Search Results (29,948)

Background: Given their intraoral service for clinically relevant periods, it is important to clarify whether additive manufacturing parameters influence the surface characteristics of 3D-printed provisional restorations and thereby affect microbial colonization. Methods: This study evaluated the effects of printing orientation and layer thickness on surface roughness, wettability, and Streptococcus mutans biofilm formation of LCD-printed provisional restorations. Disk-shaped specimens were fabricated from a methacrylate-based provisional resin at two orientations (0° and 90°) and two layer thicknesses (50 and 100 µm) (n = 7 per group). Surface roughness (Ra) was measured by contact profilometry, wettability by sessile-drop contact angle analysis, and biofilm formation by crystal violet staining after 72 h. Results: Data were analyzed by two-way ANOVA, aligned rank transform (ART) ANOVA, and correlation analysis (α = 0.05). Orientation alone did not affect Ra (p = 0.992), whereas layer thickness (p = 0.012) and the orientation × layer thickness interaction (p = 0.002, η² = 0.339) were significant. At 50 µm, 90° oriented specimens showed higher Ra than 0° (p = 0.021); this pattern reversed at 100 µm (p = 0.020). Neither parameter significantly affected contact angle or biofilm formation (p > 0.05). Conclusions: Both printing orientation and layer thickness altered the surface microtopography of the specimens; however, no significant differences were observed in short-term S. mutans biofilm formation among the tested groups. Within the limitations of the present single-species 72 h in vitro model, the findings suggest that material-related characteristics may have contributed more prominently to the observed biofilm behavior than the printing-induced surface differences evaluated in this study. Full article

Human eyes do not have perfectly aligned optical components; the fovea is displaced from the posterior pole, and the crystalline lens is tilted away from the eye’s optical axis. Important in the study of vision quality, it is included here in binocular and oculomotor research. In the binocular system, with the eye’s optical asymmetry, all axes differ. The eye’s posture change is decomposed into the torsion-free part that gives the change in visual axis direction and the torsional part that best approximates the rotation about the lens’s optical axis. This geometric formulation, supported by computer simulations and modern ophthalmology studies, leads to binocular Listing’s law and the related half-angle rule, important for oculomotor control by constraining the eye’s redundant torsional degree of freedom. The eye’s primary position and the Listing plane, indispensable ingredients of Listing’s law, are replaced with the binocular eyes’ posture corresponding to the eye muscles’ natural tonus resting position, which serves as a zero-reference level for convergence effort. Further, the binocular constraints couple 3D changes in the torsional positions of the eyes within the ab initio formulation of Listing’s law here, which was previously proposed ad hoc. Finally, the noncommutativity rule underlying Listing’s law and the half-angle rule are discussed by specifying the configuration space of sequences of fixations of binocularly constrained eyes, which are visualized in 3D simulations. The results obtained in this study should be a part of the answers to the questions posted in the literature on the relevance of Listing’s law to clinical practices. Full article

Background/Objectives: Pediatric dyslipidemia is a major modifiable risk factor for future cardiovascular disease, and lifestyle modification is recommended as first-line therapy. However, real-world longitudinal evidence on the effectiveness of repeated lifestyle education delivered during routine clinical practice remains limited. In this study, we assessed longitudinal metabolic changes following repeated lifestyle education and explored developmental and early-life factors associated with treatment responsiveness. Methods: In this retrospective longitudinal cohort study, we included 437 children and adolescents newly diagnosed with dyslipidemia at a tertiary hospital between 2019 and 2024. Participants received repeated lifestyle education during routine outpatient visits. Anthropometric and laboratory parameters were assessed over time. Linear mixed models were used to evaluate longitudinal changes, and multivariable logistic regression analyses were performed to identify predictors of lipid improvement. Results: Repeated lifestyle education was associated with gradual improvements in BMI SDS, total cholesterol, and non-HDL cholesterol over time. Linear mixed model analyses demonstrated significant time effects for total cholesterol and non-HDL cholesterol, while HDL cholesterol remained relatively stable. Thyroid-stimulating hormone (TSH) also demonstrated a significant time-dependent reduction during follow-up. Multivariable logistic regression analysis revealed that pubertal stage was associated with a lower likelihood of improvement in LDL and non-HDL cholesterol, whereas large-for-gestational-age birth was associated with a higher likelihood of HDL improvement. Conclusions: Repeated lifestyle education delivered during routine clinical practice was associated with meaningful improvements in lipid profiles in children with dyslipidemia. Developmental stage and early-life characteristics may influence treatment responsiveness, highlighting the importance of individualized and developmentally informed management strategies. Full article

Hypoxia is a hallmark feature of solid tumors and is increasingly recognized as an important factor in tumor progression, aggressiveness, and therapeutic resistance. In the tumor microenvironment, hypoxia is associated with genetic instability, abnormal angiogenesis, metabolic reprogramming, and crosstalk with oncogenic signaling pathways, thereby potentially enhancing tumor invasiveness and metastatic potential. Furthermore, hypoxia may impair the sensitivity of tumor cells to conventional therapies and contribute to treatment resistance. This article reviews current evidence on the role of hypoxia in thyroid cancer, focusing on its biological effects, clinical implications, and therapeutic relevance. Available studies suggest that hypoxia may affect thyroid cancer progression and treatment tolerance by modulating hypoxia-inducible factor (HIF) signaling, epithelial–mesenchymal transition (EMT), angiogenesis, metabolic adaptation, cancer stem-like properties, extracellular matrix remodeling, and stress-adaptive responses. However, the strength of evidence varies across these pathways, and many hypoxia-targeted strategies remain under preclinical investigation. Approaches such as HIF inhibition, redifferentiation therapy, and vascular modulation may offer potential therapeutic directions for advanced and refractory thyroid cancer. Given the marked heterogeneity of thyroid cancer, further thyroid cancer-specific studies are needed to clarify the prognostic and therapeutic significance of hypoxia. Full article

Introduction/Objective: Patient satisfaction with nursing care quality is an important patient-reported indicator of hospitalization experience. Previous studies have mainly examined sociodemographic, clinical, and organizational factors, while personality traits have rarely been included in explanatory models. This study examined the association of sociodemographic characteristics, hospitalization-related variables, and personality traits with patient satisfaction. Methods: A single-center cross-sectional study was conducted among hospitalized patients in a general hospital in Croatia. Data were collected at discharge using a demographic and hospitalization questionnaire, the NEO Five-Factor Inventory, and the Croatian version of the Patient Satisfaction with Nursing Care Quality Questionnaire. Group differences were analyzed using non-parametric tests, and hierarchical regression analysis was performed. Results: Younger age, employment, male gender, and better self-rated health were associated with higher satisfaction. Patients admitted on a scheduled basis and those staying alone or with one other person in the room were more satisfied. Sociodemographic variables explained 21.5% of the variance in satisfaction (R² = 0.215; adjusted R² = 0.168). After hospitalization-related variables were added, the explained variance increased to 30.1% (R² = 0.301; adjusted R² = 0.232). The addition of personality traits further increased the explained variance to 45.6% (R² = 0.456; adjusted R² = 0.385). In the final model, staying with two or more persons was negatively associated with satisfaction, whereas agreeableness and conscientiousness were positively associated with satisfaction. Conclusions: Patient satisfaction with nursing care quality was associated with patient characteristics, hospitalization conditions, and personality traits. Accommodation conditions and individual psychological differences should be considered when interpreting satisfaction as an indicator of nursing care quality. Full article

The growing integration of rehabilitation robotics and artificial intelligence has created new opportunities for developing control strategies that better support clinicians during patient therapy. This study investigates machine learning and deep learning approaches for classifying upper limb motion using encoder-based biomechanical data, with the goal of identifying a model suitable for implementation in a rehabilitation exoskeleton. Several classical algorithms such as k-Nearest Neighbors, Random Forest, multiclass logistic regression, XGBoost, and an SVM classifier were evaluated alongside three deep learning architectures: convolutional layers, GRU and LSTM units. Models were trained and tested on two types of datasets using both standard cross-validation and leave-one-subject-out validation. The analysis included assessments of class separability, signal features’ importance, and comparative performance based on F1-score, accuracy, and confusion matrices. Results showed notable differences between validation strategies, with LOSO evaluation revealing limitations of the available dataset and emphasising the need for broader data collection. Overall, the findings indicate that, in the LOSO evaluation of the five-class multi-subject dataset—the most clinically realistic validation scenario—the LSTM-based model achieved the highest generalisation performance (accuracy 92.8%, macro-F1 0.927), supporting its suitability for integration into exoskeleton control systems aimed at detecting and mitigating compensatory movements. Full article

Chronic pancreatitis (CP) is a fibro-inflammatory condition defined by permanent anatomical changes in the pancreas. The causes of CP are described by the TIGAR-O classification system: toxin-related, idiopathic, genetic mutations, autoimmune disorders, episodes of recurrent acute pancreatitis, and obstructions. Pain is multifactorial in nature, and common psychopathological consequences of CP, including depression and anxiety, complicate the clinical picture of chronic pancreatitis. As a result, the quality of life of patients with CP is decreased. This review describes the pathophysiology of pain and its relationship to underlying psychological consequences, with a focus on a long-term, holistic management approach. Strategies that combine physical and psychological management align with SDG 3 (Good Health and Well-being). CP predominantly affects patients from low socioeconomic backgrounds due to disparities in medical care, underscoring the relevance of achieving SDG 10 (Reduced Inequalities). This review emphasizes the importance of targeted research in developing a holistic care model for CP that aligns with the SDGs. Full article

High-density microelectrode arrays (HDMEAs) have become increasingly important tools in neuroscience and biomedical engineering because of their high spatial and temporal resolution for recording and modulating electrical activity across diverse biological systems. Initially developed for in vitro studies of cultured cells, HDMEAs are now being applied to increasingly complex models, including organoids, animal systems, and even human neural systems. These advancements enable a deeper investigation of cellular interactions, network dynamics, and disease mechanisms, as well as providing novel therapeutic and diagnostic tools for neurological disorders. This review explores the evolution of HDMEAs, emphasizing recent innovations in their design, fabrication, and functionalization. We discuss their applications across cellular models, organoid systems, animal studies, and human electrophysiology, and highlight current challenges such as biocompatibility, long-term stability, scalability, and translational deployment. Finally, we outline future directions for advancing HDMEA technologies in both research and clinical settings. Full article

Background: The importance of evidence-based practice (EBP) is well recognized, yet its implementation remains challenging across healthcare systems, especially in low- and middle-income countries, where resource constraints, workforce turnover, and organizational barriers can hinder practice change. The traditional approach to implementation has focused on training, guidelines, and leadership support; however, these strategies do not always sustain frontline staff engagement. Objective: This descriptive case study examined how social movement strategies supported a multi-year EBP implementation initiative within a Philippine academic–clinical partnership. Methods: Program documents, training records, implementation reports, curriculum materials, and internal records of guideline-related activities were reviewed. Data were organized using the Social Movement Action Framework, with attention to preconditions for change, social movement mechanisms, and implementation outcomes. Results: The initiative included champion training, guideline integration, awareness activities, academic–clinical collaboration, and practice-focused implementation efforts related to breastfeeding, vascular access device management, and pressure injury prevention. These activities provided observable process indicators of stakeholder engagement, shared ownership, and continued use of guideline-informed practices. Conclusions: Social movement strategies may offer a useful complementary lens for understanding how EBP implementation gains momentum in real-world healthcare settings. Additional studies should explore their relationship to implementation outcomes and clinical care processes. Full article

Background: Pregnancy presents unique immunological and obstetrical challenges for women with Common Variable Immune Deficiency (CVID). No standardized guidelines currently exist to guide pregnancy management, as CVID is a rare diagnosis, with pregnancy outcomes limited to case reports and case series. Establishing a structured approach to care is important to optimize maternal and fetal outcomes. Methods: A narrative review of the literature with a structured search was performed to detail pregnancy outcomes in CVID and management strategies. A 10-year retrospective chart review of women with CVID who became pregnant while receiving care at the McGill University Health Centre between January 2015 and January 2025 was conducted to add to the existing clinical data. Results: Pregnancy outcomes were improved through pre-conception planning, regular serum Immunoglobulin G (IgG) monitoring, trimester-based immunoglobulin replacement dose adjustments, proactive management of autoimmune or infectious complications, and multidisciplinary care. Subcutaneous immunoglobulin may offer better flexibility and stability of IgG levels. Conclusions: In the available observational literature and our institutional experience, many patients with CVID have carried pregnancies to term with favorable maternal and neonatal outcomes when managed with IgRT and multidisciplinary coordination. We outline a stepwise multidisciplinary framework for clinicians caring for women with CVID who are planning or undergoing pregnancy, and we identify gaps in knowledge for future studies. Full article

Generalized pustular psoriasis (GPP) is a rare, severe, and potentially life-threatening inflammatory dermatosis increasingly recognized as a distinct disease entity rather than a variant of plaque psoriasis. Emerging evidence indicates that GPP is primarily driven by dysregulation of the interleukin-36 (IL-36) signaling axis, leading to amplification of proinflammatory cascades in keratinocytes and a predominantly innate, neutrophil-driven immune response. This promotes rapid neutrophil recruitment, sterile pustule formation, and abrupt cutaneous and systemic inflammation. Consistent with this, GPP demonstrates a greater predominance of innate immune and neutrophil-driven inflammation, whereas plaque psoriasis is more strongly associated with IL-23/Th17-mediated adaptive immune responses. Transcriptomic and genetic studies further support this distinction, demonstrating enrichment of IL-36-associated and neutrophil-related signatures, activation of MyD88-dependent pathways, and mutations in genes regulating the IL-36 axis, including IL36RN, AP1S3, and CARD14. Consequently, conventional systemic therapies and biologics targeting TNF-α, IL-17, and IL-23 pathways show variable efficacy and may act more slowly in GPP. In contrast, IL-36 receptor inhibitors represent a more mechanism-aligned approach and have demonstrated rapid and clinically meaningful responses in acute flares. However, important gaps remain, including the lack of validated biomarkers and limited data on long-term treatment outcomes. This review provides an integrated perspective on IL-36-driven inflammation in GPP, including comparison with plaque psoriasis, and outlines its implications for mechanism-based therapeutic approaches. Full article

High-fidelity simulations have become an important aid in clinical practice and research. In the pediatric field, they allow for the creation of scenarios involving emergency situations, in which decision-making algorithms must be rapidly applied, as is the case with airway management. Our narrative review examines articles in English indexed in PubMed, using the following search terms: high-fidelity simulation, pediatric, difficult airway management, bag mask ventilation, intubation, mechanical ventilation, tracheostomy, cricothyrotomy, laryngoscopy, fiberoptic bronchoscopy, and emergency situations. Airway management, along with venous access management, has always been one of the most challenging issues in pediatric anesthesia. The scarcity of patients and procedures, combined with the need to ensure high quality standards, necessitates simulations. Using high-performance devices and realistic settings allows us to reproduce not only the desired technical scenario, but also the emotions and group dynamics. High-fidelity simulations therefore prove to be an excellent aid for pediatric airway management, enhancing the hard and soft skills of both the team and the individual. Simulations allow us to replicate scenarios that are uncommon in clinical practice but have a significant impact due to their potential severity. Full article

Compounds of plant origin have increasingly emerged as anticancer agents through direct cytotoxicity and sensitizing mechanisms. Melanoma remains the most aggressive form of skin cancer that exhibits a steadily increasing number of new cases globally each year, thus urgently requiring more effective therapeutic strategies. Therefore, phytochemicals can be considered promising candidates, particularly when used in combination with immune checkpoint inhibitors. Their ability to optimize therapeutic efficacy and strengthen antitumor immune responses is mediated through various mechanisms that include the stimulation of T cell activity, the regulation of the TME, the activation of intrinsic immune responses and cytokine signaling, and the regulation of immune checkpoints such as PD-1/PD-L1, CTLA-4, and LAG-3. Additionally, these compounds can alter key signaling pathways that control immune regulation. Nevertheless, the extrapolation of preclinical studies to clinical applications remains limited by insufficient clinical evidence, the lack of standardized therapeutic protocols, and poor pharmacokinetic behavior. Consequently, further studies are required in order to clarify their actual efficacy and to better define their role in modern oncology. This article aims to review the mechanisms that underlie the anticancer sensitizing activity of major classes of plant-derived compounds such as polyphenols, flavonoids, terpenoids, alkaloids, and isothiocyanates. The available preclinical and clinical evidence were reported together with their potential synergistic effects when combined with immune checkpoint inhibitors. An important aspect related to the anticancer effects of these compounds lies in their ability to simultaneously target multiple signaling pathways. Furthermore, advanced formulations such as nanoparticulated delivery systems are discussed as strategies to optimize their clinical application and therapeutic outcomes. Full article

Acute kidney injury (AKI) lacks targeted pharmacological interventions. While the DanShen–DaHuang (DS-DH) herb pair shows clinical potential for AKI treatment, and our prior study has validated its nephroprotective efficacy in a cisplatin-induced murine model, its specific molecular targets within the renal microenvironment remain undefined. In this study, we integrated network pharmacology and weighted gene co-expression network analysis (WGCNA) to screen AKI-related targets of the DS-DH pair. A multi-algorithmic machine learning pipeline (including LASSO, Boruta, Random Forest, GBM, XGBoost, and Decision Trees) was utilized to calculate feature importance scores and rank core genes. Subsequently, single-cell RNA sequencing (scRNA-seq) data (GSE197266) were analyzed for transcriptomic mapping, pseudotime trajectory, and cell–cell communication. Finally, molecular docking evaluated theoretical binding affinities. After database screening, a total of 603 drug–disease intersecting targets were obtained. Subsequently, 917 module genes significantly associated with AKI were identified by WGCNA, and 62 core candidate genes were determined after intersecting with the above targets. Multi-algorithm machine learning ranked the importance of the 62 targets, with transketolase (TKT) ranking the highest. To elucidate the mechanism of TKT in AKI, scRNA-seq analysis was performed on 77,593 high-quality cells. The results showed that Tkt was specifically enriched in renal macrophages, with the highest expression in the M2-polarized subset. Pseudotime analysis further revealed that Tkt expression dynamics were highly synchronized with the differentiation trajectory of M2 macrophages and positively correlated with the repair markers Arg1 and Mrc1. Cell–cell communication analysis predicted that Tkt⁺ M2 macrophages act as active communication hubs via the Spp1 and Mif signaling axes. Molecular docking validated the favorable binding affinity between core DS-DH compounds and the TKT active pocket. This computational framework predicts that the DS-DH herb pair might mitigate AKI by potentially targeting TKT, a metabolic enzyme closely associated with macrophage M2 polarization. By prioritizing targets via multi-algorithmic scoring, we provide a data-driven rationale and candidate targets for future experimental validation. Full article

Background and Objectives: Elective electrical cardioversion (eECV) in patients with atrial fibrillation (AF) or atrial flutter is associated with a low risk of thromboembolic events (TEs) when adequate anticoagulation is provided. However, the role of routine transesophageal echocardiography (TEE) prior to eECV remains uncertain. This study aimed to assess thromboembolic outcomes in patients undergoing eECV with or without TEE guidance in a real-world clinical setting. Methods: A single-center, combined retrospective–prospective observational study including 296 adequately anticoagulated patients with AF or atrial flutter scheduled for eECV was conducted. The retrospective cohort (n = 220) underwent eECV without routine TEE, while the prospective cohort (n = 85) underwent TEE prior to eECV. The primary outcome was the occurrence of thromboembolic events (ischemic stroke or systemic embolism) within 30 days after eECV. Arrhythmia recurrence at 30 days was assessed as a secondary, exploratory outcome. Results: Among patients undergoing eECV, thromboembolic events were rare. In the retrospective cohort, 3/220 patients (1.36%) experienced a TE, whereas no events were observed in the prospective cohort (0/76). Due to the low number of events, the study was underpowered to detect meaningful differences between strategies (RR 2.44; 95% CI 0.13–46.7; p = 0.55). TEE identified left atrial appendage thrombus in 9/85 screened patients (10.6%), who were subsequently excluded from cardioversion. Arrhythmia recurrence at one month was more frequent in the prospective cohort (19.7% vs. 7.3%), likely reflecting differences in baseline clinical characteristics. Conclusions: Thromboembolic events after eECV in adequately anticoagulated patients were infrequent in this real-world cohort. While the study design limits direct comparison between strategies, the results indicate that a conventional anticoagulation-based approach without routine TEE is associated with a low risk of thromboembolic events in most patients. At the same time, the detection of left atrial appendage thrombus in a subset of patients underscores the importance of individualized risk assessment and supports the selective use of TEE in higher-risk clinical settings. Full article