The Dominant white (I) allele in chickens suppresses the expression of black eumelanin, resulting in white plumage. However, both previous reports and our observations showed that some heterozygous (I/i+) individuals exhibited black-flecked plumage rather than completely white plumage, unlike homozygous dominant white chickens. This phenomenon suggests incomplete penetrance and incomplete dominance of the I allele. The genetic mechanisms underlying the phenotypic divergences in I/i+ individuals remain unclear.In this study, through integrated genomic and transcriptomic analyses of chickens with different I locus genotypes and feather color phenotypes, we identified candidate variants in MC1R (p.T143A) and TUBB3 (p.R202R) that may be associated with phenotypic variation in pigmentation. Notably, PMEL serves as the primary causal gene underlying the Dominant white phenotype, while the identified loci may act as modifying factors influencing residual melanin deposition in heterozygous individuals. Furthermore, our data suggest that biological processes such as glial cell formation and development, as well as responses to organic cyclic compounds, may participate in regulating the spatiotemporal distribution of melanin, thereby influencing the formation of black-flecked feathers. This finding provides a new perspective on the molecular mechanisms of incomplete penetrance and incomplete dominance of I and reveals the complexity of the melanin deposition regulatory network.
The aim of this study was to evaluate the effects of concentrated growth factor (CGF) and platelet-rich plasma (PRP) on postoperative pain and edema following impacted mandibular third molar surgery, and to investigate postoperative complications. This prospective, randomized controlled clinical trial included a total of 42 patients divided into three groups: control, CGF, and PRP (n = 14 per group). Pain was evaluated using a 10-cm Visual Analog Scale (VAS), and edema was assessed using standard linear facial measurements on postoperative days 1, 3, and 7. Changes over time and differences between groups were analyzed using Generalized Estimating Equations (GEE). According to the GEE analysis, both CGF and PRP applications demonstrated a statistically significant reduction in facial edema (tragus-pogonion) compared to the control group; however, the absolute reduction was minimal (0.2-0.5 mm) and likely of limited clinical significance. These applications appear to be effective in edema control following mandibular third molar surgery (CGF: B=-1.056, 95% CI [-1.835, -0.276], p = 0.008; PRP: B=-1.002, 95% CI [-1.750, -0.254], p = 0.009). However, the clinical magnitude of the differences between the groups remained limited. Although pain scores were lower in the CGF group, they did not show a statistically significant difference between the groups. The healing process was completed uneventfully in all groups, and no alveolar osteitis or serious postoperative complications were observed in any patient during the study. While CGF and PRP applications provided a statistically significant reduction in facial edema following impacted tooth surgery, the minimal magnitude of this reduction suggests it is unlikely to meaningfully improve the patient's postoperative quality of life. Furthermore, their effects on postoperative pain and complications did not offer an additional clinical advantage compared to a standard and atraumatic surgical procedure. Therefore, case-based evaluation is recommended rather than the routine use of these biomaterials. This study was registered retrospectively at ClinicalTrials.gov under the number NCT07320170 on January 06, 2026. Although patient recruitment and data collection began prior to registration due to an initial oversight, the study protocol, including primary and secondary outcome variables and the statistical analysis plan, was established before recruitment commenced, and no changes were made following data collection.
Obesity is a significant public health issue that has been increasingly linked to various musculoskeletal disorders, including intervertebral disk degeneration (IVDD). The interplay between metabolic dysfunction, chronic inflammation, and biomechanical stress suggests a multifactorial link between obesity and IVDD, warranting further investigation. This review aims to explore the pathophysiological mechanisms through which obesity contributes to IVDD and discuss this relationship's clinical implications. Obesity induces an occurrence of minor chronic inflammation and metabolic abnormalities, which can exacerbate degenerative changes in the intervertebral disks. Pro-inflammatory cytokines (TNF-α and IL-6) secreted by visceral adipose tissue can promote disk degeneration by enhancing catabolic processes and inhibiting anabolic repair mechanisms within the disk matrix. Additionally, mechanical loading due to excess body weight increases stress on the spinal structures, accelerating wear and tear of the intervertebral disks. This review summarizes current research findings on the biochemical and biomechanical pathways linking obesity to IVDD. We examine evidence from epidemiological studies, clinical trials, and animal models that highlight the multifaceted impact of obesity on spinal health. Furthermore, we discuss the implications of these findings for clinical practice, emphasizing the importance of weight management in preventing and treating IVDD. Interventions such as lifestyle modifications, dietary changes, and bariatric surgery are evaluated for their effectiveness in mitigating the adverse effects of obesity on the spine. The review also addresses the potential for targeted pharmacological therapies that modulate inflammatory pathways and mechanical stress responses. Understanding the association between obesity and IVDD is crucial when establishing all-encompassing management approaches for those who are impacted by the growing global prevalence of obesity. By elucidating the pathophysiological underpinnings and clinical consequences of obesity-induced IVDD, this review aims to inform future research directions and clinical guidelines, ultimately improving patient outcomes in this growing population.
Ischemic stroke is a leading cause of mortality and disability worldwide. Emerging evidence suggests that the gut microbiota, acting through the gut-brain axis, may play a critical role in stroke pathophysiology. Dysbiosis, an imbalance of gut microbiota, has been associated with neuroinflammation and poor stroke outcomes. This study aimed to compare gut microbiota composition in ischemic stroke patients versus healthy controls to explore potential microbial changes linked to stroke. A case-control study was conducted on 30 ischemic stroke patients and 30 healthy age- and gender-matched controls. Fecal samples were analyzed using real-time PCR to assess the relative abundance of four key gut bacterial phyla (Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria). Statistical analysis was performed with SPSS, and results were considered significant at p < 0.05. Ischemic stroke patients exhibited significant alterations in gut microbiota composition compared to controls. Firmicutes levels were significantly decreased (p = 0.04), while Proteobacteria levels were significantly elevated (p = 0.003). Although reductions in Bacteroidetes and Actinobacteria were observed, these differences were not statistically significant. The Firmicutes-to-Bacteroidetes (F/B) ratio was increased in ischemic stroke patients, indicating dysbiosis associated with stroke. The study identified gut microbiota dysbiosis in ischemic stroke patients, suggesting its potential role in stroke pathophysiology. Reduced Firmicutes and increased Proteobacteria may contribute to inflammation and oxidative stress, potentially worsening stroke outcomes. These findings highlight the potential for gut microbiota modulation as a therapeutic strategy to improve stroke management and recovery.
Lemierre's syndrome is a life-threatening infection characterized by septic thrombophlebitis of the internal jugular vein and septic embolism. Antimicrobial therapy is an established treatment for Lemierre's syndrome; however, its role in anticoagulation therapy remains unclear. To evaluate the association between anticoagulation therapy initiated concurrently with antimicrobial therapy and the clinical outcomes in patients with Lemierre syndrome. We comprehensively searched the PubMed, Embase, and Ichushi databases for case reports, case series, and cohort studies. Lemierre syndrome was defined as (1) a preceding oropharyngeal infection and (2) internal jugular vein thrombophlebitis or septic pulmonary emboli confirmed by imaging or pathology. We performed a case-control analysis and estimated odds ratios using multivariate logistic regression after adjusting for potential confounders. Of the 2051 screened records, internal jugular vein thrombus progressed in 15 patients (7.18% [15/209]) who received anticoagulation therapy and in 21 patients (18.8% [21/112]) who did not. The median age of the patients was 25 years (interquartile range, 18-45 years), and the baseline characteristics were generally balanced between the anticoagulated and non-anticoagulated patients. For the primary outcome of thrombus progression, anticoagulation therapy was associated with a significantly lower risk compared with no anticoagulation therapy (multiple imputation odds ratio 0.34, 95% CI 0.16-0.70). We observed no clear differences in the incidence of new septic pulmonary emboli (multiple imputation odds ratio 0.45, 95% CI 0.18-1.13) or major bleeding events (multiple imputation odds ratio 1.50, 95% CI 0.44-5.08). Our study suggests that although anticoagulation therapy is associated with a significantly reduced risk of IJV thrombus progression, it does not confer a clear benefit for other clinically important outcomes, such as new septic pulmonary emboli or mortality. Therefore, routine initiation of anticoagulation therapy may not be supported for Lemierre syndrome, particularly when the thrombus is limited to the internal jugular vein. Further well-designed observational studies are warranted. Not applicable.
Nutrition plays a vital role in musculoskeletal health, bone density, fall risk, and postural stability, alongside being a reflection of overall health status. Nutritional assessment indices are rapid and noninvasive tools for several indications, yet their association with falls remains uncertain. We aimed to investigate four commonly used nutritional indices: GNRI (Geriatric Nutritional Index), PNI (Prognostic Nutritional Index), CONUT (Controlling Nutritional Status), and MNA-SF (Mini Nutritional Assessment Short Form) to establish their relationship with falls in older adults with potential implications for clinical practice. Patients aged ≥ 65 years who underwent comprehensive geriatric assessment between 1 January 2022 and 31 January 2024 were included in the analysis. After application of the exclusion criteria, the final study population comprised 952 individuals. Fall history and fall frequency during the preceding 12 months were recorded. Associations between nutritional indices and falls were evaluated using receiver operating characteristic (ROC) analysis and logistic regression models, with additional post-hoc group comparisons based on fall frequency. MNA-SF, GNRI, and PNI were significantly associated with both fall risk and fall frequency (all p < 0.001), whereas CONUT showed no significant association (p = 0.171). Post-hoc analyses demonstrated that MNA-SF was the only index that showed significant differences between single and recurrent fallers in post-hoc group comparisons (p = 0.010). MNA-SF (OR:0.67, 95% CI:0.62-0.74), GNRI (OR:0.85, 95% CI:0.82-0.88), and PNI (OR:0.92, 95% CI:0.86-0.97) continued to have an independent association with falls in regression analysis (all p < 0.005). ROC analysis showed the highest discrimination for MNA-SF (AUC: 0.697, 95% CI: 0.660-0.733), followed by GNRI (AUC: 0.619, 95% CI: 0.581-0.656) and PNI (AUC: 0.615, 95% CI: 0.578-0.653). Fallers also exhibited greater frailty, poorer physical performance, and higher medication burden (all p < 0.001). In older adults, poorer nutritional status assessed by MNA-SF, GNRI, and PNI was independently associated with falls, supporting the potential role of nutritional assessment within a broader fall-risk evaluation framework. However, the discriminative performance of all indices was low, indicating that these tools should not be solely considered predictors of falls, but rather complementary markers. In exploratory analyses, MNA-SF showed differences between single and recurrent fallers, which suggests a potentially relevant association that warrants prospective validation. Variability in cut-off definitions across nutritional indices remains an important limitation, underscoring the need for prospective studies to refine clinically relevant thresholds.
Despite foundational quadruple guideline-directed medical therapy (GDMT), patients with heart failure with reduced ejection fraction (HFrEF) face substantial residual risk. Vericiguat, a novel soluble guanylate cyclase (sGC) stimulator, provides a crucial therapeutic option by directly targeting the impaired NO-sGC-cGMP signaling pathway to mitigate this risk. This review synthesizes current literature tracking vericiguat's trajectory from pivotal clinical trials (VICTORIA, VELOCITY, and VICTOR) to its emerging real-world implementation. We examine its efficacy, hemodynamic and renal tolerability, and safety profile across the HFrEF spectrum. Additionally, we provide a framework for clinical decision-making, addressing optimal patient selection, initiation timing, and the navigation of polypharmacy. Current evidence suggests that vericiguat may represent a valuable adjunctive therapy for selected high-risk patients with HFrEF, with a generally favorable hemodynamic and renal tolerability profile that appears not to substantially exacerbate hypotension or hyperkalemia when integrated with contemporary guideline-directed medical therapy. To maximize its real-world implementation, clinicians must overcome clinical inertia and embrace the purposeful deprescribing of non-essential symptomatic medications. Future research should prioritize advanced renal disease cohorts and biomarker-guided phenotyping, ultimately shifting vericiguat from a reactive post-decompensation therapy to an earlier, proactive intervention within a personalized treatment strategy.
Neuromyelitis optica spectrum disorder (NMOSD) can cause severe neurological disability after a single relapse. Although relapse rates have markedly decreased with the emergence of targeted biologics, treatment switches are increasingly encountered due to long-term treatment considerations and adverse events. However, safe switching strategies, especially within 12 months after a relapse, which we defined operationally as the "cluster phase", have not been established. We investigated relapse risk and potential preventive strategies when switching from complement inhibitors in AQP4-IgG-positive NMOSD. We retrospectively reviewed patients with AQP4-IgG-positive NMOSD treated at St. Marianna University School of Medicine who underwent at least one biologic switch. Clinical records were assessed for patient characteristics, treatment history, timing of switching, and relapse occurrence. Particular attention was given to switching from complement inhibitors during the cluster phase. Among 14 patients who switched biologics, 5 switched from complement inhibitors, 4 switched between complement inhibitors, 2 between B-cell-depleting therapies, and 3 from IL-6 receptor inhibitors. Six of the 14 switches occurred during the cluster phase, including 3 from complement inhibitors (all to B-cell-depleting agents). One of the two patients switched without bridging therapy during the cluster phase experienced optic neuritis relapse, while no relapses occurred in the other 13 switching cases. This observation suggests a possible vulnerability during the cluster phase, although definitive conclusions cannot be drawn due to the small sample size. Switching from complement inhibitors during the cluster phase may be associated with an increased susceptibility to relapse. Bridging strategies, such as plasma exchange or temporary biologic overlap, may help reduce the likelihood of therapeutic gaps, but these findings remain hypothesis-generating. Clinicians should proactively discuss future switching scenarios and develop long-term treatment plans with patients.
Glioblastoma (GBM) is one of the most aggressive and lethal primary brain tumors in adults, characterized by dynamic clonal evolution and extensive genomic, cellular, spatial, and microenvironmental heterogeneity. Multi-omics studies have revealed that GBM follows complex evolutionary trajectories involving genetic, epigenetic, transcriptional, and immune-microenvironmental remodeling as tumors grow, adapt to the brain microenvironment, and acquire therapeutic resistance. Increasing evidence suggests that GBM may originate from aberrant neural stem or progenitor cells, including those residing in the subventricular zone, and that glioblastoma stem cells (GSCs) contribute to tumor propagation, heterogeneity, and recurrence. A key conceptual challenge is to reconcile hierarchical cancer stem cell models, in which GSCs are viewed as relatively stable tumor-propagating subpopulations, with dynamic state plasticity models, in which stem-like properties can be reversibly acquired or lost during transitions among proneural-like, mesenchymal-like, invasive, and therapy-tolerant states. Recent advances in single-cell profiling, spatial transcriptomics, lineage tracing, organoid culture, 3D bioprinting, genetically engineered models, and artificial intelligence (AI)-assisted computational modeling have substantially improved the ability to study these processes. However, no currently available model fully recapitulates human GBM heterogeneity, recurrence, treatment history, and tumor-microenvironment interactions. Therefore, model selection should be guided by clearly defined mechanistic questions rather than by reliance on any single platform. This review summarizes current advances in in vitro, ex vivo, in vivo, and computational models for studying GBM evolution and heterogeneity, and discusses how integrated model pipelines may improve preclinical drug testing, treatment-response prediction, and precision neuro-oncology.
To assess and compare the time-dependent disinfection efficacy against standard microbial strains and the neutralization kinetics of two commercially available soft contact lens care systems, one based on 0.05% povidone iodine and one based on 3.42% hydrogen peroxide. To assess neutralization kinetics of each system, the concentration of the active disinfectants was quantified via iodometric titration (hydrogen peroxide) and high-performance liquid chromatography (povidone iodine) at intervals from 0.5 min to the minimum recommended disinfection time (MRDT). Disinfecting efficacy against the five ISO 14729 microbial strains (Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, Candida albicans, Fusarium solani) was assessed at intervals from 0.5 min to each system's respective MRDT. Microbial log reductions and disinfection rates were calculated using standard plate count methods. Statistical significance between systems was determined using ANOVA and post-hoc comparisons (p < 0.05). The povidone iodine system reached a peak concentration (∼0.05%) within 2 min, maintained this level for 5 min, and was neutralized by 20 min. Despite rapid neutralization, povidone iodine exceeded the standardized criteria for all strains within 1 min and disinfected below the detectable limit within 5 min. Conversely, the hydrogen peroxide system's concentration began declining immediately and fell below 1% within 30 min, before disinfection was complete for three strains. Significant kinetic differences (p < 0.05) favored povidone iodine across four strains, most notably against S. aureus, where hydrogen peroxide lagged by several hours. This study possesses a conflict of interest, and external validation is encouraged. The povidone iodine system achieved remarkably rapid disinfection across all strains at a 5000-fold lower molar concentration than the hydrogen peroxide system, well below the ocular irritation threshold. Povidone iodine's consistent, rapid disinfection, along with its high safety profile, suggests it may be a more optimal care option than the current gold standard.
Gastric cancer (GC) with peritoneal metastasis frequently leads to malignant ascites (MA), a highly immunosuppressive "liquid tumor microenvironment" associated with poor prognosis. Although immune checkpoint blockade (ICB) demonstrate efficacy in some GC patients, treatment response to gastric cancer-associated peritoneal metastasis (GCPM) remains heterogeneous. The immune mechanisms driving this variability and predictive biomarkers remain unclear. We performed single-cell transcriptomics and TCR/BCR repertoire analyses on paired MA and peripheral blood mononuclear cell (PBMC) samples from 10 advanced GC patients. Cellular clustering, trajectory inference, and intercellular communication analyses characterized immune remodeling. Clinical cohorts were used to validate prognostic and therapeutic predictive significance. Immune landscape of GCMA was delineated, which unveils extensive remodeling of T cells, B cells, and myeloid lineages. Notably, we identified a novel epithelial-immune dual-phenotype cell (EIDPC) population, validated by single-cell RNA sequencing and flow cytometry, exhibiting moderate malignant characteristics and potent immunoregulatory capacity. Transcriptomic and trajectory analyses suggest an epithelial origin with reprogramming toward immune evasion. Based on 10 EIDPC core genes, we developed the immune response signature of EIDPC (IRS-EIDPC), which accurately predicts anti-PD-1 therapy response and prognosis in independent gastric cancer cohort (AUC 0.929). This study reveals the immune landscape of malignant ascites in gastric cancer, and confirms EIDPC as a transitional malignant subpopulation with potent immunomodulatory functions. The IRS-EIDPC signature may aid in predicting immunotherapy responses and survival outcomes, provides insights into immune plasticity in malignant gastric ascites, and may help inform future precision therapeutic strategies.
Diffusion tensor imaging (DTI) and electroencephalography (EEG) may serve as structural and functional biomarkers for cognitive impairment following basal ganglia stroke; however, their relative contributions are uncertain. This study compared findings of DTI and EEG between healthy controls and patients with left basal ganglia stroke without cortical lesions and identified cognitive outcome imaging predictors. Twenty-seven participants (17 controls, 10 patients) underwent comprehensive cognitive testing, DTI, and EEG. Two DTI metrics (fractional anisotropy [FA], mean diffusivity [MD]) were extracted from major association tracts involved in cognitive processing. EEG indices included the alpha-to-beta ratio and delta-to-alpha ratio across cortical lobes. Group comparisons demonstrated significant global cognitive decline in the stroke group. Structural alterations included reduced FA in ipsilesional association tracts and increased MD in ipsi- and contralesional tracts. No significant group differences were observed in EEG spectral indices. Brain-behavior associations were examined using covariate-adjusted partial correlations with Benjamini-Hochberg false discovery rate (FDR) correction. No DTI-cognition associations survived FDR correction in controls, and only four DTI association remained significant in pooled stroke analyses. In contrast, 25 EEG-cognition associations survived FDR correction in pooled stroke analyses, whereas none survived in controls. Higher ABR values were associated with better cognitive performance, while higher DAR values were associated with poorer cognition. These findings suggest that DTI and EEG provide complementary information, with structural metrics reflecting white-matter integrity and EEG indices demonstrating more widespread associations with cognitive performance following subcortical injury. Functional EEG measures may offer sensitive markers of post-stroke cognitive vulnerability when interpreted alongside structural imaging. As a proof-of-concept study in a small, strictly selected cohort, these findings should be regarded as preliminary and hypothesis-generating, requiring replication in larger samples.
Artemisia annua L., is the primary natural source of the antimalarial drug artemisinin. In nature, fluctuating light is a major environmental stress that affects plant growth and artemisinin biosynthesis. Although the light-harvesting chlorophyll a/b-binding (LHC) superfamily plays a key role in mediating plant responses to fluctuating light, systematic research of this gene family in A. annua has not yet been conducted, limiting our understanding of light adaptation in this medicinally important species. This study investigated the evolutionary dynamics and functional adaptation of the light-harvesting chlorophyll a/b-binding (LHC) superfamily in A. annua, with a focus on the early light‑induced protein (ELIP) subfamily. Comparative genomics of 24 plant species showed that the LHC superfamily recently expanded in the examined Asteraceae lineages through duplication events. In A. annua, 229 LHC genes identified from four haplotype genomes comprised 205 allelic and 24 haplotype-specific loci, with the ELIP subfamily expanding significantly via tandem duplication. Notably, compared to non-Asteraceae plants, ELIPs exhibited a uniform single-exon architecture, indicating it is a genomic feature unique to Asteraceae plants. Population genomics of 41 individuals showed dynamic copy number variations ranging from 1 to 4 copies per locus. Interestingly, a structurally disrupted ELIP allele remained transcriptionally active and produced long aberrant transcripts, showing that this subfamily is still actively evolving. Under UV-B stress, AaELIP loci showed synchronized induction trend but differed in expression levels, suggesting a division into major and auxiliary roles within the expanded tandem cluster. Overall, while the response of ELIPs to light stress is evolutionarily conserved, this dramatic expansion and structural streamlining of AaELIPs may represent a key evolutionary adaptation that enhances the plant's ability to cope with intense light and radiation stress. Collectively, this study demonstrates a significant expansion of the LHC superfamily in A. annua, especially within the ELIP subfamily, as well as its robust response to UV-B treatment, underscoring the essential role of ELIPs in mediating light stress responses. These findings provide a valuable foundation for future research to uncover the molecular mechanisms underlying A. annua's adaptation to complex light environments.
Reproduction traits constitute the primary objective of porcine genetic improvement programs, with litter size being the principal determinant of herd reproduction output. Relative to the intensively selected Large White line, as a breed derived from Large White (LW) and Beijing Black (BJB) pigs, Jishen Black (JSB) pigs exhibit markedly lower litter size, indicating substantial potential for genetic improvement. Whole-genome resequencing data were obtained from 110 individuals of six pig populations differed in litter size: a Large White line with high litter size (> 16, LWH), cryopreserved Large White samples from 1977 (LW1977), dam-selected (LWD) and sire-selected (LWS) lines derived from LW1977, Berkshire (BKS), and Jishen Black pigs (JSB). Principal component analysis (PCA) captured clear population genetic structure along PC2, with the observed distribution pattern descriptively coinciding with litter size variation across populations, though such an association was not statistically verified. A composite selection-signature scan that integrated Fst, π-ratio, and XP-EHH was performed between multiple population groups. Candidate signals were filtered by excluding those also detected in a control comparison (Jishen Black vs. Berkshire) that showed minimal litter‑size difference, to screen selection signatures with potential relevance to reproductive trait differentiation at the population level. Twelve genes were identified as putative candidate genes for litter size, including PEX14, CDK15, KCNQ1, SPAG17, TTF2, CD101, CASQ2, VANGL1, ARID5B, KLHL32, EML1, and NAV1. Functional enrichment analysis indicated that these genes significantly over-represented in microtubule-related biological processes. Among them, KCNQ1 was consistently detected by all methods and comparison groups. Further analysis of KCNQ1 revealed multiple SNPs with significant allele-frequency differentiation among populations; notably, two intronic variants (chr2:A1,861,604G and chr2:A1,867,076G) showed population-specific allele frequency patterns that descriptively aligned with the stratification of litter size performance. By comprehensively dissecting population genomic differentiation among multi-breed populations divergent in litter-size performance, this study implemented established a feasible framework for screening candidate loci associated with porcine prolificacy at the population level, expanded the gene list with suggestive selection signatures, and provided potential molecular markers requiring further independent cohort validation and functional verification to support future genetic improvement in swine reproduction efficiency.
Active learning methods like flipped classrooms, case-based learning (CBL), and game-based learning (GBL) are increasingly important in medical and pharmacy education. While studies suggest integrating these methods may improve outcomes, direct comparisons of CBL and GBL within flipped classrooms are limited, often focusing on small sample sizes and different student populations. This study compares the effectiveness of GBL and CBL in a flipped classroom for pharmacy education which are held completely virtual, aiming to assess learning outcomes and student satisfaction. Participants were randomly assigned to the GBL or CBL group. In-class activities for both groups followed virtual flipped instruction classrooms on pharmacotherapy topics. Knowledge-based tests were used to assess learning outcomes, and a reliable and validated questionnaire was employed to measure student satisfaction. The basis for data analysis would include demographic data and the results of tests and questionnaires on satisfaction assessment. Data were analyzed via descriptive statistics methods (means, frequencies, percentages, standard deviations, and variances) and inferential analyses (Student's t-test, analysis of variance, and correlation). The 56 fourth-year PharmD students completed the study. Whereas both groups showed significant learning outcome gains (CBL T1-T3: ρ = 0.006, GBL: T1-T3 ρ = 0.001, T2-T3 ρ = 0.002), the scores for all tests were invariably higher in GBL; however, none of them are significant. Satisfaction with the learning method as also greater in the GBL group (3.82) than in the CBL group (3.61), particularly for students with lower GPAs in the GBL group (t = -0.412, ρ = 0.033). No statistically significant differences were observed for either the test scores or the satisfaction levels of either group; however, for the final test scores and progress rates, GBL had a slight-to-moderate effect size advantage (Cohen's d = -0.36, -0.34 respectively). This study demonstrated that both case-based learning (CBL) and game-based learning (GBL) within a virtual flipped classroom framework significantly enhanced student learning outcomes, without any statistically significant differences in test performance or student satisfaction between the two methods. Overall, both CBL and GBL prove to be equally effective in pharmacy education in a virtual environment.
Heart failure (HF) is accompanied by chronic inflammation and metabolic stress, but the relationship between HF severity and the oral microbial ecosystem remains incompletely understood. This study aimed to investigate bacterial, fungal, and predicted functional alterations in supragingival plaque from patients with HF. This case-control study enrolled 63 patients with HF and 31 healthy controls (HC). Supragingival plaque samples were profiled by 16S rRNA and ITS sequencing. Community structure, differential amplicon sequence variants (ASVs), bacterial-fungal co-abundance networks, HF severity-associated ASVs and predicted MetaCyc pathways were analyzed using QIIME2, SparCC, weighted LASSO regression, and PICRUSt2. Pathway-ASV correlations were further assessed to explore links between taxonomic and predicted functional shifts. HF status and NYHA class were among the strongest explanatory factors for oral bacterial and fungal community variation. Differential abundance analysis identified 102 bacterial and 68 fungal ASVs between HF and control groups. Weighted LASSO analysis retained six ASVs associated with the NYHA III-IV phenotype: ASV586 (Geotrichum candidum), ASV238 (Nectriaceae), and ASV182 (Neisseria bacilliformis) showed positive coefficients, whereas Haemophilus (ASV1), Streptococcus (ASV0), and Pseudopropionibacterium (ASV148) showed negative coefficients. A combined 6-ASV score discriminated HF from controls with an AUC of 0.804 and NYHA III-IV from the remaining cohort with an AUC of 0.842. PICRUSt2 identified 165 pathways differing between HF and controls. TCA cycle I was enriched in HF and positively correlated with NYHA class, whereas pyruvate fermentation to butanoate, a butyrate-related fermentative pathway, was enriched in controls and negatively correlated with NYHA class. Robust pathway-ASV correlations linked HC-enriched oral biofilm taxa with HC-enriched functional modules, suggesting functional uncoupling of the supragingival plaque ecosystem in more severe HF. HF severity is associated with oral bacterial-fungal dysbiosis, characterized by enrichment of opportunistic pathogens, depletion of commensal biofilm organisms and predicted functional shifts involving microbial TCA cycle and fermentative capacity. These findings support an "oral-heart axis" in HF and warrant validation by longitudinal multi-omics studies.
Polyploidy is a major driver of plant evolution and crop improvement, generating novel variation in morphology, physiology, and agronomic traits. Brassica juncea (AABB, 2n = 36), a natural allotetraploid derived from B. rapa (AA) and B. nigra (BB), is an important oilseed and vegetable crop; however, its narrow genetic base limits further breeding gains. Resynthesized B. juncea (RBJ), developed from known progenitors, provides a tractable system to investigate polyploid stabilization, trait diversification, and generational variation. This study evaluated RBJ across nine generations (F1-S8) to elucidate generational variation in morphological, molecular, cytological, and oil content traits during progressive stabilization. Substantial variation was observed for key yield-related traits, including siliqua length, seeds per siliqua, and thousand-seed weight. High estimates of heritability, genotypic variance, and genetic advance indicated their potential utility in selection based improvement. Comparative analyses revealed a clear generational progression, characterized by relatively enhanced performance in early generations, increased recombination-driven variability in intermediate generations, and the partial stabilization of several traits in later generations. Generation mean analysis suggested the involvement of additive, dominance, and epistatic gene effects in trait inheritance. Molecular analysis using SSR markers confirmed the amphidiploid origin and genomic integrity of RBJ generations. Cytological assessments, pollen viability assays, and flow cytometric analysis collectively demonstrated stable chromosome numbers, improved fertility, and maintenance of ploidy stability across successive generations. The study provides valuable insights into the generational variation and stabilization of morphological, molecular, and oil content traits in resynthesized B. juncea. The findings suggest that variability arising from polyploidization and interspecific hybridization undergoes gradual reorganization across successive generations, leading to increased trait stabilization and more consistent expression of selected agronomic characteristics. Collectively, these results contribute to the understanding of early stabilization processes in RBJ, highlighting resynthesized polyploids as useful systems for studying variation and stabilization in allopolyploid crops.
Fly ash (FA) is a heterogeneous industrial byproduct composed of several valuable, lightweight microspherical components, including cenospheres. The continued extraction of these components, particularly cenospheres for tailored applications, has raised concerns about the potential depletion in quality of the residue fly ash (RFA). This may affect the microstructural, physico-mechanical and durability properties of the resulting concrete, thereby increasing the likelihood of the RFA being entirely abandoned as waste, increasing environmental pollution and industrial waste management cost. To evaluate the potential variations, this study investigated the pre- and post-cenosphere extraction performances of four fly ash samples from Malaysian power plants, with focus on microstructure, physical, mechanical and durability performance. A range of cement pastes and concrete mixes was examined, each case incorporating FA and RFA in proportions ranging from 0 to 40% with cement. The durability of the concrete in a chloride-exposed environment was assessed using a simulation-based approach. The findings indicated a moderate enhancement in early compressive strength development in the RFA concrete at 7 and 14 days, which is attributed to the enhanced surface area and reduced setting time. Overall, an increase of about 8-37% in surface area was observed, with a corresponding 10-33% reduction in workability, a 4% -12% decrease in compressive strength at 28days, and a 13-15% reduction in flexural strength. Furthermore, only slight variations were observed in the initial corrosion ingress, concrete deterioration propagation and overall durability performance. These findings demonstrate that despite the reduced workability, strength, and setting time, the RFA concrete retains its durability in chloride environments, suggesting its viability as a sustainable cementitious material in concrete production with minor modification.
Neonatal sepsis can disrupt brain development through oxidative stress, blood-brain barrier (BBB) dysfunction, peripheral leukocyte infiltration, and white matter injury. N-acetylcysteine (NAC), a glutathione precursor with antioxidant and immunomodulatory properties, is a promising neuroprotective candidate, but its effects in neonatal sepsis-like brain injury remain incompletely defined. The purpose of this study was to investigate whether early NAC pretreatment, followed by continued treatment, was associated with protection in a neonatal LPS model and examine the principal mechanisms associated with its effects. In this study, neonatal C57BL/6J mice received lipopolysaccharide (LPS; 3 mg/kg, subcutaneously) on postnatal day (PND) 3 to model sepsis-like injury. NAC was administered intraperitoneally 2 h before LPS (200 mg/kg), followed by daily treatment (100 mg/kg/day) through PND14. Survival was monitored to PND21. Acute outcomes at PND4 included oxidative stress, glial/inflammatory markers, MPO-positive cell accumulation, apoptosis, and BBB-related injury. Longer-term outcomes included myelination, dentate gyrus proliferation, and behavior. NAC improved survival after neonatal LPS exposure, with exploratory sex-stratified analyses suggesting greater benefit in males. NAC partially restored cortical glutathione levels and reduced lipid peroxidation, indicating improved redox balance. Although it did not significantly alter galectin-3, GFAP, or NLRP3 at the time point examined, NAC reduced cortical MPO-positive cell burden and attenuated markers associated with neurovascular injury and BBB-associated pathology, including matrix metallopeptidase-9 expression and albumin extravasation. NAC also decreased apoptosis in selected brain regions and partly improved white matter-related outcomes, including oligodendrocyte precursor cell abundance, myelination, and early sensorimotor performance. However, long-term behavioral performance in the open field and novel object recognition tests was not significantly improved at PND60. Overall, early NAC pretreatment followed by continued treatment mitigated neonatal LPS-induced sepsis-like brain injury and improved survival, with protection associated with restoration of redox homeostasis and reduction of MPO-positive leukocyte and markers associated with neurovascular injury and BBB-associated pathology rather than broad suppression of measured inflammatory mediators. These findings are consistent with a potential role for a redox-neurovascular-leukocyte pathway in NAC-associated neuroprotection and support further evaluation of NAC in prevention-oriented experimental paradigms relevant to high-risk preterm populations.
Patient safety emerges where clinical risk governance intersects with ethical duties of non-maleficence, respect for autonomy, and institutional accountability. Safety culture surveys and patient-reported experience measures often evolve on separate analytic tracks, leaving uncertainty about how staff-facing metrics translate into patient-facing ethical practices such as disclosure after harm. We conducted an exploratory cross-sectional multi-informant survey in an acute-care hospital in Romania. Healthcare workers (defined as physicians, nurses, hospital auxiliary staff, and other clinical/non-clinical personnel involved in care delivery or immediate supervision; n = 104) completed the AHRQ Hospital Survey on Patient Safety Culture version 2.0 and the Speaking Up About Patient Safety Questionnaire, capturing safety culture composites, speaking up behaviour, and psychological safety. Inpatients (n = 101) completed a project-specific, not externally validated structured questionnaire covering perceived safety, communication and information, consent and involvement, confidentiality and complaint mechanisms, coordination and organisational reliability, observed safety practices, and experiences of incident communication. We conducted exploratory analyses including composite means, percent positive scores, internal consistency estimates, and examined ward-level associations. Staff composites peaked for teamwork (mean 3.84/5; 74.3% positive) and communication about error (3.74/5; 70.8% positive), while staffing and work pace (2.74/5; 29.3% positive), response to error (31.7% positive), and hospital management support (34.0% positive) showed marked compression. Patients rated coordination and organisation (mean 3.67/5) and consent and involvement (3.60/5) higher than communication and information (3.42/5). Eleven patients (10.9%) perceived a safety incident; among them, ratings for apology, explanation and follow-up clustered at the lower end of the scale (mean 1.73/5). Ward-level overall safety culture scores showed negligible associations with patient global safety, perceived safety and recommendation. Exploratory ward-group analyses suggested that patient-rated coordination aligned more closely with handoffs and information exchange than with global safety culture measures. Other cross-level associations were inconsistent and were interpreted cautiously because of broad clinical-area aggregation and limited between-group variation. Favourable speaking up climate correlated with overall safety culture (r = 0.484, p < 0.001) and management support (r = 0.547, p < 0.001). In this setting, patient-perceived safety aligned more closely with interface processes than with global culture scores, and incident communication surfaced as a salient ethical deficit. Strategies integrating psychological safety, management responsiveness, and structured disclosure practices warrant prospective evaluation as potential ways to advance moral accountability and risk governance. Given the cross-sectional, single-site design and modest sample size, these associations should be interpreted as exploratory and non-causal. Not applicable.