Search Results (247,273)

Background: Gliomas are among the most common and heterogeneous primary brain tumors, exhibiting substantial molecular and transcriptomic diversity that complicates diagnosis, grading, and treatment planning. Advances in artificial intelligence (AI), particularly machine learning (ML), offer powerful opportunities to analyze high-dimensional gene expression data and support precision oncology. Methods: This study proposes an interpretable ML framework to classify brain tumor subtypes—glioblastoma, astrocytoma, and oligodendroglioma—and to predict tumor grades (2, 3, and 4) using microarray-based gene expression data. The analysis was conducted on the REMBRANDT dataset, comprising 464 labeled samples (221 glioblastoma, 148 astrocytoma, 67 oligodendroglioma, and 28 controls) and 314 tumor samples for grade classification. Results: The ML models achieved high performance for disease classification, with accuracies of 99.6% (AUC 99.89%) for glioblastoma, 98.3% (AUC 99.83%) for astrocytoma, and 98.95% (AUC 100%) for oligodendroglioma. Tumor grade predictions also performed strongly, achieving 83.7% accuracy (AUC 88.2%) for grade II vs. III, 91.3% (AUC 94.8%) for grade II vs. IV, and 84.2% (AUC 90.8%) for grade III vs. IV. SHAP analysis identified key genes contributing to the model predictions (e.g., WIF1, STX6, RGS5, and ACTR2), and KEGG enrichment identified the candidate pathways involved in vesicular transport, metabolism, and immune signaling. Conclusion: Overall, our findings demonstrate that interpretable ML models can accurately differentiate glioma subtypes and grades, and SHAP analysis can help identify the strongest predictors of our models. These findings provide additional insights into the heterogeneous genetic and molecular landscape of brain gliomas and are intended to complement, not replace, conventional histopathological diagnosis. Full article

Background: Neuroinflammation is recognized as a key contributor to Parkinson’s disease (PD), but the relationships between inflammatory signaling, immune-state alterations, and cell-type-specific transcriptional programs remain unclear. Methods: Public transcriptomic datasets, including GSE20141 (discovery cohort) and the substantia nigra subset of GSE114517 (external validation cohort), were analyzed. Genes identified by exploratory differential-expression screening in the discovery cohort were intersected with predefined inflammation- and chemokine-related gene sets to define a candidate space for downstream prioritization. Protein–protein interaction, Gene Ontology, KEGG, and immune-signature analyses were performed, followed by machine learning-based feature prioritization using Elastic Net, support vector machine-recursive feature elimination, and random forest. Prioritized candidates were further evaluated by cross-platform validation, single-nucleus transcriptomic mapping, and a hypothesis-generating in silico perturbation analysis in PD astrocytes. Results: Seventeen genes were retained at the intersection of PD-related differentially expressed genes and inflammation-/chemokine-associated gene sets. These candidates formed a response module enriched in mitochondrial organization, oxidative phosphorylation, and mitophagy pathways. Immune-signature analysis suggested an altered transcriptome-derived immune landscape in PD, with changes in NK cell-related signatures and significant correlations between immune-state scores and the candidate genes. Machine learning-based prioritization yielded five shared candidates, of which only CCL2 and PAK6 showed same-direction support with nominal significance in the external validation cohort. Single-nucleus transcriptomic analysis localized CCL2 predominantly to astrocytes, whereas PAK6 was more strongly associated with neuronal populations, particularly OTX2-positive ventral midbrain neurons. In silico perturbation analysis further predicted that CCL2 suppression in PD astrocytes may be associated with translational- and ribosome-related regulatory programs. Conclusions: CCL2 and PAK6 emerged as prioritized candidate biomarkers associated with PD-related inflammatory and chemokine-linked transcriptional alterations in the substantia nigra. More broadly, this study provides a multi-layered framework for candidate prioritization, cross-platform validation, and cell-type-level contextualization in PD neuroinflammation. Because the study is computational and the perturbation analysis is predictive, orthogonal experimental validation will be required to determine whether CCL2 and PAK6 are biomarkers of disease-associated transcriptional states, functional contributors to PD pathogenesis, or both. Full article

Rheumatoid arthritis (RA) has traditionally been managed after the onset of clinically apparent synovitis; however, accumulating evidence indicates that disease-related immune abnormalities precede clinical diagnosis by several years. This preclinical phase is characterized by systemic autoimmunity, early musculoskeletal symptoms, and subclinical inflammation in genetically and environmentally susceptible individuals. In this review, we summarize current concepts regarding the pathogenesis, risk stratification, and therapeutic interception of preclinical RA. Particular attention is given to the mucosal origin hypothesis and to the roles of immunosenescence, peripheral helper T cells, and fibroblast-like synoviocytes in early disease evolution. Recent advances in clinical, serological, and imaging-based risk stratification have improved the identification of individuals at high risk of progression to clinical RA, and emerging intervention trials have shown that selected therapies may delay disease onset or reduce early inflammatory burden. Although complete prevention of RA has not yet been achieved, these findings support a paradigm shift from the treatment of established RA toward earlier, risk-adapted intervention before irreversible joint damage occurs. Future efforts should focus on refining predictive biomarkers, optimizing the timing and intensity of intervention, and establishing safe, individualized preventive strategies. Full article

Ceramides are central bioactive sphingolipids that regulate diverse cellular processes, including membrane organization, energy metabolism, and stress signaling. Emerging evidence has implicated that ceramide dysregulation is associated with the onset and progression of heart failure. This review introduces the understanding of ceramide metabolism, focusing on its biosynthesis, and functional roles in cardiomyocytes. In addition, the contribution of systemic ceramides derived from circulating lipoproteins and peripheral tissues to cardiovascular risk is also discussed. In parallel, it is highlighted that cardiomyocyte-intrinsic ceramide synthesis plays physiological and pathological roles in the heart. Particularly, excessive ceramide accumulation is detrimental for cardiac function, through multiple mechanisms, such as lipotoxic effects, mitochondrial impairment, inflammation, and cell death. The current review discusses the potential diagnostic and therapeutic strategies targeting ceramide metabolism, as well as the open questions about ceramide association with heart disease. Full article

Dickkopf-1 (DKK1) is a secreted glycoprotein that traditionally acts as an antagonist of canonical Wnt/β-catenin signaling. Although it functions as a tumor suppressor in some specific biological background and disease stages, growing evidence links DKK1 to tumor progression, immune evasion, and therapy resistance in a variety of multiple malignancies. This review provides a comprehensive bench-to-bedside overview of DKK1 in cancer. We first delineate how DKK1 regulates both Wnt-dependent and Wnt-independent pathways. From a clinical perspective, we evaluate the application potential of DKK1 as a diagnostic and prognostic biomarker. We further discuss the progress of DKK1-targeted interventions, ranging from monoclonal antibodies in clinical trials to next-generation therapeutic modalities. Finally, we discuss the challenges in clinical translation and suggest future directions for DKK1-based precision medicine. In summary, by integrating preclinical insights with current clinical data, this review provides a strategic roadmap for advancing DKK1-targeted therapies in cancer. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex pathogenesis involving epidermal barrier dysfunction, microbiome dysbiosis, and immune dysregulation. Despite significant advances in therapy, including biologics and targeted treatments, their use may be limited by adverse effects, highlighting the need for safe adjunctive strategies. Polyphenols are naturally occurring bioactive compounds that are abundant in plant-based foods and are known for their anti-inflammatory, antioxidant, and immunomodulatory properties, making them promising candidates for supportive AD management. This review integrates current evidence on the effects of polyphenols on epidermal barrier lipids, microbiome interactions, and key inflammatory pathways, including NF-κB and JAK/STAT signaling. Additionally, the role of polyphenols in modulating dendritic cell and neutrophil activity, and reducing reactive oxygen species (ROS) production and neutrophil extracellular trap (NET) formation, as well as their potential involvement in mitophagy regulation, is discussed. Polyphenols support epidermal barrier integrity by modulating the expression of key structural proteins, including filaggrin, involucrin, and loricrin, leading to a reduction in transepidermal water loss (TEWL). Furthermore, they interact bidirectionally with the gut microbiome, acting as metabolic substrates for beneficial bacteria and promoting the growth of short-chain fatty acid (SCFA)-producing species such as Lactobacillus, Bifidobacterium, and Akkermansia, while simultaneously inhibiting pathogenic strains. These findings highlight the role of polyphenols in maintaining microbiome homeostasis and supporting epidermal barrier integrity. The review encompasses findings from clinical studies, animal models, and mechanistic investigations, while also addressing limitations related to polyphenol bioavailability. Overall, polyphenols may represent a valuable adjunctive approach in AD management; however, further well-designed clinical and mechanistic studies are required to confirm their therapeutic potential. Full article

Plant-derived sweet proteins are promising low-calorie natural sweeteners that may reduce dietary sugar intake and prevent non-communicable diseases. Although seven have been identified—thaumatin, miraculin, monellin, mabinlin, brazzein, pentadin, and curculin (neoculin)—only thaumatin is currently approved as a food additive. The development of others requires comprehensive safety assessments, particularly regarding allergenicity. This systematic review aims to investigate and synthesize allergenicity assessment methods (in silico, in vitro, in vivo, and clinical) applied to these seven sweet proteins. The literature searches were conducted following PRISMA guidelines across Scopus, PubMed, and Wiley Online Library databases, up to 30 November 2025, with no time restrictions. The risk of bias in selected studies was evaluated using GRADE. After the selection process, 14 out of 2634 studies met the inclusion criteria. Thaumatin, miraculin, monellin, and brazzein emerged as the most extensively studied proteins. In silico approaches (sequence and structural homology) and in vitro assays (digestibility and cell-based methods) were the most commonly employed methods. In contrast, in vivo studies (animal models) and clinical evaluations (skin prick tests, oral food challenges) were rarely reported. Allergenicity studies on pentadin, mabinlin, and curculin (neoculin) are limited, indicating a research gap that requires further study to support regulatory approval and consumer acceptance. Full article

Purpose: To investigate the association between COVID-19 infection and the 1-year risk of acute urinary retention (AUR) and related urological complications in patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTs). Materials and Methods: Using the TriNetX global network, patients with BPH and LUTs between January 2020 and January 2024 were identified. Participants were classified into a COVID-19 cohort (N = 32,948) and a non-COVID control cohort (N = 434,123). Propensity score matching (1:1) balanced demographics, comorbidities, medications, and laboratory parameters. The primary outcome was AUR within one year. Secondary outcomes included Foley catheterization, urinary tract infection (UTI), gross hematuria, bladder stones, and prostate-related surgery. Results: After matching, 32,918 patients remained in each cohort. The COVID-19 group showed a significantly higher 1-year incidence of AUR compared with controls (2.18% vs. 0.32%; aHR 6.89, 95% CI 5.62–8.45; p < 0.0001). Increased risks were also observed for Foley catheterization (aHR 4.10), UTI (aHR 3.52), and prostate-related surgery (aHR 6.02). Kaplan–Meier analysis demonstrated persistent divergence in AUR-free survival. Conclusion: COVID-19 infection is independently associated with a markedly increased risk of AUR and urological complications in patients with BPH, highlighting the need for closer post-infection monitoring. Full article

Laparoscopic cholecystectomy is now established as the worldwide gold standard for the treatment of benign gallbladder disease. Despite technical advancements, bile duct injury (BDI) remains a major concern, especially in patients with obesity. It is well known that in patients with a Body Mass Index (BMI) ≥ 30 kg/m², identification of Calot’s triangle and the achievement of the Critical View of Safety (CVS) during laparoscopic cholecystectomy (LC) are made more challenging due to excessive visceral adiposity and concomitant hepatic steatosis reducing the workspace. Near-Infrared Fluorescence Cholangiography (NIRF-C) with Indocyanine Green (ICG) has emerged as an innovative, safe and effective technique to visualize the biliary anatomy and minimize the risk of iatrogenic BDI. However, its specific benefit in patients with obesity remains under-discussed compared to the general population. The main aim of this narrative review is to evaluate whether the intraoperative use of ICG in patients with obesity may reduce operative times and the risk of BDI. A focused review of the literature is performed on articles from 2010 to 2025 published on PubMed, Scopus and Web of Science. The application of ICG fluorescence in LC for patients with obesity represents a tangible clinical advantage, not only for anatomical identification and significant improvement of procedural efficiency, but also for the reduction in operative time. Full article

Over the past several decades, the gut microbiome (GM) has been the focus of extensive investigation. In recent years, major discoveries such as the role of maternal breastfeeding in infant GM development and mode of delivery on infant GM health have expanded scientific knowledge on this topic. As this is a rapidly expanding field of research, substantial work remains to further elucidate and integrate the existing evidence on its role in allergic response and immunological development. This comprehensive review will examine the latest discoveries in GM research and its role in the development of food allergies across the lifespan. Examining the existing literature may identify knowledge gaps regarding precise mechanisms through which the development of GM influences the maturation of the immune system. Given the abundance of the literature, we conducted a database search for articles published within the past 10 years. A total of 56 original research articles were retrieved, analyzed, and included in our review. This review article aims to integrate the current evidence on understanding how the development of GM impacts the immune system and food allergy response throughout the lifespan. We aim to uncover microbial mechanisms of allergy response, host and microbe interactions, and opportunities for therapeutic intervention. Additionally, we aim to reveal gaps in the current knowledge of the GM’s influence on allergy development, offering directions for future research. Full article

Adult neural stem cells (NSCs) maintain lifelong neurogenesis, a fundamental process for neuroplasticity, memory and brain homeostasis. Despite decades of research, translating basic NSC biology into effective clinical therapies remains a central challenge. Here we present a narrative review that provides a comprehensive update on the current landscape of adult NSC research, associating molecular mechanisms with the emerging translational technologies. First, we analyze the biological features and neurogenic sequences within canonical niches such as the subventricular lateral zone and the subgranular zone, emphasizing phylogenetic and migratory differences between rodent models and humans. Second, we integrate these mechanisms with the influence of environmental and pathological modulators, describing how aging, metabolic changes, chronic stress and neuroinflammation disrupt NSC quiescence and lineage progression. Finally, we highlight recent technological advances driving the field toward clinical applications. By examining current NSC isolation strategies, induced pluripotent stem cell modeling, direct somatic reprogramming and the use of CRISPR-Cas9-based gene-editing therapies, this review delineates the pathways to overcome existing methodological limitations. Ultimately, we provide an integrated context that connects the modulation of the neurogenic niches with advanced in vitro technologies, offering new perspectives for regenerative medicine and the treatment of neurological disorders. Full article

Brown spot on the leaf sheath is an emerging disease of sweet corn (Zea mays L.) in Sinaloa, Mexico, with an unknown etiology. This study aimed to identify the causal agent of the disease and assess its pathogenicity on commercial sweet corn hybrids. Bacterial strains were isolated from symptomatic leaf sheaths collected from commercial fields. Identification was performed through biochemical profiling (API 50CHB/E), pathogenicity tests on alternative hosts (potato, onion, celery), and molecular analysis (16S rRNA and recA genes sequencing and phylogenetic reconstruction). Pathogenicity and virulence were confirmed by inoculating four sweet corn hybrids in a greenhouse. The strains were Gram-negative rods, identified as Burkholderia gladioli based on biochemical profiles and molecular data (99% 16S rRNA+ recA similarity; phylogenetic clustering within the B. gladioli clade). In greenhouse trials, the strains induced brown spot lesions on the leaf sheaths of all tested hybrids, replicating field symptoms fulfilling Koch’s postulates. This is the first report of B. gladioli as the causal agent of brown spot on the leaf sheath of sweet corn in Mexico. The pathogen’s broad host range highlights its potential as an emerging threat to horticultural crops in the region. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a multisystemic disease with overlapping metabolic, renal, and cardiovascular effects. Within the Diabetic@ project, which aims to characterize individuals with T2DM using real-world data extracted from electronic health records (EHRs), this substudy sought to develop a predictive model for two-year heart failure (HF) risk. Methods: Multicenter, retrospective study including T2DM individuals across eight Spanish hospitals (2013–2018). Data were extracted exclusively from EHRs’ unstructured free text using clinical natural language processing (cNLP) and mapped to SNOMED CT. At inclusion, individuals were categorized as having or not prevalent HF (pHF). Predictive modeling was performed in non-pHF to assess two-year risk of developing HF, termed incident HF (iHF). Logistic regression (LR), decision trees, random forest, and XGBoost were compared, selecting for accuracy and interpretability. Results: Of 588,756 individuals with T2DM, 84,197 (14.3%) had pHF. Among non-pHF, 353,371 (60%) were used for model development (90.7% training, 9.3% validation). iHF occurred in 13.6% of the training set and 11.4% of the validation set. Ischemic heart disease was present in 16.2% overall, 37.9% in pHF, and 12.6% in non-pHF. Glycosylated hemoglobin data was rarely reported (<15%). LR achieved the best performance (AUC-ROC 0.73) using 27 predictors. Reduced 12- and clinically refined 9-predictor models performed similarly, with the latter implemented in a web-based tool. Conclusions: Unstructured data from EHRs enabled development of a two-year HF risk model for individuals with T2DM, underscoring the potential of cNLP for risk stratification across the cardiovascular–renal–metabolic spectrum. Full article

Emery–Dreifuss muscular dystrophy (EDMD) is a rare inherited neuromuscular disorder within the spectrum of nuclear envelope diseases, classically characterized by early musculo-tendinous contractures, slowly progressive myopathy, and cardiac involvement dominated by conduction disease and arrhythmias, with variable evolution toward cardiomyopathy and heart failure. This narrative review provides a comprehensive and clinically actionable synthesis of cardiovascular manifestations across EDMD genotypes and phenotypes, outlining pragmatic diagnostic and therapeutic pathways for real-world care. A targeted literature search was performed in PubMed, Embase, and Web of Science, focusing on studies addressing cardiovascular involvement in EDMD. Relevant original studies, case series, registries, guideline documents, and high-quality reviews were selected and synthesized narratively, with particular emphasis on diagnostic strategies, risk stratification, and management approaches. Cardiac involvement in EDMD encompasses a broad and heterogeneous spectrum, including atrial disease and conduction disturbances, ventricular arrhythmias, dilated cardiomyopathy, thromboembolic complications, and sudden cardiac death. Phenotypic expression varies according to the underlying genetic substrate, with distinct atrial- and ventricular-dominant trajectories. Early recognition and structured cardiovascular surveillance are essential to guide timely intervention, including anticoagulation, device therapy, and heart failure management. Despite growing awareness, significant gaps remain in risk prediction and standardized management strategies. EDMD represents a paradigmatic model of cardiomyopathy characterized by prominent electrical instability and systemic involvement. A structured, genotype- and phenotype-informed approach centered on early surveillance, proactive arrhythmia and thromboembolic risk management and timely device therapy may improve clinical decision-making in real-world settings. Future perspectives include the integration of precision medicine and the development of gene- and pathway-targeted therapies, with the potential to shift from symptomatic management toward disease-modifying strategies. Full article

This case-control study investigated the association between polymorphisms in the dedicator of cytokinesis 2 (DOCK2) gene and susceptibility to COVID-19 in a Mexican population. Methods: Genotyping of five single-nucleotide polymorphisms (SNPs) in the DOCK2 gene (rs9307 A/G, rs1045176 G/T, rs1045168 C/T, rs2112703 A/C, and rs2287727 A/C) was performed using TaqMan assays in 248 COVID-19 patients and 288 healthy controls. Results: No significant differences were observed in the allelic or genotypic distributions of rs1045176 G/T and rs2287727 A/C between cases and controls. However, under multiple genetic inheritance models (co-dominant, dominant, recessive, heterozygous, and additive), the rs9307 A, rs1045168 C, and rs2112703 A alleles were significantly associated with a reduced risk of COVID-19 (p < 0.05). Furthermore, sub-analyses stratified by genotype in COVID-19 patients revealed that the rs9307 AA, rs1045168 CC, and rs2112703 AA genotypes correlated with altered plasma concentrations of lactic acid dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and ferritin. Conclusions: The DOCK2 SNPs rs9307 A/G, rs1045168 C/T, and rs2112703 A/C are associated with decreased susceptibility to COVID-19 in this population and influence plasma levels of LDH, ALT, AST, and ferritin, suggesting a potential role in disease pathogenesis and severity. Full article