Search Results (5,158)

Health is increasingly understood as a multidimensional phenomenon shaped by complex interactions among biological, psychosocial, environmental, and informational factors. Building on the human exposome and its extensions, this paper introduces the interpretive exposome, a conceptual framework that captures cumulative exposure to how health-related information is framed, recorded, interpreted, and communicated by clinicians, artificial intelligence (AI) mechanisms, and institutions across the life course. We argue that the interpretive process, including biased clinical health records, algorithmic decision-support outputs, and inequitable communication, operates as exposures that can accumulate and influence downstream health outcomes. We further describe how AI systems function as interpretive filters that may reproduce, alleviate, or amplify bias through training data and recursive deployment. While remaining conceptual in nature, this proposed framework outlines methodological pathways for operationalization using natural language processing (NLP), bias auditing, and multi-modal data integration. The interpretive exposome complements existing exposome models and offers a theoretical foundation for future empirical validation aimed at promoting equitable, transparent, and context-aware healthcare. Full article

Background/Objectives: Pediatric HIV case-finding and monitoring remain constrained by delayed early infant diagnosis (EID), loss to follow-up, and limited viral load (VL) testing—challenges particularly consequential in the operationally diverse Asia–Pacific region. We systematically reviewed innovations in point-of-care (POC) and near-patient HIV diagnostics and digital monitoring relevant to children and adolescents. Methods: Following a registered protocol (INPLASY2025110058) and PRISMA 2020 guidance, we searched PubMed, EMBASE, Cochrane Library, and WHO Global Index Medicus for studies on POC/near-patient EID and VL testing, dried blood spot (DBS) workflows, and digital monitoring tools. Risk of bias was assessed using RoB 2, QUADAS-2, and MMAT. Results: Fifty-three primary studies were included (39 sub-Saharan Africa, 12 Asia–Pacific, 1 multi-country/global, 1 Americas/Caribbean). Patient selection and flow/timing were common limitations in diagnostic accuracy studies; sample representativeness and nonresponse bias were frequent concerns in implementation studies. The most consistent benefits of POC EID and near-patient VL testing were shorter turnaround times and improved cascade completion when paired with quality assurance and connectivity. Conclusions: POC diagnostics and digital monitoring can help close pediatric HIV cascade gaps, though evidence derives predominantly from sub-Saharan Africa. Impact depends on implementation design. Asia–Pacific programs should prioritize generating context-specific evidence alongside the adaptation of established lessons. Full article

Tree mechanical stability is essential for forest management and urban safety. Although static pulling tests are currently the standard for non-destructive advanced risk assessments, these tests have significant methodological limitations. Large trees require high applied forces to produce measurable signals, which poses safety risks and causes equipment wear. Conversely, structurally compromised ancient, veteran, or dead trees (snags) may yield poor signal-to-noise ratios at low loads, leading to unstable model fits and unreliable safety factor extrapolations. Additionally, standard inclinometers often experience interference from motion-induced accelerations. This study introduces a high-resolution, low-noise measurement approach that resolves small basal inclinations and stem bending responses. This method uses laser-based tracking to monitor stem bending, torsion, and inclination under mechanical load. Experimental data were collected by combining traditional pulling tests with this novel system, as well as by conducting a pilot study that monitored tree movement during low-strength wind gusts. The proposed method enables more precise characterization of the initial load-response curve. Improving the signal-to-noise ratio at lower force levels allows for more robust safety extrapolations. When combined with a 3D LiDAR scan, the method can reveal deviations from the theoretical bending line in order to locate internal defects and variations in wood properties. These findings bridge a critical gap in tree risk assessment by improving the applicability of static testing to massive trees, as well as ecologically valuable yet structurally vulnerable snags and ancient and veteran trees. Full article

Objectives: To determine if global epicardial adipose tissue (EAT) radiomics, derived from non-contrast coronary artery calcium (CAC) scans, improves acute coronary syndrome (ACS) prediction beyond traditional risk factors (TRFs) and Agatston score (AS) in individuals without angina. Methods: We retrospectively analyzed 2020 subjects without angina who underwent CAC scans from 2016 to 2019, among whom 76 patients developed acute coronary syndrome (ACS) during a follow-up period until December 2023. One-to-one propensity score matching (PSM) based on TRFs (age, sex, BMI, smoking, diabetes, hypertension, dyslipidemia) and Agatston score ranks (ASR) created 76 ACS and 76 matched non-ACS subjects. A radiomics model was built using 5-fold cross-validation on the matched cohort and tested on the entire unmatched cohort. Statistical tests included AUC comparison. Results: PSM effectively mitigated disparities of TRFs and ASR. The radiomics model achieved AUCs of 0.91 ± 0.01 and 0.89 ± 0.03 for the training and matched test sets, respectively, and 0.89 ± 0.03 on the unmatched cohort. The radiomics score significantly improved ACS prediction over TRF and CAC models (p < 0.001) in both matched and unmatched cohorts. Conclusions: Global EAT radiomic phenotypes from conventional CAC scan improve ACS risk stratification beyond TRFs and AS in individuals without angina. In contrast to PCAT on CCTA, our simple approach appears to be suitable for large-scale applications using preventative CAC scans. Full article

Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon characterized by dysregulated mucosal immunity and progressive epithelial injury. Upadacitinib (UPA), a selective Janus kinase 1 (JAK1) inhibitor, has demonstrated clinical efficacy in UC, but its therapeutic application is often constrained by adverse effects arising from systemic drug exposure. This underscores the need for advanced, site-specific delivery systems that enhance local efficacy while minimizing systemic toxicity. Here, we developed a colon-targeted natural lipid nanoparticle formulation of UPA (UPA-nLNP) to improve therapeutic performance and safety. UPA-nLNP was prepared by thin-film hydration using digalactosyldiacylglycerol (DGDG), monogalactosyldiacylglycerol (MGDG), and phosphatidic acid (PA), mimicking the lipid composition of ginger-derived exosomal particles, and was characterized for particle size, surface charge, and encapsulation efficiency. The formulation exhibited excellent mucus-penetrating capability and was evaluated in a dextran sulfate sodium (DSS)-induced acute colitis model in C57BL/6 mice following oral administration (5 mg/kg). Pharmacokinetic analysis demonstrated increased colonic accumulation with reduced systemic exposure compared to free UPA. Treatment with UPA-nLNP improved body weight recovery, reduced disease biomarkers, and suppressed key proinflammatory cytokines in the colon, with no evidence of systemic toxicity. This innovative strategy holds strong potential to enhance the clinical utility of JAK1 inhibitors by providing a safer and more effective therapeutic approach for ulcerative colitis. Full article

(1) Background: Nurses are exposed to occupational stressors that may impair their well-being and quality of life. This study examined whether burnout and secondary traumatic stress mediate the relationship between perceived stress and physical and psychological quality of life. (2) Methods: A cross-sectional study included 294 nurses employed at the Clinical Hospital Center Osijek, Croatia. Data were collected using the Perceived Stress Scale (PSS-10), the Burnout and Secondary Traumatic Stress subscales of the Professional Quality of Life Scale (ProQOL-5), and the physical and psychological domains of the WHOQOL-BREF. Pearson correlations and path analysis were used. (3) Results: Perceived stress showed significant negative effects on physical (β = −0.291; p < 0.001) and psychological quality of life (β = −0.217; p < 0.001), and positive effects on burnout (β = 0.230; p < 0.001) and secondary traumatic stress (β = 0.171; p = 0.002). Burnout significantly mediated both relationships, while secondary traumatic stress did not. The model explained 20.8% and 19.3% of variance in physical and psychological quality of life. (4) Conclusions: Burnout represents an important pathway linking perceived stress with poorer quality of life among nurses. Full article

Corneal scarring is a result of unregulated fibrotic processes in wound healing, which causes visual impairment. Bioactive sphingolipids (SPLs) are known to modulate physiological processes that are central to wound healing. Of these bioactive SPLs, sphingosine-1-phosphate (S1P) is perhaps the most studied. Previous research has shown that knocking out sphingosine kinase 1 (Sphk1), which produces S1P, alters SPL species metabolism and improves wound healing in mice corneas. However, it is unknown how SphK1 knockout (SphK1^-/-) affects SPL metabolism during stages of corneal wound healing. Following an alkali burn procedure on wild-type (WT) and SphK1^-/- mice, corneal lipidomic profiles in unburned corneas at 1, 7, 14, and 28 days post-injury (DPI) were measured. Significant differences in SPL species between genotypes, both in uninjured mouse corneas and during distinct stages of corneal burn healing, were observed. WT mice expressed burn healing stage-dependent modulation of SPL species, with decreased expression of most SPL species observed at 1 and 14 DPI. Interestingly, this wild-type SPL modulation was absent in most measured SPL species in the SphK1^-/- corneas. These findings provide evidence for a previously unknown modulatory role of SphK1 and S1P on the expression of SPLs during corneal wound healing. Full article

People with disabilities continue to face significant barriers when flying, despite decades of policies enacted to protect their rights and ensure equitable and dignified access. These challenges are often linked not to a lack of policy but to inconsistencies, fragmentation, and unclear responsibilities across operators and jurisdictions. This review examines international, U.S., and Canadian air travel policies to assess their comprehensiveness, coherence, and alignment across jurisdictions, to promote accessible air travel for travelers with disabilities. We conducted a structured policy review following Arksey and O’Malley’s framework. We systematically identified, selected, charted, and analyzed 28 U.S. policies, Canadian policies, and international guidelines. Policy content was compared using the themes of a scoping review on air travel experiences of people with disabilities and the Disability Policy Lens to examine definitions, aims, and coverage. Findings highlighted substantial variation across jurisdictions in the allocation of responsibilities among actors and the specificity of policy provisions. These variations contribute to uneven interpretation and implementation of accessibility measures, shaping inconsistent travel experiences for people with disabilities. International guidelines have the potential to serve as an important reference point, but currently lack comprehensiveness. There is a need for greater cross-jurisdictional coherence in air travel policies. Full article

Purpose: To determine which age of mice should be used to compare the effects of ADAM8 mutation on intervertebral disc (IVD) responses to injury. Methods: IVDs of ADAM8 mutant (Adam8^EQ) and wild type (WT) mice, aged 3, 10 and 18 months were injured. IVD tissues were harvested 1 week post injury for histological and molecular studies. Results: Histological scores increased with aging in intact IVDs, and there were no differences between Adam8^EQ and WT mice (n = 11–28; p > 0.05). Safranin O-staining was less intense in 10-month than in 3-month-old mice, in both intact and injured IVDs (n = 3–15; p < 0.05). Cxcl1, Il6, and Adam8 gene expression levels were higher in the injured tail IVDs of 3-month-old Adam8^EQ than WT mice (n = 18–30; p < 0.05); the injury-related differences diminished with increasing age. Conclusions: No histological differences were found between Adam8^EQ and WT mouse IVDs at 3, 10 or 18 months of age, in the intact or injured discs. The differences in inflammatory marker gene expression were detectable at age 3 months, but were less evident when the injury occurred at age 10 or 18 months. Therefore, to identify differences in injury responses between WT and Adam8^EQ mouse IVDs, 3-month-old mice are superior to older mice. Full article

Background: Calcaneus secundarius (CS) is an accessory ossicle located at the anterior aspect of the calcaneus and is typically an incidental and asymptomatic radiographic finding. However, it may become symptomatic following trauma or repetitive mechanical stress and can mimic anterior calcaneal process fracture or tarsal coalition, leading to diagnostic confusion. The presence of multiple independent CS ossicles represents a rare morphological variant and a potential source of diagnostic ambiguity. Methods: We report the case of a 19-year-old male soldier who presented with progressive anterior foot pain following soccer activity without a clearly identifiable traumatic event. Radiographs, computed tomography (CT), and magnetic resonance imaging (MRI) were performed to evaluate the underlying pathology. Results: CT demonstrated two separate, well-corticated accessory ossicles adjacent to the anterior calcaneal process without bony continuity. MRI revealed focal bone marrow edema (BME) at the calcaneus–ossicle interface, suggesting mechanical irritation at the fibrous connection. Due to persistent symptoms and concordant imaging findings, surgical excision was performed, resulting in immediate pain relief and return to full daily and sports activities without recurrence at the 1-year follow-up. Conclusions: Multiple CS ossicles may produce fragment-like imaging appearances and increase the risk of misdiagnosis. Recognition of characteristic imaging features, particularly well-corticated ossicles and focal BME at the ossicle–calcaneus interface, together with clinical correlation, is essential for accurate diagnosis and appropriate management in patients with persistent anterior foot pain. Full article

Background/Objectives: Echocardiography reports are essential diagnostic tools, but their complexity and specialized English terminology frequently hinder comprehension for non-specialists and patients. This study addresses these accessibility gaps by developing a resource-efficient large language model (LLM) system designed to translate and summarize English echocardiography results into Traditional Chinese. Methods: To overcome significant hardware constraints, we utilized Quantized Low-Rank Adapter (QLoRA) techniques and the Unsloth acceleration framework to fine-tune LLaMA-3.2-1B and LLaMA-3.2-3B-Instruct models on a single mid-tier GPU. The system employs a dual-stage inference architecture: the first stage provides technical medical translation for clinicians, while the second stage generates simplified, patient-centric educational summaries to enhance health literacy. Results: Evaluation across multiple metrics, including BLEU, ROUGE, METEOR, and Perplexity, demonstrated that the LLaMA-3.2-3B-Instruct model with the AdamW 8-bit optimizer achieved the most stable validation performance, excelling in semantic coherence and structural consistency. A preliminary qualitative error analysis conducted in the Discussion section further identified clinical nuances, such as terminology simplification and minor hallucinations, underscoring the critical necessity of a Human-in-the-Loop verification procedure. Conclusions: These findings validate the feasibility of deploying cutting-edge medical AI in resource-limited clinical environments. While the results reflect validation-only performance on a specialized dataset, the platform offers a scalable foundation for enhancing clinical decision support and health literacy through accessible, automated medical text processing. Full article

Betaine-homocysteine methyltransferase (BHMT) is an enzyme involved in one-carbon metabolism and plays a crucial role in maintaining liver health. In this study, we investigated the impact of liver-specific deletion of BHMT on liver dysfunction using a mouse model. We generated BHMT floxed mice and bred them with albumin Cre to generate liver-specific BHMT knockout (BHMT LKO) mice. Liver tissues harvested from six-month-old chow-fed BHMT floxed and LKO mice were characterized through histological, biochemical, and molecular analyses. BHMT LKO mice displayed a complete loss of hepatic expression of BHMT mRNA, protein and enzyme activity. Histopathological analysis revealed the development of hepatic steatosis in BHMT LKO mice compared to the floxed mice. These morphological changes were supported by biochemical analysis showing elevated levels of hepatic triglycerides in conjunction with a profound decrease in the methylation potential (i.e., reduced S-adenosylmethionine (SAM): S-adenosylhomocysteine (SAH) ratio), which was mainly driven by a six- to sevenfold increase in SAH levels. BHMT LKO mice also exhibited increased lipid peroxidation and lysosomal dysfunction compared to floxed mice. Early signs of inflammation were seen in the livers of BHMT LKO mice of both sexes, as evident from significant increase in CD68-positive cells and interleukin 1β levels. Additionally, there was a moderate increase in fibrosis, as evidenced by the upregulated expression of α-smooth muscle actin and collagen II levels and the histological assessment of picrosirius red-stained liver sections of BHMT LKO mice of both sexes compared to their respective counterparts. These findings demonstrate that hepatic BHMT deficiency promotes lipid accumulation, lysosomal/proteasomal dysfunction, and early inflammatory and fibrotic changes in the liver by reducing the methylation potential. Collectively, our results underscore BHMT as a critical regulator of liver homeostasis and a potential therapeutic target in liver-related disorders. Full article

Integrins and other cell adhesion molecules play a critical role in the migration and homing of leukocytes. This study investigates whether metastatic tumor cells can exploit leukocyte-like rolling and arrest mechanisms during early vascular steps of metastatic dissemination. B16 melanoma cell adhesion to activated bEnd.3 endothelial monolayers or immobilized VCAM-1 were analyzed under defined shear flow using a parallel-plate chamber. Function-blocking antibodies, divalent cation modulation, pertussis toxin, and low-temperature conditions were used as classical controls. B16-BL6 melanoma cells exhibited robust VLA-4-dependent rolling and arrest on activated endothelial monolayers and on immobilized VCAM-1 under physiological shear stresses (0.7–2 dyn/cm²), independent of chemokine-related Gαi signaling. These findings identify a chemokine-independent mechanism of VLA-4-mediated vascular capture by melanoma cells under shear flow, providing a potential mechanistic basis for early steps in metastatic dissemination. Full article

Background: Connexins (Cx) are a family of transmembrane proteins that form gap junctions and connexin hemichannels (HCs), enabling direct intercellular communication within the nervous system. Connexin 43 (Cx43), the principal astrocytic connexin, exhibits a context-dependent dual role: under physiological conditions it maintains tissue homeostasis and metabolic support, whereas under pathological conditions excessive activation of Cx43 hemichannels promotes neuroinflammation, excitotoxicity, blood–brain barrier disruption, and secondary neural tissue damage. Other connexin isoforms also contribute to the pathogenesis of neurological and psychiatric disorders through alterations in neuronal synchronization, glial signaling, and myelin integrity. Objective: To systematize current evidence on the role of key connexin isoforms in acute nervous system injuries—including stroke, traumatic brain injury, spinal cord injury, and peripheral nerve injury—as well as chronic disorders such as neurodegenerative diseases, epilepsy, and psychiatric disorders, with particular emphasis on the functional duality of connexin channels and the therapeutic potential of their selective modulation. Methods: A systematic literature search was conducted in the PubMed, Scopus, and Web of Science databases in accordance with the PRISMA framework and the PRISMA Extension for Scoping Reviews guidelines. The review included data from experimental models, postmortem brain studies, genetic association analyses, and pharmacological intervention studies. The retrieved studies were screened, assessed for eligibility, and integrated using a qualitative narrative synthesis approach. Results: In acute neural injuries, hyperactivation of Cx43 hemichannels amplifies inflammatory signaling, edema formation, and neuronal death, whereas selective HCs inhibitors reduce lesion volume and improve functional outcomes in experimental models. Connexin 36 (Cx36) contributes to cortical spreading depolarization and seizure propagation, while Connexin 32 (Cx32) and Connexin 47 (Cx47) are critically involved in oligodendrocyte function and white-matter demyelination. In PNI, Cx43 upregulation contributes to neuropathic pain, whereas mutations in Cx32 cause hereditary demyelinating neuropathies. In neurodegenerative diseases—including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis—Cx43 hemichannel activity promotes neuroinflammation and pathological protein accumulation, while reduced Cx32/Cx47 expression disrupts metabolic support of axons. In psychiatric disorders such as major depressive disorder, bipolar disorder, and schizophrenia, decreased astrocytic connexin expression (Cx43 and Cx30) has been associated with impaired glial–neuronal communication and cognitive–emotional dysfunction. In epilepsy, increased Cx43/Cx30 expression contributes to neuronal hypersynchronization and blood–brain barrier dysfunction, whereas selective hemichannel blockade suppresses seizure activity. Conclusions: Cx—particularly Cx43—occupies a central position in the molecular mechanisms of secondary neural injury and network dysfunction. The dual functional properties of gap junctions and hemichannels determine their context-dependent effects across neurological and psychiatric diseases. Selective inhibition of pathological HCs activity shows significant neuroprotective and anticonvulsant potential and represents a promising direction for the development of targeted therapeutic strategies. Further studies are required to determine optimal therapeutic time windows, tissue-specific effects, and the long-term safety of Cx modulation. Full article

Background/Objectives: High-grade serous ovarian cancer (HGSOC) is usually discovered in advanced stages and often relapses shortly after initial conventional therapy. Survival in HGSOC patients might be improved with the use of novel immune therapies, which potentiate autologous anti-tumor responses. Dendritic cells (DCs) are potent antigen-presenting cells that can initiate immune responses, activate cytotoxic T cells and drive T-cell differentiation. This pilot trial evaluated the safety and efficacy of a unique DC vaccine (α-DC-1) in relapsed, advanced HGSOC patients with minimal tumor burden. Methods: Monocytes from patient leukaphereses were used to propagate a unique autologous DC, the α-DC-1, generated with granulocyte–macrophage colony-stimulating factor and interleukin-4, pulsed with keyhole limpet hemocyanin (KLH) and tumor lysate (from debulking surgery) on day 5, and matured with a cocktail of cytokines and chemokines on day 6. Mature α-DC-1 were harvested on day 7 and administered intranodally (inguinal nodes) every other week for three doses/cycle for up to three DC vaccine cycles (nine vaccines). The primary endpoints were progression-free survival (PFS) and overall survival (OS). Results: In 19 patients treated, the median PFS was 9.7 months (95% CI: (5, NA)) and the median OS was 42.2 months (95% CI: (31.2, 68.3)). In 5/19 (26.3%) patients, OS exceeded five years. Administration of six or more vaccines was associated with a significant improvement in PFS. No grade 2 or higher toxicities were noted. Conclusions: Our α-DC-1 vaccine was safe, and 94.2% elicited an immune response to KLH. The long OS, exceeding 5 years in some patients, suggests this DC vaccine may improve survival for some with relapsed HGSOC. Full article