Ferroptosis, an iron-dependent form of regulated cell death, is frequently dysregulated in both tumor and immune cells, contributing to tumor progression and limiting the effectiveness of cancer immunotherapy. Defining the molecular mechanisms that govern ferroptosis and its effects within the tumor immune microenvironment is critical for understanding its dual role in cancer biology. While modulation of ferroptosis presents a promising therapeutic strategy, non-specific targeting may also impair normal tissues and tumor-infiltrating immune cells. In this context, nanoparticle-based delivery systems offer a potential approach to selectively regulate ferroptosis within tumors. Such strategies may enable precise remodeling of the tumor microenvironment and enhance antitumor immune responses, thereby improving immunotherapy outcomes. This review highlights the regulatory mechanisms linking ferroptosis and the tumor immune microenvironment, provides a critical discussion of recent developments in bionanomaterial-based therapeutic platforms, and outlines the challenges and prospects for clinical application of these platforms for immunotherapy.

Stroke is the second most common neurological complication in cancer patients after metastases. Cancer-associated coagulopathy (CAC) is an important mechanism of ischemic stroke in this population. We systematically reviewed the epidemiological, clinical, radiological, and pathophysiological features of CAC-related stroke, as well as associated biomarkers and treatment strategies.

A systematic search of PubMed/MEDLINE, Scopus, Cochrane Library, and Embase (2000-2025) was performed according to PRISMA 2020 guidelines. Search terms included "stroke", "cancer", "hypercoagulability", "coagulopathy", "disseminated intravascular coagulation", and "non-bacterial or marantic thrombotic endocarditis". Studies published in English or Spanish were included, whereas case reports and review articles were excluded. Data were synthesized qualitatively.

Eighty-two studies met inclusion criteria. CAC-related stroke occurs predominantly within six months of cancer diagnosis and is strongly associated with advanced or metastatic disease and a high risk of early recurrence. Adenocarcinoma, particularly lung and pancreatic cancer, is the most frequently associated histological subtype. Proposed mechanisms include mucin-mediated platelet aggregation, tissue factor-driven coagulation, extracellular vesicles, and neutrophil extracellular trap formation, leading to thromboinflammation and platelet-rich thrombi. D-dimer is the biomarker most consistently associated with recurrence and mortality, while C-reactive protein, fibrinogen, CA-125, and transcranial Doppler microembolic signals show limited specificity. Characteristic imaging findings include multiple infarcts involving more than two vascular territories, particularly the 'three territories sign'. Low-molecular-weight heparin and direct oral anticoagulants are the most commonly used secondary prevention strategies. Thirty-day mortality rates range from 25 to 50%.

CAC-related stroke is a distinct and underrecognized entity characterized by specific biological and radiological features and poor outcomes. Earlier recognition and optimized antithrombotic strategies may improve prognosis.

IQGAP2 gene defects can lead to aberrant cell proliferation and are associated with multiple diseases. Previous studies suggest that IQGAP2 knockdown can activate AKT/mTORC1 and thereby promote aberrant cell proliferation. However, the upstream molecular regulatory mechanisms remain unclear. In our study, we found that IQGAP2 knockdown enhances PI3K activity, leading to accumulation of PI(3,4,5)P₃, thereby activating downstream AKT and mTORC1 activity. Integrative multi-omics and co-immunoprecipitation analyses revealed that IQGAP2 downregulation promotes PI3K activation within the IQGAP1 complex, while simultaneously activating the Wnt/β-catenin and AREG/EREG-EGFR signaling axes, thereby directly or indirectly enhancing PI3K activity. Furthermore, we found that the IQGAP1/IQGAP2 expression ratio is significantly elevated in tumor tissues and this ratio is associated with poor patient survival prognosis by TCGA pan-cancer analysis. This study provides insights into the signaling mechanisms associated with IQGAP2 downregulation, suggesting that the IQGAP1/IQGAP2 expression ratio may have clinical potential as a pan-cancer prognostic biomarker, and providing a basis for further investigation of targeted interventions for IQGAP2-related diseases.

Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and reduce flux through the mevalonate pathway, which supplies both cholesterol and the non-sterol isoprenoids required for prenylation of small GTPases. Because this pathway is frequently activated in cancer, statins have become one of the most intensively studied candidates for oncological drug repurposing. Preclinical work indicates that statins can lower the threshold for apoptosis, modulate autophagy in either a pro-death or a cytoprotective direction, induce pyroptosis, and sensitize cells to ferroptosis, while also acting on CD8⁺ T cells, macrophages, dendritic cells, and cancer-associated fibroblasts within the tumor microenvironment. Clinical evidence, however, remains discordant with the strength of these mechanistic claims: favorable observational associations are susceptible to immortal-time bias, healthy-user bias, and confounding by indication, and randomized trials have been largely neutral for tumor-directed endpoints. This narrative review appraises the mechanistic, preclinical, and clinical literature using an explicit five-tier evidence hierarchy, and treats two constraints as analytical tools rather than closing caveats: the pharmacological heterogeneity of individual statins, and the one-to-two order-of-magnitude gap between concentrations used in cancer-cell experiments and free drug concentrations achievable in patients. We conclude that statins are biologically plausible but clinically unproven anticancer agents whose evaluation should proceed through biomarker-selected, pharmacodynamically validated combination trials rather than unselected add-on designs.

Severe acute kidney injury (AKI) is frequent in critically ill patients with chronic obstructive pulmonary disease (COPD), but predictive importance does not establish causality.

To model severe AKI (KDIGO stage 3), evaluate temporal robustness at a 24-hour ICU landmark, and explore adjusted exposure-effect estimates.

This retrospective MIMIC-IV v3.1 cohort included 4,705 adults with COPD. The original modeling dataset was split into training (n = 3,294) and testing (n = 1,411) sets. Consensus features from LASSO, Boruta, and random-forest importance informed 15 classifiers; the highest observed test-set AUC was interpreted with SHAP. A 24-hour landmark analysis excluded earlier stage 3 AKI and used pre-landmark predictors for incident stage 3 AKI thereafter. CausalForestDML estimated exploratory adjusted effects of the most recent valid creatinine within 365 days before ICU admission.

Severe AKI occurred in 1,085 patients (23.06%). The original six-feature CatBoost model included total ICU length of stay and had an AUC of 0.848 (95% CI, 0.825-0.872); it is interpreted as a retrospective trajectory model. The landmark cohort included 4,171 patients and 841 events. The temporal five-feature AUC was 0.679 (95% CI, 0.641-0.717); without pre-ICU creatinine it was 0.686 (95% CI, 0.648-0.724; paired difference, -0.0067; P = 0.293). The adjusted creatinine risk difference was 0.0547 per 1 mg/dL (95% CI, -0.0021 to 0.1115) and 0.0705 (95% CI, 0.0022-0.1387) after 1st-99th percentile trimming.

This study establishes a COPD-specific benchmark showing that a parsimonious model can characterize severe-AKI trajectories and that temporal separation materially changes performance and interpretation. Integrating model comparison, SHAP, adjusted-effect estimation, and landmark validation provides a rigorous framework for distinguishing prognostic importance from causal relevance and defines priorities for external validation.

Depression is common among individuals with asthma and is linked to increased mortality. However, whether socioeconomic factors contribute to this association remains unclear. We explored whether income may partially account for the association between depressive symptoms and reduced survival in adults with asthma.

A total of 4945 asthma patients were included using baseline data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 linked to the National Death Index (NDI) mortality follow-up through December 31, 2019. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), and mortality was identified through linkage to the NDI. Cox proportional hazards models were used to evaluate the association between depression symptoms and all-cause mortality, and restricted mean survival time (RMST) analysis quantified survival differences over 15 years. Exploratory mediation analysis with quasi-Bayesian simulation was conducted to evaluate whether the poverty-income ratio (PIR) may partially account for the observed association, adjusting for demographic, behavioral, and clinical covariates.

Depression was associated with all-cause mortality in asthma patients, and the strength of this association decreased after adjustment for demographic, behavioral, and clinical factors. Over a 15-year period, patients with depression symptoms (PHQ-9 ≥ 10) had markedly shorter survival, losing 9.89 months in RMST (155.2 vs. 165.1 months; p < 0.001). In exploratory mediation analysis, PIR accounted for 23.8% of the observed association between depressive symptoms and reduced survival, suggesting a potential socioeconomic contribution to the survival gap.

Depressive symptoms were associated with reduced survival among adults with asthma, and income may partially account for this observed relationship. These findings should be interpreted cautiously because depressive symptoms and income were measured at baseline, limiting causal interpretation of the mediation analysis. Further longitudinal studies are needed to confirm these findings and clarify temporal relationships.

Allergic diseases are typically regarded as type 2 inflammatory disorders driven by interleukin-4, interleukin-5, and interleukin-13, which mediate immunoglobulin E class switching, eosinophilic inflammation, mucus hypersecretion, pruritus, tissue remodeling, and epithelial barrier dysfunction. However, type 2 cytokine activity alone does not fully account for variations in exacerbation risk, susceptibility to infections, comorbidities, or responses to biologic therapy. This narrative review proposes an asthma-centered type 2-interferon imbalance framework and discusses its cautious, disease-specific extension to atopic dermatitis, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, and food allergy. The model emphasizes that, particularly in asthma, allergic barrier inflammation arises and persists in injured tissues where excessive type 2 inflammation may coexist with impaired interferon-mediated host defense. Evidence is strongest in asthma, where deficiencies in type I and type III interferon responses are linked to rhinovirus susceptibility, delayed viral clearance, and recurrent exacerbations. In other allergic diseases, interferon dysfunction appears more variable, reflecting differences in tissue context, disease stage, and environmental exposure. In asthma, and potentially in selected allergic barrier diseases, persistent inflammation may result from a cycle of epithelial injury, alarmin release, cytokine amplification, impaired antiviral defense, ongoing exposure, and incomplete tissue repair. These mechanisms provide a rationale for tiered intervention, including blockade of upstream epithelial alarmins, inhibition of downstream type 2 effector pathways, and selected investigational approaches aimed at restoring mucosal host defense.

Lower respiratory tract infections (LRTIs) are among the leading causes of clinical deterioration and death in critically ill patients. In the intensive care unit (ICU), timely identification of the causative pathogen is essential for appropriate antimicrobial therapy; however, conventional culture methods take 3 to 5 days and have suboptimal positivity rates, particularly for fungi. Molecular approaches such as PCR shorten turnaround time but still depend on manual nucleic acid extraction and thermocycling, limiting their suitability for bedside use. This protocol describes a point-of-care workflow built around a fully integrated, disc-shaped microfluidic chip (CD chip) that couples magnetic bead-based nucleic acid purification with loop-mediated isothermal amplification (LAMP). After a simplified manual liquefaction and lysis step, the processed specimen is loaded onto the chip together with two prepackaged reagent vials. The instrument then autonomously performs extraction, amplification at 65 °C, and real-time fluorescence readout, returning qualitative results for 15 targets, namely 11 bacteria, 3 fungi, and 1 atypical pathogen, within 45 min of instrument run time (approximately 1 h for the complete sample-to-answer workflow, including the manual preprocessing step). We present detection data from 10 ICU specimens, including sputum, bronchial aspirates, and bronchoalveolar lavage fluid, encompassing both single-pathogen and polymicrobial co-infections involving up to 7 organisms on a single chip. The closed cartridge design minimizes the risk of aerosol contamination, and the single loading step requires no specialized training, positioning this system as a practical bedside diagnostic tool for ICU teams.

Olive pollen allergy, a leading cause of seasonal allergic rhinitis and asthma in Mediterranean regions, is becoming increasingly relevant worldwide due to the expansion of olive cultivation. Despite its significant public health impact, the molecular mechanisms underlying sensitization to olive pollen remain poorly understood.

In this study, RNA sequencing was used to perform transcriptomic profiling on in vitro-stimulated Peripheral Blood Leukocytes (PBLs) from both allergic patients and healthy controls, to identify gene expression changes triggered by olive pollen in allergic individuals. Validation by RT-qPCR was subsequently performed in an independent cohort to confirm the expression patterns of selected DEGs.

A total of 37 differentially expressed genes (DEGs) were found exclusively in the patient group. Validation by RT-qPCR in an independent cohort confirmed the expression patterns of selected DEGs. Functional enrichment analyses associated these DEGs with immune pathways, ossification processes, and cytokine activity. Notably, upregulated genes such as AREG, IL31RA, and IL18R1 were associated with TH₂ responses and asthma pathogenesis, while downregulated genes including GREM1 and CCL1 were related to chemotaxis and immune regulation. Protein-protein interaction (PPI) network and hub gene analyses highlighted potential molecular drivers of allergic inflammation. Chromosomal mapping revealed clustering of DEGs on chromosomes previously associated with asthma susceptibility. Furthermore, exploratory correlation analyses identified correlation between TGM2 expression and total IgE, and between SHROOM2 expression and Ole e 7-specific IgE, highlighting these genes as candidates for future evaluation.

Overall, this study provides new insights into the transcriptomic landscape of olive pollen allergy, identifying candidate biomarkers and biological pathways with translational relevance for improving diagnosis and advancing personalized treatment strategies in allergic diseases.

Hypertrophic cardiomyopathy is the most common structural myocardial disease. Based on the literature, its estimated prevalence in the adult population is 1 : 500. It is distinguished by an exceptionally heterogeneous clinical presentation and a broad spectrum of disease trajectories. The disorder is recognised in only about 10% of the patients. In 90% of cases, patients remain undiagnosed, often due to the absence of symptoms. Hypertrophic cardiomyopathy is frequently the underlying cause of sudden cardiac death. In recent years, mortality of hypertrophic cardiomyopathy has declined due to improved device and pharmacotherapies. We aim to present the epidemiological significance of the disease in line with recent international guidelines, emphasizing the importance of diagnostic awareness and multiparametric evaluation. By promoting a cardiomyopathy mindset, we aim to raise awareness of clinical red flags. Early identification of patients with suspected hypertrophic cardiomyopathy in primary and cardiology outpatient care can facilitate prompt diagnosis and timely initiation of appropriate therapy. The review provides an overview of the diagnostic pathway recommended by the 2023 European Society of Cardiology Guidelines for the management of cardiomyopathies, describes the key components of the multiparametric, multimodal evaluation and presents clinical red flags. A significant proportion of the clinical red flags emphasized in the 2023 European Society of Cardiology Guidelines for the management of cardiomyopathies can be identified at lower levels of care and in primary care settings, thereby accelerating the diagnostic process and shortening the time to treatment. The diagnostic algorithm includes performing an ECG, assessing specific laboratory parameters, searching for extracardiac symptoms and conducting a comprehensive pedigree analysis focused on age-related phenotypic features. When clinical suspicion is high, advanced multimodal imaging should be included in addition to conventional imaging modalities. Orv Hetil. 2026; 167(38): 1495-1506.