Search Results (8,088)

Given the importance of friendships and the increased risk for suicide during adolescence, potential socialization of suicidality among peers is essential to examine. Data were obtained from 93 friendship dyads (N = 186) in a community-based, longitudinal study of adolescents (Mage = 15.68, SD = 1.49, 69.9% female, 86.6% white). Adolescents’ and friends’ suicide risk and frequency of non-suicidal self-injury (NSSI) were assessed at baseline and at 3-month and 6-month follow-up assessments. Cross-lagged, Actor–Partner Interdependence Models (CL-APIM) examined socialization effects over time with the nested, dyadic data. Results indicated that direct socialization of suicide risk did not occur within the whole sample. However, socialization of suicide risk was observed for friends of adolescents with a past-year history of NSSI. The findings underscore the potential for NSSI to function as a susceptibility marker for socialization of suicide risk within adolescent friendships. Current study strengths, limitations, and clinical implications are further discussed. Full article

Intraprocedural rupture (IPR) during stent-assisted coiling (SAC) after stent deployment can create a narrow and rapidly changing management problem: hemorrhage control, anticoagulation reversal, acute thrombotic occlusion, and postprocedural cerebrospinal fluid diversion may all become urgent within the same clinical sequence. We report a fatal IPR during SAC of an unruptured anterior communicating artery (AComA) aneurysm and use the case as an anchor for a targeted case-based narrative review. A 71-year-old woman underwent SAC for a 5.1-mm posteriorly directed AComA aneurysm with a bleb after treatment for vertebrobasilar ischemia. Fourth-coil insertion produced tactile resistance and contrast extravasation. Protamine reversal and temporary A1 flow control reduced the leak, but filling defects then developed from the internal carotid artery terminus to the A1 and M1 segments, requiring rescue thrombectomy. Computed tomography showed subarachnoid hemorrhage and intraventricular hemorrhage; same-day progression with hydrocephalus required bilateral external ventricular drainage. The patient died on postoperative day 7. This case highlights IPR during SAC as a time-dependent hemorrhagic–thrombotic escalation rather than a single technical event. We propose a staged assistant–operator communication model for risk mapping, rupture recognition, hemostatic-route preservation, thrombotic surveillance, and transition to computed tomography, external ventricular drainage, and intensive care. Full article

Background: Segmental arterial mediolysis (SAM) is a rare, non-inflammatory, non-atherosclerotic, non-hereditary arteriopathy of unknown etiology that typically affects medium-sized visceral arteries. The absence of reliable diagnostic criteria poses a significant challenge. Consequently, the diagnosis of SAM should be considered in the setting of a distinctive combination of clinical features, angiographic findings, and histopathology. Renal artery involvement is uncommon, and its occurrence in the donor graft during kidney transplantation (KT) has not previously been reported. Case presentation: We report the case of a kidney graft from a deceased donor in her seventh decade of life, transplanted into a recipient in her seventh decade of life. Donor–recipient ABO compatibility was confirmed, and both complement-dependent cytotoxicity crossmatch and flow cytometry crossmatch were negative. Cold ischemia time was 14 h, and warm ischemia time was 20 min. Immediately after declamping, massive thrombosis of the graft renal artery was observed and confirmed using an intraoperative flowmeter. The arterial anastomosis was taken down, the thrombus was removed, the artery was flushed with heparin, and the anastomosis was reconstructed using interrupted sutures. Despite revision, no arterial flow was detected, and the graft was deemed unsalvageable and explanted. Histopathological examination showed thinning of the tunica media, reduced smooth muscle cells on desmin staining, medial-adventitial dissection, and occlusive thrombosis, findings considered likely attributable to SAM. Conclusions: This case suggests that occult donor arterial wall disease compatible with SAM may present catastrophically during KT and may lead to immediate graft loss despite standard surgical salvage attempts. Although no validated strategy currently exists to screen for or prevent occult SAM in asymptomatic donors, awareness of this entity may assist transplant surgeons and pathologists in the evaluation of unexplained early graft arterial thrombosis, donor-graft vascular pathology, and communication with centres receiving paired organs from the same donor. Full article

Background: Mobile health has been increasingly integrated into tuberculosis care to support patient education, communication, and treatment engagement. However, evidence remains limited regarding whether positive engagement with mHealth is associated with knowledge, attitudes, and practices among patients with multidrug-resistant tuberculosis. This study aimed to examine the association between positive mHealth engagement and knowledge, attitude, practice, and total KAP among patients with multidrug-resistant tuberculosis, and to evaluate the psychometric properties of the engagement score used as the primary exposure variable. Methods: A cross-sectional study was conducted among patients with multidrug-resistant tuberculosis. A positive mHealth engagement score was constructed from 12 mHealth-related items after harmonizing item directionality so that higher scores indicated more favorable engagement. The 12 items reflected five behavioural domains: intensity of use, ease and acceptability of use, functional engagement (communication with providers, access to health information, and perceived benefit for disease self-management), continuity of use, and barriers to sustained engagement. The composite score was computed as the mean of the 12 standardised items, with higher values indicating more positive engagement. Internal consistency was assessed using Cronbach’s alpha and corrected item–total correlations, and structural validity was explored using principal component analysis. Adjusted linear regression models were used to examine associations between the engagement score and Knowledge, Attitude, Practice, and total KAP scores, controlling for age, sex, and occupation. Sensitivity analyses were performed after excluding a poorly performing item, and tertile analyses were used to assess dose–response patterns. Results: The positive mHealth engagement score showed good internal consistency, with a Cronbach’s alpha of 0.852. One item demonstrated poor psychometric performance, and Cronbach’s alpha increased to 0.864 after its exclusion. The data were suitable for dimensionality assessment, with a Kaiser–Meyer–Olkin value of 0.870 and a significant Bartlett’s test. Principal component analysis identified a dominant first component explaining 43.29% of the total variance. Using the refined score, higher positive mHealth engagement was significantly associated with higher Knowledge scores (β = 2.06; 95% CI: 1.28–2.85; p < 0.001), higher Attitude scores (β = 4.68; 95% CI: 3.30–6.06; p < 0.001), and higher total KAP scores (β = 6.68; 95% CI: 4.62–8.74; p < 0.001), whereas no significant association was observed for the Practice score (β = −0.07; 95% CI: −0.63 to 0.49; p = 0.804). In tertile analyses, Knowledge, Attitude, and total KAP scores increased significantly across engagement levels, while Practice scores did not. Conclusions: Positive mHealth engagement was associated with better knowledge, attitudes, and overall KAP among patients with multidrug-resistant tuberculosis, but not with practice. These findings are associative; the cross-sectional design does not permit causal conclusions. The engagement score demonstrated good reliability and acceptable structural validity and may be a useful summary measure for evaluating patient interaction with mHealth interventions in tuberculosis care. Integrated strategies combining mHealth with clinical follow-up, adherence counseling, and structural support may be needed to translate informational and attitudinal gains into practice change. Full article

Objective: To provide a comprehensive literature review of original work on artificial intelligence in ocular oncology. Methods: Scoping review of PubMed-indexed original articles (n = 94) on the use of artificial intelligence in ocular oncology, retrieved during the month of February 2026 and independently screened by two ocular oncologists. Results: Most of the literature on artificial intelligence (AI) in ocular oncology focuses on uveal melanoma and its differentials (n = 39, 41%), followed by retinoblastoma (n = 14, 15%) and orbital tumors (n = 12, 13%). The purpose of using the AI models was to screen, diagnose, and classify the disease (n = 59, 62%) and to treat, predict outcomes, and monitor the disease (n = 35, 37%). Most literature (n = 32, 34%) on AI in ocular oncology originates from China. Datasets comprised images in 78% (n = 73) of the studies, clinical parameters in 14% (n = 13), and omics data in 12% (n = 11). Most studies worked on developing AI models (n = 83, 88%), of which two reached a deployment stage. Few studies evaluated or incorporated pre-existing models (n = 11, 12%). Supervised learning strategy was most commonly employed (n = 75, 80%). Among studies that developed AI models, traditional machine learning architectures were used in 36, deep learning in 39, and a combination in 8. Most studies (n = 59, 63%) were at a Clinical AI Readiness Evaluator Technology Readiness Level 4, i.e., at the prototype development stage. Conclusions: Despite the limitation of a single database search, a surge in AI applications in ocular oncology after 2020 is evident. Most studies are in the model development stage, and few have been deployed in the real world for clinical implementation. Very few models have proven effective in real-world clinics and the community, holding promise for the future. Full article

The survival of complex multicellular organisms depends on continuous inter-organ communication networks that coordinate organism-wide responses across physiological conditions and stress states, including adaptation to environmental challenges, infection, and injury. Rather than operating as isolated units, organ systems are integrated through interconnected signaling networks that transmit biological information across tissues. Building on prior work examining individual physiological pathways, this review introduces a unified systems-level framework that integrates inter-organ communication into a coherent model of organism-wide regulation. This review proposes a systems-level framework in which homeostasis is maintained through eight principal communication systems: neural, endocrine, immune-inflammatory, vascular, lymphatic, metabolic, microbiome–gut, and mechanical-structural. Epithelial barriers function as dynamic signaling interfaces within multiple systems, while extracellular vesicles act as cross-system mediators of information transfer rather than as independent communication networks. These systems operate across distinct temporal scales to coordinate host defense, metabolic adaptation, vascular regulation, and tissue repair. The framework further introduces a temporal hierarchy of signaling dynamics that links communication systems to phase-specific responses during physiological stress. Within this integrated network, glucocorticoid receptor α (GRα) is proposed to function as a systems-level regulator of inter-organ communication, supported by converging mechanistic, experimental, and clinical evidence, with variability in the strength of evidence across domains. In contrast to prior reviews, which addressed GRα function within individual systems, this work conceptualizes GRα as a central rheostat coordinating cross-system signaling and temporal transitions in homeostatic correction. Evidence was identified through hypothesis-driven searches using the Consensus AI platform and verified through manual review of primary biomedical literature. GRα, a ligand-activated transcription factor expressed in most nucleated cells, enables hormonal stress signals to coordinate gene-expression programs across tissues, modulating neuroendocrine responses, endothelial function, inflammatory signaling, metabolic regulation, microbiome–host interactions, and tissue remodeling. Systemic responses to stress progress through three phases of homeostatic correction—Priming, Modulatory, and Restorative—within which GRα supports integrated organism-wide adaptation. This integrative framework provides a mechanistic basis for understanding the emergence and temporal evolution of biological responses in health and critical illness. Full article

Acute respiratory distress syndrome (ARDS) is characterized by systemic inflammation, immune dysregulation, oxidative stress, and frequent extrapulmonary organ involvement. Neurological complications of ARDS, such as neuroinflammation, cognitive impairment and delirium, are common and worsen outcomes. Early evidence highlights bidirectional communication between the lungs and brain, the lung–brain axis, through which inflammation may amplify both pulmonary and cerebral injury. This narrative review synthesizes recent experimental and clinical data on the immunomodulatory and neuroprotective effects of commonly used sedative agents in ARDS, focusing on their influence on inflammatory mediators (IL-1β, IL-6, IL-8, IL-10, TNF-α) and neuronal injury biomarkers (S100B, neuron-specific enolase). Sedative agents seem to exert effects beyond sedation by modulating systemic and neuroinflammatory responses. Evidence suggests they can influence cytokine profiles and reduce biomarkers associated with neuronal injury, potentially mitigating neuroinflammation and delirium in ARDS patients. Sedatives may modulate lung–brain crosstalk in ARDS through immunoinflammatory pathways, integrating sedative and neuroprotective effects. Mechanistic clarification may enable targeted sedation strategies to improve pulmonary and neurological outcomes. Full article

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID-19 syndrome (LC) show substantial clinical overlap, but direct comparative microbiome studies remain limited. Methods: In this cross-sectional study, we compared the fecal gut microbiome of patients with ME/CFS, LC, and healthy controls (HC) within a unified analytical framework using 16S rRNA profiling, differential abundance testing, and multivariate modeling. We also examined associations between microbiome variation and questionnaire-derived symptom-domain scores. Results: Alpha-diversity did not differ significantly among groups, whereas beta-diversity analyses showed small but significant disease-associated community differences with broad overlap between cohorts. Differential abundance analysis identified stronger signals in disease-versus-control contrasts than in the direct ME/CFS vs. LC contrast. Both ME/CFS and LC shared enrichment of Sutterella and depletion of Terrisporobacter and Lachnospiraceae relative to HC. Predicted functional profiling showed shared disease-versus-control changes in pathways related to anaerobic acetate/H₂ carbon flow, inositol/polyol degradation, phosphonate/C1-related metabolism, and lysine-derived fermentation. Regression analyses showed the strongest microbiome associations with fatigue-related and physiosomatic domains, while affective, cognitive, and gastrointestinal outcomes showed weaker signals. Conclusions: Overall, these findings support the presence of overlapping but non-identical gut microbiome alterations in ME/CFS and LC. The results provide a basis for future longitudinal and multi-omics studies aimed at clarifying the stability, functional relevance, and clinical utility of these microbial patterns. Full article

The gut microbiome, often termed the human “second genome”, profoundly influences host physiology through metabolic interactions, immune modulation, and gut–brain axis signaling. Dysbiosis is implicated in the pathogenesis of obesity, inflammatory bowel disease (IBD), malignancies, and neuropsychiatric disorders. However, traditional gut microbiota interventions, such as probiotic supplementation and fecal microbiota transplantation (FMT), still exhibit significant limitations in precision therapeutics. Probiotic intervention fails to achieve precise regulation at the strain or genetic level, and although FMT demonstrates definitive efficacy against recurrent Clostridioides difficile infection (rCDI), its therapeutic outcomes and safety profiles show marked interindividual variability in ulcerative colitis (UC), metabolic syndrome, and other diseases, with insufficient treatment specificity to meet the practical demands of clinical precision intervention. Recent advancements in genome editing technologies, particularly Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)–CRISPR-associated (Cas) proteins systems and base editors, have enabled targeted functional manipulation of specific gut commensals and optimization of community architectures. These engineered strategies, combined with sophisticated delivery systems, demonstrate substantial potential in disease treatment, diagnostic monitoring, and immune modulation. This review systematically examines core editing methodologies, innovative delivery platforms, and targeted design strategies, elucidating their applications in metabolic disorders, IBD, cancer immunotherapy, and neuropsychiatric conditions. We critically analyze current technical bottlenecks and biosafety concerns while prospecting future directions, including in situ editing, artificial intelligence (AI)-driven design, and personalized engineering. Collectively, these insights aim to facilitate the clinical translation of gut microbiome engineering from bench to bedside. Full article

This pilot study investigated the effects of estradiol and clindamycin on mono- and dual-species biofilms of selected reference and clinical isolates of Lactobacillus gasseri and Cutibacterium acnes, including one vaginal isolate of C. acnes. Our findings demonstrate complex, strain-dependent effects of both compounds and their combinations. Estradiol inhibited biofilm formation in L. gasseri strains but exhibited divergent impacts on C. acnes isolates, stimulating the skin-derived strain while suppressing the vaginal isolate. The observation that pre-adsorbed estradiol tended to enhance its biological activity is consistent with, though does not prove, the hypothesis of a direct hormonal interaction with the bacterial cell envelope. Crucially, estradiol modulated the susceptibility of both species to clindamycin. At the working concentration selected, clindamycin susceptibility varied considerably between strains, with the antibiotic stimulating biofilm growth in skin-derived C. acnes HM514 biofilms. In dual-species communities, an apparent inversion of clindamycin activity was observed, suggesting that estradiol may alter antibiotic efficacy in a manner dependent on community composition and strain identity. Furthermore, while transcriptional changes in bacteriocin genes were evident under hormonal and antibiotic pressure, these shifts did not consistently correlate with observed phenotypic antagonistic activity. These results underscore the limitations of traditional mono-species assays and highlight the importance of considering hormonal background, community context, and the substantial phenotypic variability among individual microbial isolates when evaluating antimicrobial interventions. Full article

With colorectal cancer (CRC) accounting for over 1.9 million new cases and 930,000 deaths globally in 2020, there is a critical need for innovative indicators to forecast disease advancement and therapeutic outcomes. The gut microbiome has emerged as a fertile area for discovering such diagnostic and prognostic signals. This narrative review collected current evidence on intestinal microorganisms and their metabolic products as candidate markers for CRC control. Intestinal communities influence malignancy through diverse mechanisms, including metabolic shifts, immune modulation, inflammation, proliferation/apoptosis regulation, genotoxicity, and mucosal barrier disruption. Pathogenic species, such as Fusobacterium nucleatum and enterotoxigenic Bacteroides fragilis, facilitate tumorigenesis via FadA-mediated signaling and Th17/IL-17 responses. In contrast, beneficial taxa like Faecalibacterium prausnitzii and Akkermansia muciniphila provide protective effects through short chain fatty acid production. Macrophage phenotype physiological equilibrium is altered and inflammatory status fluctuates under the former. Metabolically, hydrogen sulfide damages mitochondrial DNA and secondary bile acids stimulate cellular proliferation. While 16S rRNA sequencing and shotgun metagenomics are established detection strategies, innovative platforms like organoids and gene arrays remain in the exploratory stage. Clinical data indicates that F. nucleatum aligns with advanced tumor stage, and its combined detection with colibactin-producing E. coli achieves high sensitivity for early-stage screening. Additionally, A. muciniphila levels can anticipate the efficacy of PD-1 blockade immunotherapy. Microbiota-derived tools represent a transformative direction in oncology. Future research must focus on standardizing protocols and validating multi-marker panels to enhance clinical translation. Full article

Neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), arise from highly interconnected molecular and cellular abnormalities that progressively lead to neuronal dysfunction, synaptic failure, and cell death. This review provides a unified framework to understand the interrelated molecular mechanisms driving these diseases, with a focus on identifying key disease-specific intervention nodes. Core contributors include oxidative stress, mitochondrial dysfunction, protein aggregation, neuroinflammation, and emerging roles of peroxisomal dysfunction in redox imbalance, lipid dysregulation, and inflammatory amplification. Single-target therapies often show limited efficacy due to the complex, interconnected nature of these pathways. In contrast, polypharmacology, which targets multiple disease-relevant mechanisms simultaneously, offers a more promising therapeutic strategy. This review critically examines how pathway crosstalk drives neurodegenerative progression, with particular emphasis on mitochondrial–ROS–inflammatory signaling, aggregation–proteostasis failure, synaptic–neuroimmune dysfunction, and gut–brain communication. It evaluates various multi-node intervention strategies, including multi-target-directed ligands (MTDLs), molecular hybrids, natural products, drug repurposing, and nanocarrier-based delivery systems. Advances in network pharmacology, artificial intelligence (AI), bioinformatics, and multi-omics have enhanced the identification of actionable therapeutic nodes, candidate compounds, and brain-targeted delivery platforms. Notably, the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome and cyclic GMP–AMP synthase (cGAS)—stimulator of interferon genes (STING) pathways—play distinct roles in neuroinflammation, amplifying neuronal damage by releasing inflammatory cytokines and inducing mitochondrial dysfunction. However, successful translation into clinical practice remains constrained by challenges such as blood–brain barrier penetration, patient heterogeneity, and biomarker limitations. The review advocates for a shift towards mechanism-informed, patient-stratified polypharmacological strategies to better address the network pathology of neurodegeneration, despite significant translational hurdles. Full article

Background/Objectives: Inborn errors of immunity (IEI) are rare and complex pediatric disorders that create significant information gaps for families and non-specialist healthcare professionals. Large language models (LLMs) such as ChatGPT are increasingly used as on-demand health information resources; however, evidence on their performance in rare pediatric diseases remains limited. This study aimed to evaluate the reliability, quality, readability, understandability, reproducibility, and safety-related concerns of ChatGPT-4o responses to frequently searched questions about pediatric IEI posed by healthcare professionals and patients/caregivers. Methods: This cross-sectional evaluation used the publicly accessible ChatGPT-4o interface to generate responses to 20 frequently searched questions about pediatric IEI, equally distributed between healthcare professional (n = 10) and patient/caregiver queries (n = 10). Three pediatric allergy-immunology specialists independently evaluated response quality using the modified DISCERN (mDISCERN) and Global Quality Scale (GQS) tools, supplemented by a structured expert-based assessment of misinformation, safety-related concerns, suspected factual issues, missing disclaimers, and clinically meaningful inter-iteration inconsistency. Text readability was assessed using four validated indices (ARI, FRES, FKGL, GFR), comprehensibility using the Patient Education Materials Assessment Tool (PEMAT), and reproducibility using natural language processing methods. Results: ChatGPT-4o demonstrated strong overall performance, with median mDISCERN and GQS scores of 4 (IQR: 3–5) for both query types. Readability scores substantially exceeded recommended thresholds, with FKGL scores of 12.96 ± 0.69 and 10.83 ± 0.67 for professional and patient/caregiver queries, respectively. Mean PEMAT understandability scores were 71.80 ± 5.75% for professional queries and 80.80 ± 4.73% for patient/caregiver queries (p = 0.001). Reproducibility was high, with semantic similarity rates of 86.10 ± 3.84% and 87.30 ± 3.68%, respectively. Suspected factual issues were identified in 4 of 20 responses (20%), safety-related concerns in 3 (15%), clinically meaningful inter-iteration inconsistencies in 3 (15%), and missing medical disclaimers in all 20 responses (100%). Conclusions: ChatGPT-4o showed strong performance across validated quality metrics for pediatric IEI information support; however, its high reading level, universal absence of medical disclaimers, and occasional clinically meaningful inconsistencies limit its suitability as a standalone source for clinically sensitive guidance. These findings underscore the need for AI-driven patient education tools with improved readability, adaptive complexity adjustment, and safety-oriented communication. Full article

Ovarian cancer (OC) remains one of the most lethal gynaecological malignancies, which is mainly due to late diagnosis, high frequency of metastasis, and the risk of developing resistance to systemic therapy. In recent years, exosomes—small extracellular vesicles (EVs) secreted by cancer cells and components of the tumour microenvironment (TME)—have been identified as potential mediators of OC progression. Exosomes participate in intercellular communication and enable the transfer of RNA, proteins, and lipids. These vesicles may modulate the immune response, promote angiogenesis, remodel the extracellular matrix, and drive epithelial–mesenchymal transitions. Exosomes also appear to play a role in the development of drug resistance via direct transfer of resistance factors or indirect modification of TME. In this review article, we summarise current knowledge on the biological role of exosomes in OC pathogenesis. We also discuss their possible diagnostic, prognostic, and therapeutic relevance. The properties and composition of exosomes make them promising noninvasive liquid biomarkers and convenient carriers for anticancer drugs. However, to fully exploit their potential, further large-scale preclinical and clinical studies are required, which should focus primarily on standardising research methods and assessing the safety and efficacy of exosome-based diagnostic and therapeutic methods. Full article

Background: Clostridioides difficile is classified within the first 18 threats for antimicrobial resistance and is the leading cause of hospital-acquired enteric infection. Community-associated cases have notably increased in recent decades, highlighting that accurate and up-to-date statistics characterizing the epidemiology of C. difficile infection (CDI) are critical. Methods: We conducted a retrospective (2019–2023) case-control study evaluating the prevalence of CDI in 249 stool samples from hospitalized patients in the sanitary region III of Buenos Aires, Argentina. The presence of C. difficile was detected by combining EIA, PCR, and toxigenic culture via a diagnostic algorithm. Clinical and demographic data from patients were analyzed to identify CDI-associated risk factors. We also conducted a systematic review and a meta-analysis contrasting our results with 38 studies selected from different countries. Results: One in five patients presented C. difficile as the etiological agent of diarrhea. Eighty percent of the CDI+ cases carried toxigenic strains, with a third of cases associated with community environments. Age ≥ 69 years, previous use of antibiotics, previous hospitalization, and previous episodes of CDI emerged as predisposing factors for CDI in our study cohort. In an exploratory evaluation of clinical data, CDI+ patients showed higher leukocytes and platelets counts, a decreased basophil count, and increased urea concentration. At the global level, the meta-analysis reinforced advanced age, previous consumption of antibiotics, previous consumption of proton pump inhibitors, previous hospitalization, and previous CDI as risk factors for CDI. Conclusions: These results emphasize the importance of continued epidemiological surveillance of CDI. Our findings confirm previously described risk factors, both in our cohort and at the global level. Exploratory alterations in laboratory parameters were observed, although their clinical relevance and specificity require further investigation. Full article