Search Results (1,682)

This paper proposes a real-time physiological monitoring and biofeedback model based on the console of an indoor cycling bike, applied within high-school physical education. The system uses heart rate (HR) as a control signal for exercise intensity within a closed-loop human–machine system, complemented by the Borg Scale of Perceived Exertion (RPE 6–20) as a subjective validation of the objective feedback loop. The 12-week intervention, conducted with 48 adolescents aged 15–17 years, was evaluated using a battery of six standardized psychomotor tests from EUROFIT and cardiovascular indicators, including 1-min heart rate recovery (HRR). The results show significant improvements in balance, coordination, agility, and autonomic recovery in the experimental group, confirming the effectiveness of the integrated biofeedback system as an accessible biomedical monitoring platform in the school setting. These findings suggest that heart-rate-based biofeedback, delivered through the bicycle console, may represent an accessible and effective strategy for regulating exercise intensity and supporting psychomotor and cardiovascular adaptation in the school environment. Full article

Background/Objectives: Glycyl-L-histidyl-L-lysine (GHK) and its copper(II) complex GHK-Cu have been studied for matrix remodeling, inflammation, redox regulation, angiogenesis, and tissue repair, yet the literature frequently treats GHK-Cu as a single active ingredient despite formulation-dependent variation in coordination state, speciation, stability, pharmacokinetics, and toxicity. We critically evaluate GHK-Cu simultaneously as a bioactive metallopeptide and as a drug-delivery cargo, with explicit separation of apo-GHK, canonical GHK-Cu, GHK-derived copper peptides, and non-GHK copper-peptide systems. Methods: We conducted a structured systematic evidence-mapping review of PubMed/MEDLINE, Europe PMC, major publisher platforms, ClinicalTrials.gov, backward citation chains, and official European Union, U.S., and ICH regulatory sources from database inception through 12 August 2026. Biological evidence level and chemical/formulation quality were graded independently using an author-defined two-axis framework. Delivery studies were extracted against a fixed matrix comprising formulation, claimed loading, molar copper occupancy, labile copper, species-resolved release, factorial controls, stability/manufacturability, and objective outcome. Quantitative pooling was not performed because active-entity definitions, formulations, doses, models, comparators, and endpoints were not quantitatively commensurable. Results: Preclinical data consistently support effects on matrix remodeling, epithelial repair, inflammatory/redox regulation, and angiogenesis, but the clinical evidence remains sparse and does not meet contemporary active-entity quality standards. Historical cosmetic reports are small or incompletely characterized; a 13-participant post-CO2-laser study was negative on objective endpoints, whereas a 2026 18-participant split-face eyebrow study reported positive cosmetic hair outcomes but did not define GHK-Cu speciation or local exposure. The ongoing phase 2 acute-wound study NCT07437586 remains recruiting and has no efficacy results; its registration cannot be used as evidence of clinical translation. Across delivery studies, particle size, polydispersity, encapsulation efficiency, total peptide/copper content, and bulk release are often reported, whereas molar occupancy, labile copper, and release of intact GHK-Cu versus apo-GHK/free copper are usually not resolved. Conclusions: Translation is limited less by biological plausibility than by pharmaceutical definition and evidence attribution. We define the “active pharmaceutical entity” operationally as the reproducible chemical state intended to mediate pharmacology at administration, not as an established regulatory designation or a claim that one immutable molecular species persists in biological fluids. We further propose, explicitly as an author-derived development framework rather than a consensus standard, a control strategy based on molar occupancy, route-specific labile copper specifications, orthogonal speciation, mechanism-linked potency, species-resolved release, factorial controls, route-specific safety decision thresholds, ICH-aligned stability, and GMP-scalable manufacture. Until these requirements are met and controlled clinical efficacy is demonstrated, GHK-Cu should be regarded as a promising but unproven therapeutic cargo rather than a clinically validated regenerative drug. Full article

This research evaluates the compounding, processing, and performance of a sustainable biocomposite filament for additive manufacturing, utilizing poly(lactic acid) (PLA) filled with raw pine cone (Pinus sylvestris) flour at 5 and 10 wt% filler contents. Tensile properties, surface topography, and processability of extruded filaments and 3D-printed specimens were systematically investigated. Incorporating pine cone flour yielded unprinted filament tensile strengths of 21.06 MPa (5 wt%) and 18.51 MPa (10 wt%), while 3D-printed specimens retained ~85% (5 wt%) and ~79% (10 wt%) of their corresponding unprinted composite filament tensile strength. This reduction in strength is hypothesized to stem from weak interfacial adhesion and polarity mismatch between the hydrophobic PLA and hydrophilic biomass, which is suggested to promote micro-void formation. Topographical analysis revealed surface anisotropy: top surface roughness increased ($Ra$ up to 9.85 µm; $Sz$ up to 100.2 µm), likely influenced by melt viscosity, whereas lateral roughness decreased ($Ra$ down to 3.10 µm; $Sz$ down to 45.4 µm), potentially associated with suppressed die swell. Printed ductility increased (>8%), a trend attributed to potential inter-layer re-melting during deposition. To overcome limited interfacial bonding, future work should incorporate coupling agents or chemical surface modifications. Overall, among the evaluated formulations, the composite with 5 wt% filler demonstrates a favorable balance of processability, mechanical integrity, and surface quality, showing high potential for non-load-bearing prototypes, indoor decorative elements, and light-duty packaging. Full article

Java middleware may expose Java Management Extensions (JMX) through Jolokia’s Hypertext Transfer Protocol (HTTP) bridge. In affected ActiveMQ deployments, reachable Log4j 2 configuration managed beans (MBeans) become write capabilities and, with compatible triggers, enable remote code execution (RCE). We ask: in a specified product/version state, which writes and triggers compose into RCE, and which operational guard first fails or remains unresolved? We synthesize two published case studies into an evidence-coded method. Four write and four trigger classes recover four observed chains, isolate one model-implied pairing, and reject dependency-level candidates through failed or unresolved guards. It distinguishes ActiveMQ paths from documentation-limited Apache James, WildFly, Apache Karaf, and Red Hat AMQ cases. Egress filtering and static-file ownership do not stop every observed chain. Observed (O), derived (D), and model-implied (H) labels separate findings from hypotheses. The contribution is a falsifiable, product- and version-scoped management-plane instrument, not a new attack-stage sequence. Full article

The transition from early non-standalone 5G deployments to 5G Standalone and, more recently, 5G-Advanced has turned mobile networks into flexible, programmable infrastructures capable of supporting private, industrial, and research-oriented deployments for the development of beyond-5G applications and architectures. Evaluating these networks’ capabilities, however, remains challenging because commercial platforms often provide limited access to internal interfaces, radio parameters, and network measurements. This paper presents an open-source private 5G SA testbed for beyond-5G application validations built using Open5GS, srsRAN, Ettus USRP N310 software-defined radio, programmable SIM cards, and commercial 5G customer-premise equipment. The platform is deployed in a semi-anechoic chamber. End-to-end operation is validated through subscriber registration, authentication, PDU session establishment, and external data connectivity. The performance of the implemented 5G network is evaluated using throughput, block error rate, modulation and coding scheme, and gNB trace logs. Unlike previous open-source 5G testbeds that primarily use RF waveguides, individual network components, or a limited set of radio configurations, the proposed platform combines COTS SIM-based UE operation with a controlled over-the-air evaluation of FDD/TDD and multiple antenna configurations and correlates application-level throughput with internal gNB radio metrics. For FDD downlink operation, the average throughput increased by approximately 74% from 1 × 1 to 2 × 2 and by a further 57% from 2 × 2 to 4 × 4, although the additional peak-throughput gain from 2 × 2 to 4 × 4 remained limited. The platform provides a reproducible environment for validating beyond-5G mechanisms, comparing network configurations, and studying the behavior of future open-source 5G SA systems under controlled conditions. Full article

Background: Relapse and opportunistic viral infections remain major causes of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adoptive transfer of natural killer (NK) cells is a promising strategy to enhance post-transplant immune reconstitution. Adaptive NKG2C+ NK cells exhibit enhanced cytotoxicity and persistence, but the influence of baseline donor immunophenotype on GMP manufacturing has not been systematically investigated. We evaluated whether donor NKG2A/NKG2C immunophenotypes are associated with successful manufacture of adaptive NK-cell products. Methods: Eighty-three healthy donors from the ReDoCel registry underwent immunophenotypic characterization of circulating NK-cell subsets by multiparametric flow cytometry. Donors were stratified by unsupervised hierarchical clustering according to NKG2A/NKG2C expression. Representative donors from NKG2C- and NKG2A-dominant clusters underwent feeder-free GMP-compliant expansion using the automated CliniMACS Prodigy® platform (Miltenyi Biotec, Bergisch Gladbach, Germany). Expanded products were evaluated for manufacturing efficiency, immunophenotype, cytotoxic function, and post-thaw stability. Results: Baseline NKG2C frequencies showed marked inter-donor variability, allowing identification of four immunophenotypic clusters. Only the NKG2C-dominant donor achieved successful GMP manufacturing, exceeding the predefined expansion threshold while maintaining high viability and purity. Both NKG2A-dominant donors showed limited proliferative capacity under identical manufacturing conditions. Expanded NK cells acquired an activated phenotype characterized by increased expression of DNAM-1, NKG2D, NKp30, NKp46, and TIM-3 while preserving mature differentiation and KIR expression. Functional analyses demonstrated potent degranulation against leukemia targets with minimal autoreactivity, resulting in a predominantly cytotoxic effector profile. The successfully expanded product maintained viability, phenotype, and function after long-term cryopreservation. Conclusions: This proof-of-concept study suggests that baseline donor NKG2A/NKG2C immunophenotype may influence GMP manufacturing of adaptive NK-cell products. These findings support prospective evaluation of donor immunophenotyping as a biomarker for donor qualification and manufacturing optimization to facilitate standardized off-the-shelf adaptive NK-cell therapies after allo-HSCT. Full article

Background: Combat sports require athletes to repeatedly perform explosive actions under conditions of fatigue, demanding high levels of neuromuscular coordination, reactive agility, and intermittent effort capacity. This study examined changes in biomechanical and neuromuscular performance over a 15-week period during which competitive Sambo athletes completed a CrossFit-based functional training program alongside their regular sport-specific training. Methods: Forty male Sambo athletes (22.4 ± 2.6 years) completed a longitudinal repeated-measures intervention consisting of three weekly CrossFit-based sessions integrated into regular sport-specific training. The program was periodized across four progressive mesocycles emphasizing functional strength, explosive power, reactive agility, and fatigue resistance. Pre- and post-intervention assessments included upper- and lower-limb reaction speed, vertical jump height, repeated jump endurance, reactive agility, grip endurance, body-weight squat performance, Romanian deadlift repetitions, and the Special Judo Fitness Test (SJFT). Statistical analyses included paired-samples t-tests or Wilcoxon signed-rank tests with Benjamini–Hochberg false discovery rate correction (α = 0.05). Results: Significant post-intervention improvements were observed in most performance variables. Upper- and lower-limb reaction performance improved by 22.9% and 9.7%, respectively (p < 0.001), while vertical jump height increased by 11.4% and repeated jump endurance by 16.6% (p < 0.001). Reactive agility time decreased by 6.6% (p < 0.001), indicating faster cognitive-motor responsiveness. Functional strength improved substantially, with increases of 43.7% in body-weight squat performance and 71.9% in Romanian deadlift repetitions (p ≤ 0.001). Grip endurance improved by 6.3% (p = 0.007), whereas maximal handgrip strength showed no significant changes. The SJFT index decreased by 5.0% (p < 0.001), reflecting enhanced intermittent effort efficiency and fatigue tolerance. Large effect sizes were identified for upper-limb reaction speed (d = 1.42), explosive endurance (d = 1.46), and reactive agility (d = 0.96). Conclusions: Over the 15-week study period, participation in a CrossFit-based functional training program integrated into regular Sambo practice was associated with improvements in several biomechanical and neuromuscular performance outcomes, including reaction performance, explosive power, agility, muscular endurance, and sport-specific work capacity. However, because the study did not include a control group, these changes cannot be attributed exclusively to the CrossFit-based intervention. Controlled studies are required to distinguish intervention-specific effects from seasonal training adaptations, continued sport-specific practice, and test familiarization. Full article

This research investigates the relationships between climate change, biodiversity and nature-based tourism in the Danube Delta Biosphere Reserve (DDBR), integrating the behavioural perspective of Generation Z into an adaptive management framework. This study uses a mixed methodological approach, combining time series analysis of the period 2000–2025 with behavioural modelling, based on the primary data study. The analysis of this study includes indicators for the four complementary dimensions, namely: the climate dimension, the biodiversity dimension, the tourism activity dimension, and the behavioural dimension. The relationships among climate variables, biodiversity and tourism are investigated using AutoRegressive Distributed Lag (ARDL) models, while the behavioural component is analysed using the Partial Least Squares Structural Equation Modelling (PLS-SEM) method, applied to a sample of 419 respondents. The results highlight the existence of relationships among climate change, biodiversity and tourist activity, confirming the role of biodiversity as a central element of the attractiveness of nature-based tourism. At the same time, concern for biodiversity significantly influences the intention to visit natural destinations among Generation Z people. Therefore, our research contributes to the literature regarding socio-ecological systems and provides recommendations for the development of adaptive management aimed at biodiversity conservation and strengthening the resilience of sustainable tourism in the Danube Delta. Full article

Breast cancer (BRCA) possesses prominent molecular heterogeneity, where aberrant expression of genes annotated to asparagine metabolism networks drives malignant progression and therapeutic resistance. However, systematic construction of prognostic signatures from a holistic asparagine metabolic pathway perspective remains scarce, limiting the clinical translation of metabolic insights into prognostic tools. We integrated TCGA and GEO BRCA transcriptomic datasets to screen asparagine metabolism-related differentially expressed genes and build a prognostic model. Six biomarkers, SLC35A2, SRD5A2, NT5E, CEL, IFNG and CNR1, were selected via univariate Cox, LASSO and multivariate Cox regression. SRD5A2 and IFNG were enriched in low-risk patients, while the other four genes were upregulated in high-risk subgroups. This signature reliably stratifies patient prognosis, with risk scores correlating strongly with pathway activity, immune infiltration, immune checkpoints, mutation landscapes and drug responsiveness. Bioinformatic results were validated via TCGA cohort analysis, in vitro cellular assays and Western blot. Two in vivo models were established: 4T1 xenografts in 6-week-old BALB/c mice and DMBA/hormone-induced spontaneous breast tumors in 8-week-old SD rats. Tumors were generated by cell injection or DMBA gavage plus cyclic hormone treatment, and tissue sections were processed for immunohistochemistry. Consistent differential expression of the six core genes was validated across all in vitro and in vivo systems. In conclusion, this asparagine metabolism-associated signature offers candidate biomarkers for personalized prognosis and provides preclinical evidence for metabolism-targeted BRCA therapy. Full article

Background/Objectives: Artificial intelligence may improve obstetric risk stratification by identifying clinically meaningful patterns that are not captured by single-outcome prediction models. This study evaluated whether unsupervised machine learning applied to first-trimester maternal, biophysical, and biochemical data could identify phenotypes associated with adverse obstetric outcomes. Methods: We analyzed 1583 first-trimester records that were ambispectively collected including maternal characteristics, obstetric history, mean arterial pressure, uterine artery pulsatility index, nuchal translucency, and PAPP-A. Principal component analysis followed by k-means clustering was used to derive AI phenotypes. Associations were tested for hypertensive, metabolic, delivery, neonatal, and actionable obstetric outcomes. Robustness of the clustering solution and phenotype–outcome associations was assessed using inverse probability weighting, false discovery rate correction, adverse-event burden scoring, cross-algorithm agreement analyses, and multiple sensitivity analyses. Results: Four clinically interpretable phenotypes were identified. Phenotype 4 represented a cardiometabolic–vascular subgroup that showed the greatest enrichment for adverse obstetric outcomes. It had higher rates of maternal metabolic or hypertensive complications (52.4%; RR 4.31) and clinically actionable adverse pregnancy outcomes (57.1%; RR 2.31). These associations remained significant after false discovery rate correction and were consistent in inverse probability weighting analyses. Phenotype 4 also had the highest cumulative adverse-event burden score (1.29 versus 0.35–0.47). Exploratory analyses demonstrated high specificity (97.2%) but limited sensitivity for clinically actionable adverse pregnancy outcomes. Incremental discrimination over conventional predictors was observed only for selected secondary outcomes, including early preterm birth and low Apgar score. Conclusions: Unsupervised AI phenotyping identified a cardiometabolic–vascular pregnancy subgroup associated with increased obstetric morbidity. Full article

This study analyzes land use dynamics in Fălticeni Municipality over four decades (1985–2025), examining the influence of major political, socio-economic, and demographic changes on urban development. The transition from a centrally planned economy to a market economy, Romania’s democratic transformation and European integration, together with migration and population dynamics, have driven largely unregulated urban expansion at the expense of agricultural land and natural landscapes. Recent urban growth has also extended into areas with varying geomorphological vulnerability, increasing exposure to landslide hazards, while the city continues to face challenges related to abandoned industrial areas and insufficient forested land and green spaces. By integrating land use change analysis with physical vulnerability indicators, this study highlights the need for risk-informed and sustainable urban planning in medium-sized cities. It proposes a planning framework based on ecological zoning, controlled urban expansion on suitable terrain, brownfield redevelopment, the establishment of peri-urban forests, and the implementation of essential infrastructure supported by comprehensive geomorphological susceptibility assessments. The proposed approach provides practical guidance for enhancing urban resilience and can be replicated in other cities facing similar environmental and development challenges. Full article

Background: Emergency departments (EDs) operate under severe time pressure, diagnostic uncertainty, and resource constraints, making the consistent application of clinical protocols challenging. This scoping review aimed to map the barriers to protocol adherence and the strategies reported to support implementation in emergency care. Methods: PubMed/MEDLINE, Scopus, and Web of Science were searched for publications from January 2000 to June 2026. Following predefined eligibility criteria, 58 publications were included and charted according to clinician-related, guideline-related, patient-related, and organizational determinants, and we reported the implementation strategies. No formal design-specific risk-of-bias or certainty-of-evidence assessment was performed; therefore, the synthesis was intended to map the available evidence rather than establish the comparative effectiveness. Results: Commonly reported barriers included limited guideline knowledge and clinical experience, cognitive overload and occupational fatigue, poor guideline usability and workflow compatibility, patient communication difficulties and clinical complexity, overcrowding, staffing shortages, and limited organizational support. The reported strategies included education and simulation, audit and feedback, clinical decision support, workflow redesign, multidisciplinary collaboration, and leadership engagement. However, the heterogeneity in study designs, clinical settings, definitions of adherence, and reported outcomes precluded ranking these strategies or determining whether particular combinations were superior. Conclusions: Protocol adherence in EDs appears to be shaped by interacting clinician-related, guideline-related, patient-related, and organizational factors. The identified strategies may support implementation, but their relative and comparative effectiveness remains uncertain. Digital health and artificial intelligence should be considered priorities for prospective evaluation rather than established solutions. Full article

As road transport is a major contributor to anthropogenic CO₂ emissions, the importance of sustainable mobility planning and fleet management becomes very clear. Therefore, this article proposes a physics-based mathematical framework for dynamic estimation of CO₂ emissions. The proposed framework is very flexible and enables CO₂ assessment for different types of vehicles (i.e., combustion engine and electric vehicles), traffic and operating conditions. The proposed software prototype is evaluated through representative urban and peri-urban simulation scenarios. These scenarios involve conventional public transport, private vehicles, and demand-responsive ride-hailing services. The simulation results show that vehicle occupancy is one of the main factors impacting specific CO₂ emissions. In this context, in low-passenger-demand and dispersed travel conditions, demand-responsive mobility services can achieve lower emissions per passenger-kilometer than conventional public transport. In contrast, when occupancy levels are sufficiently high, public transport remains the most efficient option. These results indicate that there is no universally optimal transport mode and that emission efficiency is the result of a matching between vehicle capacity and passenger demand. Therefore, the proposed framework delivers a transparent and practical decision-support tool for transport mobility services. Full article

The accurate prediction of anchor penetration depth is critical for assessing the potential risk of emergency anchoring to subsea infrastructure. In this study, a three-dimensional coupled Eulerian–Lagrangian (CEL) model was developed to investigate the dynamic penetration behavior of a Hall anchor in homogeneous clay and soft-over-stiff layered clay. The model was validated against published experimental results and showed good agreement with measured penetration depths. For homogeneous clay, an energy-based prediction model was proposed by introducing a resistance modification coefficient, and the relationships between this coefficient and soil strength parameters were established from CEL simulations. The proposed model accurately predicted the penetration process and final penetration depth, with errors generally within ±5%. For layered clay, the evolution of the resistance coefficient revealed three penetration stages: initial impact energy dissipation, penetration through the upper soft layer with increasing resistance, and penetration of the lower hard layer with approximately constant resistance. An energy loss coefficient and layer-dependent resistance formulations were subsequently introduced to develop a simplified prediction model. Comparisons with CEL results demonstrated that the proposed model effectively predicts anchor penetration behavior under various soil strength conditions and impact velocities, with most errors within 10%. The proposed approach provides a computationally efficient tool, reducing the computational cost from hours of CEL simulation to seconds of engineering calculation, for the rapid assessment of penetration depth for Hall anchors with similar geometric characteristics under soft-over-stiff layered clay seabed conditions. Full article

Antimicrobial resistance is a major global health challenge that has created an urgent need for new antibacterial agents capable of overcoming emerging resistance mechanisms. Among nitrogen-containing heterocycles, pyrrolidine has been widely investigated in medicinal chemistry due to its structural versatility, favourable physicochemical properties, and ability to enhance interactions with biological targets. This review provides a comprehensive and critical overview of pyrrolidine-based compounds investigated for antibacterial applications. Relevant studies describing clinically approved antibiotics, natural products, synthetic derivatives, hybrid molecules, and antibacterial adjuvants containing a pyrrolidine scaffold were collected, classified, and critically evaluated, with particular emphasis on structural features, antibacterial activity, and structure–activity relationships. The reviewed evidence demonstrates that the pyrrolidine moiety is present in several antibacterial drug classes, including carbapenems, cephalosporins, fluoroquinolones, lincosamides, streptogramins, and tetracyclines, where it contributes to improved target affinity, antibacterial potency, and pharmacokinetic behaviour. Numerous recently reported pyrrolidine derivatives have shown promising activity against clinically relevant, multidrug-resistant bacterial pathogens. The pyrrolidine scaffold is valuable for the design of next-generation antibacterial agents and resistance-modifying compounds, though further in vivo studies and pharmacological evaluation are required to support their clinical development. Full article