel Mabongo,&nbsp;Grace Beloumou Angong,&nbsp;Laetitia Bissai,&nbsp;Aude Christelle Ka'e,&nbsp;Alex Durand Nka,&nbsp;Ezechiel Ngoufack Jagni Semengue,&nbsp;Nadine Fainguem,&nbsp;Daniele Simnoue,&nbsp;Florine Tsimene,&nbsp;Sandrine Djupsa,&nbsp;Jaurès Metambou,&nbsp;Aurelie Kengne,&nbsp;Arlette Messeh,&nbsp;Gilbert Tchatchoua,&nbsp;Naomi-Karell Etame,&nbsp;Michel Tommo,&nbsp;Krystel Zam Nnomo,&nbsp;Edith Temgoua,&nbsp;Basil Yaba,&nbsp;Gregory Edie Halle Ekane,&nbsp;Carlo-Federico Perno,&nbsp;Vittorio Colizzi,&nbsp;Nicaise Ndembi,&nbsp;Diaby Ousmane,&nbsp;Joelle Bouba Pamen,&nbsp;Alexis Ndjolo,&nbsp;Celine Lastrucci,&nbsp;Joseph Fokam,&nbsp;Malachie Manouada","doi":"10.1002/jcla.70333","DOIUrl":"10.1002/jcla.70333","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In a context of HIV seropositivity below 5%, transitioning from a two- to a three-test algorithm is required to secure positive predictive values &gt; 99% for mitigating false reactivity. With Cameroon having 2.7% seroprevalence, we sought to ascertain events of false reactivity from eight WHO-prequalified HIV rapid diagnostic tests (RDTs) and design suitable combinations for the country three-test algorithm.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A facility-based study was conducted in July–August 2021 among 172 consenting clients attending health facilities in Yaoundé-Cameroon. Whole blood was collected and samples characterized in parallel using KHB Diagnostic Kit for HIV (1 + 2) Antibody and INNO-LIA HIV I/II Ag/Ab to rule out reactive cases. Two lots of each selected RDT were tested simultaneously in quadruplicate on HIV non-reactive samples and repeated by a different tester. RDTs were considered false positive if any reactivity was detected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Following characterization, 25 samples were HIV-reactive (i.e., ruled out) and 147 non-reactive. Following random selection, 100 non-reactive samples tested for false reactivity revealed: 0% (0/100) First Response HIV 1–2-O Card, 0% (0/100) First Response HIV1 + 2/Syphilis Combo, 0% (0/100) STANDARD Q HIV/Syphilis Combo, 0% (0/99) ONE STEP Anti-HIV1&amp;2 (one invalid result); 1% (1/100) Determine HIV Early Detect and Bioline HIV/Syphilis Duo, 2% (2/100) Alere Determine HIV-1/2, 4% (4/100) Rapid Test for Antibody to HIV.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In the Cameroonian context, HIV false reactivity ranged from 0% to 4% across selected RDTs. Thus, a reliable three-test algorithm ranks First Response HIV 1–2-0 Card, First Response HIV1 + 2/Syphilis Combo or STANDARD Q as suitable RDT-1 to mitigate false-positive events at the country-level.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 18","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13462474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712396","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}

{"title":"DNA Extracted From Aged Formalin-Fixed Paraffin-Embedded Specimens of Patients With Papillary Thyroid Carcinomas Can Be Used for Whole Exome Sequencing","authors":"Kousuke Tanimoto,&nbsp;Tomonori Hayashi,&nbsp;Hidewaki Nakagawa,&nbsp;Kazuhiro Maejima,&nbsp;Koji Arihiro,&nbsp;Megumu Fujihara,&nbsp;Takashi Nishisaka,&nbsp;Masahiro Ito,&nbsp;Masahiro Nakashima,&nbsp;Naohiro Kato,&nbsp;Zhenqiu Liu,&nbsp;Misa Imaizumi,&nbsp;Alina Brenner,&nbsp;Stephen J. Chanock,&nbsp;Osamu Tanabe,&nbsp;Kotaro Ozasa","doi":"10.1002/jcla.70324","DOIUrl":"10.1002/jcla.70324","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In Hiroshima, thyroid cancer tissue samples from A-bomb survivors have been preserved since 1958. However, the feasibility of using these old formalin-fixed paraffin-embedded (FFPE) specimens for genetic analysis has not been fully evaluated. Here, we aimed to assess the quality of DNA extracted from long-term stored FFPE specimens obtained from patients with papillary thyroid carcinoma (PTC) in Hiroshima and to evaluate their applicability to whole exome sequencing (WES).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We extracted DNA from tumor and adjacent normal regions of FFPE thyroid tumor specimens from 57 cases stored for up to 55 years at three hospitals in Hiroshima and confirmed the quality of the extracted DNA. From this cohort, tumor and paired normal samples from 24 patients with PTC were selected for WES, and sequencing metrics were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both DNA yield and DNA integrity number were negatively correlated with storage duration. WES analysis showed that storage duration was also negatively correlated with mean insert size and normalized read depth. In contrast, the uniformity score, which reflects the evenness of sequence coverage across targeted regions, did not show a significant correlation with storage duration. Among the 22 <i>BRAF</i> V600E-positive cases identified by droplet digital PCR, 18 cases (82%) had at least one sequencing read supporting the mutation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings suggest that FFPE samples preserved for up to 55 years may be amenable to sequencing with increased read depth. However, the progressive decline in DNA quality with longer storage periods indicates that careful interpretation of sequencing results is warranted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 18","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13423888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630593","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}

{"title":"Clinical Rationale of Dual-Parameter Tumor Markers Reporting Without Reliance on Normal Reference Ranges","authors":"Jurate Civinskaite,&nbsp;Daiva Gudaviciene,&nbsp;Gintaras Zaleskis,&nbsp;Aleksandras Petrauskas,&nbsp;Dainius Characiejus,&nbsp;Tatjana Ivaskiene","doi":"10.1002/jcla.70320","DOIUrl":"10.1002/jcla.70320","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>This review offers clinicians a novel view of tumor markers (TM). We suggest reporting the TM with two values: the TM level itself and the specific growth rate (SGR). Clinicians are well informed about the limitations of TM-based cancer screening and early recurrence detection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Review of Current TM Interpretation</h3>\u0000 \u0000 <p>Current TM interpretation is based merely on the TM value. TM cannot provide the information equivalent to histological data. An asymptomatic patient with rising TM is assigned to imaging procedures only if TM is found above the norm.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Proposal to Report TM in Two-Parameter Format</h3>\u0000 \u0000 <p>We offer to universally report TM as a two-parameter value: (a) TM itself; (b) specific growth rate of TM. The rate of change of TM, rather than the TM norm, is a reliable criterion for recurrence monitoring. For the moment, serial TM values of individual patients are becoming universally available in electronic format.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Review of Literature Exploring Velocity, Doubling Time, and SGR in Laboratory Reports and Radiological Assessment</h3>\u0000 \u0000 <p>We offer medical laboratories to put into service a specific growth rate (SGR) parameter which precisely associates: (a) the current TM value; (b) the previous TM value; and (c) the time interval between. Radiologic tumor progression with SGR calculations significantly aided prognosis assessment, but the implementation of SGR in laboratory practice has not been tested. This review focuses on clinical data in which SGR could have been employed to guide therapy or to monitor for recurrence. The obvious advantages of the SGR-TM format are ease of interpretation (it indicates the percentage change in TM per day), cost-effectiveness, and mathematical consistency.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 18","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591621","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}

{"title":"Low-Level Human Epididymis Protein 4 in Seminal Plasma Is an Independent Risk Factor for Poor Semen Liquefaction: A Case Control Study","authors":"Feifei Wang,&nbsp;Jiangnan Wu,&nbsp;Shijie Gao,&nbsp;Zhuohan Zheng,&nbsp;Zhiheng Wang,&nbsp;Jing Gao","doi":"10.1002/jcla.70328","DOIUrl":"10.1002/jcla.70328","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim of this study was to investigate the relationship between human epididymis protein 4 (HE4) levels in seminal plasma and semen liquefaction in males.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 314 healthy men from the andrology department were included. The correlations between HE4 levels and prostate-specific antigen (PSA) levels as well as conventional semen parameters (sperm density, the proportion of non-progressively motile spermatozoa, seminal liquefaction time) were analyzed, and logistic regression was further employed to examine the association between HE4 levels and the risk of poor semen liquefaction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The level of HE4 in seminal plasma was negatively correlated with semen liquefaction time (r = −0.207, <i>p</i> &lt; 0.001) and positively correlated with seminal plasma PSA levels (<i>r</i> = 0.280, <i>p</i> &lt; 0.001), suggesting a potential link to the process of semen liquefaction. Continuous HE4 levels were standardized by dividing by 100, and participants were then categorized into quartiles (Q1–Q4) based on the standardized HE4 values. After adjusting for confounding factors, the risk of poor semen liquefaction in the Q3, Q2, and Q1 groups of the lower HE4 level was 4.024 times (95% CI: 1.908–8.485; <i>p</i> &lt; 0.001), 6.320 times (95% CI: 2.818–14.175; <i>p</i> &lt; 0.001), and 5.190 times (95% CI: 2.217–12.15; <i>p</i> &lt; 0.001) higher, respectively, compared to the highest HE4 quartile (Q4).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This suggests that a low level of HE4 in seminal plasma is an independent risk factor for poor semen liquefaction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 18","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13462476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712428","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}

{"title":"Integrated Bioinformatics Analysis Identifies FCER1G, IL1R2, and BST1 as Diagnostic Biomarkers and Therapeutic Targets in Sepsis","authors":"Junjie Li,&nbsp;Guanghui Xiu,&nbsp;Ping Liu,&nbsp;Xianzhong Chen,&nbsp;Kailv Zhou,&nbsp;Yunfeng Yang","doi":"10.1002/jcla.70299","DOIUrl":"10.1002/jcla.70299","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sepsis remains difficult to diagnose since blood culture has low sensitivity and current biomarkers lack sufficient specificity. We sought to identify robust diagnostic and therapeutic targets for neonatal sepsis through an integrated bioinformatics and experimental workflow.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The GSE69686 dataset (108 neonates; 48 sepsis, 60 controls collected ≤ 3 days after birth) was analyzed using a multi-step pipeline: WGCNA to identify sepsis-associated modules; limma-based differential expression; feature selection by LASSO and SVM-RFE; immune deconvolution (CIBERSORT); and pathway interrogation (GSEA). Drug enrichment (Enrichr/DSigDB) and molecular docking (AutoDock) supported targetability. Experimental validation employed a THP-1 sepsis-like model (1 μg/mL LPS, 24 h) with qRT-PCR, shRNA-mediated <i>BST1</i> knockdown, Western blot, ELISA (IL-6, TNF-α, IL-1β), CCK-8, and Annexin V/PI flow cytometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Intersecting the outputs of LASSO and SVM-RFE yielded three robust biomarkers—<i>FCER1G</i>, <i>IL1R2</i>, and <i>BST1</i>. These genes are associated with broad shifts in inferred immune infiltration, and GSEA linked their high expression to INFLAMMATORY RESPONSE; <i>BST1</i> and <i>FCER1G</i> were additionally enriched for TNFα/NF-κB signaling. In THP-1 cells, LPS upregulated all three genes; focusing on <i>BST1</i>, shRNA knockdown partially rescued proliferation (0–72 h), reduced IL-6/TNF-α/IL-1β secretion, and lowered apoptosis relative to sh-NC. Docking analysis suggested artesunate as a candidate modulator with a binding energy of −6.27 kcal/mol to <i>BST1</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our integrated pipeline nominates <i>FCER1G, IL1R2,</i> and <i>BST1</i> as biologically coherent biomarkers of sepsis and highlights <i>BST1</i> as a plausible therapeutic target warranting further investigation. These findings support external validation in multicenter cohorts and mechanistic extension—particularly functional testing of predicted modulators—in primary cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 18","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13469782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148724648","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}

{"title":"Establishment of Reference Intervals for Thrombus Biomarkers in a Single-Center Chinese Population Using Indirect Methods","authors":"Lei Zhang,&nbsp;Qiyu Hu,&nbsp;Yiming Chen,&nbsp;Hui Yuan","doi":"10.1002/jcla.70315","DOIUrl":"10.1002/jcla.70315","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Thrombin-antithrombin complex (TAT), plasmin-α2-antiplasmin complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) are key biomarkers reflecting coagulation/fibrinolysis activation and endothelial injury. Population-specific reference intervals (RIs) are essential for accurate diagnosis, but Chinese-specific RIs remain limited. This study aimed to establish reliable RIs for these four markers in a Chinese population using indirect methods applied to clinical big data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Anonymized clinical data for TAT, PIC, TM, and t-PAIC from 2020 to 2024 at Beijing Anzhen Hospital, Capital Medical University, were collected. After data reduction, deduplication, and outlier removal, RIs were calculated for the overall population and stratified by sex and age using indirect methods (Hoffmann and Bhattacharya). Reliability was verified by comparing the derived RIs with manufacturer-provided ranges using reference change value (RCV) criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall RIs determined by the Hoffmann method for TAT, PIC, TM, and t-PAIC were 0.64–3.57 ng/mL, 0.25–1.08 μg/mL, 5.64–13.42 TU/mL, and 3.22–15.88 ng/mL, respectively. Those determined by the Bhattacharya method were 0.58–2.84 ng/mL, 0.25–1.11 μg/mL, 5.60–14.53 TU/mL, and 3.46–15.44 ng/mL, respectively. TAT and PIC levels were higher in females, whereas TM and t-PAIC were higher in males. All four markers increased with age. Relative differences between method-derived RIs and manufacturer ranges were within RCV limits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Both Hoffmann and Bhattacharya's indirect methods are reliable for establishing RIs for TAT, PIC, TM, and t-PAIC. The study provides population-specific RIs for a Chinese cohort, supporting accurate early detection and risk assessment of thrombotic diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 18","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912519","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}

{"title":"Hemoglobin Lepore-Boston-Washington: A Rare Cause of Unmeasurable HbA1c and Diagnostic Challenge in Diabetes","authors":"Filippo Russo,&nbsp;Silvia Trombetti,&nbsp;Maria Rosaria Storino,&nbsp;Raffaele Sessa,&nbsp;Carmela De Felice,&nbsp;Giuseppe Schiavone,&nbsp;Michela Grosso","doi":"10.1002/jcla.70325","DOIUrl":"10.1002/jcla.70325","url":null,"abstract":"&lt;p&gt;Hemoglobin Lepore variants comprise a small group of structurally abnormal hemoglobins with a thalassemia-like phenotype. They result from the in-frame fusion of the 5′ end of the δ-globin gene (HBD) with the 3′ end of the &lt;i&gt;β&lt;/i&gt;-globin gene (HBB) and have been identified across diverse ethnic groups [&lt;span&gt;1&lt;/span&gt;]. When co-inherited with β-thalassemic alleles, Hb Lepore produces a wide clinical spectrum, from non-transfusion-dependent to transfusion-dependent thalassemia, depending on the degree of globin chain imbalance and compensatory HbF production. Hb Lepore-Boston-Washington is the most prevalent Lepore variant (HbVar database: https://globin.cse.psu.edu/). It is relatively common in Southern Italy, particularly in the Campania region, where its prevalence has been recently characterized by Ricchi et al. [&lt;span&gt;2&lt;/span&gt;]. The fusion gene (δ87/β116) consists of the 5′ portion of the &lt;i&gt;δ&lt;/i&gt;-gene (from the 5′ UTR to codon 87 of exon 2) fused to the 3′ portion of the &lt;i&gt;β&lt;/i&gt;-gene (from intron 2 nucleotide +8 to the 3′ UTR). The two genes share a 58-base-pair region of homology at the crossover junction [&lt;span&gt;3&lt;/span&gt;]. In heterozygous carriers, the presence of a functional &lt;i&gt;β&lt;/i&gt;-globin allele allows for the formation of adult hemoglobin (HbA&lt;sub&gt;0&lt;/sub&gt;), thereby ensuring the analytical feasibility of HbA1c measurement. Homozygosity for Hb Lepore-Boston-Washington is a very rare condition in which β-globin synthesis is virtually abolished, leading to an absence of HbA&lt;sub&gt;0&lt;/sub&gt; [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Diabetes Mellitus (DM) is a chronic metabolic disorder resulting from defects in insulin secretion, insulin action, or both [&lt;span&gt;4, 5&lt;/span&gt;]. According to the International Diabetes Federation (IDF), approximately 66 million adults in Europe are living with diabetes, emphasizing the critical need for accurate diagnostic and monitoring strategies [&lt;span&gt;6, 7&lt;/span&gt;]. In particular, Type 1 Diabetes Mellitus (T1D) accounts for approximately 5%–10% of all diabetes cases and is caused by autoimmune destruction of pancreatic β-cells, leading to absolute insulin deficiency [&lt;span&gt;8&lt;/span&gt;]. Chronic hyperglycemia is associated with long-term vascular complications, including diabetic retinopathy, nephropathy, neuropathy, and increased cardiovascular risk [&lt;span&gt;9&lt;/span&gt;]. Hemoglobin A1c (HbA1c) remains the gold standard for assessing glycemic status in diabetic patients, serving as a critical metric to guide therapeutic decisions and long-term clinical management [&lt;span&gt;10&lt;/span&gt;]. HbA1c originates through the spontaneous, non-enzymatic glycation of the N-terminal valine residue on the β-chain of normal adult hemoglobin (HbA&lt;sub&gt;0&lt;/sub&gt;) [&lt;span&gt;11&lt;/span&gt;]. Due to the approximately 120-day lifespan of erythrocytes, HbA1c levels reflect average blood glucose concentrations over the preceding 8–12 weeks. Since 2010, the American Diabetes Association (ADA) has recognized HbA1c ≥ 6.5% as a diagnostic criterion for diabetes mellitus, further","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"40 18","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13420343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620210","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}