Search Results (759)

Metabolomic studies in COPD reveal systemic metabolic perturbations, yet sex is often treated as a covariate rather than a biological driver. We aimed to identify plasma metabolites differentiating COPD from controls and to define sex-specific metabolic signatures in both groups. Methods: In this controlled observational study (BIOMEPOC cohort), untargeted plasma metabolomics was performed by LC-MS/MS. Differential abundance was tested across four contrasts (COPD vs. controls; men vs. women within controls; men vs. women within COPD; sex-by-disease interaction) with a false discovery rate (FDR) correction. Because smoking history differed between COPD and controls, a post hoc ever-smokers analysis was conducted. Results: COPD differed from controls in nine metabolites (all decreased): DL-stachydrine, 3-methyl-L-histidine, fructose, pipecolinic and nipecotic acids, 5-nitro-o-toluidine, conjugated linoleic acid, aminoadipate, and creatinine. This pattern is compatible with metabolic depletion, remodeling, and/or altered flux across multiple compartments rather than simple substrate deficiency, spanning muscle-related pools, amino acid handling, carbohydrate-associated metabolism, and exposome-linked inputs. In ever-smokers, results were directionally consistent, with five metabolites remaining nominally significant. Among controls, five metabolites were higher in men after FDR correction (PABA, cis-4-hydroxy-D-proline, N-acetylasparagine, deoxycarnitine, and creatinine), consistent with physiological sex dimorphism in energy pathways, connective-tissue remodeling, and diet/microbiome-related metabolism. Within COPD, six metabolites differed by sex after FDR correction, defining three axes: creatine energy buffering (men: higher GAA/creatinine, lower creatine), purine/urate handling (men: higher urate), and conjugated bile acids (men: higher GCDCA), implicating muscle bioenergetics, redox/inflammatory tone, and gut–liver crosstalk. Conclusions: Plasma metabolomics identifies a pattern compatible with systemic remodeling in COPD and sex-associated divergences in creatine, purine/urate, and bile-acid pathways, supporting a sex-influenced view of systemic COPD heterogeneity and highlighting targets for mechanistic validation. Full article

Background/Objectives: Breast cancer (BC) represents a major public health problem that is influenced by social and systemic factors. This study evaluates disparities in the BC care continuum based on health insurance type and determines whether these patterns differ according to neighborhood-level deprivation. Methods: Using the Puerto Rico Central Cancer Registry-Health Insurance Linkage Database, we conducted a retrospective cohort study of women aged ≥18 years and diagnosed with BC in Puerto Rico between 2012 and 2016. The main outcomes were diagnostic delay (>60 days) and six-year mortality. Insurance type (private, Medicare, Medicaid, and dual enrollment in Medicare and Medicaid) was the main predictor, with neighborhood deprivation as a modifier. Logistic and Cox models assessed delay and survival, adjusting for key covariates. Results: Disparities in diagnostic delays and risk of death across insurance types were most evident in areas with low to average deprivation, whereas, in neighborhoods with above-average to highest deprivation, these differences diminished for diagnostic delay and disappeared for risk of death. Conclusions: These findings reveal that neighborhood environment, an intermediary social determinant of health, may affect the timeliness and quality of care provided to women diagnosed with BC. Full article

Sustainability monitoring relies on environmental indicator systems that integrate heterogeneous multivariate measurements across space and time; however, collinearity, non-Gaussian variability, and influential observations frequently destabilize classical multiblock methods and may bias indicator-based assessment and decision support. This study proposes a robust extension of the STATICO (STATIS–CO-inertia) framework to model common structures among paired environmental indicator blocks under realistic data contamination. The approach preserves the original triadic algebraic formulation while incorporating robust covariance estimation and adaptive weighting to reduce the influence of outliers and structurally unstable blocks. Robustification is implemented at the interstructure stage through a reformulated Escoufier’s RV coefficient and in the construction of the compromise space via robust distances. The RV coefficient, a multivariate generalization of the squared Pearson correlation computed between cross-product matrices, is used to quantify structural similarity between paired data blocks and to evaluate the stability of the compromise structure. Performance is evaluated using simulated datasets calibrated to represent Ecuadorian coastal monitoring conditions. The results show that Robust STATICO increases compromise dominance and stability, redistributes inter-block similarities more coherently, and improves discriminative representation in the factorial space, yielding more interpretable and environmentally plausible structures. Overall, the proposed method provides a reliable analytical tool for sustainability-oriented environmental monitoring by supporting stable identification of persistent multivariate patterns and robust comparison of indicator structures in complex systems. Full article

Background: Alcohol use patterns influence health outcomes. This study examined sex-specific drinking trajectories and their associations with all-cause mortality and coronary heart disease (CHD) in the US-based Framingham Heart Study. Method: Among 6570 participants (mean age: 55 ± 13; 55% women) followed for 15 years, a growth mixture model identified four sex-specific alcohol consumption trajectories. Cox models examined associations of alcohol trajectories with CHD and mortality over 10 years of follow-up, adjusting for covariates. Results: This study identified four distinct, sex-specific alcohol consumption trajectories: the Moderate-Decreasing group (1179 women, 0–14 g/day; 1534 men, 0–28 g/day) showed a declining moderate intake, The Low-to-None group included light or non-drinkers (992 women, 826 men), the Inverse-U group (606 women, 199 men) showed variable intake over time, while the High-Decreasing group (858 women, 376 men) had high initial consumption (women > 14 and men > 28 g/day) that declined over time. Compared with the Moderate-Decreasing group, women in other groups had higher CHD risks (HRs 1.58–1.61) and greater mortality risk in the Low-to-None (HR 1.25) and Inverse-U (HR 1.28) groups. Men in Low-to-None had higher mortality (HR 1.17) and CHD (HR 1.60), while High-Decreasing showed the highest mortality (HR 1.27). Low-to-moderate drinking was associated with lower mortality and CHD risks; however, these findings do not confirm the protective effects of alcohol use. Discussion: Our findings suggest that sustained low to moderate drinking was associated with lower risks of mortality and CHD in both women and men, compared to high-level or fluctuating patterns. Although these associations may not confirm causality, our findings emphasize the importance of investigating long-term drinking patterns in public health. Nevertheless, we caution against promoting moderate alcohol use as a strategy to reduce mortality risk or prevent CHD. Full article

The continuous growth in both the number of phenotypic records and the range of traits included in beef cattle genetic evaluations poses substantial statistical and computational challenges for the estimation of genetic and residual (co)variance matrices required for breeding value estimation. Structural equation models (SEM), implemented using either factor analysis (FA) or recursive model (REC) structures, provide a flexible framework to model genetic and residual (co)variance matrices while yielding more parsimonious and computationally efficient parameterizations. Here, SEM was applied to estimate parameters for growth and ultrasound-measured carcass traits in beef cattle. The dataset comprised 2942 animals, and six traits were evaluated using standard multiple-trait mixed models (SMTM) and SEM. We considered FA and REC models implemented with six alternative parameterizations, in which random effects were represented as linear combinations of fewer unobservable random variables. Relative to the SMTM, both the model with two factors in the genetic covariance matrix (FA2G) and the model in which six recursive effects were constrained to zero in the residual covariance matrix (REC1) demonstrated a strong ability to capture genetic variability, as reflected by comparable heritability estimates. Correlations between estimated breeding values (EBV) for the same traits across models were consistently high, ranging from 0.94 to 1.00, indicating strong agreement among model estimates. The FA2G model was the most parsimonious in terms of the effective number of parameters ($p_D$), with 431.2 $p_D$, corresponding to a reduction of 25.3 parameters relative to the SMTM. The REC1 model also emerged as a competitive alternative for this dataset, exhibiting a lower $p_D$ (443.6) than the SMTM (456.5) and the most favorable deviance information criterion among all models evaluated (e.g., 37,868.6 for REC1 versus 37,874.7 for SMTM). Overall, these results demonstrate that mixed-effects multi-trait models for beef cattle genetic evaluation can be effectively implemented using FA or REC structures, which provide parsimonious representations of the underlying covariance patterns while maintaining high agreement in EBV. Full article

Background: Tuberculosis (TB) remains a major global public health challenge, with substantial variation across countries. South Africa has one of the highest TB incidence and mortality rates globally, while Bulgaria, a low-incidence country, faces a persistent TB burden among vulnerable populations. Objectives: To compare national trends in TB incidence and mortality in South Africa and Bulgaria from 2000 to 2023 and explore associations with selected socioeconomic indicators and health system coverage. Methods: An ecological, descriptive, analytical study used national-level data from the WHO, World Bank, and official statistics. TB trends were analyzed alongside income, poverty, unemployment, and Universal Health Coverage indicators. Time series measures and Pearson correlation were used descriptively to summarize co-variation over time. Results: Between 2000 and 2023, TB incidence declined by approximately 44% in the Republic of South Africa and 69% in Bulgaria. In both countries, TB incidence co-varied strongly with unemployment (RSA: r = 0.805; BG: r = 0.723). In Bulgaria, TB incidence was also strongly negatively associated with GDP per capita (r = −0.910), whereas no significant association with GDP was observed in South Africa. These findings indicate that TB trends co-varied more closely with labour market conditions in both contexts, while broader economic growth co-occurred with declining TB incidence only in Bulgaria. Conclusions: TB trends co-occurred with changes in socioeconomic conditions and health system coverage, with differing patterns across contexts. Findings highlight the relevance of equity-oriented, context-specific TB control strategies integrated with social and economic policies. Full article

Background/Objectives: Autism spectrum disorder (ASD) is biologically heterogeneous, and immune-linked variation may be associated with differences in tryptophan–kynurenine pathway (KP) metabolism. Here, we report a targeted urinary profile of KP metabolites, NAD (nicotinamide adenine dinucleotide), and neopterin in a Bulgarian pediatric ASD cohort to describe within-cohort patterns and associations. Methods: Second-morning, acid-stabilized spot urine was collected from 73 children with ASD in Bulgaria (3–13 years; 57 males; 16 females). No contemporaneous neurotypical control group was enrolled; therefore, laboratory-provided reference limits are reported only as contextual benchmarks and are not interpreted as ASD-specific abnormalities. Tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), quinolinic acid (QUIN), NAD, and neopterin were quantified and derived indices were computed (KYN/TRP × 1000; QUIN/KYNA). Non-parametric statistics, Benjamini–Hochberg false discovery rate (FDR) correction, and Spearman correlation analyses were applied. Results: Neopterin was strongly associated with QUIN and KYN in creatinine-normalized data (QUIN: ρ = 0.59, q36 = 2.64 × 10⁻⁷; KYN: ρ = 0.54, q36 = 3.69 × 10⁻⁶); these associations persisted when reconstructed as absolute concentrations (e.g., QUIN_abs: ρ = 0.68, q36 = 2.69 × 10⁻¹⁰) and after partial Spearman correlation controlling for spot creatinine (partial ρ = 0.46, q = 2.52 × 10⁻⁴). One NAD value was <LOQ and was imputed as ½LOQ; sensitivity analyses did not materially change inference. Conclusions: In this ASD-only cross-sectional dataset, urinary neopterin levels co-varied with urinary KYN and QUIN and with KP indices. Clinical interpretation and causal inference require controlled and longitudinal studies with richer covariate capture. Full article

This study evaluates whether theory-informed, mathematically focused support can ease the school-to-university transition in an unequal South African STEM context. First-year students could voluntarily attend Mathematical Thinking Workshops (MTWs) grounded in constructivism, the zone of proximal development, APOS theory, and cognitive load theory, providing low-threat, collaborative practice with non-routine, representation-rich tasks. Because attendance was self-selected, we used a quasi-experimental design: participation was modeled from pre-university covariates (school-leaving Mathematics and English grades and standardized university preparedness tests in Mathematics and Quantitative Literacy), and MTW participants were matched to comparable non-participants using nearest-neighbor propensity-score matching. Average treatment effects on the treated were estimated for multiple assessments and for a composite score capturing performance on higher-order items within those assessments. MTW participants outperformed matched peers on early first-semester assessments, especially those containing the most higher-order items, indicating that workshops helped when cognitively demanding tasks first appeared. Effects on later, more distal assessments were positive but attenuated, producing an “early gains, fading effects” pattern. Although estimates were imprecise, benefits appeared largest for students who had scored 70–84% in school-leaving mathematics. Overall, the findings suggest that transitional workshops can deliver timely, assessment-visible gains, although these effects may weaken over time when they are not reinforced or well aligned with later summative assessment. Full article

As Thailand advances regional economic revitalization through the Southern Thailand Special Economic Corridor (SSEC), small and medium-sized enterprises (SMEs) have become pivotal to sustainable economic transformation. However, limited empirical evidence explains how environmental pressures are translated into sustained firm-level performance within policy-driven regional economies. To address this gap, this study examines the structural relationships among the external environment, dynamic capabilities, business model innovation, and SMEs’ business success across four SSEC provinces. Drawing on Dynamic Capabilities Theory (DCT) and the Resource-Based View (RBV), the study proposes that external conditions stimulate internal adaptive capabilities, which subsequently enable firms to reconfigure business models and achieve durable business performance. Using stratified sampling, data were collected from 412 SMEs in the manufacturing, trade, and service sectors. The data were analyzed using covariance-based structural equation modeling. The results reveal that while the external environment does not exert a significant direct effect on business success, it influences performance indirectly through a sequential capability–innovation pathway, supporting an indirect-only mediation pattern. Dynamic capabilities significantly enhance both business model innovation and business success, whereas business model innovation emerges as the strongest direct predictor of performance. By identifying an indirect-only mediation mechanism, the study specifies the structural boundary condition under which environmental dynamism translates into sustainable firm performance within regional economic corridors. From a sustainability perspective, the findings further demonstrate that long-term regional resilience in emerging economic corridors depends not solely on macro-level policy initiatives but on SMEs’ capability to continuously reconfigure resources, renew business models, and adapt strategically under structural volatility. Accordingly, the study provides integrated theoretical and policy insights for capability-driven sustainability and innovation-oriented regional development. Full article

Intramuscular fat (IMF) significantly influences meat quality, particularly flavor. The gastrointestinal microbiota can regulate lipid metabolism. The relationship between intramuscular fat metabolism, rumen microbiota, and beef quality remains unclear. This study enrolled 22 30-month-old Xinjiang Brown Beef cattle, which were randomly allocated to two groups: an intact bull group (n = 15) and a castrated bull group (n = 7). All experimental animals were housed and maintained under consistent feeding and management conditions throughout the entire experimental period. By combining in vivo ultrasonography, slaughter trials, rumen microbiome diversity analysis, and metabolomics techniques, and after adjusting for covariates including intramuscular fat (IMF) content, body weight, and backfat thickness, the present study demonstrated that castration regulates muscle lipid metabolism by reshaping the composition of the rumen microbial community, thereby exerting a cascading effect on key beef quality traits. (1) Production and meat quality: Live weight, carcass weight, eye muscle area, backfat thickness, and intramuscular fat (IMF) content were significantly higher in the YN group than in the GN group (p < 0.01). Conversely, dressing percentage, shear force value, and muscle protein content were significantly lower in the YN group than in the GN group (p < 0.01 or p < 0.05). (2) Rumen microbiota–metabolite correlation: Significant differences existed in microbial composition and community structure between groups (with significant differences in both α and β diversity). Core microbes regulated by castration exhibited distinct co-variation patterns with metabolites: genera such as Anaeroplasma showed significant positive correlations with hydroxy fatty acids, while Sharpea and others showed significant negative correlations with saturated fatty acids. (3) Microbial–metabolite axis and host phenotype correlation: Axes composed of Eubacterium uniforme and others showed significant positive correlations with IMF, while Docosapentaenoic acid (22n-3) exhibited significant negative correlations with IMF. Anaeroplasma and others showed significant positive correlations with oleic acid and others, as well as BFT, while saturated fatty acids showed significant negative correlations with BFT. (4) Covariate validation: After adjusting for covariates including body weight, backfat thickness, and IMF, castration was confirmed to significantly regulate the abundance/content of core genera such as Anaeroplasma, Eubacterium uniforme, as well as key metabolites such as hydroxy fatty acids and docosapentaenoic acid (22n-3) (p < 0.05 after adjustment), making it a core driver regulating rumen microbial composition and muscle lipid metabolism. After adjustment, the regulatory effects of IMF, body weight, and backfat thickness on the aforementioned microorganisms and metabolites were no longer significant (adjusted p > 0.05). Intramuscular fat (IMF), body weight, and backfat thickness are not independent drivers but rather indirect effects resulting from castration-induced physiological state remodeling. This study did not include feeding rate measurements, which represents a limitation. Future research should incorporate this data to further validate the conclusions. This study elucidates the interactive mechanisms between rumen microbiota and their metabolites, identifies the key pathways governing intramuscular fat (IMF) deposition, pinpoints potential regulatory targets for beef quality optimization, and clarifies the intermediate regulatory mechanisms underlying the modulation of meat quality traits by castration. Full article

This study used 3D landmark-based geometric morphometrics under an object-symmetry framework to quantify pelvic asymmetry in domestic cats and dogs while explicitly accounting for measurement error through replicate digitizations. Procrustes ANOVA revealed significant components of both directional asymmetry (DA) and fluctuating asymmetry (FA) in the overall dataset, and DA was further visualized as a structured, non-random pattern across the landmark configuration. Measurement error remained smaller than the FA component, yielding high repeatability, indicating that the detected asymmetry patterns were not driven by landmarking imprecision. Group-wise summaries are presented as descriptive patterns of the sample (rather than direct between-group inference). In these descriptive summaries, cats tended to show a more coherent DA pattern, whereas dogs showed greater individual variation consistent with a relatively stronger FA component; males also tended to exhibit greater FA-related dispersion than females. In regression models of FA, age showed no association, body mass exhibited only a weak trend, and sex emerged as a significant predictor, while species showed no detectable effect when covariates were included. Collectively, these results support the hypothesis that pelvic shape contains both systematic (DA) and individual-specific (FA) asymmetry components, with sex-related differences in FA magnitude, but limited evidence for age- or weight-related effects within the sampled range. The study provides a repeatable framework and baseline reference for pelvic asymmetry in cats and dogs. Full article

Background: Despite the confirmed beneficial effects on preventing neural tube defects, concerns about high intakes of synthetic folate, or folic acid, in promoting cancer progression have been raised. This study evaluated the association between folate intake and prostate cancer (PCa) aggressiveness among African-American (AA) and European-American (EA) males. Methods: This study included 722 AA and 775 EA men with prostate cancer. Folate intake (dietary folate equivalent (DFE), synthetic folate, natural folate) was estimated using the National Cancer Institute Dietary History Questionnaire and detailed dietary supplement use questionnaire. Analyses included univariable comparisons of demographic and clinical characteristics of the two racial groups using the t-test or its non-parametric counterpart, the Wilcoxon test for continuous variables, and the Chi-square test for categorical variables. Logistic regression analysis was performed to evaluate the associations of each source of folate intake with PCa aggressiveness. Interaction effects between folate intake levels and racial groups were tested to evaluate if the association between folate intake and PCa differed by racial groups. Results: A greater proportion of AA subjects were diagnosed with high PCa aggressiveness compared to EAs (31.6% vs. 21.7%; p < 0.001). Both AAs and EAs had associations between decreased DFE intake and PCa aggressiveness after adjusting for covariates. Among AAs, men with the highest quartile levels of synthetic folate intake had higher odds of high-aggressive PCa compared to those with the lowest levels of intake (adj. OR = 1.39; p = 0.27), while the reversed association became stronger among EAs (adj. OR = 0.62; p = 0.14). Conclusions: The association between folate intake and prostate cancer aggressiveness appears to be source-specific and modified by race. These findings highlight the need for population-informed nutritional guidance and further investigation into nutrient–gene and dietary pattern interactions in prostate cancer progression. Full article

Long-term tillage management fundamentally reshapes soil’s physical and chemical environment, yet an integrated, predictive characterization of the distinct chemical signatures induced by no-tillage (NT) versus chisel tillage (CT) remains limited. We analyzed an eight-year dataset (2010–2017) from a long-term experiment in Iowa, USA, focusing on pH, available phosphorus (Bray1-P), and macro- and micronutrients (K, Ca, Mg, Cu, Fe, Zn) at two depths (0–5 and 5–15 cm). A convergent multi-method framework combined robust univariate statistics, multivariate ordination (PCA, PERMANOVA), linear mixed-effects models, and machine learning (Random Forest and Firth-penalized logistic regression). Results reveal a clear stratification–homogenization pattern. NT is associated with surface accumulation of Zn (+14%), Fe (+16%), and Cu (+5%), with mild acidification (−0.4 pH units) and high temporal stability. CT favored vertical nutrient redistribution, marked by subsurface K enrichment (up to 6% higher than NT), progressive alkalinization, and greater temporal variability. Predictive modeling highlighted subsurface K and surface Zn/Fe as key discriminators, with Firth regression confirming their complementary effects. These findings indicate that long-term NT and CT are associated with distinct, depth-specific chemical configurations—integrated systems defined by concentration gradients, temporal stability, and element covariation—rather than isolated element changes. This work provides a robust, quantitative framework for diagnosing soil management history and characterizing the pedochemical imprint of tillage. Full article

Permafrost thickness serves as a critical indicator of hydrogeological conditions in cold regions and significantly influences the safety of engineering infrastructure. Due to the combined effects of climate, ecology, and human activities, the thermal characteristics and spatial distribution of permafrost in the Greater and Lesser Khingan Mountains of Northeast China exhibit high complexity, rendering existing permafrost thickness estimation methods largely inapplicable in this region. We developed an integrated estimation framework that bridges the gap between limited deep ground temperature measurements and regional-scale mapping. To overcome the scarcity of deep borehole (>20m) data, a physical-statistical inversion method was employed to derive permafrost base depths from shallow borehole temperature profiles, thereby expanding the foundational dataset to 104 representative sites. Integrating these ground observations with satellite-derived products (e.g., MODIS NDVI) and auxiliary environmental covariates (e.g., DEM-based topography and gridded climatic data), a Random Forest algorithm (RF) was applied to generate a 1 km-resolution permafrost thickness distribution map across Northeast China with a classification accuracy of 0.74. The results indicate that the average permafrost thickness in the study area is 47.71 ± 10 m, exhibiting a spatial pattern of thicker in the north and west, thinner in the south and east, and greater in mountainous areas than in plains. The top three influencing factors of permafrost thickness are atmospheric precipitation, surface thawing degree days (TDDs), and topographic position index (TPI), revealing that the thickness of discontinuous permafrost in northeastern China is primarily governed by local factors such as soil moisture, represented by the thick permafrost existed under a small patch of ground surface. This study provides a new methodological framework for estimating permafrost thickness in regions with limited ground temperature gradient measurement in deep boreholes. Full article

Urban wetlands, encompassing both natural and constructed ecosystems, are vital for urban resilience. Understanding how plant functional traits adapt to these distinct habitats is crucial for ecological management. This study investigates the intraspecific variation and trait covariation patterns of the common reed (Phragmites australis) in two contrasting urban wetland types in Ganzhou City: a stagnant, engineered constructed wetland and a dynamic, natural riverine wetland. This contrast represents a key gradient in hydrological regime and anthropogenic influence. We measured 22 morphological and chemical traits to assess trait differences, variability (coefficient of variation), and correlation patterns. Volcano plot analysis revealed significant habitat effects: reed in natural wetlands exhibited higher levels of Cu, P, N, and leaf moisture content (LMC), whereas those in constructed wetlands had higher Ca content. Traits such as Na, Mn, and Al showed high intraspecific variability. Correlation analyses revealed significant trade-offs and integrations among traits, such as positive correlations between LMC and nutrients (K, Cu), and negative correlations between Ca and key leaf morphological traits. Principal component analysis (PCA) further confirmed a significant separation along PC1, driven primarily by nutrient elements (Cu, P, K) and LMC, with natural wetlands scoring higher. In contrast, PC2, associated with leaf morphological traits (e.g., leaf area, leaf width), showed no significant inter-habitat difference. Our findings demonstrate that P. australis employs distinct ecological strategies by adjusting its functional traits and resource allocation in response to different urban wetland environments. This highlights the critical role of intraspecific trait variation in plant adaptation and has important implications for wetland restoration and the design of constructed ecosystems. Full article