Cancer is a major global public health problem. Epigenetic regulation, such as DNA methylation, histone modifications, and non-coding RNA (ncRNA) dysregulation, is a main driver of tumorigenesis and progression. Recent studies are suggesting that the human microbiota, commonly referred to as a “super-organ,” are not only associated with tumors but play an active role in regulating the epigenetic state of the host. The aim of this review is to systematically explain the main regulatory mechanisms of the “microbiota-epigenetic-cancer regulatory axis”, their heterogeneous manifestations across various tumors, and the exploration of novel diagnostic biomarkers and therapeutic strategies of this regulatory axis. Microbiota mainly drive tumor epigenetic remodeling through three levels. First, microbial metabolites (e.g., butyrate) can act as natural histone deacetylase inhibitors (HDACis), or tryptophan metabolites can directly regulate the host chromatin state by activating the aryl hydrocarbon receptor (AhR) pathway. Second, bacterial structures such as lipopolysaccharide (LPS) can induce inflammation and disease by activating inflammatory signaling pathways. Third, specific pathogens like HBV and Helicobacter pylori can hijack the host’s epigenetic machinery or induce epigenetic reprogramming via virulence factors. The tumor-resident microbiota (TRM) is an emerging and important field. TRM that actively partake in the tumor microenvironment (TME) may promote immune evasion through in situ mechanisms (e.g., lactylation), thereby confirming a direct and causal role for microbes within tumors. The epigenetic therapeutic strategies based on these mechanisms are being rapidly developed, including, for example, the regulation of microbial community structure (e.g., FMT), the targeting of microbial metabolic pathways, and TRM-specific approaches and key pathways (e.g., engineered bacteria). These strategies also have great potential as biomarkers for tumor prognosis prediction and therapy response evaluation. Overall, microbes and tumor epigenetics are part of a network that brings together their metabolism, inflammation, immunity, and gene regulation. Future research will shift from exploring the correlation of the gut microbiota at the macro level to exploring TRM’s causality within the TME. By using gnotobiotic mouse models, organoid co-cultures, and multiomics, we will deeply analyze the microenvironment specificity of this network and develop precision interventions targeting TRM that could transform cancer therapy.

Circulating plasma DNA has found important applications in diverse medical fields, including prenatal testing, transplantation, and especially cancer. Many companies have developed products for detecting minimal residual disease, selecting or monitoring therapy, assessing prognosis, and confirming diagnosis. One major application is in screening asymptomatic individuals for the presence of cancer. Screening may facilitate better clinical outcomes through earlier interventions. Collectively, these technologies are widely known as “liquid biopsies”. After the extraction of free DNA from the circulation, it is analyzed by various molecular techniques to explore differences between DNA originating from normal cells and cancer cells. Circulating plasma DNA originating from tumors (ctDNA) is expected to harbor the same molecular changes as tumor tissue itself. Thus, ctDNA is considered a surrogate of cancer tissue, but without the need to perform invasive biopsies to obtain it. Many new diagnostic companies have taken advantage of this new biomarker and developed technologies for screening for one or multiple cancers. We previously estimated the amount of ctDNA in circulation, which is admixed with DNA originating from normal cells. We concluded that since only a small fraction of the whole plasma (3 liters) is used for testing (3 to 4 mL), it is possible that the retrieved ctDNA may not be enough for cancer diagnosis in all patients. This problem is more acute with small tumors. Here, we mention some companies in the “liquid biopsy” arena and analyze their clinical data to establish if their tests are close to entering the clinic. We conclude from this analysis that current data do not support the use of these technologies for population screening due to many false negative and false positive results.

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.

The One Health Approach recognizes the interconnectedness of human, animal, and environmental health. Emerging infectious diseases, climate change, and food/water insecurity impact all three. Global health improvement requires collaborative, holistic strategies at all levels to mitigate harmful factors and promote sustainable development. This review defines the One Health approach and illustrates its role in combating antibiotic resistance, emerging infectious diseases, and food/water insecurity. Laboratory medicine for both human and veterinary health, as well as environmental monitoring, are crucial in this context.

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, outlining how methodologically robust computational omics can be advanced toward clinically actionable tools for Long COVID.

Antiphospholipid antibodies (aPL) may interfere with prothrombin time (PT) and international normalized ratio (INR) assays. Patients with antiphospholipid syndrome (APS) are often treated with vitamin K antagonists and require therapeutic monitoring with the INR. However, it remains unclear to what extent these assays are influenced by aPL and the consequent clinical relevance. This scoping review aimed to map the available evidence on the impact of APS and aPL on PT/INR assays, describe the methods used in research in this area, and identify gaps to guide future investigations. Two databases (MEDLINE and Embase) were searched, in the date range of 1 January 1984 to 10 June 2025, for reports describing clinical or in vitro research involving human subjects with APS or aPL that were analyzed with INR/PT assays. Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews (PRISMA-Scr) guideline. 3,824 records were retrieved and after deduplication, title/abstract screening, and full-text screening, 39 studies were included in the review. Based on study design, we identified 23 observational clinical studies, 11 case reports/series, and 5 studies reporting in vitro aPL investigations with one report also including a case-control study. Observational studies showed that INR assays utilizing thromboplastin with recombinant human tissue factor (TF), including point-of-care tests (POCT), are more influenced by aPL than assays based on tissue-derived thromboplastins, although not consistently. Case reports described patients, mostly with the presence of multiple aPL, with clinically significant misinterpretation of their anticoagulation status. In vitro studies demonstrated reagent- and antibody-dependent effects, with anti–β2-glycoprotein I and antiprothrombin immunoglobulin G antibodies variably prolonging or shortening the PT. Evidence from both clinical and in vitro studies indicates that INR results in APS patients may be unreliable, particularly with specific recombinant human TF-based and POCT reagents, although not systematically. Interference is antibody profile-, antibody level-, and reagent-dependent. However, studies remain heterogeneous, often small in scale, and methodologically inconsistent with variable evaluation criteria. Well-defined future research should aim to identify in which APS patient subgroups an INR would not be reliable with specific assays.

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.

Pleural fluid biochemical analyses are of great value in verifying the etiology of undiagnosed pleural effusions. The preanalytical phase of pleural fluid biochemical analyses refers to the potential errors associated with specimen collection procedures, transportation, and sample stability. The analytical phase refers to the matrix effects and interference. The post-analytical phase refers to the clinical interpretation of the biochemical analyses. This review summarizes the preanalytical, analytical, and postanalytical phases of pleural fluid biochemical analyses. Evidence regarding potential preanalytical errors (e.g. stability, interference, and effects of anticoagulants on biomarker results) was summarized. In addition, we compiled evidence on the clinical interpretation of pleural fluid biomarkers, particularly from systematic reviews and meta-analyses. Finally, we discuss the future directions of biochemical analyses of pleural fluid.

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 validated through rigorous research. This review underscores the importance of characterizing the composition and functional roles of the genital and gut microbiomes in order to inform the development of novel diagnostic tools and therapeutic strategies aimed at improving reproductive health and pregnancy outcomes.

Several immune/inflammatory components have been associated with arthritis. The role of monocytes/macrophages in inflammatory arthritis has been explored over the last years; however, the role of other myeloid cells, such as neutrophils and dendritic cells, in driving the pathophysiology of arthritis is largely overlooked. In this article, we aim to discuss literature pointing to the role of these immune cells in inflammatory arthritis and emphasize the multiple and dynamic phenotypic roles these cells can hold either in the persistence or in the resolution of inflammation. We also highlight the interactions between neutrophils, macrophages, and/or dendritic cells in the arthritic joint space. We further discuss pathways and features that may be of importance for characterizing neutrophils and dendritic cells, the phenotype of which can be “reprogrammed” to direct the resolution of inflammation efficiently in the arthritic joint. Identifying novel and patient-tailored approaches for addressing persistent or recurrent inflammation through these cellular pathways, might address unmet needs in arthritis management. Types of arthritides discussed in this review include osteoarthritis, spondyloarthritis and rheumatoid arthritis. Brief reference to the role of these immune cells in the acute gouty inflammation is also included.