Search Results (4,302)

Glaesserella parasuis (G. parasuis) is a major respiratory pathogen in piglets, but the regulatory mechanisms underlying its induced pulmonary inflammation remain poorly understood. In this study, whole-transcriptome sequencing was carried out on lung tissues from colostrum-deprived piglets with mild and severe serotype 5 G. parasuis infection and healthy controls. Differential expression (DE) analysis revealed 299 nominally DE mRNAs and 408 nominally DE lncRNAs in the mild group, increasing to 625 and 1193, respectively, in the severe group. Ingenuity Pathway Analysis identified the S100 family signaling pathway as a core inflammatory module predicted to be activated across both infection grades, with its transcriptional involvement expanding from 8 genes in mild infection to 42 genes in severe infection. Notably, G-protein-coupled receptors (GPCRs) accounted for nearly half (19/42) of the S100-associated DE genes in severe infection, covering multiple functional categories including chemokine receptors, lipid mediator receptors, and metabotropic receptors, suggesting systemic activation of the GPCR family in severe inflammation. Weighted gene co-expression network analysis identified multiple lncRNA candidates, among which two—LOC110256217 and LOC110259349—showed severity-associated connectivity patterns and were selected for further validation. Following G. parasuis infection, time-series RT-qPCR in 3D4/21 cells confirmed their co-expression with corresponding mRNAs and revealed distinct temporal patterns, suggesting their potential differential involvement at early and late stages of the inflammatory response. Collectively, these findings identify a putative lncRNA-S100-GPCR-associated inflammatory module linked to pulmonary inflammation in G. parasuis infection, providing a transcriptomic resource and candidate lncRNA-mRNA pairs for further functional studies and investigation into host resilience. Given the limited sample size (n = 3 per group), these findings should be considered exploratory and warrant validation in larger cohorts. Full article

The transition from high school to university is a critical developmental period marked by substantial academic, social, and lifestyle changes that may increase vulnerability to academic difficulties, disengagement, and dropout. Given the importance of academic achievement for student retention and long-term success and the growing recognition of sleep as a modifiable determinant of academic performance, this scoping review examined how the relationship between sleep and academic achievement has been investigated among first-year university students. Following PRISMA guidelines, a systematic search identified 20 records representing 21 studies published between 2013 and 2026. Sleep duration and sleep quality were the most frequently examined domains, although findings were heterogeneous. Nevertheless, shorter sleep duration, particularly below 6–7 h per night, was generally associated with poorer academic achievement. Poor sleep quality was also linked to lower academic performance in some studies, with affective factors influencing this relationship. Sleep problems, including chronic sleep deprivation and risk of sleep disorders, showed consistent associations with poorer academic outcomes. Similarly, an evening chronotype was generally associated with poorer academic performance and adjustment. These findings emphasize sleep as an essential target for future research and initiatives aimed at promoting academic success and student retention during the transition to higher education. Full article

Objective: To examine the reliability, construct validity, and discriminative capacity of the Spanish version of the Economic Living Standards Index Short Form (ELSI_SF) in a sample of older adults in Spain. Methods: This analysis was conducted using baseline data from 133 participants (mean age = 66.2 years, SD = 5.6; 53.8% women) recruited from community health and social centers in the provinces of Cuenca, Albacete, and Toledo within the PEPE cohort. Participants completed the ELSI_SF (25 items), sociodemographic measures, the SF-12 Health Survey, and the International Fitness Scale (IFIS). Internal consistency was assessed using Cronbach’s alpha. Convergent validity was examined through correlations between ELSI_SF scores and education, occupation, physical and mental health, and perceived fitness. Discriminative ability for health-related variables was analyzed using ANOVA and partial η². The internal structure was explored using exploratory factor analysis (EFA) and subsequently examined against the original four-factor theoretical model using confirmatory factor analysis (CFA), based on polychoric correlations and estimation methods appropriate for ordinal data. Results: The mean ELSI_SF score was 23.0 ± 3.9, with most participants classified as having comfortable or good living standards. Internal consistency was acceptable for the total scale (α = 0.779), whereas the ownership restrictions (α = 0.441) and self-rating (α = 0.319) subscales showed low reliability. Significant associations were observed between the ELSI_SF total score and selected socioeconomic and health-related measures. Factor-analytic findings provided only partial support for the original four-domain structure. Although CFA showed favorable CFI, TLI, and RMSEA values, the elevated SRMR and instability of the self-rating factor warrant cautious interpretation of the factorial solution. Conclusions: The Spanish ELSI_SF provides preliminary psychometric evidence supporting the use of its total score among relatively socioeconomically advantaged older adults. However, limitations in subscale reliability, factorial stability, and the restricted socioeconomic variability of the sample preclude definitive validation across the full spectrum of material living standards. Further evaluation in larger, independent, and more socioeconomically heterogeneous samples, particularly including older adults experiencing material deprivation, is required. Full article

Background: Depressive symptoms have become a significant public health issue faced by middle-aged and older adults in China. Although previous studies have primarily focused on demographic and socioeconomic factors, the association between modifiable lifestyle behaviors and depressive symptoms still requires further investigation. Objective: To examine the associations between sleep duration, physical activity, digital participation, social participation, and depressive symptoms as well as life satisfaction among middle-aged and older adults in China. Methods: A cross-sectional analysis was conducted using data from the 2020 China Health and Retirement Longitudinal Survey (CHARLS). Depressive symptoms were defined as CES-D-10 scores ≥10, with 13,576 individuals included in the analysis sample. Adjusted prevalence ratios (aPRs) were estimated using modified Poisson regression, while ordinal logistic regression was employed to analyze life satisfaction. The analysis controlled for covariates such as demographics, socioeconomic status, and health status, and accounted for the complex sampling design. Results: The weighted prevalence of depressive symptoms was 44.5%. Sleep deprivation (<7 h/day) was significantly associated with elevated depressive symptoms (aPR = 1.49, 95% CI: 1.33–1.68); participation in recreational activities was significantly associated with reduced depressive symptoms (aPR = 0.86, 95% CI: 0.77–0.96); adequate physical activity was associated with a higher prevalence of elevated depressive symptoms (aPR = 1.17, 95% CI: 1.04–1.32); watching videos (aPR = 0.87, 95% CI: 0.76–0.99) and playing online games (aPR = 0.65, 95% CI: 0.50–0.83) were significantly associated with reduced depressive symptoms; and overall internet use was correlated with lower life satisfaction (OR = 0.90, 95% CI: 0.81–1.00). Women, rural residents, and low-income groups exhibited higher prevalence of elevated depressive symptoms. Conclusion: Sleep deprivation, as well as different types of social engagement, physical activity, and digital behavior, exhibit distinct associations with depressive symptoms in middle-aged and older adults. Behavioral intervention strategies targeting sleep hygiene, leisure activities, and tailored digital behaviors warrant further attention. Full article

Background/Objectives: Social determinants of health are implicated in metabolic dysfunction–associated steatotic liver disease (MASLD), yet longitudinal evidence on incident disease is scarce, and whether individual- and community-level determinants act independently remains unclear. The objective of this study was to examine whether individual food insecurity and neighborhood deprivation are independently associated with incident MASLD. Methods: In this retrospective cohort of 40,693 U.S. adults without baseline MASLD in the diverse NIH All of Us Research Program, food insecurity (two-item Hunger Vital Sign) and neighborhood deprivation (validated five-domain composite) were co-primary exposures, with incident MASLD ascertained from validated diagnostic codes. Proportional hazards models were adjusted for demographic, socioeconomic, and metabolic factors, including obesity. Results: Over 116,220 person-years, 1240 (3.0%) participants developed MASLD. Both associations remained significant after adjustment for demographic, socioeconomic, and major metabolic risk factors, including obesity (food insecurity adjusted hazard ratio [aHR] 1.32, 95% CI 1.13–1.53; neighborhood deprivation aHR 1.20, 95% CI 1.05–1.37). Unadjusted cumulative incidence was highest among participants with both exposures and lowest among those with neither. Findings were consistent across sensitivity analyses; the food-insecurity association remained when neighborhood disadvantage was specified with a census-based index. Conclusions: Food insecurity and neighborhood deprivation were independently associated with higher incidence of MASLD. Nutrition-focused, equity-oriented interventions warrant evaluation to reduce MASLD burden and advance health equity. Full article

Colorectal cancer, especially the microsatellite-stable subtype, which accounts for 85% to 95% of cases, resists immune checkpoint inhibitors largely due to metabolic reprogramming in the tumor microenvironment. Lactate has evolved from a waste product into a central immunosuppressive regulator. Oncogenic KRAS and BRAF mutations drive aerobic glycolysis, causing glucose deprivation and massive lactate accumulation in the tumor microenvironment. Lactate suppresses immunity through three parallel mechanisms. It signals via GPR81 to recruit polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and inhibit T-cell function. It contributes to histone H3K18 lactylation, which silences effector genes including IFN-γ and GZMB while upregulating PD-L1 expression. It also acidifies the microenvironment to pH 6.0–6.5, directly impairing NK and T-cell activity. Concurrent lipid abundance stabilizes the MCT4 lactate exporter, forming a bidirectional feed-forward loop that amplifies lactate effects. Spatial metabolic heterogeneity creates distinct immune battlefields, with a supportive ‘metabolic oasis’—a concept proposed in this review—at the invasive front and a deeply immunosuppressive core. Thus, lactate acts as an epigenetic and signaling hub that bridges oncogenic mutations, metabolic competition and immune evasion. Targeting lactate metabolism through LDHA or MCT4 inhibition, modulation of histone lactylation, or disruption of lactate-lipid crosstalk, when combined with classical immune checkpoint blockade and guided by spatial biomarkers, offers a promising strategy to overcome immunotherapy resistance in this challenging subtype. Full article

Background/Objectives: High-risk prostate cancer is a biologically heterogeneous group of tumors carrying a substantial risk of progression to lethal, castration-resistant disease. Although androgen deprivation therapy (ADT) remains the therapeutic backbone, nearly all advanced disease eventually progresses to castration-resistant prostate cancer (CRPC) through Darwinian clonal evolution under sustained therapeutic pressure. This narrative review reframes high-risk prostate cancer management as an effort to reprogram the evolutionary trajectory and delay castration resistance, addressing current risk stratification, androgen receptor (AR)-dependent and AR-independent mechanisms of resistance, and multidisciplinary strategies that modify selective pressure. Methods: A narrative review of the literature was conducted, including peer-reviewed studies, pivotal phase III trial reports, and current clinical practice guidelines indexed in PubMed, Scopus, and Web of Science up to 2026. Sources on high-risk and castration-resistant prostate cancer, the biology of treatment resistance, and multidisciplinary treatment intensification were selected and synthesized. Results: Treatment intensification has been extended to high-risk biochemical recurrence (EMBARK), directed by biomarkers in PTEN-deficient disease (CAPItello-281), and moved earlier through prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (PSMAfore, PSMAddition). In localized disease, effective AR-pathway intensification with abiraterone (STAMPEDE) contrasts with the failure of chemotherapy (PEACE-2) and enzalutamide (ENZARAD). Emerging therapies targeting lineage plasticity exploit its dynamic and potentially reversible biology, raising the prospect of reversing established resistance rather than merely delaying it. CAPItello-281 and PSMAddition have immature overall survival data and are not yet standard of care. Conclusions: Coordinated multidisciplinary care, matched to the disease stage and molecular context, offers a realistic path to delay castration resistance and improve survival. Full article

The financial well-being of urban middle-income households in developing economies is an urgent yet theoretically underexplored issue. In Malaysia, the Middle 40 percent (M40) group faces a middle-income squeeze, where wage growth has failed to keep pace with rising urban costs, leaving them ineligible for means-tested aid but lacking the financial resilience of higher income-earners. Existing research largely links financial vulnerability to absolute poverty among the Bottom 40 percent (B40), treating financial strain, financial behaviour, and perceived inequality as separate factors. This leaves the M40’s financial erosion conceptually disjointed and untested as a cohesive system. This paper fills that gap by proposing an integrated framework positioning financial well-being as shaped by strain and perceived inequality, with financial behaviour as a mediator and household size as a moderator. It draws on the Family Economic Stress Model, Relative Deprivation Theory, and the Life Cycle Hypothesis to explain how economic pressure, social comparison, and life-stage disruptions interact. By synthesising these three theoretical lenses the framework repositions financial well-being, rather than income or poverty status alone, as the central outcome of interest for Malaysia’s structurally underserved urban middle class, and offers a theoretically grounded and testable basis for future empirical validation and policy design. Full article

Prostate cancer is among the most frequently diagnosed cancers in men globally, with metastatic disease contributing substantially to morbidity and mortality. While conventional therapies remain the standard of care, dietary and lifestyle behaviors are increasingly explored as potentially modifiable factors influencing clinical outcomes, although their role in advanced disease is not well established. We report a 60-year-old, physically active male, lifelong non-smoker without significant comorbidities, diagnosed with de novo metastatic prostate adenocarcinoma (Gleason score 9) and an initial prostate-specific antigen (PSA) of 808.3 µg/L. The patient received standard androgen deprivation therapy. By personal choice, he adopted a whole-food, low-fat (WFLF) vegan diet, structured physical activity, and periodic fasting-mimicking diet cycles. These interventions complemented, but did not replace or delay, conventional treatment. During the 14-month follow-up period, serial PSA measurements, laboratory tests, blood pressure monitoring, dietary assessment, body composition analysis, imaging, and germline genetic testing were performed. PSA declined from 808.3 µg/L to 1.7 µg/L (>99.8%), and remained suppressed throughout follow-up. Concurrent improvements were observed in body composition and metabolic biomarkers. The WFLF vegan diet increased fiber and micronutrient intake while reducing saturated fat and cholesterol. This case demonstrates the successful application and execution of an integrative oncology approach and highlights metastatic prostate cancer managed with standard therapy alongside patient-initiated lifestyle modifications. The findings should be interpreted as descriptive, exploratory, and hypothesis-generating. Given the single-patient design, the independent impact of lifestyle interventions cannot be determined. Controlled studies are warranted to clarify their potential role in advanced prostate cancer management. Full article

Background/Objectives: Childhood cancer outcomes are influenced by clinical, socioeconomic, and territorial factors, particularly in resource-limited settings. This study characterized pediatric cancer patients from Córdoba and Sucre, Colombia, and evaluated factors associated with clinical outcomes in a regional referral center. Methods: A retrospective hospital-based study included 434 patients aged 0–18 years diagnosed between 2018 and 2024. Sociodemographic, clinical, and territorial socioeconomic variables were analyzed using the Multidimensional Poverty Index (MPI). Clinical outcomes were classified as favorable, non-favorable, or death. Firth-penalized logistic regression models were used to assess adjusted associations. Results: Hematologic malignancies predominated (65.9%), with acute lymphoblastic leukemia as the most frequent diagnosis. Most patients came from municipalities with moderate or high multidimensional poverty (85.2%), and the rural territories of origin showed greater deprivation in education, employment, housing, water access, and sanitation. Favorable outcomes occurred in 82.9% of patients, while 8.5% had non-favorable outcomes and 8.5% died. Older age and non-hematologic malignancies were associated with non-favorable outcomes. Mortality was associated with older age, subsidized health insurance, and non-hematologic malignancies. MPI and rural residence were not independently associated with outcomes after adjustment. Conclusions: Although MPI was not independently associated with clinical outcomes, it identified substantial territorial deprivation. Integrating clinical and territorial indicators may support equity-oriented surveillance and pediatric oncology interventions. Full article

Extreme heat events are associated with increased morbidity and mortality, disproportionately affecting vulnerable populations. However, evidence from disadvantaged urban settings in Africa remains scarce. This systematic review aimed to synthesize existing research on the health impacts of extreme heat in Africa’s disadvantaged urban communities. A systematic literature search was conducted in accordance with PRISMA guidelines across eleven databases (PubMed, Cochrane, VHL, Google Scholar, ScienceDirect, Research4Life, DOAJ, Emerald, Taylor & Francis, Annual Reviews, and IRIS), carried out over two search periods (December 2023–March 2024 and December 2024–February 2025). Eligible studies were published between 2010 and 2024 in English, French, or Portuguese, and examined direct or indirect heat-health effects in disadvantaged urban settings. Screening of 96,608 titles and 59 abstracts yielded 21 eligible studies. Geographically, the evidence was concentrated in South Africa (n = 7), Kenya (n = 6), and Tanzania (n = 4), with single studies from Cameroon, Egypt, Nigeria, and Ghana. Heat-related morbidity was examined in 17 studies and mortality in four. Commonly reported conditions included dehydration, heat exhaustion, skin rashes, heatstroke, and cardiovascular and respiratory diseases. Extreme heat was further associated with mortality from non-communicable diseases, pneumonia, and acute respiratory infections. Children, older adults, and the most economically deprived communities exhibited heightened vulnerability, driven by adverse socioeconomic and environmental conditions. The available evidence confirms substantial heat-health impacts on disadvantaged urban populations across Africa, while revealing a notable research gap in French- and Portuguese-language literature. These findings underscore the urgent need for expanded, geographically and linguistically diverse research to inform climate adaptation strategies and health protection policies. Full article

Coal phase-out regions concentrate the distributional risks of the energy transition, yet the tools used to identify energy-poor households in these territories still rely mainly on income and welfare criteria. This study asks whether such criteria can identify the households that suffer. Drawing on a survey of 706 households across six municipalities of Western Macedonia, Greece, the core territory of the national lignite phase-out, we validate a four-item Thermal Stress Index (polychoric ω = 0.885; loadings = 0.71–0.88; no differential item functioning by gender, income, or survey wave) and test nine hypotheses and one descriptive benchmark on prevalence, mechanisms, typologies, and targeting. Winter thermal inadequacy reaches 22.9%, which sits above the 19.0% national EU-SILC figure, reported as descriptive context. Dwelling energy features dominate all socioeconomic predictors of severe thermal stress (pseudo-R-squared 0.482 against 0.024), and no direct tenure association remains once envelope quality is included, while the protective association of income operates primarily through dwelling quality and is not observed across the range of inefficient dwellings. Latent class analysis identifies a hidden energy poverty class, 19.5% of households with severe experiential deprivation, above-average income, and no payment problems. A machine learning targeting audit shows that administrative criteria alone identify severely stressed households and show no discriminative capacity for identifying severely stressed households (AUC = 0.517), whereas adding dwelling and financial-strain information raises discrimination to an area under the curve of 0.938. Finally, in this sample, income-based screening is weakly associated with the households reporting severe thermal deprivation. Full article

There is a widespread interest in Gen Z today. From a religious perspective, Gen Z tend to, firstly, disaffiliate themselves from institutionalized religion, secondly, find it incompatible with reason, and thirdly, find it exclusivist. In this context, the Tamil epic Neelakesi can be read hermeneutically alongside the three phenomena mentioned above. Firstly, this epic can provide inspiration to Gen Z, who live in a quick-paced world that deprives them of inner peace. Secondly, it inspires religions to intellectually engage with the youth. Thirdly, Neelakesi calls for social justice, overcoming casteism and patriarchal demons that commodify women. This interdisciplinary study uses the hermeneutical method. Firstly, the three elements are drawn from Neelakesi. Secondly, theological foundations, reasonable to the public, are given. Lastly, the discussion is taken up to provide perspectives on how Catholic parishes, and youth groups in particular, can foster better religious practices among Gen Z. Full article

Alcohol consumption contributes substantially to global morbidity and mortality. The alcohol-harm paradox describes the phenomenon where more deprived areas experience higher levels of alcohol-related harms despite reporting similar or lower levels of alcohol consumption compared to less deprived areas. This paradox is particularly evident in Gwent, South-East Wales, where more deprived areas experience greater levels of harms despite having lower annual alcohol consumption. This research aims to explore the impacts of various hypothesised contributors to the alcohol-harm paradox in Gwent. Publicly available cross-sectional data sources are used to explore health behaviours, demographics, alcohol outlet density, and proximity to alcohol-related venues. Factors are studied in relation to both annual alcohol consumption and binge drinking prevalence. Alcohol-related harms are considered in terms of alcohol-specific deaths and alcohol-attributable hospital admissions. The findings reinforce the known complexity of the alcohol-harm paradox, and suggest that it is unlikely to be attributable to a single factor. Elevated prevalence of unhealthy behaviours in more deprived areas and proximity to alcohol venues traditionally associated with cheaper alcohol emerged as potential influential factors. These exploratory findings highlight the importance of targeted public health messaging addressing an overall healthier lifestyle and less harmful consumption behaviours, to reduce alcohol-related health inequalities. Full article

Human secreted phospholipase A₂ group IIA (hGIIA) is a Ca²⁺-dependent extracellular enzyme that supports host defense and amplifies inflammation through lipid mediator generation and receptor-linked signaling. In prostate cancer (PCa), hGIIA is commonly elevated compared with benign tissue and can persist after androgen deprivation, implicating it in tumor progression. PCa is typically an immunologically “cold” disease sustained by an immunosuppressive tumor microenvironment enriched in regulatory T cells ( T_reg), myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and pro-tumor stromal cells, alongside hypoxia and metabolic rewiring. Because hGIIA is released by innate immune cells and is inducible in macrophages, it is well positioned to strengthen inflammatory lipid networks and promote immune dysfunction within the prostate tumor microenvironment. Here, we review the PCa microenvironment and evaluate evidence linking hGIIA to tumor–stroma crosstalk, angiogenic programming, and therapy resistance, highlighting major knowledge gaps in prostate-focused immune studies. Full article