Clinica Chimica Acta最新文献

{"title":"Integrative metabolomics and proteomics of heat stress","authors":"Shab M. Alkhoujah ,&nbsp;Ruba A. Zenati ,&nbsp;Munazza Ahmed ,&nbsp;Ahmad Y. Abuhelwa ,&nbsp;Shereen M. Aleidi ,&nbsp;Mohammad A.Y. Alqudah ,&nbsp;Waseem El-Huneidi ,&nbsp;Eman Abu-Gharbieh ,&nbsp;Zainab M. AlShareef ,&nbsp;Karem H. Alzoubi ,&nbsp;Yasser Bustanji ,&nbsp;Mohammad H. Semreen","doi":"10.1016/j.cca.2026.120869","DOIUrl":"10.1016/j.cca.2026.120869","url":null,"abstract":"<div><div>Heat stress (HS) is an escalating global health concern driven by climate change. Despite increasing epidemiologic recognition, the molecular mechanisms underlying HS pathophysiology remains poorly defined. This review systematically synthesizes metabolomic and proteomic findings to elucidate these mechanisms and identify molecular targets for intervention. Current management remains limited to symptomatic relief, with no targeted therapies available to prevent or reverse HS-induced injury. To address this gap, metabolomics and proteomics offer powerful approaches for elucidating the molecular and cellular mechanisms underlying HS responses. Metabolomic studies demonstrate that HS disrupts central energy metabolism, promotes lipid remodeling, elevates oxidative stress, alters amino acid and sulfur metabolism, disrupts hormone regulation, and induces hepatic stress. Complementary proteomics studies reveal significant upregulation of heat shock proteins (HSPs), particularly HSP70 and HSP90, as well as remodeling of inflammatory mediators, cytoskeletal proteins, and signaling pathways. Together, these omics-based findings highlight a coordinated reprogramming of metabolic pathways and proteomic signatures that underpins both susceptibility and adaptation to HS. This review explores recent metabolomic and proteomic investigations into HS, underscoring how integrative multiomics approaches provide a coherent view of its molecular complexity. By bridging metabolite–protein crosstalk with therapeutic exploration, the review highlights how these insights advance the identification of biomarkers and molecular targets, ultimately guiding the development of more precise interventions for HS.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"584 ","pages":"Article 120869"},"PeriodicalIF":2.9,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075553","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}

{"title":"Antibody response against HERV-K polymerase and envelope by patients with multiple sclerosis","authors":"Bruna Reimberg Flose ,&nbsp;Kevin Cézar Nascimento Silva ,&nbsp;Maria Aparecida Juliano ,&nbsp;Virginia Fernandes Moça Trevisani ,&nbsp;Carolina Nunes França ,&nbsp;Marcelo Andreetta Corral ,&nbsp;Luiz Henrique da Silva Nali ,&nbsp;Marina Tiemi Shio","doi":"10.1016/j.cca.2026.120870","DOIUrl":"10.1016/j.cca.2026.120870","url":null,"abstract":"<div><h3>Introduction</h3><div>Human Endogenous Retroviruses (HERVs) are viruses that have infected germ cells of our ancestors millions of years ago and compose 8% of human genome. The expression of HERVs is associated with neurological disorders such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). The humoral immune response against peptides from the envelope proteins, but not to polymerase, of HERV-K has been previously described. The aim of this study is to evaluate anti-HERV- K polymerase (pol) humoral response in patients with MS.</div></div><div><h3>Methods</h3><div>GenBank platform were used to select peptides with similarity above 50%, comparing HERV sequences (K or W) with the protein Myelin Oligodendrocyte Glycoprotein (MOG). The synthesized peptides were used in the ELISA test for anti-HERV-K (pol – polymerase) and W (env - envelope) antibodies in serum of patients with MS (31) and healthy population (54) with no history of autoimmune diseases.</div></div><div><h3>Results</h3><div>One peptide (pep) related to HERV-W env and 8 peptides of HERV-K env or pol were selected and synthesized. Validation of the indirect ELISA with sera from MS patients showed that there was immunoreactivity for all peptides compared to healthy population (<em>p</em> &lt; 0.0001). HERV-K env peptide 5 (WSGNQTLETRD) and 7 (ECVANSAVIL) showed the highest values of sensitivity and specificity, as well as diagnostic accuracy with 95.16% and 96.77%, respectively. HERV-K pol peptides 6 (LGIPTYAM), 8 (VTHVPSFR) and 9 (STVKTFTYLD) have demonstrated high values of accuracy 82.26, 80.65 and 82.26, respectively. These cutoff values were used to calculate the ELISA index - EI. The MS samples had a higher EI compared to the healthy population for almost all peptides of HERV-K pol (<em>p</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>The present work showed a humoral response related to HERV-K pol and env, as well as HERV-W env, by patients with MS. All diagnostic parameters are appreciable, which makes it possible to use this tool to better understand the mechanisms related to viral immunology in patients.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"584 ","pages":"Article 120870"},"PeriodicalIF":2.9,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146084463","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}

{"title":"Exosome biosensors for detection of Lung cancer","authors":"Obaid Afzal ,&nbsp;Pavan Goud ,&nbsp;Kavita Goyal ,&nbsp;Ali Altharawi ,&nbsp;Mubarak A. Alamri ,&nbsp;Manal A. Alossaimi ,&nbsp;Abdulmalik S.A. Altamimi ,&nbsp;Surya Nath Pandey","doi":"10.1016/j.cca.2026.120847","DOIUrl":"10.1016/j.cca.2026.120847","url":null,"abstract":"<div><div>Lung cancer is the leading cause of cancer-related mortality worldwide. It is frequently diagnosed at an advanced stage and exhibits significant morphological and molecular heterogeneity, encompassing both small- and non-small-cell types, as well as major histological variations. Conventional imaging and tissue biopsies are invasive and may fail to reflect dynamic tumor biology. Exosomes (30-150 nm, extracellular vesicles that are products of the endosome) are present in plasma, serum, saliva, and urine and contain tumor-reflective proteins, lipids, and RNAs. This review summarizes the strategies used in biosensors to detect exosomes in lung cancer using various approaches, including electrochemical, optical, microfluidic, and nanomaterial-assisted biosensors, which detect various markers, such as PD-L1, EGFR, and oncogenic miRNAs/lncRNAs. Exosomes possess inherent biocompatibility, intrinsic cargo protection, and the ability to target tumors (homing capabilities), attributes that synthetic nanocarriers, such as liposomes, polymeric, and inorganic nanoparticles, lack. These characteristics render exosomes advantageous for biosensing and delivery applications. We also discuss exosome-enabled therapeutic directions, such as drug- and nucleic-acid-loaded exosomes and immunomodulatory cargos, and indicate the new clinical-study environment. The most important obstacles are the non-uniformity of vesicles, variability in isolation/quantification, and lack of standardization. The discussion concludes with an examination of the practice performance standards, reporting priorities, and emerging trends. These include AI-assisted analysis and the use of portable point-of-care devices, which aim to expedite the development of clinically deployable exosome platforms for lung cancer diagnosis. We examined the integration of a sample into an answer, validation of assays on cohorts, and conceptual implications of regulatory considerations for reproducible measurements. This approach facilitates practical applications, such as screening, treatment monitoring, and early relapse detection.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"584 ","pages":"Article 120847"},"PeriodicalIF":2.9,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017605","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}

{"title":"Klotho protein and insulin resistance","authors":"Yaqin Cai ,&nbsp;Bin Liu ,&nbsp;Dandan Song ,&nbsp;Yulong Zhao ,&nbsp;Bibo Xie ,&nbsp;Yingping Zhang ,&nbsp;Yuqiu Zhou","doi":"10.1016/j.cca.2026.120840","DOIUrl":"10.1016/j.cca.2026.120840","url":null,"abstract":"<div><div>Klotho was initially identified as an anti-ageing protein expressed mainly in renal distal tubular cells and the choroid plexus. The Klotho family comprises several members, including α-Klotho (αKl), β-Klotho (βKl), Klotho-LPH related protein (KLPH; lactase-phlorizin hydrolase), and Klotho-related protein (KlrP), which perform a multitude of functions related to various physiological processes. The effects of Klotho on various ageing-related and renal diseases, such as its antiapoptotic effects, ability to reduce oxidative stress, anti-inflammatory effects, and other functions, have extensively been reviewed, suggesting the significant cardiorenal benefits of Klotho. Klotho expression deficiency promotes age-related pathology and is correlated with renal impairment. Studies have shown that serum Klotho is significantly decreased in type 2 diabetes (T2DM) and is linked to the duration of diabetes, indicating that Klotho may be involved in multiple pathological mechanisms of T2DM. Insulin resistance (IR) plays an essential role in the onset and progression of T2DM. Research has demonstrated that the expression of Kl is closely correlated with insulin secretion, insulin signaling pathways, and insulin sensitivity and may serve as a potential predictive marker for the IR and diabetes risk. We comprehensively reviewed the relevant literature in PubMed using the keywords “Klotho”, “Type 2 diabetes”, and “Insulin resistance”. This review summarizes the relationship between Klotho and IR.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"583 ","pages":"Article 120840"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975616","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}

{"title":"Circulating suPAR as a noninvasive biomarker of fibrosis and immune activation in autoimmune liver diseases","authors":"Fuguo Zhan ,&nbsp;Tianbin Chen ,&nbsp;Jun Liang ,&nbsp;Can Liu ,&nbsp;Mingdong Huang ,&nbsp;Longguang Jiang","doi":"10.1016/j.cca.2026.120831","DOIUrl":"10.1016/j.cca.2026.120831","url":null,"abstract":"<div><h3>Aim</h3><div>Noninvasive assessment of fibrosis in autoimmune liver diseases (AILDs) remains challenging. Soluble urokinase plasminogen activator receptor (suPAR) is a marker of systemic immune activation, but its role in AILDs is unclear. This study aimed to evaluate the diagnostic performance of circulating suPAR in AILDs and its association with fibrosis severity and immune activation.</div></div><div><h3>Methods</h3><div>A retrospective study included 117 patients with AILDs (<em>n</em> = 61), chronic hepatitis B (CHB, <em>n</em> = 33), metabolic dysfunction-associated steatotic liver disease (MASLD, <em>n</em> = 23), and 44 healthy controls. Serum suPAR was measured by chemiluminescent immunoassay. Correlations with fibrosis indices (APRI, FIB-4), liver stiffness measurement (LSM), and IgG were assessed. ROC analysis evaluated diagnostic accuracy.</div></div><div><h3>Results</h3><div>Serum suPAR was significantly higher in AILDs than in controls, CHB, and MASLD (median 5.16 vs. 3.58, 3.92, and 3.13 ng/mL; all <em>P</em> &lt; 0.001). suPAR correlated strongly with APRI (<em>r</em> = 0.66), FIB-4 (<em>r</em> = 0.65), and LSM (<em>r</em> = 0.62), and modestly with IgG (<em>r</em> = 0.31). ROC analysis demonstrated robust discrimination between AILDs and controls (AUC = 0.839), CHB (AUC = 0.724), and MASLD (AUC = 0.944). Patients with higher suPAR levels exhibited more advanced fibrosis and greater biochemical evidence of liver injury.</div></div><div><h3>Conclusions</h3><div>Circulating suPAR is elevated in AILDs, reflecting fibrosis and immune activation. suPAR provides complementary, antibody-independent diagnostic value and may serve as a noninvasive biomarker for differentiating AILDs from CHB and MASLD in clinical practice.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"583 ","pages":"Article 120831"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932462","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}

{"title":"MicroRNA-CRISPR biosensors for cancer diagnostics","authors":"Alaa H. Habib ,&nbsp;Ziaullah Mirza Sain ,&nbsp;Misbahuddin Rafeeq ,&nbsp;Mohammed Matoog Karami ,&nbsp;Hadeel A. Alsufyani ,&nbsp;Johar Iqbal ,&nbsp;Kamel Chaieb ,&nbsp;Hisham N. Altayb ,&nbsp;Muhammad Shahid Nadeem ,&nbsp;Fahad A. Al-Abbasi ,&nbsp;Imran Kazmi","doi":"10.1016/j.cca.2026.120837","DOIUrl":"10.1016/j.cca.2026.120837","url":null,"abstract":"<div><div>Circulating microRNAs (miRNAs) are promising minimally invasive biomarkers for cancer and cardiovascular disorders. However, their low sequence length, low abundance, high sequence homology (including iso-miRs), and strong matrix and preanalytical effects in biofluids require highly sensitive and robust analytical technologies. CRISPR-Cas systems, particularly Cas12a, Cas12b, Cas13a, and Cas9, offer programmable nucleic acid recognition with high mismatch discrimination combined with collateral nuclease activity, enabling versatile signal amplification through fluorescence, electrochemical, electrochemiluminescent (ECL), photoelectrochemical (PEC), colorimetric, and lateral-flow readouts. This review critically evaluates the latest advances in CRISPR-based miRNA biosensors, emphasizing their analytical performance and translational potential in clinical diagnostics across plasma/serum, saliva, whole blood, and extracellular vesicle samples. The detection limits are typically within the femtomolar to attomolar range. The requirements for clinical translation are equally influenced by factors such as sample preparation, inhibitor tolerance, miRNA panel multiplexing, quantitative readout, and reagent stability. We compared CRISPR-based workflows with RT-qPCR and digital PCR and provided a roadmap for standardization and quality control, as well as the minimal analytical and clinical validation standards required for adopting CRISPR technology in clinical chemistry laboratories.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"583 ","pages":"Article 120837"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948028","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}

{"title":"Phenotype-genotype correlation in a cohort of 15 patients with hereditary ichthyosis","authors":"Yu-jie Ma ,&nbsp;Jing Li ,&nbsp;Yang Liu ,&nbsp;Tian-ying Wei ,&nbsp;Jia-en Liu ,&nbsp;Jing Zhang ,&nbsp;Hua-ying Hu ,&nbsp;Kai Yang","doi":"10.1016/j.cca.2026.120844","DOIUrl":"10.1016/j.cca.2026.120844","url":null,"abstract":"<div><h3>Background</h3><div>Hereditary ichthyosis is a heterogeneous group of skin disorders classified within the Mendelian disorders of cornification (MEDOC). Its primary clinical manifestations include hyperkeratosis, dryness, and scaling as a result of desquamation. Due to symptomatic overlap with other keratinization disorders, accurate differential diagnosis is essential. Furthermore, genetic diagnosis of hereditary ichthyosis provides critical information for genetic counseling and informed reproductive decision-making for affected families.</div></div><div><h3>Methods</h3><div>In this study, we performed a comprehensive genetic analysis on 15 probands with clinically confirmed or suspected ichthyosis. Using whole-exome sequencing (WES) and chromosomal microarray analysis (CMA), we identified potential pathogenic variants, which were subsequently verified in family members using Sanger sequencing or Quantitative fluorescent PCR (QF-PCR). The functional impact of detected missense variants was assessed by analyzing the conservation of the affected amino acid residues using the MEGA7 software.</div></div><div><h3>Results</h3><div>Our analysis revealed disease-associated variants in several genes, including <em>FLG, STS, TGM1</em>, and <em>ABCA12</em>. Notably, we identified four previously unreported variants: c.82 T &gt; A (p.L28M) and c.9774C &gt; A (p.H3258Q) in the <em>FLG</em> gene, and c.974C &gt; T (p.S325F) and c.614 A &gt; C (p.N205T) in the <em>ABCA12</em> gene.</div></div><div><h3>Conclusion</h3><div>This study establishes a clear molecular diagnosis for the enrolled ichthyosis patients. The findings expand the known variant spectrum of hereditary ichthyosis, providing a solid basis for genetic counseling and valuable insights for future reproductive planning in these families.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"583 ","pages":"Article 120844"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994390","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}

{"title":"Clinical utilization of beta-hydroxybutyrate and comparison with urine ketones in a quaternary care health system","authors":"Maxwell L. Harsha ,&nbsp;Mary Ann Ness ,&nbsp;Mark A. Marzinke","doi":"10.1016/j.cca.2026.120838","DOIUrl":"10.1016/j.cca.2026.120838","url":null,"abstract":"<div><div>Blood beta-hydroxybutyrate (BHB) and urine ketones (UK) are key biomarkers for assessing ketosis, including life-threatening diabetic ketoacidosis (DKA). BHB is the primary ketone produced during ketotic states and shows greater sensitivity and specificity than UK, which do not detect BHB. Current professional guidelines recommend BHB testing over UK for assessing DKA. This study retrospectively examined the utilization of serum BHB and its clinical performance compared to UK over a one-year period within our quaternary care healthcare system.</div><div>BHB ordering metrics and patient demographics were obtained from the electronic health record system between November 1, 2023, and October 31, 2024. The clinical performance of BHB compared to UK was assessed through concordance analysis of specimens collected within one hour of each other, alongside comparisons to other serum analytes and chart review of patients with discordant BHB and UK results.</div><div>During the one-year period, our academic medical center's laboratory performed 3235 BHB tests from 2011 unique patients. The majority of tests were performed on adults over 60 years of age (42%) in high-acuity settings (64%), and for patients exhibiting DKA symptoms (86%). Concordance analysis revealed that 24% of BHB and UK contemporaneously ordered results were discordant, with the majority showing elevated BHB concentrations and normal UK results. Assessment of this discordant group suggested that kidney function may may be a driving factor of observed discrepancies.</div><div>These findings align with existing guidelines and highlight the need for further investigation of BHB utilization in specific populations, such as surgical and medically complex patients.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"583 ","pages":"Article 120838"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975617","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}

{"title":"Consistency study of IGF-1 detection by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and chemiluminescence immunoassay (CLIA)","authors":"Wu Yan ,&nbsp;Ruifang Shi ,&nbsp;Wen Zheng ,&nbsp;Wentao Yang ,&nbsp;Francis Manyori Bigambo ,&nbsp;Wei Pan ,&nbsp;Wenjing Zhang ,&nbsp;Xu Wang","doi":"10.1016/j.cca.2026.120835","DOIUrl":"10.1016/j.cca.2026.120835","url":null,"abstract":"<div><h3>Background</h3><div>Insulin-like Growth Factor I (IGF-1) is crucial for growth, metabolism, and cell proliferation. Its detection is significant for diagnosing and monitoring various diseases. Chemiluminescence immunoassay (CLIA) is commonly used for IGF-1 detection but is prone to interference and variability. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) offers higher specificity and sensitivity but is less clinically applied. This study compared the consistency of serum IGF-1 levels detected by MALDI-TOF MS and CLIA.</div></div><div><h3>Methods</h3><div>A total of 660 serum samples from healthy individuals aged 0 to 90 years were included and analyzed using MALDI-TOF MS and CLIA methods. Initially, the MALDI-TOF MS results for the full cohort were assessed for agreement with age- and sex-specific reference intervals provided by the CLIA kit. Subsequently, a subset of 108 participants underwent paired testing under identical conditions to evaluate method comparability. The consistency between the two methods was evaluated using linear regression, the intraclass correlation coefficient (ICC), and Bland-Altman analysis.</div></div><div><h3>Results</h3><div>In most age groups, the results of IGF-1 concentration measured by MALDI-TOF MS fell within the reference range established by CLIA. A strong correlation (<em>R</em>² = 0.982) was observed between the two methods, with the regression equation defined as IGF-1_CLIA = 0.972 × IGF-1_{MALDI-TOF MS} + 5.041. The correlation coefficients were 0.994 in children and 0.985 in adults (<em>P</em> &lt; 0.001), and ICC values exceeded 0.80, indicating high consistency. Bland-Altman analysis showed a mean difference of −0.25 ng/mL, with 95% limits of agreement ranging from −24.54 to 24.04 ng/mL, which falls within the clinically acceptable range.</div></div><div><h3>Conclusions</h3><div>MALDI-TOF MS shows good consistency with CLIA in detecting serum IGF-I levels, providing evidence for its clinical application.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"583 ","pages":"Article 120835"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965273","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}

{"title":"A novel CLPP variant in a Pakistani family with Perrault syndrome associated with recurrent fevers","authors":"Nisar Ahmad ,&nbsp;Pingchuan Zhang ,&nbsp;Muhammad Muzammal ,&nbsp;Wasim Shah ,&nbsp;Li Ran ,&nbsp;Maryam Niaz ,&nbsp;Jia-Da Li ,&nbsp;Meichao Men","doi":"10.1016/j.cca.2026.120832","DOIUrl":"10.1016/j.cca.2026.120832","url":null,"abstract":"<div><div>Perrault syndrome (PRLTS) is an autosomal recessive disease with sensorineural hearing loss and ovarian dysfunction in girls, and either a fluctuating neurological phenotype or not. PRLTS type 2 is known to be caused by pathogenic variants of the <em>CLPP</em> gene that encodes mitochondrial ATP-dependent protease. This paper involved clinical and genetic studies on a Pakistani family with PRLTS. Whole-exome sequencing identified a novel homozygous <em>CLPP</em> missense mutation (NM_006012.4: c.250 A &gt; C; p.Ile84Leu). Its pathogenicity was assessed with the help of multiple sequence alignment, AlphaFold protein modeling, and docking with CLPX with the help of ClusPro. Auditory brainstem responses and tympanometry were in clinical assessment. The individuals were found to have a uniform phenotype of severe sensorineural hearing loss, mild intellectual disability, ataxia and frequent fever. There was one patient in whom the unilateral Eustachian tube dysfunction was hinted at by Tympanometry. At the molecular level, the identified CLPP variant involved a highly conserved residue. Structural modeling showed preserved protein architecture, whereas docking simulations revealed disrupted CLPP-CLPX interaction, suggesting a basis for impaired proteostasis. We report a novel <em>CLPP</em> missense variant (p.I84L) in a Pakistani family with PRLTS, expanding the mutational spectrum of <em>CLPP</em>. To the best of our knowledge, recurrent fever was reported in PRLTS for the first time, which expanded the PRLTS phenotype spectrum.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"583 ","pages":"Article 120832"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959025","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}