Search Results (3,420)

Background/Objectives: Knee osteoarthritis (OA) significantly impairs physical function and quality of life, particularly in women. Although muscle strength and postural stability are known to influence functional outcomes, their independent contributions after controlling for age, body mass index (BMI), and pain remain unclear. This study aimed to investigate the differential roles of lower extremity muscle strength and postural stability on functional status, evaluated through both performance-based tests and patient-reported outcomes, in women with bilateral knee OA. Methods: Sixty-four women with bilateral knee OA (mean age: 55.71 ± 5.99 years) were included in this study. Lower extremity muscle strength was assessed using the five-times sit-to-stand test, and postural stability was evaluated with the Biodex Balance System. Performance-based function was measured using the Six-Minute Walk Test (6MWT) and the stair climbing test (SCT), while self-reported function was assessed using the WOMAC function subscale (WOMAC-F). Hierarchical linear regression analyses were conducted, controlling for age, BMI, and pain. Results: Muscle strength emerged as the strongest independent predictor of performance-based outcomes, significantly contributing to both SCT (β = 0.330, p = 0.005) and 6MWT (β = −0.409, p = 0.001). In the 6MWT model, the effects of age and BMI became non-significant after the inclusion of muscle strength, indicating a mediating role. In contrast, self-reported function (WOMAC-F) was primarily associated with pain (β = 0.385, p = 0.001) and postural stability (β = 0.243, p = 0.040), while muscle strength showed no significant contribution. Conclusions: Muscle strength is the primary determinant of objective functional performance, whereas pain and postural stability are more influential in shaping perceived functional limitations. These findings highlight a dissociation between actual performance and patient-reported function. Rehabilitation strategies should prioritize strength training to improve physical performance, while also addressing pain and balance to enhance patients’ perceived function. Full article

Stem cells, with their self-renewal and multi-lineage differentiation potential, hold promise for tissue repair and intractable diseases treatment. Yet clinical translation of stem cell therapies has long been hindered by insufficient scalable stem cell manufacturing, stemness loss and functional decline in 2D expansion, and poor post-transplantation cell retention, unregulated fate control. Programmable microcarriers (MCs) paired with 3D dynamic culture offer an emerging strategy to address these bottlenecks and enable stem cell fate regulation. In this review, we systematically review advanced MC fabrication strategies for stem cell fate regulation, comparing features of emerging technologies (microfluidics, electrospraying, in-air microfluidics, integrated in situ functionalization) and their implications for programmable MC control and scalable manufacturing. We analyze how MCs modulate stem cell behaviors (adhesion, proliferation, stemness maintenance, differentiation) via synergistic static physicochemical cues and dynamic stimuli-responsive properties. We map the latest advances in functionalized MC-mediated stem cell therapy across osteochondral defects, autoimmune, skin, ophthalmic and neurodegenerative diseases. Finally, we pinpoint unresolved challenges for clinical translation of MC–stem cell system and outline key future research directions. This review offers a systematic roadmap for advancing programmable MC fabrication, clinical-grade stem cell biomanufacturing, and precise cell therapy development. Full article

In this work, we investigate deterministic chaos in external-cavity semiconductor lasers with delayed optical self-feedback. A noise-free quadrature-based delay differential model is used to isolate the intrinsic nonlinear dynamics produced by phase-sensitive delayed reinjection and carrier–photon interactions. Sensitivity to initial conditions is quantified by computing the leading Lyapunov exponents through a variational approach that integrates the base delay differential equations together with their delayed variational equations using a fourth-order Runge–Kutta method of steps and periodic QR orthonormalization. High-resolution Lyapunov maps are constructed in the $({\log }_{10}C,{\varphi }_f)$ parameter space for different pump ratios and selected short-feedback delays. The delay values are interpreted through the reference-normalized ratio ${\tau }_f/T_{R,\mathrm{ref}}$, where $T_{R,\mathrm{ref}}\approx 131.9\mathrm{ps}$ is a fixed reference timescale derived from a reference solitary-laser operating point. The results show that both the spatial organization of positive-${\lambda }_1$ regions and the mean positive Lyapunov exponent are strongly affected by feedback delay, feedback phase, feedback strength, and pump ratio. Within the selected short-delay set, delayed self-feedback produces broader, more connected, and more strongly unstable chaotic regions as the external-cavity memory time increases toward the fixed reference timescale, particularly at larger pump ratios. These findings show that short external-cavity self-feedback can support robust deterministic chaotic regimes relevant to compact and integrated photonic implementations. The proposed framework provides a reproducible deterministic reference for identifying and interpreting feedback-induced chaos in short-delay external-cavity semiconductor lasers, while stochastic effects such as spontaneous-emission and Langevin noise are left for future robustness studies. Full article

Autoimmune endocrine diseases constitute a group of disorders characterized by immune-mediated destruction or dysfunction of hormone-producing glands. The pathogenesis of these diseases reflects a breakdown of immune tolerance in which regulatory T cells (Tregs) play a key role. The transcription factor forkhead box P3 (FOXP3) is a master regulator of Treg differentiation and suppressive function. Also, it is central to maintaining self-tolerance. Genetic mutations in FOXP3, including those responsible for immune dysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome, highlight the critical role of FOXP3 in endocrine immune tolerance. Emerging evidence suggests that autoimmune endocrine disorders may reflect organ-specific destabilization of FOXP3 expression rather than complete Treg deficiency. The reversibility or irreversible loss of FOXP3 gene expression represents a key determinant of Treg plasticity and the persistence of autoimmune inflammation. This review proposes an integrated genetic–epigenetic model of FOXP3 instability and examines how the endocrine microenvironment shapes Treg plasticity. Genetic or epigenetic alterations affecting FOXP3 expression can impair Treg activity and precipitate endocrine organ-specific autoimmunity. Epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNA-mediated regulation that modulate FOXP3 transcriptional activity are discussed. From a translational perspective, the potential of FOXP3 as a biomarker for endocrine disease susceptibility and progression was summarized. Furthermore, therapeutic strategies employed for expanding or engineering functional FOXP3⁺ Tregs using antigen-specific vaccines, chimeric antigen receptors (CAR)-Tregs, gene therapy, or low-dose interleukin-2 (IL-2) were described. Full article

Background: Non-suicidal self-injury (NSSI) is highly prevalent during adolescence and is associated with a range of emotional, cognitive, and interpersonal vulnerabilities. Although prior research has identified key correlates such as emotion dysregulation, hopelessness, interpersonal distress, and attachment insecurity, these factors have largely been examined in isolation, limiting understanding of how they jointly contribute to NSSI. Methods: The present study examined the network structure of NSSI and associated vulnerability processes in a community sample of 2067 Spanish adolescents (M age = 14.62, SD = 1.80). A regularized partial correlation network (EBICglasso) was estimated, including NSSI frequency and functions, emotion dysregulation, hopelessness, perceived burdensomeness, thwarted belongingness, and attachment representations. Centrality and network stability were evaluated using standard indices and bootstrapping procedures. Results: The network revealed a differentiated structure of associations. Perceived burdensomeness and intrapersonal NSSI functions emerged as the most influential nodes, whereas emotion dysregulation occupied a key bridging position connecting attachment-related experiences, interpersonal vulnerability, and NSSI processes. In contrast, NSSI frequency and interpersonal functions showed a more peripheral role. Attachment security was negatively associated with core risk variables, consistent with a protective role within the network. Conclusions: Findings suggest that NSSI in adolescence is embedded within a system of interacting emotional and interpersonal processes, structured around the functional meaning of the behavior and key interpersonal appraisals. Emotion dysregulation emerged as a highly connected node linking multiple domains, while attachment was associated with several key variables within the network. These findings suggest potential targets for early identification and intervention, particularly focusing on emotion regulation, perceived burdensomeness, and intrapersonal functions of NSSI. Full article

Background/Objectives: Stem cells with the ability to differentiate into other cell types and self-renewal afford a powerful apparatus for the healthcare system to replace and rejuvenate damaged tissues and organs in the treatment of various diseases. For the last few decades, stem cell therapy (SCT) has evolved from being an experimental approach to a recognized clinical treatment. SCT and regenerative medicine have garnered tremendous attention and become prominent tools, especially in treating chronic and acute disease and addressing organ failures, and in their repair and replacement, which are directly associated with human health, life, and longevity. Methods: In this review, after providing a brief history and need for the SCT, the employed delivery techniques utilizing various biomaterials, as well as recent developments in nanotechnological methods, are presented. It is focused on the current literature for the recent progress of stem cell therapy and tissue engineering for the application fields in neurological, ophthalmological, cardiovascular, orthopedic, and oncology, followed by the challenges associated with their applications. Results: In addition to safety concerns, challenges such as uncontrollable differentiations, genetic and epigenetic instability, limited cell survival and integration, immunological rejections, scaling and manufacturing drawbacks, as well as unpredictable behaviors and clinical limitations were reviewed. Conclusions: Future aspects with respect to regenerative medicine and tissue engineering, gene editing and personalized therapies, immunomodulation and anti-inflammatory applications, as well as neuroregeneration and treatment of neurodegenerative disorders are reflected. Full article

Background and Objectives: Low participation rates in exercise programs among older adults highlight the need for theory-driven, biopsychosocial interventions that enhance adherence, self-efficacy, and functional outcomes. Grounded in principles of motor learning and behavioral reinforcement within physiotherapy practice, this study aimed to examine the effect of periodic assessments combined with verbal feedback on functional and psychological outcomes in community-dwelling older adults. Methods: A pilot RCT was conducted involving 54 individuals aged ≥65 years (53 women and 1 man), recruited from senior community centers. Participants were randomly allocated to an intervention group (periodic assessment and verbal feedback; n = 27) or a control group (n = 27). Both groups participated in an identical 12-week structured exercise program, delivered twice weekly, focusing on balance, gait, and lower-limb functional training. An intention-to-treat approach was applied. Data were analyzed using Linear Mixed Models, with statistical significance set at p < 0.05. Results: Significant group × time interactions were observed in favor of the intervention group for key kinesiology-related functional outcomes, including the Short Physical Performance Battery (SPPB; p < 0.001), Timed Up and Go test (TUG; p = 0.011), and Activities-specific Balance Confidence Scale (ABC; p < 0.001). No statistically significant differences were identified between groups for the Behavioral Regulation in Exercise Questionnaire–2 (BREQ-2; p = 0.164) and the Self-Efficacy for Exercise Scale (ESE; p = 0.108), indicating that the primary psychological outcome (ESE) was not confirmed. However, both ESE and BREQ-2 demonstrated significant baseline differences favoring the intervention group, and, therefore, these findings should be interpreted with caution despite statistical adjustment. Conclusions: Periodic assessments followed by verbal feedback appear to selectively improve the functional effectiveness of structured exercise programs in older women, particularly physical performance, functional mobility, and balance confidence, with no significant differential effect on the primary psychological outcome (ESE; group × time interaction: p = 0.108). These findings support assessment-informed and feedback-driven physiotherapy strategies as a promising adjunct to exercise programs in older adults, with potential implications for optimizing functional outcomes within applied kinesiology and rehabilitation contexts. Full article

Insufficient physical activity (IPA) among university students remains an important public health concern associated with adverse health outcomes. Although barriers to physical activity (PA) are widely documented, less is known about how these barriers cluster within different university contexts and student subgroups. This study examined hierarchical configurations of perceived barriers associated with IPA in a multicountry university sample. A cross-sectional analytical study was conducted with 686 undergraduate students (60.8% women; mean age = 22.4 ± 5.1 years) from Chile, Mexico, Spain, and Italy. Perceived barriers were assessed using the BBAQ-21 and self-reported PA using the IPAQ–Short Form. CART and Exhaustive CHAID decision-tree models were applied to identify subgroup configurations based on cumulative barrier burden. Country-based subsamples and self-reported post-pandemic PA emerged as the principal segmentation variables. The Mexican subsample showed the highest barrier burden. Students reporting increased PA generally clustered within lower-barrier configurations, whereas stable or reduced PA tended to coincide with greater perceived barrier burden. Perceived barriers formed differentiated and context-dependent configurations associated with PA patterns. These findings provide exploratory insight into how barriers cluster within university populations and support more context-aware interpretation of PA-related constraints within higher education settings. Full article

We develop SAFIRE (Self-Attention Fuzzy-Inspired Rule Estimator), a differentiable fuzzy-inspired rule-scoring surrogate for binary medical tabular classification coupling multi-head self-attention, Gaussian membership functions, and Hard Concrete gates for continuous rule scoring. We position SAFIRE as a smooth surrogate of the discrete $L_0$-regularised rule-selection problem and establish five mathematical results and one complexity remark: (1) the relaxed objective is differentiable almost everywhere under positive Gaussian widths (enforced by a Softplus reparameterisation) and fixed batch-normalisation statistics; (2) the deterministic-inference active threshold is strictly stricter than the expected-nonzero training threshold, identifying Hard Concrete gates as continuous rule-scoring devices rather than automatic pruning mechanisms; (3) per-sample forward complexity identifies attention and rule layers as the dominant terms; (4) the Softplus–BatchNorm–linear rule operator violates all four triangular-norm axioms—with necessary and sufficient conditions per axiom and a no-finite-parameterisation impossibility result—while a Softplus reparameterisation restores coordinate-wise monotonicity; (5) a margin-based upper bound characterises disagreement between the full classifier and a top-k rule-only surrogate; and (6) the Softplus-reparameterised constrained variant is provably coordinate-wise monotone with explicit asymptotic regimes. Evaluated on four University of California, Irvine (UCI), medical binary tabular benchmarks under repeated stratified cross-validation, SAFIRE-Prog is statistically competitive with strong interpretable, modern, and gradient-boosting baselines, with one Bonferroni-significant gain over RuleFit on the Diabetic Retinopathy Debrecen corpus. The 48-configuration Hard Concrete sweep, constrained-variant comparison, and a top-k fidelity analysis (per-fold range 0.73–0.95) provide quantitative companion measurements for the mathematical framework. A supplementary large-scale hospital electronic health record (EHR) benchmark (Diabetes 130-US Hospitals, $n=101,766$) shows the rule-scoring mechanism scales to ∼${10}^5$ records and, under severe class imbalance, statistically matches gradient boosting on accuracy while significantly exceeding it on macro-F1. The results offer a mathematically auditable pathway towards interpretable, auditable rule scoring for medical tabular classification, with rule signatures defined in a projected latent space rather than over raw clinical variables. Full article

Background: Hematopoietic stem cell (HSC) ex vivo culture causes severe loss of repopulation and regenerative capacity without compromising multilineage differentiation, which greatly limits the efficacy of HSC transplantation. The molecular mechanisms underlying culture-triggered HSC dysfunction remain poorly understood. Methods: Human CD34⁺ HSCs were cultured ex vivo for 96 h to establish a culture-induced HSC dysfunction model. Single-cell RNA sequencing was applied to screen key regulatory genes. TSC22D3 function was verified via overexpression assays, and immunodeficient mice were used to assess HSC engraftment. Transcriptomic profiling were performed to explore downstream molecular mechanisms. Results: Ex vivo culture induced G0 quiescence exit, elevated early apoptosis and impaired in vivo repopulation in human CD34⁺ HSCs. TSC22D3 was highly enriched in freshly isolated quiescent HSCs and gradually downregulated during culture. TSC22D3 overexpression restored HSC G0 arrest and improved hematopoietic engraftment in mice. Mechanically, TSC22D3 upregulated HSC self-renewal genes, suppressed cell cycle-related genes (CDK2/4), and activated the P53-P21-P27 pathway. Conclusions: This study demonstrates that TSC22D3 preserves HSC function during ex vivo culture by maintaining stem cell quiescence and restricting excessive proliferation. These findings reveal a novel transcriptional mechanism regulating HSC homeostasis and provide a promising target for improving functional HSC ex vivo expansion for clinical transplantation. Full article

Microplastics (MPs) are an emerging environmental pollutant, and their contamination has emerged as a pressing global environmental concern. Developmental processes exhibit heightened sensitivity to environmental perturbations, and MP exposure can induce long-term adverse effects on organismal health by disrupting fundamental cellular processes. This review focuses on the toxicity and developmental toxicity risks of microplastics investigated using stem cell models. The core section comprehensively summarizes the primary mechanisms through which MP exposure interferes with the biological functions of stem cells, including the impairment of self-renewal capacity and lineage specification, as well as the inhibition of tissue-specific differentiation and organogenesis. Finally, the integration and application of modern toxicological methods in deepening research and improving risk assessment capabilities are synthesized. This review aims to provide a systematic perspective to understand the developmental hazards of MPs and look forward to future risk studies based on stem cell modeling, providing theoretical basis and fundamental support. Full article

Atopic dermatitis (AD) is a chronic immune-mediated inflammatory skin disease characterized by a complex and dynamic interplay between immune dysregulation and epidermal barrier dysfunction. Emerging evidence supports an integrated pathogenic model in which immune activation and barrier impairment form a bidirectional and self-reinforcing axis rather than representing separate processes. This review synthesizes current knowledge on the role of IL-4/IL-13-dependent signaling in regulating keratinocyte lipid metabolism and its impact on epidermal barrier integrity. IL-4/IL-13 signaling via the JAK-STAT pathway, particularly STAT6, contributes to keratinocyte dysfunction, resulting in impaired differentiation and coordinated alterations in lipid metabolism, including fatty acid elongation and ceramide synthesis. These cytokine-driven processes disrupt the organization of the stratum corneum lipid matrix, resulting in increased transepidermal water loss, enhanced skin permeability, and susceptibility to microbial colonization, thereby promoting chronic inflammation. Collectively, these findings support the concept that IL-4/IL-13-mediated dysregulation of keratinocyte lipid metabolism may represent an important immunometabolic mechanism linking type 2 inflammation with secondary barrier dysfunction in atopic dermatitis, thereby contributing to disease persistence. Targeting both immune pathways and epidermal lipid homeostasis may represent an effective strategy to restore barrier function and improve clinical outcomes. Full article

Population aging has become a major demographic process in modern societies, with its course varying considerably across space. This study examined the scale and dynamics of population aging across Poland’s voivodeships in 2015–2024 and identified its regional patterns. The analysis used data from Statistics Poland’s Local Data Bank for 16 voivodeships and included indicators capturing age composition, demographic dependency, and fertility. The analysis was conducted for 16 Polish voivodeships using data from Statistics Poland’s Local Data Bank for 2015–2024 and indicators describing age structure, demographic dependency, and fertility. An analysis of changes in indicator values over time and Kohonen self-organizing maps (SOM) were applied in two model variants, differing in the measure of population aging adopted. To ensure a consistent direction of interpretation, the variables were appropriately transformed and then standardized. The results indicate spatial variation in the level of population aging and differing dynamics of change during the study period. Four regional profiles were identified, reflecting different patterns of indicators describing age structure, demographic burden, and fertility. Kohonen self-organizing maps were used as an exploratory tool to organize voivodeships according to the similarity of their demographic profiles and to describe changes in their profile assignment over time. From the perspective of sustainability, the identified profiles make it possible to capture territorially differentiated demographic conditions that may be relevant to healthcare, long-term care, regional labor markets, social services, and family policy. The results may support sustainable regional development by providing a basis for designing public policy tailored to the specific characteristics of individual voivodeships. Thus, the study links a multidimensional typology of demographic aging with the need for socially sustainable regional policy. The results suggest that SOM can serve as a useful exploratory tool for visualizing and classifying regional demographic aging profiles. Full article

Accurate prediction of contaminant transport and self-purification processes in rivers remains challenging because pollutant dispersion, biochemical reactions, and hydrodynamic conditions interact across multiple spatial scales. This study aims to develop and compare mathematical models for soluble contaminant transport and biodegradable organic matter removal in channels and rivers. Unsteady advection–diffusion–reaction equations were formulated for one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D) transport scenarios and solved through numerical techniques based on the transformation of partial differential equations into systems of ordinary differential or algebraic equations. In parallel, the classical Streeter–Phelps model and an extended formulation incorporating turbulent diffusion were implemented to evaluate organic load degradation and oxygen deficit dynamics. Simulations were performed using a Matlab R2019a-based computational framework under representative hydraulic and reaction conditions obtained from literature data and empirical correlations. The results showed that, under specific conditions, the 3D model reproduced trends comparable to those predicted by the 2D model, while the latter approached the behavior of the 1D formulation. The Streeter–Phelps model predicted an organic load removal efficiency of 97.74%, a purification index of 1.9564, a critical time of 18.43 h, and a critical distance of 6.93 km. These findings provide a useful framework for river water-quality assessment and support future applications involving complex hydrodynamic and pollutant-loading scenarios. Full article

Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation into different cellular lineages, including adipocytes, chondrocytes, and osteocytes. This makes them strong candidates for repairing degenerative joint conditions such as osteoarthritis, in which native cartilage lacks repair capacity. The synovium is an attractive MSC source, with synovial MSCs demonstrating superior chondrogenic and proliferative potential compared to those from bone marrow or adipose tissue. The synovial joint is a heterogeneous environment, and MSCs can be isolated from the membrane, fluid, different histological subtypes of fibrous and adipose synovium, and different anatomical regions of synovium. This systematic review assesses whether MSCs from different synovial sources possess distinct properties. 2312 papers were identified, of which 10 met the inclusion and exclusion criteria and were included in the final review. Significant differences were identified in proliferation characteristics, immunophenotype and differentiation potential. Proximity to vasculature appeared to correlate with proliferation and differentiation potential, and MSCs from the synovial membrane may have superior proliferative characteristics compared to those from synovial fluid. More work is required to fully characterise these differences and understand their underlying molecular bases, but these findings may help inform the choice of MSC source for regenerative therapies. Full article