Search Results (9,084)

In a sample of university employees, longitudinal data were examined to test a biopsychosocial model of whether exposure to workplace sexual harassment increases hazard for chronic disease, in the context of other known biological, psychological, and social risk factors for chronic disease. Proportional hazards multiple regression was used to predict incidence of first chronic disease across 23 years of follow-up based on experience of sexual harassment. Out of a sample of N = 525, 288 incident diagnoses were observed. Effects of harassment, drinking behavior, cigarette use, depressive symptoms, anxiety, and other work stressors were considered as either fixed at baseline or as time-dependent covariates in separate models, controlling for age and baseline occupational group, which were significantly associated with disease onset. Higher scores on reported workplace sexual harassment at baseline of the study were predictive of chronic disease incidence over the next 23 years (HR = 1.038 for each increase of one unit, p = 0.0133), adjusting for age and occupation. The effect was only partially attenuated when adjusting for depressive symptoms at baseline and alcohol intake throughout follow-up (HR = 1.031, p = 0.0475), the only other covariates tested that were consistently associated with chronic disease onset and included in final models. Considering the binary comparison of any versus no harassment at baseline revealed a stronger effect on chronic disease onset (HR = 1.437, p = 0.004), which again was attenuated after considering effects of baseline depressive symptoms and previous year alcohol use (HR = 1.357, p = 0.017). Experience of sexual harassment in the workplace was the only work stressor found to be significantly associated with an elevated risk of chronic disease onset across the study period. Full article

The tardigrade Ramazzottius varieornatus exhibits extraordinary resilience to extreme environmental stresses, yet the functional diversity of its proteome remains largely unexplored. In this study, the structural and biochemical characterization of RvCA5, an atypical α-carbonic anhydrase (CA) identified in R. varieornatus, is presented. Expression analysis in E. coli revealed the spontaneous formation of a truncated RvCA5 species, which was confirmed to be unrelated to signal peptide cleavage. RvCA5 exhibited distinct structural features, including extended intrinsically disordered regions (IDRs) at both termini. Unlike canonical α-CAs, RvCA5 exhibited negligible CO₂ hydration activity, which was partially enhanced by the removal of the N-terminal IDR, suggesting that this region acts as a dynamic entropic barrier hindering substrate diffusion. RvCA5 possesses multiple surface-exposed reactive cysteine residues, resembling the redox-sensing human CA 3. Notably, consistent with a predicted nuclear localization signal, in silico modeling predicted that RvCA5 can bind DNA via a positively charged patch near the C-terminal IDR. The DNA-binding capability of RvCA5 was experimentally demonstrated by electrophoretic mobility shift assays. Collectively, these findings suggest that RvCA5 potentially functions as a redox-responsive transcriptional regulator. Full article

Background/Objective: Informal caregiving for individuals with severe mental disorders (SMDs) often leads to significant psychological distress. However, the specific coping strategies that determine mental health outcomes among siblings remain poorly understood. This study aimed to analyze the predictive capacity of various coping strategies regarding health, perceived stress, self-esteem, and caregiving experience for siblings. Methods: A cross-sectional study was conducted with a sample of siblings of patients with SMDs (N = 60) from mental health service. Self-report measures were used to assess perceived health, perceived stress, self-esteem, coping strategies, and caregiving experience. Multiple linear regression analyses were performed for each dependent variable, controlling for collinearity. Results: The siblings reported a higher mean use of problem-focused coping strategies compared to emotion-focused coping strategies. Regression models were statistically significant for all analyzed variables, except for somatic symptoms. Emotion-focused maladaptive coping (EFMC) strategies emerged as the most consistent and powerful predictor, showing a significant association with positive caregiving appraisal (β = 0.657), depression (β = 0.500), poor health (β = 0.453), negative stress (β = 0.449), social dysfunction (β = 0.429), self-esteem (β = −0.390), and anxiety (β = 0.368). In contrast, problem-focused strategies were largely non-significant, except for an association with positive and negative aspects of caregiving (β_PFMC = 0.509, β_PFMC = 0.312, respectively), and positive stress (β_PFAC = −0.272). Conclusions: These results suggest that while siblings of people with SMDs report a greater use of problem-focused coping strategies, the adoption of EFMC strategies is the most detrimental factor observed, given their negative influence on mental health, self-esteem, and caregiving experience. Full article

Background: Immune checkpoint blockade (ICB) has revolutionized lung adenocarcinoma (LUAD) therapy, yet predictive bio-markers remain suboptimal. We hypothesized that BCL2A1 expression in CD8⁺ T cells may reflect immune endurance and complement PD-L1 in predicting ICB response. Methods: Integrating bulk and single-cell RNA-seq across multiple LUAD cohorts, this study performed differential expression, survival, and pathway analyses in a discovery cohort (n = 60) and validated findings across five independent cohorts (n = 126). Results: Single-cell profiling identified BCL2A1 enrichment in tissue-resident memory and proliferating subsets that appeared preferentially expanded in responders; cell–cell communication analysis revealed that BCL2A1^high CD8⁺ T cells exhibited significantly enhanced outgoing signaling capacity (p = 0.0278), with proliferating subsets serving as intra-CD8⁺ coordination hubs and MIF pathway interactions achieving the highest intensity among all axes examined. BCL2A1 was significantly upregulated in responders (FDR < 0.05) and associated with improved ICB survival (HR = 0.43, p < 0.05), but not in non-ICB settings, suggesting treatment-specific prognostic relevance. A tri-marker model integrating BCL2A1, PD-L1 (CD274), and a 27-gene HOT score demonstrated favorable predictive performance (AUC = 0.826 discovery; macro-AUC = 0.774 validation), outperforming PD-L1 alone (AUC = 0.706) and established signatures including TIDE, IPS, TIS, and IFNG. Cross-platform simulations suggested high reproducibility (ρ = 0.982–0.993). Conclusions: These findings suggest BCL2A1 may serve as a bio-marker of CD8⁺ T-cell survival and enhanced intercellular coordination, and its integration with PD-L1 and immune activation markers may yield a reproducible ICB response predictor, pending clinical validation. Full article

Background/Objectives: Brucella is a major global One Health threat, causing an estimated 2.1 million human infections and substantial livestock losses annually, with no vaccine currently available for humans, underscoring the urgent need for a safe and effective vaccine. Methods: Employing a reverse vaccinology approach, a novel 175-mer multiepitope vaccine (Mvax) targeting Brucella FrpB was computationally designed in this study, incorporating two B-cell, two MHC class I (MHC-I), and three MHC class II (MHC-II) epitopes selected for their high predicted antigenicity, safety, and IFN-γ-inducing potential. Human β-defensin-3 (hBD3) was fused to the N-terminus as an adjuvant, followed by comprehensive in silico evaluation of the construct. Results: Population coverage analysis predicted 99.59% global MHC class I/II coverage for selected epitopes. In silico analyses predicted that Mvax has high solubility (Protein-SOL score: 0.808), a high antigenicity score (VaxiJen: 1.06), and a negative GRAVY index (−0.881), indicating favorable predicted physicochemical characteristics. iMODS, CABS-Flex 3, and molecular dynamics simulations suggested theoretical stability trends for the modeled vaccine complexes. C-ImmSim immune simulations further predicted elevated Th1 cell populations and associated cytokines (IL-12, IFN-γ, IL-2) following both single and multiple simulated Mvax exposures. Conclusions: The computational analyses described here provide a theoretical modeling basis for an antivirulence multi-epitope vaccine design against human brucellosis, with predicted metrics and simulated immune responses requiring empirical validation. Full article

1,3-Dipolar cycloaddition reactions of nitrile imines are a powerful tool for the construction of spirocyclic frameworks, yet controlling chemoselectivity remains challenging when dipolarophiles contain multiple reactive sites. In this study, we investigated the cycloaddition of nitrile imines with 5-arylmethylene-2-methylthiohydantoins, which possess both exocyclic C=C and endocyclic C=N bonds. Nitrile imines were generated from hydrazonoyl chlorides under basic conditions and reacted with the thiohydantoin substrates under optimized reaction conditions. The cycloaddition proceeded smoothly, affording spiro-fused thiohydantoin–pyrazoline derivatives. In all cases, the reaction occurred selectively at the exocyclic C=C bond, while the C=N bond remained unreactive even in the presence of excess dipole. This chemoselectivity is attributed to the greater steric accessibility of the exocyclic double bond. These results clarify key factors governing nitrile imine chemoselectivity and provide a reliable approach to structurally complex spirocyclic thiohydantoin derivatives. Full article

Background/Objectives: High-risk, low-frequency incidents such as building collapses and large chemical fires can result in acute, high-dose exposures to toxic agents for first responders and the surrounding community. While these exposures may last for hours to days, their contribution to firefighters’ risks for cancer and other diseases is relatively unknown. In February 2023, a freight train transporting chemicals derailed and caught fire in East Palestine, Ohio, US. More than 350 firefighters, primarily volunteer, responded to the incident. In this cross-sectional study, we evaluated epigenetic markers of toxicity in responding firefighters. We hypothesized that exposures from responding to the train derailment would alter the expression of microRNAs (miRNAs) linked to carcinogenesis. Methods: We enrolled 62 responding firefighters and a comparison group of 26 firefighters from the same region who did not respond to the incident. We measured the relative expression of 800 miRNAs in blood samples using the nCounter Human v3 miRNA expression panel. We compared the expression of miRNA between exposure groups in negative binomial regression models, adjusting for potential confounders. Results: At a false discover rate cut-off of 5% (q-value < 0.05), 16 miRNAs had significantly higher expression and one significantly lower among firefighters that responded to the incident. Top disease-related pathways in which these miRNAs were enriched included those relevant to neurodegenerative diseases, vascular disease, and multiple cancer sites. Conclusions: Overall, results suggest responding to one large incident can have non-transient impacts on miRNA expression. Whether this translates into longer-term health risks or adaptive responses to exposures is unclear. Full article

Background/Objectives: Otitis media (OM), including acute otitis media (AOM) and chronic otitis media (COM), is a common middle ear disease that can lead to significant morbidity if not accurately diagnosed. Otoscopic interpretation remains subjective and operator-dependent, underscoring the need for objective and reproducible diagnostic support. Recent advances in artificial intelligence (AI) offer promising solutions for automated otoscopic image analysis. Methods: We developed an AI-based diagnostic framework consisting of three sequential steps: (1) semi-supervised learning for automatic recognition and semantic segmentation of tympanic membrane structures, (2) region-based feature extraction, and (3) disease classification. A total of 607 clinical otoscopic images were retrospectively collected, including normal ears (n = 220), AOM (n = 157), and COM with tympanic membrane perforation (n = 230). Among these, 485 images were used for training and 122 for independent testing. Semantic segmentation of five anatomically relevant regions was performed using multiple convolutional neural network architectures, including U-Net, PSPNet, HRNet, and DeepLabV3+. Following segmentation, color and texture features were extracted from each region and used to train a neural network-based classifier to differentiate disease states. Results: Among the evaluated segmentation models, U-Net demonstrated superior performance, achieving an overall pixel accuracy of 96.76% and a mean Dice similarity coefficient of 71.68%. The segmented regions enabled reliable extraction of discriminative chromatic and texture features. In the final classification stage, the proposed framework achieved diagnostic accuracies of 100% for normal ears, 100% for AOM, and 91.3% for COM on the independent test set, with an overall accuracy of 96.72%. Conclusions: This study demonstrates that a semi-supervised, segmentation-driven AI pipeline integrating feature extraction and classification can achieve high diagnostic accuracy for otitis media. The proposed framework offers a clinically interpretable and fully automated approach that may enhance diagnostic consistency, support clinical decision-making, and facilitate scalable otoscopic assessment in diverse healthcare screening settings for disease prevention and health education. Full article

Objective: This study evaluated the effects of a 12-week High-Intensity Functional Training (HIFT) program combined with thylakoid supplementation on plasma adipo-myokine levels (Decorin, Myostatin, Follistatin, Activin A, and TGF-β1) in men with obesity. Secondary outcomes included anthropometric indices, lipid profiles, and insulin resistance markers. Methods: Sixty men with obesity (age: 27.6 ± 8.4 years; BMI: 32.6 ± 2.6 kg/m²) were randomly assigned to four groups (n = 15 per group): Placebo (PG), Supplement (SG), HIFT + placebo (TPG), and HIFT + supplement (TSG). To ensure robustness against the 27% attrition rate, statistical analyses included both per-protocol and intention-to-treat (ITT) models. HIFT was performed for 3 sessions/week (Borg scale: 15–17). Results: Following Bonferroni correction for multiple endpoints, repeated-measures ANOVA showed significant Time × Group interactions for most adipo-myokines and metabolic markers. Both training groups (TPG and TSG) demonstrated improvements in body composition and insulin sensitivity compared to PG (p < 0.05). While no significant differences were observed between TPG and TSG for systemic metabolic markers, preliminary data suggested that thylakoid supplementation might provide modest complementary modulations in specific myokines (e.g., decorin and follistatin). However, these observed trends did not reach clinical superiority over exercise alone in the broader metabolic profile. Conclusions: Twelve weeks of HIFT is an effective primary driver for modulating the adipo-myokine network in obese men. Although thylakoid supplementation showed potential for selective complementary effects on certain myokines, these findings are exploratory given the small sample size. The clinical significance and long-term complementary value of thylakoid-exercise interactions require further validation in larger, more diverse cohorts. Full article

A genome-wide identification and expression analysis was performed to examine the response of the amino acid permease (AAP) gene family to drought stress in tomato (Solanum lycopersicum L.). Ten AAP genes were identified across seven of the twelve chromosomes and classified into four subfamilies (I–IV) based on phylogenetic relationships. Expansion of the SlAAP family appears to have been driven mainly by segmental and tandem duplication events. Members within the same subfamily displayed high similarity in exon–intron organization and conserved motif architecture. Promoter analysis revealed the presence of multiple cis-acting elements associated with stress and defence regulation. Under drought stress, all putative genes exhibited significant transcriptional induction, with SlAAP8, SlAAP9 and SlAAP10 showing the strongest upregulation, suggesting their potential involvement in drought adaptation. Drought treatment also led to a marked decline in nitrate (NO₃⁻) and total nitrogen (N) contents, while simultaneously increasing the accumulation of total amino acids, ammonium (NH₄⁺), and proline in both leaf and root tissues of tomato. The expression profiles of the ten putative SlAAP genes showed strong positive correlations with total amino acid levels in both organs, suggesting their involvement in amino acid redistribution under stress. Collectively, these results underscore the functional complexity of the SlAAP gene family and provide a robust foundation for future investigations into their molecular roles and potential applications in enhancing drought tolerance in tomato and other crop species. Full article

Examinations are central to higher education, yet students consistently describe them as detrimental to well-being. Drawing on self-determination theory (SDT), we conducted three studies to examine whether multiple-choice examinations could be redesigned to satisfy students’ basic psychological needs (BPNs) and support well-being. In Study 1 (n = 400), we developed and validated the Basic Psychological Need Satisfaction and Frustration Scale for Classroom Assessment (BPNSF-CA). Using bifactor exploratory structural equation modeling (bifactor ESEM), results supported a well-defined single global need fulfillment factor (G-factor) alongside six specific factors (autonomy support/frustration, competence support/frustration, relatedness support/frustration) as well as evidence of validity. In Study 2 (n = 387), we conducted a randomized experiment with three versions of a multiple-choice exam serving as the independent variable (flawed items, high-quality items, and high-quality + need-supportive features). Results showed that high-quality items improved performance, while only the addition of need-supportive features satisfied BPNs with differential patterns for the single G-factor and S-factors. In Study 3 (n = 101), we applied the intervention in a real classroom and tested the mediational role of BPN satisfaction. Results showed that redesigned exams (high-quality + need-supportive features) significantly enhanced perceptions of fairness and success via BPNs. We conclude with a discussion of all three studies, including implications and limitations. Full article

The topic of chaotic thresholds for piecewise linear discontinuous (PWLD) systems with multiple-well potentials is a persistent topic in the research of a number of authors. In this article we investigate the chaos of a modified piecewise linear discontinuous (MPWLD) system. The model, containing N free parameters, could be of interest to specialists working in this area. With a specially developed software product, we generate the Melnikov equation $M\left(t\right)=0$ and examine all its zeros. This opens up an opportunity for researchers to correctly understand and formulate the classical Melnikov criterion for the possible occurrence of chaos in dynamical systems. Several simulations are composed. We also demonstrate some specialized modules for investigating the dynamics of the proposed model. Intriguing and new generalizations made through probabilistic constructions are considered. Full article

Scrub typhus, caused by Orientia tsutsugamushi, remains a neglected cause of acute febrile illness. Molecular testing of blood supports early diagnosis, yet once doxycycline is started, blood qPCR positivity can drop rapidly, complicating short-term follow-up and relapse surveillance. We compared detection across multiple clinical specimens and evaluated nasopharyngeal swabs (NPSs) as noninvasive supplementary specimens during treatment initiation. In a prospective single-center cohort from Hainan, China, we enrolled 20 patients with scrub typhus. Blood, NPS, urine, and stool were collected before doxycycline administration 24 h after the first dose and on day 5. qPCR was performed for the analysis of Orientia tsutsugamushi. qPCR-positive specimens were subjected to nested PCR targeting TSA56, and nested PCR-positive amplicons were Sanger sequenced for genotyping. Before treatment, O. tsutsugamushi DNA was detected in 15/20 blood samples (75.00%) and 5/20 NPS samples (25.00%), but 0/20 urine samples (0%) and 0/20 stool samples (0%). At 24 h after treatment, detection in blood was 0/20 (0%) while NPS samples were positive in 3/20 (15.00%). All specimens were negative by day 5 after treatment. Across sequenced NPS positives (n = 3), Karp 2/3 (66.77%) and Gilliam 1/3 (33.33%) predominated. In paired blood–NPS positives, inter-specimen homology was high (percentage nucleotide identity 100% for Karp and 100% for Gilliam). NPS is not sensitive enough for primary diagnosis; however, within the first 24 h after doxycycline it offers a practical, noninvasive supplementary specimen to support short-term follow-up and community-based sampling when venipuncture or transport are constrained. Larger, multi-center studies are warranted to refine sampling windows and diagnostic performance. Full article

Nonsense-mediated mRNA decay (NMD) is a highly conserved RNA quality and quantity surveillance machinery in eukaryotic cells, serving as an important node in the post-transcriptional gene expression. Previous studies using the complete knockout of individual NMD factors in cells or animals reveal that NMD deficiency causes developmental defects and compromises tissue homeostasis. However, because most NMD factors participate in multiple molecular functions, a direct link between NMD and cell fate determination is missing. SMG6 is a core NMD effector and the only endoribonuclease among all NMD factors. The NMD function of SMG6 is exclusively mediated by its PIN (PilT N-terminus) domain. In this study, we engineered a mouse model with the capability of specifically deactivating the SMG6’s PIN domain/endoribonuclease activity (Smg6-PIN^F/F), but not knocking out the complete SMG6 protein. We found that SMG6’s PIN domain is essential for NMD activity in embryonic stem cells (ESCs) and various tissues of adult mice. Furthermore, loss of SMG6’s PIN domain is dispensable for the mouse ESC self-renewal, but severely compromises the differentiation, which consequently causes the mutant mice to die during the process of organogenesis. Through the induced deletion of SMG6’s PIN domain in adult mice, we found that loss of SMG6’s NMD function affects the homeostasis of several mouse tissues, including the testis and the intestine. In sum, our study establishes a mechanistic link between NMD per se and cell fate determination of mouse ESCs, as well as in the tissues of adult mice, where cell fate transitions are actively ongoing. The Smg6-PIN^F/F mouse line could be a valuable strain for elucidating the biology of NMD per se. Full article

The conversion of alkanes/alkenes into useful intermediates is highly important in the chemical industry. In this study, the physicochemical properties and catalytically active forms of bismuth molybdates (BiMo) were investigated using the selective oxidation of propene to acrolein as a model reaction. The catalysts were prepared by two methods, coprecipitation and spray-drying, with emphasis on spray-drying. The catalysts were characterized using X-ray diffraction, N₂ adsorption/desorption isotherms, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The catalytic properties of the BiMo samples were studied in a conventional fixed-bed reactor operated under different reaction conditions. The one-dimensional (1D) pseudohomogeneous model was applied to describe the obtained experimental results. The experimental kinetic data were correlated with two complex kinetic models based on multiple reactions (parallel and serial reaction systems). The proposed models were verified by comparing computer simulation data with experimental laboratory results. This study aimed to extend the understanding of the relationship between catalyst composition/structure and catalyst activity/selectivity for different BiMo structures, and to propose kinetic models using two approaches based on parallel and series reactions, in line with efforts to improve the valorization of light olefins. Full article