Medication adherence is critical to long-term graft and patient survival after liver transplantation (LT), yet the effectiveness of adherence-promoting interventions across the post-transplant survivorship continuum remains uncertain. We systematically reviewed interventions to improve medication adherence including immunosuppressive regimen simplification, pharmacist-led or counseling strategies, behavioral and multicomponent programs, and technology-based interventions. We identified 33 studies: immunosuppressive regimen simplification (n=8), pharmacist-led or counseling strategies (n=6), behavioral or multicomponent programs (n=3), virtual visits/remote monitoring (n=9) and mobile or text-based tools (n=7). In pooled analyses of randomized trials, active interventions improved adherence versus usual care (OR 4.04, 95% CI 1.94-8.41), although heterogeneity was substantial. A higher prevalence of alcohol-associated liver disease was associated with weaker intervention effects. Regimen simplification, especially conversion from twice-daily to once-daily tacrolimus, showed consistent improvement in adherence while maintaining acceptable graft outcomes. Pharmacist-led interventions improved medication knowledge, dosing compliance, and drug monitoring. Telehealth interventions reduced travel burden and, in some studies, early readmissions and hospital stay. Overall, regimen simplification and structured multidisciplinary support appear most effective, but larger longitudinal trials with standardized adherence measures are needed.

DNA double-strand breaks, including those arising from DNA interstrand crosslinks, are highly cytotoxic forms of DNA damage. Their precise repair by homologous recombination (HR) is essential for maintaining genomic stability. During HR, timely disassembly of the core machinery, RAD51 nucleoprotein filaments, is critical. The FIGNL1-FIRRM (also known as C1orf112) AAA+ ATPase has recently been identified by us and others as a novel anti-recombinase that facilitates RAD51 disassembly via an ATPase-driven unfolding mechanism distinct from all previously characterized pathways. In this study, we identify MACIR/C5orf30 as an adaptor for FIGNL1-FIRRM unfoldase. MACIR directly binds FIRRM, forming a ternary complex that promotes RAD51 filament disassembly and facilitates repair of DNA damage induced by agents including aldehydes and platinum drugs. MACIR loss leads to DNA damage accumulation and genome instability, activates inflammatory signaling, linking MACIR deficiency to autoimmune and tumor-related pathologies. We further show that MACIR's direct interactions with FIRRM and DNA are both required for DNA repair, indicating that MACIR functionally links these components. High expression of MACIR-FIRRM-FIGNL1 correlates with poor prognosis in ovarian cancer patients, and pharmacological targeting of this complex with the inhibitors (small-molecule compound 8 and 10) we identified sensitizes ovarian cancer cells to platinum drugs. Therefore, our findings reveal MACIR as a critical regulatory adaptor within this RAD51-unfolding complex, which functions in an additional layer of control over DNA repair and genome stability, and suggest that its inhibition could enhance chemotherapeutic efficacy in cancer treatment.

Honeybees of the species Apis mellifera are important pollinators of crops and wild plants. Paenibacillus larvae, a spore-forming bacterium, is a problematic pathogen that causes American foulbrood (AFB) in honeybee larvae worldwide. In many countries, AFB is a notifiable disease, requiring the destruction of diseased colonies, resulting in economic loss that impacts beekeeping and agriculture. Disease onset starts with larval ingestion of P. larvae spores, which germinate into growing cells that proliferate in the larval gut, leading to larval death and eventually bee colony collapse. As infection progresses, P. larvae produce spores, reinitiating the disease cycle. Thus, growth, sporulation and germination underlie AFB. In this study, using various microbiological assays, quantitative cell biology methods, transmission electron microscopy and genomics, we sought to identify genetic and phenotypic characteristics associated with the predominant ERIC I and ERIC II genotypes of P. larvae during growth, sporulation and germination. Extending previous findings, our data identify genetic differences between ERIC I and ERIC II strains and some genetic variation between strains of the same ERIC type. Furthermore, we describe significant differences in cellular morphology during growth, differences in spore envelope structure and differences in germination efficiency between ERIC I and ERIC II genotypes. Collectively, our findings improve understanding of P. larvae biology and provide a foundation for developing genotype-specific disease management strategies for AFB.

Learning to Rank (LeToR) methods have gained increasing attention in drug response prediction, offering a direct way to prioritize effective treatments for cancer cell lines. In this study, we systematically benchmark six ranking loss functions, including state-of-the-art listwise methods, and five types of molecular representations across two large-scale drug screening datasets, CTRP and PRISM. Using high-dimensional gene expression profiles and various drug fingerprints and descriptors, we evaluated models under multiple validation setups and ranking metrics. Our results demonstrate that listwise loss functions such as LambdaLoss and LambdaRank consistently excel in both early and overall ranking quality. Additionally, combining molecular fingerprints with physicochemical descriptors yielded improved performance. A novel attention-based mechanism and a modified version of RankingSHAP were integrated to enhance interpretability, uncovering key genes and substructures aligned with known biological insights. The explainability pipeline successfully distinguished estrogen receptor-positive (ER⁺) and estrogen receptor-negative (ER-) breast cancer subtypes. The model successfully identified critical substructures in docetaxel, an FDA-approved therapy, and triptolide, which is currently undergoing clinical evaluation for breast cancer. These findings are consistent with established structure-activity relationship (SAR) data. Overall, this study presents a comprehensive evaluation framework and underscores the importance of carefully selecting loss functions and feature representations when developing robust and interpretable drug-ranking systems.

The global dissemination of antimicrobial-resistant (AMR) bacteria along the pork supply chain is a critical concern, as pigs are significant reservoirs for multidrug-resistant (MDR) Escherichia coli, a WHO-listed priority pathogen. This study investigated the genomic characteristics of extended-spectrum β-lactamase (ESBL)-producing E. coli across the pork production chain in Central Thailand, specifically focusing on the emergence of the last-resort tigecycline resistance gene, tet(X4). ESBL-producing E. coli isolates from a slaughterhouse pig cecum (n = 14) and retail market pork (n = 26) in central Thailand were collected. Whole-genome sequencing (WGS) was employed to analyze the resistome, virulome, and phylogenomic relationships. Analysis included non-metric multidimensional scaling (NMDS) of resistance and virulence gene determinants, single-nucleotide polymorphism (SNP) phylogeny, and core genome MLST (cgMLST). Resistome, virulome, and NMDS analysis demonstrated a shared clustering of antimicrobial resistance genes (ARGs) and virulence factors (VF) genes between cecum and pork isolates. Most isolates possessed extraintestinal pathogenic E. coli (ExPEC)-associated VF genes, underscoring the widespread pathogenic risk. tet(X4) was predominantly found in the dominant ST48 clone and these tet(X4) adjacent to ISCR2, providing evidence of horizontal gene transfer (HGT). cgMLST further demonstrated that these tet(X4) isolates are genetically related to global human, animal, and environmental strains. This study provides the first genomic evidence of tet(X4) circulation in ESBL-producing E. coli population across the slaughterhouse-to-retail continuum in central Thailand. Our findings suggest that the dissemination of tet(X4) in the pork supply chain is primarily via HGT. The implementation of firm food safety policies and enhanced hygiene practices is urgently required to inhibit the transmission of these high-risk strains to consumers.

Fear of chemotherapy-induced side effects is a major concern among patients with cancer and may affect psychological well-being and treatment adherence. This methodological study aimed to translate, culturally adapt, and evaluate the psychometric properties of the Persian version of the Chemotherapy Side Effects Fear Scale (CheSeFS). The study was conducted from January to April 2024 at the Cancer Institute of Imam Khomeini Hospital Complex in Tehran, Iran, and included 600 patients undergoing chemotherapy. The CheSeFS underwent forward-backward translation and cross-cultural adaptation. Face and content validity, structural validity, convergent and discriminant validity, internal consistency, test-retest reliability, measurement error, a distribution-based MIC estimate, and factors associated with CheSeFS scores were evaluated. All statistical analyses were performed using Jamovi version 2.7.1 and included descriptive statistics, item analysis, exploratory factor analysis, confirmatory factor analysis, reliability and measurement error analyses, convergent and discriminant validity assessment, distribution-based MIC estimation, and regression analysis. Patient and expert evaluations supported face and content validity. Exploratory factor analysis identified a two-factor structure, including Physiological fear and Subjective or Psychological fear, explaining 54.4% of the total variance. Three items were removed during factor analysis, resulting in a final 11-item scale. Confirmatory factor analysis supported model fit, with χ²(df = 43) = 84.2, RMSEA = 0.06, CFI = 0.99, TLI = 0.99, and SRMR = 0.04. Internal consistency was satisfactory, with Cronbach's alpha = 0.89 for the total scale. Measurement error analysis showed an SEM of 1.64 and an MDC95 of 4.56, and the distribution-based MIC estimate was 1.01 points. The Persian 11-item CheSeFS demonstrated satisfactory validity and reliability for assessing chemotherapy-related fear among Iranian patients with cancer.

With the increasing recognition of climate change threats to agricultural productivity and food security, it is crucial to explore farming practices that increase productivity, adapt to the effects of global climate change, while lowering greenhouse gas emissions. This study investigates the factors that influence the adoption of climate-smart agricultural (CSA) practices among smallholder farmers in semi-arid Ghana, specifically, the Upper West Region (UWR) of Ghana. The study surveyed 400 smallholder farmers from eleven (11) Communities and employed stratified random sampling, and a logistic regression model for data analysis. The results revealed that knowledge of CSA benefits or motivation factors such as improved crop yields (OR=10.356; p < 0. 001), reduced input cost (OR=4.855; p < 0.05), influenced the decision of smallholder farmers to adopt CSA practices. Also, availability of support systems such as access to agricultural extension services (OR=10.358; p < 0.001) and CSA training (OR=4.374; p < 0.05) were significantly associated with the adoption of CSA practices. The findings also shows that demographic factors shape the adoption of CSA practices. Farmers within the ages of 26-45 were less likely to adopt CSA practices (OR = 0.050; p < 0. 05), while farmers with formal education were more likely to adopt CSA practices (OR = 9.262; p < 0.001) after controlling for support system variables. Based on the findings, improved crop yields, resilience, reduced input, support from Agricultural Extension Agents (AEAs), financial support, training, and government policies are factors that influence CSA adoption among smallholder farmers in the study area. The study calls for policymakers and non-governmental organizations (NGOs) to enhance financial support systems and extension services to farmers, as well as provide more training on CSA. Government policies should also be focused on education and sensitization to upscale the adoption of CSA practices for its maximum benefits.