Critical reviews in clinical laboratory sciences最新文献

{"title":"Post-translational modifications of proteins: dynamic regulatory network and therapeutic targets of tumor immune escape in pan-cancer.","authors":"Qilu Yan, Qingqing Zhai, Shuyang Yu, Wangzheqi Zhang","doi":"10.1080/10408363.2025.2598380","DOIUrl":"10.1080/10408363.2025.2598380","url":null,"abstract":"<p><p>Post-translational modifications (PTMs) are critical regulators of protein function. Nearly two-thirds of all human proteins contain at least one PTM. These PTMs introduce covalent modifications, which modulate protein activity, location, and interactions. Further, PTMs are essential for understanding both physiological homeostasis and pathophysiology, and they play a key role in tumorigenesis and cancer development. Tumor immune evasion depends on dysregulated immune homeostasis caused by interactions between tumor cells and immune cells in the tumor microenvironment (TME). In this context, PTMs have emerged as one of the key regulators. From a pan-cancer perspective, PTMs remodel the tumor immune microenvironment through diverse mechanisms. The inability to regulate these processes is a common factor contributing to immune evasion in various cancers. It also facilitates crosstalk between tumor cells and components of TME, which in turn influences the response to immunotherapy. Because PTMs are dysregulated in cancers and can be reversed through drugs, they are attractive therapeutic targets. Small-molecule modulators of PTMs have the potential to reprogram the immune microenvironment and improve immune checkpoint blockade responses. Importantly, wide-ranging signal exchange networks between PTMs collectively increase tumoral immune phenotypic diversity and reveal new shared mechanisms of pan-cancer immune evasion. Recent studies show that the ways tumor cells change their surface proteins are driven by alterations in the tumor-immune environment. Further work could lead to strategies to treat many different cancers. Targeting PTM networks may overcome immune tolerance and significantly improve the clinical prognosis of cancer patients.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"474-507"},"PeriodicalIF":6.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145826997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stage-specific circulating transcriptomic and proteomic biomarkers and regulators in colorectal cancer: bridging affordable diagnostics and translational therapeutics.","authors":"Raajesh Anand Natarajan","doi":"10.1080/10408363.2026.2682852","DOIUrl":"https://doi.org/10.1080/10408363.2026.2682852","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, driven largely by pronounced molecular heterogeneity and delayed clinical detection. Although high-throughput sequencing technologies have substantially advanced the understanding of CRC biology, their routine clinical implementation remains constrained by high costs, infrastructural requirements, and limited accessibility. This review addresses these translational barriers by systematically synthesizing circulating transcriptomic and proteomic biomarkers within a clinically scalable framework. Particular emphasis is placed on biomolecules detectable using reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), two widely accessible platforms that underwent extensive global optimization during the COVID-19 pandemic and are readily adaptable to liquid biopsy workflows. Through a stage-resolved analysis, we identify 9 genomic and 7 proteomic biomarkers associated with early-stage (I-II) CRC, alongside 9 genomic and 4 proteomic biomarkers linked to advanced-stage (III-IV) disease progression. Beyond biomarker cataloging, these molecules are integrated with Cancer Hallmark pathways, clinical-stage associations, and available clinical trial evidence to evaluate their biological relevance and translational readiness. In addition, we summarize standardized operating procedure (SOP) considerations and multiplex detection strategies to improve assay reproducibility, scalability, and cross-border clinical implementation. Collectively, this review bridges molecular discovery with clinically deployable laboratory workflows and provides a translational roadmap for the development of affordable, liquid biopsy-based diagnostic strategies aimed at improving CRC detection, patient stratification, longitudinal monitoring, and early therapeutic intervention.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-25"},"PeriodicalIF":6.2,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of vitamin D in cardiovascular health.","authors":"Markus Herrmann, Harald Sourij, Dirk von Lewinski, Wolfgang Herrmann","doi":"10.1080/10408363.2026.2692422","DOIUrl":"https://doi.org/10.1080/10408363.2026.2692422","url":null,"abstract":"<p><p>Vitamin D has multiple functions in most organs and tissues of the human body. In addition to its canonical role in bone and mineral metabolism, vitamin D impacts cell growth and differentiation, immunity, glucose homeostasis, cognition, and endocrine pathways. Mounting evidence links vitamin D deficiency to a broad spectrum of diseases including cardiovascular disease (CVD). Considering that both vitamin D deficiency and CVD are highly prevalent conditions, it is important to understand the potential interplay between these two. Observational studies consistently demonstrate an inverse relationship between the inactive prohormone 25-hydroxyvitamin D (25[OH]D) in serum, which represents the body's vitamin D reservoir, and CVD risk. Specifically, lower serum 25-(OH)D levels are associated with a higher risk of CVD events and CVD mortality. Putative mechanisms that mediate the pathophysiologic effects of vitamin D deficiency comprise oxidative stress, systemic inflammation, activation of the renin-angiotensin-aldosterone system, endothelial dysfunction, hypertension, and myocardial fibrosis. However, vitamin D supplementation failed to demonstrate significant CVD-related benefits. Although existing randomized, placebo-controlled supplementation studies yielded neutral results, most of these studies did not specifically target CVD outcomes. Another limitation of previous randomized controlled studies is the application of fixed vitamin D dosing regimens, regardless of the actual serum 25-(OH)D level. Studies that escalate the vitamin D dose until serum 25-(OH)D reaches a prespecified target range are largely lacking. This article reviews the existing literature on the role of vitamin D deficiency in CVD incidence, progression, and mortality.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-20"},"PeriodicalIF":6.2,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indirect methods for the verification of reference intervals in laboratory medicine.","authors":"Georg Hoffmann, Inga Trulson, Jakob Adler, Sandra Klawitter, Stefan Holdenrieder, Frank Klawonn","doi":"10.1080/10408363.2026.2687513","DOIUrl":"https://doi.org/10.1080/10408363.2026.2687513","url":null,"abstract":"<p><p>Despite the obligation imposed by national and international accreditation standards to periodically verify reference intervals against local conditions, this task is performed infrequently in most clinical laboratories due to the perceived complexity relative to the resources available. The CLSI/IFCC C28-A3 standard recommends a simple 20-sample binomial procedure whose statistical power is, however, fundamentally inadequate: it cannot reliably detect intervals that are too wide, requires sample sizes approaching <i>n</i> = 100 to achieve acceptable sensitivity for shifted or too narrow limits, and offers laboratories a false sense of compliance. Fifty years after the foundational conceptual framework for reference intervals was established, a critical and timely reassessment is therefore warranted. This review evaluates the limitations of the CLSI/IFCC 20-sample verification approach and systematically examines methodological advances published since the last comprehensive review in 2018, with emphasis on indirect statistical methods capable of exceeding guideline performance. A structured literature search identified 22 publications meeting inclusion criteria, and about the same number of references were added from the authors' literature collections to ensure complete coverage of the topic, especially for more recent literature that may not yet be fully indexed. Four converging lines of evidence support replacing the binomial procedure with indirect estimation methods applied to routine laboratory data. Two open-source R packages (reflimR and refineR) implement quantitative acceptance criteria based on equivalence limits (EL) and uncertainty margins (UM), respectively. Independent multi-center and multi-method studies confirm robust performance and comparable results of indirect methods over a wide range of analytes. Machine learning techniques, particularly Gaussian mixture deconvolution and regression tree modeling, extend verification capability to datasets with high pathological prevalence or complex biological confounders. Web-based platforms now make these tools accessible without programming expertise. In conclusion, indirect verification methods have reached sufficient methodological maturity for guideline endorsement. A stepwise workflow that includes rapid screening with reflimR, confirmatory analysis with refineR, and machine learning-assisted decomposition for complex cases is proposed as a practical, statistically defensible standard for routine laboratory verification. This workflow has been implemented in a new web tool at trillium.de/VeRIf.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-17"},"PeriodicalIF":6.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustainability and waste reduction in clinical laboratories.","authors":"Adetoun A Ejilemele, Ila R Singh","doi":"10.1080/10408363.2026.2687509","DOIUrl":"https://doi.org/10.1080/10408363.2026.2687509","url":null,"abstract":"<p><p>Hospitals are major generators of waste, producing an estimated 5.9 million tons of solid waste annually in the United States alone. This burden contributes to environmental pollution, rising operational costs, and downstream health impacts. While operating rooms, food services, and imaging departments have received increasing scrutiny as waste-intensive sectors, clinical laboratories, despite their high energy use, dependence on single-use plastics, and central role in every diagnostic decision, remain comparatively understudied in sustainability research. In this review, we argue that integrating environmental impact into laboratory practice represents the next evolution of quality in laboratory medicine. We propose a workflow-based framework to evaluate waste generation across the full testing continuum, including test ordering, specimen collection, transport, analysis, post-analytical practices, procurement, and accreditation. Drawing on current evidence, case studies, and emerging sustainability programs, we identify practical intervention points and critical knowledge gaps, including the lack of standardized environmental metrics such as waste-per-test, energy-per-test and water-per-test. By treating environmental performance as measurable, comparable and improvable, clinical laboratories can help lead healthcare's broader transition toward high-value, environmentally responsible care while maintaining diagnostic quality and patient-centered care.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-14"},"PeriodicalIF":6.2,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aptamer-based biosensing strategies for influenza virus detection: a systematic and critical review of electrochemical and optical platforms.","authors":"Amir Hossein Esfandiari, Hamed Afarande, Vahid Reza Amini, Behnaz Hatamluyi, Zahra Meshkat, Aida Gholoobi","doi":"10.1080/10408363.2026.2688519","DOIUrl":"https://doi.org/10.1080/10408363.2026.2688519","url":null,"abstract":"<p><p>Influenza virus remains a major global health challenge due to its genetic variability and frequent emergence of novel strains. Subtyping is determined by the diverse arrangements of hemagglutinin (HA) and neuraminidase (NA) glycoproteins, with HA frequently serving as the molecular target for diagnostic assays. Conventional detection methods, however, are labor-intensive, require specialized expertise, and often lack adaptability to rapidly evolving viral variants. Aptamer-based biosensing technologies have emerged as promising alternatives. Aptamers, synthetic single-stranded DNA or RNA oligonucleotides generated via the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process, exhibit exceptional specificity and high binding affinity, enabling precise recognition of viral proteins. This systematic and critical review synthesizes recent advances in aptamer-integrated biosensing platforms, focusing on electrochemical and optical detection strategies for influenza virus. By comparing sensitivity, specificity, operational simplicity, and translational potential, this review highlights that electrochemical platforms are better suited for point-of-care use due to their speed and simpler instrumentation, while optical platforms offer superior sensitivity for reference laboratory settings. A key finding is that despite two decades of research and remarkable analytical sensitivity (reaching fg/mL levels), the vast majority of platforms have not been validated on authentic clinical specimens or compared with gold-standard molecular methods, explaining why none have entered routine diagnostic workflows. The analysis provides evidence-based insights into which biosensing strategies are most suitable for the development of rapid, reliable, and scalable diagnostic tools against influenza virus, thereby informing future research directions and clinical translation.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-25"},"PeriodicalIF":6.2,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing patient safety through laboratory quality indicators in clinical pathology.","authors":"Jieli Li","doi":"10.1080/10408363.2026.2678823","DOIUrl":"https://doi.org/10.1080/10408363.2026.2678823","url":null,"abstract":"<p><p>Quality indicators (QIs) are widely used in clinical laboratories to support quality management, patient safety, and regulatory compliance. Although regulatory and accreditation frameworks emphasize the use of QIs across the total testing process, published literature has often focused on analytical performance or discipline-specific approaches. Less attention has been given to how QIs are selected, interpreted, and sustained across the full range of clinical pathology subspecialties in routine practice. This critical review examines the role of quality indicators within clinical pathology laboratories, with emphasis on their selection, implementation, interpretation, and integration into quality management systems. Regulatory and accreditation expectations from CLIA, CAP, ISO 15189, and the Joint Commission are used as contextual anchors. We describe a decision-oriented lifecycle for quality indicators that emphasizes risk-based prioritization, feasibility, actionability, and governance integration. Practical examples of quality indicators spanning the pre-analytical, analytical, and post-analytical phases are presented across multiple subspecialties. Approaches to quality indicator data analysis are discussed, with particular focus on longitudinal, within-laboratory monitoring as a practical strategy for identifying meaningful trends and guiding improvement in diverse practice settings. Quality indicators are most effective when used as adaptive management tools rather than static compliance measures. Their value depends on thoughtful selection aligned with patient risk and laboratory scope, consistent interpretation within local context, and sustained linkage to corrective and preventive action. By adopting a discipline-aware, practice-focused approach, clinical pathology laboratories can use quality indicators to support continuous improvement, enhance patient safety, and meet regulatory and accreditation expectations across evolving healthcare environments.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-11"},"PeriodicalIF":5.5,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omics-based computational approaches for biomarker identification, prediction, and treatment of Long COVID.","authors":"Sindy Pinero, Xiaomei Li, Junpeng Zhang, Marnie Winter, Sang Hong Lee, Thin Nguyen, Lin Liu, Jiuyong Li, Thuc Duy Le","doi":"10.1080/10408363.2025.2583083","DOIUrl":"10.1080/10408363.2025.2583083","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Long COVID, or post-acute sequelae of COVID-19 (PASC), is a major global health problem, with cumulative estimates suggesting that around 400 million people worldwide have been affected. It is characterized by persistent or new symptoms such as fatigue, cognitive impairment, and breathlessness lasting beyond four weeks after acute infection. Diverse clinical manifestations, chronic course, and incompletely understood pathophysiology-including hypotheses involving viral persistence, immune dysregulation, autoimmunity, endothelial dysfunction, and metabolic reprogramming-impede the development of diagnostic criteria, biomarkers, and targeted therapies. We conducted a critical review of 101 Long COVID omics studies, focusing on the computational methods used and their methodological quality. Using standardized criteria, we evaluated study design, statistical rigor, reproducibility, and clinical relevance across genomics, epigenomics, transcriptomics, proteomics, metabolomics, and multiomics integration, and mapped these findings onto regulatory and translational frameworks. Despite substantial methodological heterogeneity, convergent biological signals emerged. Genomic studies implicate risk loci in immune and cardiopulmonary pathways. Epigenomic analyses identify differentially methylated regions in immune and circadian genes. Transcriptomic studies reveal persistent dysregulation of innate immune and coagulation pathways, as well as reproducible molecular endotypes. Proteomic studies consistently show abnormalities in the complement cascade and coagulation, with a small panel of complement proteins showing highly reproducible changes across independent cohorts. Metabolomic studies demonstrate sustained mitochondrial dysfunction and altered cellular bioenergetics for up to two years after infection. Multiomics integration supports at least two major endotypes, characterized by predominant inflammatory versus metabolic dysregulation, and provides a basis for patient stratification and computational treatment discovery. Machine learning models frequently achieve high classification performance, but are rarely externally validated. Critical limitations restrict clinical translation. Most studies are underpowered relative to analytical complexity, use heterogeneous case definitions and controls, and report platform-specific signatures with limited overlap. External validation, preregistered analysis plans, and regulatory-aligned assay development are uncommon. To date, no regulatory-approved diagnostic assay or evidence-based therapeutic intervention has directly emerged from these computational findings. Future progress requires harmonized phenotyping protocols, adequately powered longitudinal cohorts with external validation, integration of spatial omics and explainable artificial intelligence, and early engagement with regulatory and health-technology assessment pathways. This review provides a critical assessment and a translational roadmap, ","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"332-358"},"PeriodicalIF":5.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145713614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering hidden connections: the role of the male reproductive system microbiome and gut microorganisms in implantation: a critical review.","authors":"Magdalena Jendraszak, Mirosław Andrusiewicz","doi":"10.1080/10408363.2025.2562894","DOIUrl":"10.1080/10408363.2025.2562894","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Recent advancements in sequencing technologies have uncovered complex and diverse microbial communities inhabiting various niches of the human body, including the reproductive system. This review explores the significance of the male genital and gut microbiomes in maintaining reproductive health, focusing on their potential roles in embryo implantation and pregnancy outcomes. A comprehensive literature search was conducted using MEDLINE, Web of Science, and Scopus for articles published between 2004 and 2024. Search terms included \"microbiome,\" \"implantation,\" \"inflammation,\" \"male reproductive system,\" \"recurrent miscarriage,\" \"recurrent implantation failure,\" and \"probiotics.\" From an initial pool of 1,091 articles, 107 were selected after applying filters for clinical, comparative, and observational studies. Ultimately, 21 articles met the quality criteria and were included in the review. While the female genital microbiome has been extensively studied and its role in implantation and embryo development well established, research on the male genital microbiome remains limited, and its influence is not yet fully understood. Nevertheless, emerging data suggest that the male reproductive tract harbors its own distinct microbial community, which may affect fertility, implantation, and pregnancy outcomes. The presence of certain bacteria and leukocytes in semen has been associated with sperm DNA damage, potentially compromising fertility and embryo development. Moreover, microbial exchange between partners during intercourse may alter the composition of the female reproductive microbiome, potentially influencing implantation success. The male and female reproductive tracts are colonized by microbial communities that play crucial roles in preventing infections and supporting reproductive health. Disruptions in these ecosystems have been linked to infertility, miscarriage, and preterm birth. Additionally, the gut microbiome is believed to interact with the reproductive system, possibly influencing implantation through immune and metabolic pathways. A deeper understanding of these connections is essential for identifying new preventive and therapeutic strategies for individuals experiencing recurrent pregnancy loss or implantation failure. Identifying specific microbial patterns associated with dysbiosis is critical for the development of targeted interventions. Potential therapeutic approaches include probiotics, prebiotics, and antibiotics, which may help restore microbial balance, enhance fertility, and reduce the risk of miscarriage. Antibiotic treatment may also prove beneficial in addressing infections that disrupt implantation. As microbial exchange, sperm DNA integrity, and immune regulation are all influenced by the microbiome, further research is necessary to understand its role in reproductive outcomes fully. Microbiome-targeted therapies represent a promising frontier in reproductive medicine. However, their clinical efficacy must be","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"359-389"},"PeriodicalIF":5.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parallelism in neurodegenerative biomarker tests: hidden errors and the risk of misconduct.","authors":"A Petzold, Joachim Pum, David P Crabb","doi":"10.1080/10408363.2025.2583078","DOIUrl":"10.1080/10408363.2025.2583078","url":null,"abstract":"<p><p>Biomarkers are critical tools in the diagnosis and monitoring of neurodegenerative diseases. Reliable quantification depends on assay validity, especially the demonstration of parallelism between diluted biological samples and the assay's standard curve. Inadequate parallelism can lead to biased concentration estimates, jeopardizing both clinical and research applications. Here, we systematically review the evidence of analytical parallelism in body fluid (serum, plasma, cerebrospinal fluid) biomarker assays for neurodegeneration and evaluate the extent, reproducibility, and reporting quality of partial parallelism. This systematic review was registered on PROSPERO (CRD42024568766) and conducted in accordance with PRISMA guidelines. We included studies published between December 2010 to July 2024 without language restrictions. Eligible studies included original research assessing biomarker concentrations in body fluids with data suitable for evaluating serial dilution and standard curve parallelism. The data extraction for interrogating parallelism included dilution steps, measured concentrations, and sample types. For each study, we generated parallelism plots in a uniform and comparable way. These graphs were used to come to a balanced decision on whether parallelism or partial parallelism was present. The risk of bias was assessed based on sample preparation, buffer consistency, and methodological transparency. Of 44 eligible studies, 19 provided sufficient data for generating 49 partial parallelism plots. Only 7 plots (14%) demonstrated clear partial parallelism. Partial parallelism was typically achieved over a narrow dilution range of about three doubling steps. Most assays deviated from parallelism, risking over- or underestimation of biomarker levels if determined at different dilution steps. A high risk of bias was identified in 9 studies using spiked or artificial samples, inconsistent dilution buffers, or incomplete reporting. Several studies assessed sample-to-sample parallelism rather than sample-to-standard, contrary to guidelines by regulatory authorities. In conclusion, partial parallelism was infrequently observed and inconsistently reported in most biomarker assays for neurodegeneration. Narrow dilution ranges and variable methodologies limit generalizability. Transparent reporting of dilution protocols and adherence to established analytical validation guidelines are needed. This systematic review has practical implications for clinical trial design, regulatory approval processes, and the reliability of biomarker-based diagnostics.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"305-331"},"PeriodicalIF":5.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}