Search Results (9,539)

Chronic kidney disease (CKD) involves uremic toxin-driven tubular injury and systemic vascular dysfunction, in which mitochondrial impairment and apoptotic cell loss contribute to progressive tissue deterioration. Accordingly, a targeted EV platform is required to enable efficient miRNA delivery to the toxin-stressed tubular–endothelial compartment. Based on our previous study showing that melatonin restores miR-4516 levels under CKD-related stress, we directly loaded miR-4516 into engineered extracellular vesicles (EVs) to evaluate its effects on mitochondrial function and cell survival. Here, we engineered EVs with a G3-C12/RGD surface modification and established a miR-4516 loading strategy to enhance delivery to kidney proximal tubule cells and vascular endothelial cells. miR-4516 loading increased EV-associated miR-4516 levels without major changes in particle size distribution, and EV identity was supported by CD9 and CD81 expression. Confocal microscopy and flow cytometry demonstrated increased cellular uptake of miR-4516-loaded G3-C12/RGD-EVs compared with control EVs in TH1 proximal tubule cells and HUVECs. Under indoxyl sulfate stress, engineered EV treatment restored intracellular miR-4516 and improved mitochondrial function, as indicated by recovery of respiratory Complex I and Complex IV activities and improved Seahorse bioenergetic parameters (OCR/ECAR, basal and maximal respiration, ATP-linked respiration, and spare respiratory capacity). Annexin V staining further indicated reduced toxin-induced apoptosis. In an adenine diet-induced CKD mouse model, intravenous administration of miR-4516-loaded G3-C12/RGD-EVs improved urinary albumin-to-creatinine ratio (UACR), blood urea nitrogen (BUN), and serum creatinine. These findings indicate that miR-4516-loaded, targeting-engineered EVs may mitigate uremic toxin-associated mitochondrial dysfunction and renal impairment in CKD. Full article

Purpose: Hearing loss (HL) is a prevalent condition significantly impairing quality of life, with genetic mutations accounting for a substantial proportion of congenital cases, notably those involving the GJB2 gene encoding connexin 26. This study aims to analyze the current knowledge, feasibility, and challenges of gene therapy targeting GJB2-related HL, emphasizing both embryonic and postnatal interventions. Methods: A comprehensive scoping review was conducted across electronic databases up to October 2025, including studies focusing on GJB2-associated HL, gene therapy approaches, and the timing of interventions. Data extraction encompassed mutation types, animal models, delivery strategies, outcomes, and ethical considerations. Results: The results indicated over 467 GJB2 variants which could impair cochlear ion homeostasis and development. Animal models, mainly murine, demonstrated early-onset degeneration with limited recovery following delayed gene therapy, while early postnatal intervention showed greater efficacy. Viral vectors like AAV have been employed for targeted gene delivery via cochlear injections, achieving partial restoration of connexin expression and cochlear function, yet they have faced limitations including transduction efficiency, immune responses, and long-term stability. Challenges in translating these findings to humans have been compounded by anatomical, immunological, ethical, and safety issues, particularly regarding embryonic gene therapy and germline modifications. Ethical frameworks can vary internationally, highlighting the necessity for careful regulation. Conclusions: While promising advances in gene therapy for GJB2-related HL have been achieved in preclinical studies, significant scientific, technical, and ethical barriers must be addressed before clinical application, especially during embryogenesis. A multidisciplinary, cautious approach is essential to realize the potential of gene therapy in restoring natural hearing while safeguarding individual and societal interests. Full article

Background: Persistent endodontic infections involving Enterococcus faecalis and Candida albicans are a major cause of root canal treatment failure. Although conventional irrigants, such as sodium hypochlorite and chlorhexidine (CHX), exhibit strong immediate antimicrobial activity, microbes may survive and recover from the initial antimicrobial effect, hence limiting their effectiveness, especially in complex root canal anatomies and in the apical terminus of the tooth. Antibacterial dressing techniques were not proven satisfactory due to depletion of the antibacterial component or difficulty in spreading it evenly along the entire root canal. This study aimed to develop and evaluate the antimicrobial efficacy and release characteristics of a novel sustained-release device (SRD), delivering CHX via gutta-percha points coated with a sustained-release formulation used as a temporary intracanal medicament. Methods: Gutta-percha points were coated with two sustained-release CHX varnishes (CHX1 and CHX2) or a placebo and assessed in vitro. Antimicrobial activity against E. faecalis and C. albicans was evaluated using agar diffusion assays over time. Release kinetics were analyzed using Rhodamine-labeled SRD in a 3D-printed acrylic molar tooth model via fluorescence microscopy. Additionally, biofilm-infected acrylic molar teeth were treated with a placebo, a single 2% CHX irrigation, or SRD-coated gutta-percha points placed as an intracanal dressing prior to obturation. Microbial viability was quantified by colony-forming unit (CFU/mL) analysis from root canals and gutta-percha points. Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc multiple comparison test (p < 0.05). Results: SRD-coated gutta-percha points demonstrated sustained antimicrobial activity for up to 21 days against E. faecalis and 19 days against C. albicans. Fluorescence analysis, in an acrylic tooth model, confirmed continuous release for up to 15 days, with pronounced diffusion in the isthmus and palatal canals. In biofilm-infected acrylic teeth models, SRD treatment resulted in a significant reduction of 2–3 log₁₀ CFU/mL compared to placebo groups (p < 0.001) and prevented microbial rebound over the 14-day observation period. In contrast, a single application of 2% CHX solution showed only transient reduction followed by regrowth. Conclusions: Sustained-release CHX delivery via polymer-coated gutta-percha points provided prolonged antimicrobial activity against bacterial and fungal biofilms compared to conventional single-dose CHX application in this in vitro model. These findings support the potential use of coated gutta-percha points as a removable intracanal drug delivery platform prior to final obturation, although further studies incorporating direct-release quantification and in vivo validation are required before clinical translation. Full article

Remote sensing object detection (RSOD) models play an increasingly important role in modern remote sensing systems. However, during model delivery, sharing, and deployment, RSOD models face increasing risks of unauthorized redistribution, illegal replication, and intellectual property infringement. To mitigate these threats, this paper proposes a white-box watermarking framework for RSOD models that enables reliable copyright verification while preserving the performance of the primary detection task. Specifically, a gradient-based sensitivity analysis of the detection loss is first performed to adaptively identify model parameters that minimally affect detection performance, which are then selected as watermark carriers. Subsequently, a parameter-ranking-based watermark encoding scheme is developed, where watermark bits are embedded by enforcing relative ordering constraints between parameter pairs. To further improve robustness under practical deployment conditions, an attack-simulation-driven training strategy is introduced, in which common perturbations and watermark removal attacks are simulated during the embedding process. In addition, a stealthiness enhancement strategy based on statistical distribution constraints is designed to maintain consistency between the distribution of watermarked parameters and those of the original model, thereby reducing the risk of watermark exposure and localization. Extensive experiments across multiple RSOD datasets and detection architectures demonstrate that the proposed method achieves a high copyright verification success rate with negligible impact on detection accuracy and exhibits strong robustness and stealthiness against a variety of watermark removal attacks. Full article

Live case studies are widely used in higher education to support active learning; however, their pedagogical potential is often limited by weak integration with learning theories and assessments. This research-to-practice study examines the systematic design of live case studies by integrating Kolb’s experiential learning cycle (ELC) and authentic assessment (AA) principles. This paper presents a framework that conceptualises live cases as the learning context, ELC as the learning process, and AA as evaluative logic. The framework is illustrated through a case study of an undergraduate Quality Management module in industrial engineering at a Mexican university, involving 31 final-year students. The study is design-oriented and illustrative, aiming to demonstrate framework enactment rather than evaluating causal effectiveness. Using a case study methodology, the instructional design and enactment were documented using the ADDIE model. Data were obtained from educational artefacts, assessment results, and student feedback surveys. The findings suggest that aligning teaching and assessment activities with the ELC stages and the AA principles effectively supports learning trajectories. This support covers experience, reflection, conceptualisation, and application. Live case studies enabled the integration of multiple assessment methods around shared organisational problems and supported personalised learning through students’ case selection. This study contributes a design logic and operational framework for distributing authentic assessment across Kolb’s experiential learning stages within live case pedagogy. Rather than offering statistical generalisation, the framework serves as a foundation for adaptation and research, emphasising transferability across disciplines, educational levels, and delivery modes. Limitations are acknowledged regarding the conceptual scope, methodological design, and empirical context. Full article

Background: Parents are children’s primary role models, are food and physical activity gatekeepers, and create the home structure/lifestyle environment. Thus, parents strongly influence children’s weight-related behaviors and have the opportunity to cultivate a “culture of health” within the home. Methods: The aim of the HomeStyles-2 (also called HomeStyles-Child) RCT was to determine whether this online, novel, age-appropriate, family intervention enabled and motivated the 131 systematically randomly assigned by computer parents of children in middle childhood (ages 6 to 11) in the experimental condition to shape home environments and healthy weight-related lifestyle practices to be more supportive of optimal health and reduced obesity risk in middle childhood youth more than the 134 counterparts assigned to the attention control condition. Results: This RCT demonstrated the feasibility of online delivery of a health promotion intervention to parents of children in middle childhood, which may inform the development of interventions targeting other age groups and health outcomes. Results indicate the HomeStyles-Child intervention improved healthy-weight-related behavior cognitions, which are predictors of behavior change, of the experimental group. Additionally, improvements in experimental parent and child health-related behaviors were observed. These improvements occurred during a time when families faced unprecedented and extraordinary economic and social stresses associated with the COVID-19 pandemic. Conclusions: HomeStyles-Child is one of the few interventions for families with middle childhood youth. It has the potential to help ameliorate obesity in middle childhood youth and, by extension, other family members. Full article

Background: Maternal control and the sense of support significantly influence a woman’s experience of birth. This study aimed to adapt and validate the Support and Control in Birth (SCIB) scale in Spanish women to assess maternal perceptions of support and control during birth, and to develop and validate an abbreviated version of the instrument. Methods: A cross-sectional study was conducted with a sample of 302 Spanish women who had given birth within the previous 6 months and were at least 1 week postpartum. Content, construct, and criterion validity, as well as reliability, were analysed using an expert panel, Exploratory Factor Analysis (EFA), Confirmatory Factor Analysis (CFA), Cronbach’s Alpha Coefficient, and Intraclass Correlation Coefficient (ICC). Criterion validity was assessed using the Generalised Anxiety Disorder Screener (GAD-7) and the Birth Satisfaction Scale–Revised (BSS-R). Results: The KMO test yielded a value of 0.925, and Bartlett’s test of sphericity was significant (p < 0.001). EFA identified three factors (Support, External control, and Internal control) that explained 56.49% of the total variance. CFA showed good model fit for most of the evaluated indices. The SCIB scale correlated negatively with the GAD-7 and positively with the BSS-R (p < 0.001), as well as with several obstetric and neonatal variables (p < 0.05): planned pregnancy, high-risk pregnancy, onset and type of delivery, birth plan, use of epidural analgesia, maternal involvement, postpartum complications, and newborn characteristics. Cronbach’s alpha was 0.951, and the ICC indicated excellent consistency and agreement (0.995; 95% CI: 0.990–0.998). Based on expert panel consensus, a 24-item abbreviated version was developed that exhibited psychometric properties similar to those of the original version and a high correlation with it (r > 0.90). Conclusions: The Support and Control in Birth (SCIB) scale is a valid and reliable instrument for assessing perceptions of support and control during birth in Spanish women. The 24-item abbreviated version is recommended. Full article

Background/Objectives: Nurses’ turnover intentions are strong predictors of actual turnover, which increases costs, reduces care quality, and destabilies the workforce. This study aimed to identify the key predictors of nurses’ turnover intentions using advanced machine learning methods and to explore how demographic, well-being, and work environment factors contribute to these intentions. Methods: Cross-sectional data were collected from 2459 nurses employed across various healthcare institutions. We used multichannel invitation and snowball sampling. An artificial neural network regression model was applied, combined with iterative feature selection and SHAP analysis, to identify the most important predictors of turnover intentions and to examine nonlinear and context-dependent relationships among variables. Results: Seven predictors explained 49.8% of the variance in turnover intentions, outperforming traditional linear models. Age was the strongest predictor, with younger nurses demonstrating a substantially higher likelihood of intending to leave; this association was nonlinear, with intentions decreasing more sharply at older ages. Job satisfaction and burnout were also strong predictors, particularly among younger nurses. Four work environment factors further contributed to turnover intentions: managerial support functioned as a protective factor, interpersonal conflict increased intentions to leave, limited professional development opportunities were strongly associated with higher turnover intentions, and role conflict showed heterogeneous effects. Conclusions: Machine learning approaches enhance understanding of complex workforce dynamics and enable more precise identification of high-risk groups. The findings support age-sensitive retention strategies, proactive monitoring of nurse well-being, and organizational interventions to strengthen managerial support and professional development, ensuring workforce stability and sustainable healthcare service delivery. Full article

Introduction: Interpregnancy interval (IPI) plays a critical role in neonatal health, yet optimal spacing remains controversial. This study assessed neonatal outcomes across short and long IPI using three complementary classification approaches to identify consistent patterns of risk. Materials and Methods: In this retrospective cohort study, medical records of 1194 women with a prior live birth who delivered singleton pregnancies in 2024 at a tertiary referral center were analyzed. IPI was calculated as the delivery-to-conception interval (LMP + 14 days). Three IPI classification systems were applied: (1) classical cut-offs (<6, 6–11, 12–23, 24–59, and ≥60 months), (2) quartiles, and (3) tertiles. Primary outcomes included preterm birth, low birth weight (LBW), and NICU admission. Multivariable logistic regression models adjusted for maternal age, gravidity, and previous cesarean delivery. Results: Short IPI (6–11 months) demonstrated the highest NICU admission rates (29.4%). Very long IPI (≥60 months) showed the highest prevalence of LBW (16.6%). Multivariable regression analysis revealed that intervals ≥ 24 months were independently protective against preterm birth (24–59 months: aOR 0.48, p = 0.002; ≥60 months: aOR 0.58, p = 0.042), while maternal age increased preterm birth risk by 7% per year. Short IPI (6–11 months) and very long IPI (≥60 months) independently increased NICU admission risk (aOR 2.29, p = 0.002 and aOR 1.61, p = 0.036, respectively). Previous cesarean delivery was an independent predictor of NICU admission (aOR 1.35; p = 0.048). Conclusions: Short and very long IPIs are associated with increased neonatal morbidity, particularly NICU admission, while the apparent preterm risk in long intervals is largely mediated by maternal age. Once adjusted, IPIs exceeding 24 months demonstrate protective effects against preterm birth. However, the rising trend toward LBW and NICU admission in intervals beyond 5 years suggests that birth-spacing counseling targeting an optimal window of 18–24 months provides the best balance in minimizing competing neonatal risks. Full article

Periodontitis is a chronic inflammatory disease marked by the progressive destruction of periodontal tissues, where conventional therapies often fail to maintain adequate drug levels at the target site. This study reports the development and characterization of a thermosensitive gel containing nanostructured lipid carriers (NLC) for controlled local periodontal delivery. Apigenin (AP)-loaded NLC were prepared using AP as active agent and clove essential oil (CEO) as liquid lipid subsequently incorporated into Poloxamer 407 (5–15% w/w) hydrogels. The formulations were evaluated in relation to particle size, morphology, thermal and rheological behavior, mucoadhesion, in vitro release, antibacterial activity, and stability. Optimized nanoscale NLC showed a high entrapment efficiency, and uniform morphology. Raman analysis confirmed successful AP incorporation and homogeneous distribution in the gel without incompatibility. NLC-loaded gels exhibited sol–gel transition at physiological temperature with improved viscoelasticity and enhanced mucoadhesion. The drug release was sustained for 48 h and followed the Korsmeyer–Peppas model, indicating diffusion-based and anomalous transport. The antibacterial assessment demonstrated the pronounced inhibitory activity of the NLC formulations against key periodontal pathogens, with the formulation-dependent modulation of antimicrobial efficacy observed following the gel incorporation. Stability studies showed preserved nanoparticle structure and uniform dispersion. Overall, the thermoresponsive NLC-hydrogel system offers a promising strategy for prolonged, localized periodontal therapy. Full article

Background/Objectives: Wound healing is a complex biological process involving inflammatory, proliferative, and remodeling phases. Plant-derived essential oils are increasingly investigated as topical therapeutic agents, although their biological effects are strongly influenced by composition and formulation. The present study evaluated the effects of topical Mentha spicata essential oil on cutaneous wound healing in a rat excisional wound model and explored potential molecular mechanisms using a network-based bioinformatic approach. Methods: Twenty-one male Wistar rats were randomly assigned to three groups and treated twice daily for 14 days with a formulation containing 5% Mentha spicata essential oil diluted in olive oil, olive oil alone, or no treatment. Wound healing was assessed through macroscopic monitoring and histological scoring. The chemical composition of the essential oil was characterized using gas chromatography–mass spectrometry analysis. Predicted molecular targets of the major monoterpenes were analyzed through protein interaction networks and pathway enrichment analysis. Results: Macroscopic wound closure progressed in all groups by day 14. Histological analysis revealed that the olive oil group showed more advanced collagen deposition, re-epithelialization, and granulation tissue maturation, whereas the Mentha spicata group displayed a more pronounced inflammatory and proliferative histological pattern. Network-based analysis highlighted signaling pathways related to receptor-mediated cellular responses as potential molecular mechanisms associated with early inflammatory and proliferative processes. Conclusions: These findings suggest that the biological effects of Mentha spicata essential oil in wound repair may be phase-dependent and influenced by concentration and formulation. The results support further studies aimed at optimizing dose and delivery strategies for essential oil–based wound therapies. Full article

Background and Objectives: Dental caries remains one of the most prevalent chronic conditions among children worldwide, with considerable variation in burden shaped by differences in health-system organization and preventive program implementation. Some countries have reported notable progress through coordinated school-based programs and supportive policy environments, while others continue to face challenges despite extensive public health efforts. This study aims to explore how selected structural and programmatic elements within national health systems may be associated with childhood caries outcomes, using Germany and Saudi Arabia as illustrative contexts. Materials and Methods: A descriptive comparative secondary-data analysis combined with legal and policy mapping was conducted using published national oral health surveys, systematic reviews, and governmental reports. Caries indicators (dmft/DMFT) for children aged 6–7 and 12 years were extracted following WHO criteria. Health system organization, preventive program coverage, and policy enforcement mechanisms were mapped and critically reviewed. No new primary data were collected, and no inferential modeling was performed. Results: Germany has achieved substantial reductions in childhood caries prevalence through a legally mandated school-based prevention program, supported by individual prophylaxis covered by health insurance. This framework corresponds with low mean dmft (1.73) among 6–7-year-olds and mean DMFT (0.5) among 12-year-olds. By contrast, Saudi Arabia continues to report elevated caries rates despite substantial public-health investments, with mean dmft (5.0) and mean DMFT (3.5), with over 90% of children affected. Preventive initiatives in Saudi Arabia remain fragmented across sectors and lack a unified legal mandate. Conclusions: The findings suggest that structured governance, coordinated prevention strategies, and reliable monitoring systems may be associated with more favorable oral health outcomes. In the context of Saudi Arabia, the persistently high caries burden suggests that strengthening national legislation, implementing an interoperable digital surveillance system, and improving the consistency of school-based preventive programs could support more equitable and effective oral health delivery. Full article

The efficient delivery of small interfering RNAs (siRNAs) to immune and respiratory cells represents a key methodological challenge in developing inhaled RNA interference (RNAi) approaches. A central question is whether siRNA functionality is preserved following aerosolization, as the mechanical stress of nebulization may compromise siRNA integrity and silencing activity. Here, we report a proof-of-concept study using THP-1-derived macrophage-like cells as a tractable in vitro model to characterize jet nebulization for siRNA delivery. Three siRNA candidates targeting interleukin-1 beta (IL-1β) were computationally designed and validated for potent silencing activity and low cytotoxicity. Using a commercially available, off-the-shelf jet nebulizer combined with Lipofectamine RNAiMAX, we demonstrate that siRNA-lipoplexes retain their gene-silencing activity after aerosolization, achieving robust IL-1β knockdown. The delivery efficiency was influenced by siRNA-lipoplex complexation, highlighting the importance of formulation parameters. These findings establish a practical and accessible in vitro platform for evaluating nebulized siRNA functionality, providing a foundation for future studies in more complex and physiologically relevant airway models. Full article

Fault detection in microgrids is a critical element of system stability and uninterrupted power delivery. Herein, a comparative study using LSTM and bidirectional LSTM networks is performed based on three-phase current data for multi-class fault classification. Five major fault types, namely LG, LL, LLG, LLL, and LLLG, were simulated using a Real-Time Digital Simulator (RTDS) under grid-connected and islanded modes. Collected current signals were preprocessed, normalized, and segmented for sequence learning. Later, both models were trained using the best hyperparameter setting to enhance their capabilities and classify faults. To measure how well they identified faults, evaluation metrics, like accuracy, precision, recall, F1-score, and ROC-AUC, were calculated. The results revealed that the Bi-LSTM outperformed the LSTM and classical machine learning models consistently, with more than 99% accuracy for most fault types. More importantly, the proposed framework also checked classification performance for LLLG faults, with the Bi-LSTM model having a test accuracy of 98.8%. These results confirm that the Bi-LSTM model can robustly and precisely classify and detect faults in real time within specific phases of microgrids; therefore, it provides a scalable foundation for the development of intelligent protection in smart power systems. Full article

Research on financial risk tolerance and risk-taking increasingly incorporates personality traits into predictive and descriptive models of risk-taking behavior; however, intercorrelations among traits can obscure the unique contributions of individual traits. This is known as the suppressor effect. This study employed a two-stage analytic framework to test and adjust for suppressor effects across the Big Five personality dimensions in describing financial risk tolerance. In Stage 1, correlation and OLS regression analyses identified suppression patterns, revealing that the explanatory validity of some factors was distorted by shared variance. In Stage 2, suppression-adjusted trait estimates were used to reassess their unique association with financial risk-taking mediated through financial risk tolerance. Results indicate that Openness to Experience and Extraversion are the strongest descriptors of financial risk-taking once suppressor effects are controlled. At the same time, Agreeableness and Conscientiousness contribute modestly and context-dependently to descriptions of financial risk-taking. These findings demonstrate that ignoring suppression effects can lead to mischaracterizing the role of personality in financial decision-making. This study shows that more precise estimates of trait influences can improve theoretical models of investor behavior and enhance the delivery of financial advice and education. Full article