Search Results (26,629)

Background/Objectives: Bipolar depression impairs psychosocial functioning, cognition, and quality of life. Evidence regarding adjunctive exercise remains limited. This pilot study evaluated the clinical and biological effects of adjunctive exercise in patients with bipolar depression. Methods: In this multicenter cluster-randomized controlled trial, 26 hospitalized patients were assigned by facility to treatment as usual plus supervised exercise (TAU + Ex) or supervised stretching (TAU + SC) for 6 weeks. Twenty-four completed the study (TAU + Ex, n = 14; TAU + SC, n = 10). Clinical outcomes and plasma tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1β, IL-2, brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor-A (VEGF-A) were assessed at baseline and week 6. The trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; UMIN000045877; registered on 1 December 2021). Results: FAST and QIDS-SR scores improved significantly in both the exercise and stretching groups after the 6-week intervention, but no significant group × time interactions were observed. No significant group, time, or group × time effects were observed for any plasma biomarker. Before correction for multiple comparisons, nominal correlations were observed between changes in IL-1β and FAST, BDNF and FAST, and VEGF-A and Spotter performance. None remained statistically significant after Benjamini–Hochberg FDR correction. Conclusions: Adjunctive exercise therapy was not superior to active stretching. The exploratory biomarker–outcome correlations did not remain significant after correction for multiple comparisons and should be considered hypothesis-generating. Larger, adequately powered randomized controlled trials are warranted. Full article

University Social Responsibility (USR) frames higher education institutions (HEIs) as agents of ethical, social, and environmental value creation across governance, teaching, research, and community outreach. Although the construct is well developed in Latin American and European scholarship, it is rarely named in the United States, where comparable commitments circulate under community engagement, civic engagement, service learning, engaged scholarship, campus sustainability, and the anchor-institution mission. This terminological divergence obscures U.S. practice from the international USR literature and constrains comparative learning. This systematic review, conducted and reported in accordance with the PRISMA 2020 statement, synthesises how USR is conceptualised and operationalised in U.S. HEIs under alternative labels, the institutional mechanisms that enact it, the outcomes reported, and their alignment with the Sustainable Development Goals (SDGs). Searches of Scopus, Web of Science, ERIC, and Business Source Complete/EconLit (2005–2025), supplemented by citation searching, yielded 1512 records; after duplicate removal and two-stage screening, 23 studies met the eligibility criteria. A thematic synthesis mapped the U.S. evidence onto Vallaeys’ four axes of USR impact. Findings show that U.S. HEIs enact every USR dimension, most visibly through educational and social-participation mechanisms, but under fragmented vocabularies, with the Carnegie Elective Classification for Community Engagement functioning as a de facto USR self-assessment framework. Persistent gaps include weak faculty-reward alignment, uneven measurement, and only implicit connection to the SDGs. The review argues that reading U.S. community-engagement scholarship through a USR lens offers a shared vocabulary and a mechanism-to-outcome map for advancing Education for Sustainable Development. Limitations include construct heterogeneity and English-language, publication-biased sources. Full article

Spinal cord injury (SCI) leads to severe disability in patients, and one of the key obstacles to the recovery of lost functions is inefficient axonal remyelination. The high sensitivity of oligodendrocytes to secondary damage, the formation of a glial scar, and chronic neuroinflammation sustained by pro-inflammatory/neurotoxic microglia create a physical and chemical barrier to neuroplasticity processes. This review summarizes current knowledge on the ability of the serotonergic system to modulate the functional state of the main types of glial cells: oligodendrocytes, astrocytes, and microglia. It is shown that oligodendrocyte precursor cells (OPCs) and mature oligodendrocytes express 5-HT_1A, 5-HT_2A, and 5-HT₇ receptors, whose activation can either stimulate differentiation or suppress migration or induce apoptosis, depending on the developmental stage and microenvironment. In astrocytes, serotonin, predominantly via 5-HT_2B receptors, limits pro-inflammatory transformation, reduces NLRP3 inflammasome activity, and stimulates BDNF production, glycogenolysis, and lactate release. In microglia, serotonergic stimulation (via 5-HT_1A, 5-HT_2A, 5-HT_2B, and 5-HT₇ receptors) attenuates the pro-inflammatory phenotype by suppressing production of TNF-α and IL-1β. To date, the proposed therapeutic strategies include: the use of 5-HT receptor agonists/antagonists and transplantation of serotonergic cells (hNT2.19 and RN46A-B14 lines), which reduce neuropathic pain and promote motor function recovery in rodents after SCI. The key limitations for the effective translation of these findings into clinical practice are the heterogeneity of effects of different serotonin receptor subtypes, the dependence of outcomes on the time after injury, and pronounced species specificity. Thus, the serotonergic system represents a promising but complex target for inducing neuroplasticity processes; success requires the development of subtype-selective ligands and treatment protocols that take into account the stages of pathological processes in SCI. Full article

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders driven mainly by somatic mutations in JAK2, CALR or MPL, but their clinical phenotype is also shaped by chronic inflammation, immune dysregulation, vascular complications and microenvironmental remodeling. Emerging evidence suggests that the gut microbiota may contribute to this inflammatory and immunometabolic landscape; however, the current literature remains heterogeneous and its translational relevance is still insufficiently defined. This critical narrative review maps the available evidence linking the gut microbiota, microbial metabolites and systemic microbial signatures to MPN biology. We distinguish direct human MPN data from indirect mechanistic evidence derived from studies of intestinal barrier dysfunction, thrombo-inflammation, hematopoietic regulation, allogeneic hematopoietic cell transplantation and infection risk. Across human MPN cohorts, the most consistent findings are not uniform changes in global microbial diversity, but rather alterations in specific immunoregulatory taxa, particularly reduced Firmicutes/Faecalibacterium-related communities and dysbiotic signatures associated with JAK2V617F status. Mechanistically, dysbiosis and impaired intestinal barrier integrity may facilitate low-grade endotoxemia, TLR4/NF-κB activation, cytokine amplification, endothelial activation and platelet priming. In parallel, microbial metabolites may influence hematopoietic stem cell programs, the bone marrow niche, megakaryopoiesis and thrombopoiesis. Treatment exposure and diet are relevant modifiers of the microbiota–inflammation axis, although available interventional data remain preliminary. Mendelian randomization and multi-omics studies provide hypothesis-generating evidence for microbiota–metabolome–MPN interactions, but require longitudinal validation, functional studies and contamination-aware analytical pipelines, especially for low-biomass blood and bone marrow samples. Microbiota-targeted strategies, including nutritional interventions and fecal or washed microbiota transplantation, represent promising but still investigational approaches, particularly in immunocompromised or post-transplant settings. Future studies should integrate microbiome, metabolome, genome, proteome, inflammatory biomarkers and clinical outcomes while controlling for diet, antibiotics, treatment exposure and driver mutation status. Such an approach may clarify whether the microbiota is a biomarker, mediator or therapeutic target in MPNs. Full article

Stress urinary incontinence (SUI) is conventionally viewed as a peripheral mechanical disorder, yet its psychological burden suggests that a broader biopsychosocial interpretation may be warranted. This perspective considers whether recurrent leakage, anticipatory anxiety, behavioural avoidance, and social evaluative threat may allow SUI to function as a chronic psychosocial stressor. It integrates clinical observations with established concepts in stress physiology, hypothalamic–pituitary–adrenal (HPA) axis regulation, allostatic load, inflammation, and stress-related epigenetic mechanisms, including FKBP5 and NR3C1. Direct molecular evidence in SUI populations remains limited; therefore, the proposed links are presented as a hypothesis-generating framework rather than as established causal pathways. The framework further emphasises the heterogeneity of patient outcomes. Differences in perceived symptom burden, coping, stress responsivity, prior vulnerability, and resilience may help explain why psychological symptoms improve after treatment in some individuals yet persist in others. These interacting psychosocial and biological processes may reinforce a feedback loop between symptom-related threat, sustained stress activation, and affective vulnerability. By moving beyond a solely mechanical model, this perspective supports a more interdisciplinary approach combining urogynecological and psychological assessment. The proposed stress-epigenetic framework is intended to guide future longitudinal and biomarker-informed research and to encourage more integrated approaches to the prevention and management of psychological burden in SUI. Full article

Agricultural and agro-industrial byproducts from tropical crops represent abundant sources of structurally bound and freely extractable bioactive compounds. However, variability in feedstock composition, the incomplete characterization of microbial transformations, and limited translation beyond chemical antioxidant assays constrain their development as standardized ingredients. This review critically evaluates metabolomics-guided fermentation as a strategy for converting tropical agricultural byproducts into functional and circular products. It covers fruit-processing residues, coffee and cocoa byproducts, cereal bran, cassava-processing residues, coconut and oilseed materials, and selected medicinal-crop tissues. Solid-state, submerged, lactic-acid-bacterial, yeast, filamentous fungal, Bacillus-based, and mixed-culture fermentations are compared. Particular attention is given to cell-wall deconstruction, phenolic release, flavonoid deglycosylation, phenolic-acid conversion, carotenoid stability, peptide generation, fiber modification, organic-acid production, antinutrient reduction, and undesirable metabolite formation. Analytical strategies based on untargeted and targeted LC-MS, GC-MS, NMR, volatilomics, peptidomics, and multiomics integration are assessed, together with experimental design, quality control, annotation confidence, and statistical validation. A substrate–microorganism–process–metabolite–function framework and a six-level evidence-grading system are proposed to distinguish exploratory chemical findings from mechanistically validated and industrially translatable outcomes. Applications in functional foods, nutraceutical ingredients, natural preservatives, animal feed, active packaging, agricultural inputs, and cascade biorefineries are evaluated alongside microbial safety, mycotoxins, biogenic amines, contaminants, regulatory classification, life-cycle assessment, and techno-economic feasibility. The central conclusion is that fermentation can become a programmable platform for tropical byproduct valorization only when metabolite-resolved characterization, causal validation, process standardization, safety, and sustainability are developed as an integrated pipeline. Full article

Background/Objectives: Femoroacetabular impingement (FAI) is a common cause of hip pain and functional limitation in young and active patients. Conventional hip arthroscopy commonly requires traction and central-compartment access, which may contribute to traction-related neuropraxia and access-related chondrolabral injury. This study evaluated clinical outcomes after traction-free only peripheral hip arthroscopy (OPHA) for cam-type FAI with associated labral pathology. Methods: This retrospective cohort study included consecutive patients who underwent OPHA between November 2016 and May 2022 and had complete paired preoperative and postoperative outcome data. Outcomes included the visual analog scale (VAS) pain score, Hip Outcome Score activities of daily living subscale (HOS-ADL), Hip Outcome Score sport subscale (HOS-Sport), International Hip Outcome Tool-12 (iHOT-12), and Tegner activity score. Labral status was categorized as intact, repaired, or debrided. Paired outcomes were analyzed with the Wilcoxon signed-rank test. Results: Sixty-six patients were included (mean age, 38.9 ± 10.8 years; 34 female). The mean postoperative follow-up was 5.7 years (range, 3.7–9.2 years). Labral status was intact in 32 patients, repaired in 23, and debrided in 11. Secondary intervention occurred in eight patients. In the overall cohort, VAS improved from 7.0 ± 0.6 to 3.2 ± 2.5 (p < 0.001), HOS-ADL from 59.1 ± 1.9 to 79.2 ± 17.5 (p < 0.001), HOS-Sport from 45.1 ± 2.1 to 67.6 ± 21.3 (p < 0.001), and iHOT-12 from 48.3 ± 1.8 to 72.2 ± 19.4 (p < 0.001). The Tegner activity score decreased from 5.2 ± 0.7 to 4.3 ± 1.4 (p < 0.001). Conclusions: Traction-free OPHA was associated with improvements in pain and hip-specific functional outcomes in selected patients with cam-type FAI and allowed individualized labral management without routine central-compartment distraction. The retrospective design and retrospective reconstruction of baseline PROMs in a subset of patients should be considered when interpreting the magnitude of the observed improvement. Full article

Environmental-monitoring systems often bundle sensing, communication, storage, visualization, and control into one application, making later changes difficult. We designed a service-oriented platform that separates these functions through defined interfaces. It combines a Raspberry Pi gateway, a dedicated motor-control microcontroller, five environmental sensor modules, Node-RED middleware, a database, and a web interface. Deterministic code alone evaluates threshold and composite rules and controls safety-relevant alerts; an optional large language model (LLM) turns pre-computed statistics and rule outcomes into narrative reports. We examined data acquisition and rule processing during two short indoor campaigns. In the residential campaign, the SCD41 yielded 78 valid three-minute bins (234 min of recorded data) across four sessions between 09:18 and 17:12 local time; binned CO₂ concentrations ranged from 679 to 1471 parts per million (ppm). Using the initial campaign for development and the residential campaign as a temporal holdout, the persistence model produced a 15 min forecast mean absolute error of 58.3 ppm and a root mean square error of 78.8 ppm. A separate controlled experiment generated 270 reports from nine deterministic synthetic scenarios. Every reporter preserved all deterministic alert identifiers, while the fixed template and seven of the nine locally hosted LLMs achieved 100% numerical fidelity. Qwen 3.5 9B was the only LLM that returned all required measured content without automated claim-review flags and produced identical outputs across repetitions for every scenario. These results confirm integration and functional separation under the tested conditions, but they do not demonstrate week-scale reliability, longer-horizon forecasting accuracy, robotic mobility performance, or load scalability. Full article

Dysregulated hepatic cholesterol handling and oxidative stress represent key targets for nutritional interventions. This study investigated a combination of Ophiocordyceps sinensis (formerly Cordyceps sinensis) extract and coenzyme Q10 (CoQ10) using a sequential gut–liver in vitro model. Differentiated Caco-2/HT29-MTX co-cultures were used to assess intestinal transport, transepithelial electrical resistance (TEER), and junctional organisation. The resulting basolateral intestinal-conditioned medium was applied to high-glucose-stressed HepG2 cells. The combined treatment-maintained epithelial electrical integrity (TEER > 400 Ω·cm²) and tight junction protein abundance, while transiently increasing paracellular fluorescein transport (Papp) and enhancing basolateral CoQ10 recovery (+29%). In HepG2 cells, the conditioned medium reduced superoxide production (−38%) and enhanced both DiI-labelled low-density lipoprotein (DiI-LDL) uptake (+26%) and intracellular total bile acid content (+33%). These functional outcomes were accompanied by coordinated changes in protein abundance: a decrease in sterol regulatory element-binding protein 2 (SREBP-2), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), and proprotein convertase subtilisin/kexin type 9 (PCSK9) levels, alongside increased low-density lipoprotein receptor (LDLR), cytochrome P450 family 7 subfamily A member 1 (CYP7A1), and ATP-binding cassette transporter A1 (ABCA1) expression. Pharmacological inhibition with dorsomorphin suggested a partial involvement of AMP-activated protein kinase (AMPK) signalling, although this mechanistic assessment remained exploratory. Overall, these findings demonstrate the coordinated modulation of intestinal transport, functional hepatic endpoints, and cholesterol-related protein abundance. Full article

Alkyl-chain architecture may influence both the enzymatic synthesis and antioxidant performance of phenolic esters. This study examined the esterification of dihydrocaffeic acid with four isomeric C5 alcohols catalyzed by immobilized Candida antarctica lipase B (CALB). The isolated products were evaluated using process metrics, NMR, physicochemical predictions, density functional theory calculations, DPPH and ABTS assays, and pressure differential scanning calorimetry in flaxseed and grape seed oils. The isolated yields of n-pentyl, 2-methylbutyl, and 3-methylbutyl dihydrocaffeates were 61.25%, 49.87%, and 53.08%, respectively, whereas no measurable amount of the 2,2-dimethylpropyl ester was isolated under the applied conditions. The linear derivative showed the highest biocatalyst productivity and the most favorable reaction-stage material-efficiency indices. DPPH activity was similar across all isolated esters, whereas the 3-methylbutyl derivative showed the strongest ABTS activity. The lowest calculated O–H bond dissociation enthalpy was obtained for the 2-methylbutyl derivative. At 0.01%, all three esters provided greater oxidative protection than butylated hydroxytoluene under the applied PDSC conditions. Their effects were similar in flaxseed oil, whereas the n-pentyl derivative was clearly superior in grape seed oil. Under the applied reaction conditions, the linear and branched alcohols showed different synthesis outcomes, whereas antioxidant performance in oils was strongly matrix-dependent and not predicted by any single computational or solution-based descriptor. Full article

Background: Neuropsychiatric symptoms (NPSs) are among the most clinically disruptive manifestations of major neurocognitive disorder (MND) and major contributors to caregiver distress. However, the differential contribution of specific neuropsychiatric domains to caregiver burden and sleep quality has remained insufficiently characterized. Methods: This single-center retrospective observational study included 164 patient–caregiver dyads. Patients were diagnosed with MND according to DSM-5 criteria. NPS were assessed using the Neuropsychiatric Inventory (NPI-Q). Caregiver burden and sleep quality were evaluated using the 12-item Zarit Burden Interview (ZBI-12) and the Pittsburgh Sleep Quality Index (PSQI), respectively. Beta and logistic regression models were applied to investigate associations between NPS severity and caregiver outcomes after adjustment for cognitive and functional status. Additional analyses explored the relative contribution of individual NPI-Q subdomains. Results: Greater overall NPS severity was significantly associated with both increased caregiver burden (β = 0.163, p < 0.001) and altered caregiver sleep quality (OR = 1.32, 95% CI: 1.12–1.59, p = 0.002). Clinically significant sleep disturbances (PSQI > 5) were observed in 61.6% of caregivers. Among NPS, delusions showed the strongest association with caregiver burden (β = 0.329, p < 0.001), followed by depressive symptoms (β = 0.156, p = 0.004) and irritability (β = 0.147, p = 0.005); furthermore, sleep and night-time behavior disorders emerged as the strongest contributors to altered caregiver sleep quality (p < 0.001). Conclusions: Greater NPS severity may be associated with increased caregiver burden and poorer sleep quality in caregivers of patients with MND. Different NPSs appear to be differentially associated with caregiver outcomes, despite the lack of caregiver-level covariates, supporting the need for multidimensional and caregiver-centered approaches in dementia care. Given the exploratory nature of these analyses, these findings should be interpreted as descriptive rather than confirmatory. Full article

Workplace wellbeing is a multidimensional construct shaped by psychological, physical, and organisational determinants. In higher education, human resource and governance policies influence these determinants, yet policy portfolios are often compliance-oriented rather than explicitly wellbeing-focused. Despite increasing global attention to workplace wellbeing, there remains limited empirical analysis of how institutional policy environments conceptualise and operationalise wellbeing, particularly in African higher education contexts. This study critically analysed workplace-related policies at a tertiary academic institution in Johannesburg to assess how wellbeing is conceptualised and operationalised, and to identify gaps relevant to academic employees. A qualitative single-case document study design was employed, guided by the Walt and Gilson Policy Triangle Framework (content, context, actors, processes) and complemented by a wellbeing classification lens. Policies were purposively selected based on predefined inclusion criteria relating to working conditions, inclusion, health and safety, development, and employment governance. Deductive framework analysis was followed by inductive thematic synthesis. Workplace wellbeing was not explicitly defined within the policy portfolio and was inconsistently operationalised. Most policies functioned through indirect pathways and emphasised legal compliance, governance, and procedural oversight. Five cross-cutting themes were identified, including compliance-driven policy architecture, uneven workload governance, and bounded disability inclusion. Key gaps included limited integration of psychosocial risk, insufficient support for chronic illness and non-visible disability, and lack of monitoring of wellbeing outcomes. Institutional policies provide important safeguards but do not operate as an integrated workplace wellbeing framework. Strengthening conceptual clarity, aligning policies with contemporary evidence, and embedding measurable wellbeing indicators may improve employee wellbeing and institutional sustainability. As a single-institution document analysis, the findings reflect formalities of policies rather than implementation and may therefore have limited transferability to other higher education sections. Nevertheless, the study provides a thourough framework for examining how institutional policies shape workplace wellbeing and offers a foundation for future comparative policy analyses. Full article

Objectives: The aim of this study was to evaluate long-term changes in transtympanic electrocochleography (TT-ECochG) following vestibular neurectomy in patients with Ménière’s disease (MD) and to investigate their relationship with endolymphatic hydrops (EH) degree and hearing outcomes. Methods: This pilot study included five patients with unilateral MD eligible from a cohort of twenty patients who underwent middle fossa vestibular neurectomy. All participants completed preoperative and 2-year postoperative clinical and audiological tests, including TT-ECochG; EH degree was analyzed in delayed gadolinium-enhanced magnetic resonance images (MRI). Changes in TT-ECochG parameters were analyzed in relation to MRI findings. Results: All patients achieved complete control of vertigo and improvement in the AAO-HNS functional level. Hearing deterioration of ≥10 dB was observed in two patients (40%). Cochlear EH remained unchanged in all patients, whereas vestibular EH reduction was visualized in two patients (40%) after surgery. Decreased SP/AP amplitude and/or area ratios were observed in two patients (40%), whereas increased values were found in two others (40%). No postoperative TT-ECochG response was obtained in one patient because of profound postoperative hearing loss. Overall, changes in TT-ECochG parameters did not parallel MRI findings. Conclusions: This pilot study demonstrates that postoperative TT-ECochG changes after vestibular neurectomy are heterogeneous and do not consistently parallel MRI changes in endolymphatic hydrops. Full article

Background/Objectives: Restricting anterior knee displacement is a common squat cue, but it redistributes rather than reduces mechanical demand, and comparative evidence is largely acute. This exploratory trial compared the short-term functional effects in healthy, active young adults. Methods: Sixty participants were randomized to unrestricted or restricted anterior knee displacement, or usual activity (three-arm, single-centre). Both exercise groups completed 18 remotely supervised bodyweight squat sessions over six weeks (720 repetitions; 100% session adherence among completers). The primary outcome was low-back-related disability (Oswestry Disability Index); 21 exploratory secondary outcomes covered pressure pain threshold, Y Balance Test reach, exertion, and jump flight time. Follow-up scores were compared by one-way analysis of variance, unadjusted for baseline, with post hoc ANCOVA sensitivity analyses as supplementary. Results: Fifty-seven of the 60 randomized participants completed the trial and were analysed (n = 19, 18, and 20). Follow-up Oswestry scores did not differ among groups, F(2,54) = 1.999, p = 0.145, η² = 0.069; the largest pairwise difference was −2.9 percentage points (95% CI −5.9 to 0.0). Baseline disability was minimal (floor effect). In the unadjusted analysis, only the left-hamstring pressure pain threshold reached p < 0.05, not surviving multiplicity adjustment; baseline-adjusted sensitivity analyses left the primary result unchanged while strengthening several exercise-versus-control contrasts, two below the adjusted threshold—all exploratory. Comparable changes occurred in the untreated control group. Conclusions: Within the conditions of this short-term bodyweight-squat intervention, restricting anterior knee displacement provided no detectable advantage, and no clinically important between-group difference. The trial was not an equivalence study. Full article

Despite the importance of adaptive reuse for urban renewal, municipal records of changes in property destinations remain an untapped resource for understanding regulatory barriers. This study develops an interpretable machine learning (ML) framework to screen historical administrative non-approval using 42,350 municipal records from a mid-sized city in southern Chile spanning 2010 to 2025. Historical memory features were constructed exclusively from outcomes available before each application, thereby preventing temporal leakage. Records from 2010–2022 were used for training, 2023 was reserved for validation, and 2024–2025 constituted a locked test set. A logistic regression model combining auditable risk flags derived from GIRO (declared economic or functional activity) with historical property, address, and activity category information was selected by maximizing the F1-score (the harmonic mean of precision and recall) subject to a recall ≥ 0.85. At the validation-selected threshold of 0.285, the model achieved a receiver operating characteristic area under the curve (ROC-AUC) of 0.778, a precision–recall area under the curve (PR-AUC) of 0.720, an F1-score of 0.719, recall of 0.887, and precision of 0.604. The model flagged 66.8% of applications for prioritized review. The proposed framework supports human-in-the-loop screening and institutional learning; it neither determines regulatory compliance nor automates municipal decisions. Full article