Search Results (23,092)

Objective: The goal was to investigate the relationship between methodological adherence and clinical outcomes in Progressive Resistance Training (PRT) for Parkinson’s Disease (PD), specifically identifying why findings of “superiority” over active controls remain inconsistent. Methods: This umbrella review utilized a multi-stage process to identify a sample of the primary literature for methodological analysis. An initial search identified 38 systematic reviews published within the specified timeframe. From the reference lists of these reviews, a subset of 34 primary clinical studies was purposefully selected. Inclusion was prioritized for studies providing comprehensive methodological data on PRT protocols and standardized clinical outcomes. Interventions were evaluated using a three-tiered framework: (1) training protocol with specifications of Frequency, Intensity, Time, Type, Volume, and Progression (FITT-VP) (General Exercise), (2) FITT-VP integrated with the American College of Sports Medicine (ACSM) Supplementary Guidelines (Integrated Guidelines), and (3) principles of progression (mechanistic growth). Studies were categorized by control type (active (e.g., aerobic or balance), n = 26; passive (e.g., standard care or no exercise), n = 8). Results: In trials that compared PRT with an active control group, PRT achieved clinical superiority in 57% (n = 15) of trials and 46% (n = 12) when focusing on trials with an effect on specific functional or balance outcomes. Among these successful interventions, 75% maintained high adherence (≥70%) to the Integrated Guidelines, and 58% maintained high adherence to the principles of progression. In the 53% (n = 14) of studies where PRT was found non-superior (equivalent or inferior in functional or balance outcomes) to an active control, 0% met the high adherence threshold for progression. While general FITT-VP compliance remained high (78%), the failure to implement systematic load, specificity, and variation served as a definitive barrier to competitive superiority. In the 100% of studies where PRT outperformed passive controls, high progression was present in 57% of cases. This may suggest that while a baseline resistance stimulus outperforms inactivity, it is fundamentally insufficient to outperform other active clinical therapies. Conclusions: This umbrella review indicates that adherence to the principles of progression may be an important factor influencing the clinical outcomes of PRT in individuals with PD. The variability observed in the current literature suggests that inconsistent application of established exercise frameworks—rather than the failure of the modality itself—could be a contributing element to the reported “inconclusiveness.” To potentially enhance functional outcomes and the comparative effectiveness of PRT, future research should consider prioritizing structured adherence to FITT-VP, Integrated Guidelines, and progression-based frameworks. Establishing a 70% adherence threshold is proposed as a potential benchmark to improve protocol consistency and support rehabilitation efficacy in this population. Full article

Background: Nasal valve dysfunction (NVD) is a common yet underrecognized cause of nasal airway obstruction, with a significant impact on quality of life. Despite its clinical relevance, no universally accepted diagnostic standard exists, and optimal management remains debated. Multiple diagnostic tools and surgical or minimally invasive treatments have been proposed. This systematic review and meta-analysis aimed to evaluate current evidence regarding diagnostic approaches and treatment outcomes in NVD. Methods: A systematic search of PubMed/MEDLINE, Embase, and Cochrane Library was performed for studies published between January 1990 and January 2026, in accordance with PRISMA 2020 guidelines. Randomized controlled trials, non-randomized comparative studies, cohort studies, and case series (≥10 patients) assessing diagnostic methods or therapeutic interventions for NVD were included. Diagnostic data were synthesized narratively. The primary surgical outcome was change in the Nasal Obstruction Symptom Evaluation (NOSE) score. Risk of bias was assessed using RoB 2, ROBINS-I, and QUADAS-2 tools. Results: Seventy-two primary clinical studies were included (15 diagnostic, 57 treatment-focused). Objective airflow measurements, particularly rhinomanometry and peak nasal inspiratory flow, showed greater reliability than isolated clinical maneuvers. Imaging modalities provided anatomical detail but correlated inconsistently with symptoms. Meta-analysis of 12 studies (n = 1210 patients) suggests that both traditional surgical and minimally invasive interventions can substantially improve nasal breathing, with mean NOSE score reductions of 40–55 points, though heterogeneity precludes direct comparison of their relative effectiveness. Conclusions: Diagnosis of NVD requires a multimodal approach combining clinical assessment, validated symptom scores, and selective objective testing. Surgical and minimally invasive treatments provide substantial symptom improvement when appropriately indicated. Evidence is constrained by the predominance of observational data, emphasizing the need for standardized diagnostics and robust comparative trials. Full article

During drilling in stress-sensitive fractured formations, fracture aperture dynamically evolves with wellbore pressure fluctuations. The sealing layer often undergoes repeated cycles of sealing, destabilization, and re-sealing. Formulation selection based on a single metric or empirical selection cannot simultaneously satisfy multiple objectives, including pressure-bearing capacity, loss control, and dynamic adaptability. This study proposes an entropy-weighted TOPSIS and grey relational analysis method to optimize lost circulation formulations for stress-sensitive fractured formations. A hierarchical evaluation system is established with four criteria layers and eight indicator metrics. A baseline formulation framework is determined through static fracture sealing tests. Experimental data for different elastic-material systems are obtained using a self-developed DTDL dynamic fracture plugging apparatus. Indicator weights are objectively determined using the entropy weight method. A Grey–TOPSIS model is applied to compute grey relational closeness to the positive and negative ideal solutions, enabling formulation ranking and optimal scheme identification. A case study shows that the ternary elastic formulation with Rubber:Graphite:Net = 3:2:1 achieves the highest grey relational closeness and delivers the best overall sealing performance. The ranking remains unchanged when the distinguishing coefficient ρ varies from 0.1 to 0.9, confirming the robustness and feasibility of the proposed method. Compared with entropy-weighted TOPSIS and classical TOPSIS, the proposed method provides a more integrated treatment of the multi-metric data and better aligns the evaluation with the underlying sealing behavior in stress-sensitive fractures. Therefore, it leads to more reliable and comprehensive evaluation results for formulation selection. The results demonstrate that the proposed model provides reliable support and a methodological basis for formulation optimization in dynamic fracture loss control. Full article

Background/Objectives: The COVID-19 pandemic intensified concerns regarding the resilience and financing architecture of mental health services, yet it remains unclear whether crisis-induced adjustments fundamentally altered hospital case-mix complexity or merely exposed pre-existing structural configurations. This study examines the relationship between financing regimes and case-mix complexity in psychiatric hospitals in Romania, a Central and Eastern European health system characterized by mixed financing arrangements and pronounced interregional heterogeneity. Methods: Using administrative data comprising 752 hospital section–year observations (2019–2024), we identify structural financing–organization regimes through a two-step clustering procedure (hierarchical Ward method followed by K-means refinement) based on revenue composition, expenditure allocation, workforce structure, and operational pressure indicators. Results: Three distinct regimes emerge, reflecting persistent institutional configurations rather than temporary crisis-induced groupings. Chi-square tests confirm that regime membership is statistically independent of pandemic timing. A multivariate regression model controlling for financing composition and expenditure structure shows that structural variables (particularly the share of contract-based revenues and the allocation of expenditures) exert systematic and economically meaningful effects on the case-mix index (CMI). Pandemic and post-pandemic indicators do not retain robust explanatory power once structural determinants are accounted for. Regional robustness analyses further demonstrate that financing architecture consistently outweighs temporal shock effects in explaining territorial variation in clinical complexity. Conclusions: The findings suggest that psychiatric hospital case-mix dynamics are structurally embedded within differentiated financing regimes whose influence persists beyond crisis periods. By integrating regime identification with outcome modeling in a Central and Eastern European context, this study contributes to the international literature on health system resilience and highlights the primacy of institutional financing architecture over episodic shock effects in shaping hospital complexity. Full article

Molecular spin-crossover (SCO) compounds constitute prototypical systems exhibiting first-order phase transitions. These transitions involve an abrupt switch between two well-defined states with distinctly different magnetic, optical, and vibrational properties. One state is diamagnetic (low-spin), while the other is paramagnetic (high-spin). Upon heating, the transition occurs at a characteristic temperature, T_up. Upon cooling, it takes place at a lower temperature, T_down < T_up, thereby giving rise to thermal hysteresis. Accordingly, each SCO compound is defined by a distinct pair of transition temperatures, T_up and T_down. The investigation of these molecular solids is of great importance, both for elucidating first-order phase transitions—including the potential emergence of re-entrant phases—and for their broad range of prospective applications. The critical temperatures T_up and T_down are pivotal in defining their practical utility. We present a strategy to modify and tune the transition temperatures of spin-crossover (SCO) compounds to suit different applications. The approach combines a given SCO material with layers of a second SCO system, enabling precise control of the characteristic temperatures of the resulting heterostructure. We illustrate this method with three case studies that span the 100 K–400 K temperature range. All simulations were performed using Monte Carlo methods within the Metropolis algorithm framework. Full article

In this study, we analyze the solution characteristics and dynamics of a variable-order fractional (V-OF) Arneodo system using the Liouville–Caputo fractional operator with variable order. The V-OF operator is used to describe the time-dependent memory effect in the system, which leads to more complex and diverse dynamics compared to integer-order systems. In this work, numerical simulations are performed to observe the effect of the order functions on the dynamic behaviors of the system. In addition, the phase portraits, time series graphs, and three-dimensional diagrams are used to analyze the dynamic behaviors and different types of oscillations present in the system. Furthermore, the bifurcations, chaotic behaviors, and stability of the system with variable orders are studied, and it is found that the system has more complex dynamics compared to the integer-order case. In this case, the Lyapunov exponents indicate that the system under investigation is sensitive to the initial conditions, and the memory effect can control the chaotic oscillation depending on the order of the functions. Full article

Background: Pancreatic cancer is an aggressive malignancy with poor survival. Most patients are diagnosed at advanced or metastatic stages because early disease is often asymptomatic and effective screening tools are lacking. We evaluated a three-marker model comprising serum CA19-9 in combination with the plasma proteins ITIH3 and CEACAM1 for pancreatic ductal adenocarcinoma (PDAC) detection. Methods: Matched plasma and serum samples were collected from 649 participants (250 PDAC cases and 399 controls). Plasma proteins were enriched using high-surface area magnetic covalent organic framework (COF) polymers. Serum CA19-9 was measured using the Tosoh Bioscience immunoassay. The marker panel was trained using a radial-based SVM with repeated 10-fold cross-validation using a set-aside training sample set. The derived model along with a fixed cutoff corresponding to 95% sensitivity in training samples were independently validated using a blinded sample set. Results: In the independent blinded validation, the combined panel of serum CA19-9 with plasma ITIH3 and CEACAM1 achieved an AUC of 0.917 indicating that the three-marker panel maintained strong performance in distinguishing PDAC from controls. At the prefixed threshold, the three-marker panel had a specificity of 53.3% (95% CI: 46.8–59.7%), significantly outperforming CA19-9 alone at 14.5% (95% CI: 10.4–19.7%). Conclusions: In independently blinded validation, combining plasma ITIH3 and CEACAM1 with serum CA19-9 substantially improved diagnostic performance for PDAC, achieving high specificity while maintaining 95% sensitivity compared with serum CA19-9 alone. These findings support further validation of this three-marker panel as a potential PDAC monitoring and detection approach in larger, multicenter studies. Full article

Despite the extensive literature on microalgal production, most studies focus on controlled laboratory-scale systems, resulting in a critical lack of confidence at industrial scale. This is further compounded by the frequently observed inconsistencies, with only modest increases achieved in operational scale. This work demonstrates the design, construction, and operation of a commercial-scale tubular photobioreactor and associated equipment for the production of algae using CO₂ derived from an industrial nickel refinery. The reactor was demonstrated by growing the species Nannochloropsis gaditana. Biomass concentrations of 1.0 to 1.3 g L⁻¹ were achieved with a productivity of 0.11 g L⁻¹ d⁻¹. Extrapolation to a 300-day production year showed that the reactor was capable of producing 541.2 kg algae and sequestering around 1 tonne of CO₂. A technoeconomic assessment showed that the total plant CAPEX was £583,905 and the OPEX was £98,196. Sales of algae alone showed poor economic performance. However, economic favourability is observed for species that contain phycocyanin pigment and yield a positive net present value within 4 to 7 years based on recovery yield. This work effectively provides reliable process data developed at scale that can be used to formulate business cases for further scale-up and expansion of algal production systems. This moves the technology a step closer to full-scale realisation and the potential for a net-zero, sustainable future. Full article

Finite-volume gravity currents frequently encounter bottom obstacles, particularly in underwater environments such as lakes and oceans. However, how obstacle–current interactions reorganize Lagrangian transport pathways and ultimately determine the fate of fluid elements over the full current life cycle remains unclear. Using large-eddy simulations, we focus on a low-volume lock-exchange gravity current impinging on an isolated two-dimensional triangular obstacle. Fluid-element trajectories are tracked from collapse through propagation, obstacle interaction, and final dilution and decay, and are classified using K-means clustering into five transport modes linked to characteristic flow structures. We find that increasing obstacle slenderness strengthens upstream reflection and reduces downstream overflow, thereby shifting the fate of tracer particles from downstream delivery toward upstream retention. In addition, the obstacle standoff distance controls the dynamical state of the current at impact, producing systematic yet non-monotonic changes in the fractional population of the transport modes. This study establishes an explicit correspondence between evolving flow structures and clustered Lagrangian pathways. Comparative cases with varying geometric configuration, density contrast, flow depth, and release volume indicate that the identified transport patterns are reasonably robust. Therefore, the present results provide a fate-oriented predictive framework and theoretical basis for the transport of finite-volume gravity currents near obstacles, with important implications for engineering applications. Full article

Background/Objectives: Preterm infants are particularly vulnerable to nutritional deficiencies and electrolyte imbalances during the early stages of extrauterine life. To ensure optimal metabolic support, they often require the early initiation of “aggressive” parenteral nutrition (PN), which is a known risk factor for Refeeding Syndrome (RS), a potentially serious metabolic condition characterized by fluid and electrolyte disturbances, the most significant of which is hypophosphatemia. Hypophosphatemia can impair the metabolism, survival, and function of red blood cells, leading to a reduction in key intracellular metabolites and the development of a metabolic block that alters their quality and decreases their stability. It is therefore hypothesized that RS may contribute to the development of anemia of prematurity (AOP). At the same time, early enteral nutrition (EN) may promote metabolic adaptation and reduce exposure to the complications of prolonged parenteral support, potentially protecting against AOP. The primary aim of this study was to determine whether preterm infants who develop RS are at increased risk of AOP. A secondary aim was to evaluate whether early EN may act as a protective factor against the development of AOP. Methods: This retrospective observational study was conducted on infants with a gestational age ≤ 34 weeks and/or birth weight ≤ 1500 g, admitted to the Neonatal Intensive Care Unit of Policlinico Umberto I—Sapienza University of Rome, between January 2015 and November 2022. Infants diagnosed with AOP were classified as cases, while those without AOP served as the control group. Results: A total of 412 preterm infants were enrolled (110 cases, 302 controls). Refeeding Syndrome was significantly more frequent in infants with AOP (30.9% vs. 11.6%, p < 0.001). In the logistic regression model adjusted for gestational age, RS was independently associated with AOP (OR = 2.81; 95% CI: 1.55–5.10; p < 0.001), along with gestational age ≤ 34 weeks (OR = 7.10; 95% CI: 2.13–24.0; p = 0.001). Early enteral nutrition during the first week of life was associated with a significantly lower risk of AOP (OR = 0.12; 95% CI: 0.029–0.52; p = 0.005). The association between RS and AOP was confirmed in the model adjusted for birth weight (OR = 2.06; 95% CI: 1.16–3.79; p = 0.021). Infants with AOP showed significantly higher parenteral nutrition intake, delayed initiation of enteral feeding, and later achievement of full enteral nutrition compared with controls (all p < 0.001). Conclusions: RS is significantly associated with AOP in preterm infants, likely through pathophysiological mechanisms related to hypophosphatemia. Importantly, early EN may be a protective factor against AOP, suggesting that timely initiation and advancement in enteral feeding may counteract the metabolic derangements associated with intensive parenteral support. These findings support a nutritional approach that prioritizes early and progressive enteral nutrition as a strategy to reduce the risk of both RS and AOP. Further prospective studies are needed to confirm these associations and to define optimal EN protocols for this population. Full article

Background: In dual-task (DT) conditions, individuals must walk while simultaneously engaging in cognitive or motor tasks, which impacts gait performance, especially in older adults and individuals with Parkinson’s disease (PD). Gait impairments in PD under DT conditions have implications for intersegmental coordination. Research question: Intersegmental coordination and gait biomechanics during the DTs were compared between people with PD and older adults. Methods: Thirty-two individuals (16 PD, H&Y 1–3; and 16 older adults) participated in this study and were asked to walk under the following self-selected conditions: single task, DT with a math component, and texting on a cell phone. Spatiotemporal, angular, and intersegmental coordination data were collected using a markerless motion analysis system (OpenCap). Results: Dual-task conditions significantly affected spatiotemporal and kinematic variables, as well as intersegmental coordination. A significant task effect was observed for thigh–shank coordination, whereas no significant group effect was found for the main coordination outcomes. Significance: Significant task effects were observed for intersegmental coordination (thigh–shank CRP), with no significant group differences. The concurrent demands of processing visual and motor information for texting and walking lead to significant reductions in gait speed and lower limb movement, as well as altered intersegmental coordination, with task demands rather than disease status being the primary driver of coordination changes. Full article

Background. Post-intubation cicatricial laryngeal stenosis (PICLS) represents one of the most severe long-term complications of pediatric airway management. By systematically analyzing clinical and procedural variables across different grades of PICLS, this study addresses a critical gap in pediatric airway research and provides clinically relevant descriptive data on stenosis severity. Materials and methods. A retrospective single-center case-series study was conducted and included pediatric patients (0–18 years) treated for PICLS at a tertiary referral pediatric otolaryngology center between 2016 and 2024. Spearman correlation and multiple regression analyses were used to evaluate possible associations between clinical factors and stenosis grade. Results. Among 172 children with PICLS, severe forms of stenosis (Grades 3–4) were observed in 37.2%, with predominant subglottic localization (85.3%). Age at primary intubation (p = 0.02) and the type of intubation (emergency/elective; p = 0.04) were the only variables significantly associated with stenosis severity in this cohort, whereas sex, reintubation, comorbidities, and delivery-related factors showed no significant associations. Mild stenosis (Grades 1–2) more frequently followed intubation for elective surgery and infections, whereas severe stenosis was more commonly associated with intubation due to central nervous system pathology and infections. Conclusions. Age at primary intubation and the type of intubation (emergency/elective) were associated with stenosis severity in this cohort. These findings should be interpreted in light of the retrospective case-series design and the absence of a control group, but they may contribute to improved clinical characterization of PICLS severity in children. Full article

Background: Sézary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) with distinct clinical and biological features compared to rarer entities such as primary cutaneous CD8⁺ aggressive epidermotropic cytotoxic T-cell lymphoma (PCAECTCL). Although recurrent genomic alterations in CTCL have been described, comparative analyses at the pathway level across biologically divergent subtypes remain limited. Here, we leveraged a conversational artificial intelligence (AI) platform for precision oncology to enable rapid, integrative, and hypothesis-driven interrogation of publicly available genomic datasets. Methods: We conducted a secondary analysis of somatic mutation and clinical data from the Columbia University CTCL cohort accessed via cBioPortal. Cases were stratified into SS (n = 26) and PCAECTCL (n = 13). High-confidence coding variants were curated and mapped to biologically relevant signaling pathways and functional gene categories implicated in CTCL pathogenesis. Pathway-level mutation frequencies were compared using Fisher’s exact tests, with effect sizes quantified as odds ratios. Tumor mutational burden (TMB) was compared using the Wilcoxon rank-sum test. Subtype-specific co-mutation patterns were evaluated using pairwise association analyses and visualized through oncoplots and network heatmaps. A conversational AI agent, AI-HOPE, was used to iteratively refine cohort definitions, prioritize pathway-level signals, and contextualize findings. Results: TMB was comparable between SS and PCAECTCL (p = 0.96), indicating no significant difference in global mutational load. In contrast, pathway-centric analyses revealed marked qualitative differences. SS demonstrated enrichment of alterations in epigenetic regulators, tumor suppressor and cell-cycle control pathways, NFAT signaling, and DNA damage response mechanisms, consistent with transcriptional dysregulation and immune modulation. PCAECTCL exhibited relatively higher frequencies of alterations involving epigenetic regulators and MAPK pathway signaling, suggesting distinct oncogenic dependencies. Co-mutation analysis revealed a more constrained and focused interaction landscape in SS, whereas PCAECTCL displayed broader and more heterogeneous co-mutation networks, indicative of divergent evolutionary trajectories. Notably, ERBB2 mutations were significantly enriched between subtypes (p = 0.031), highlighting a potential subtype-specific therapeutic vulnerability. Conclusions: This study demonstrates that SS is distinguished from PCAECTCL not by increased mutational burden but by distinct pathway-level architectures, particularly involving epigenetic regulation, immune signaling, and transcriptional control. These findings generate biologically grounded, testable hypotheses for subtype-specific therapeutic targeting and underscore the value of conversational AI as a scalable framework for accelerating discovery in translational cancer genomics. Full article

Endometriosis is a chronic inflammatory disease in which transforming growth factor-beta (TGF-β) has been implicated in immune dysregulation, extracellular matrix remodeling, and fibrosis. Data on baseline secretion of TGF-β isoforms by systemic immune cells remain limited. This pilot study quantified unstimulated secretion of TGF-β1, TGF-β2, and TGF-β3 by peripheral blood mononuclear cell (PBMC) cultures from women with and without endometriosis and explored stage-related patterns. In this prospective case–control study, PBMCs from 50 women with surgically confirmed endometriosis and 30 controls were cultured for 24 h without exogenous stimulation. Supernatant concentrations were measured using a multiplex bead-based immunoassay (Bio-Plex, Bio-Rad) and expressed as pg/mL; between-group and stage-related differences were assessed using non-parametric tests. Median 24 h secretion was similar between groups (TGF-β1: 103,816 vs. 114,700 pg/mL, p = 0.25; TGF-β2: 3735 vs. 3732 pg/mL, p = 0.32; TGF-β3: 3280 vs. 3284 pg/mL, p = 0.70). Within the endometriosis cohort, TGF-β2 was significantly higher in moderate/advanced disease (rASRM stages III–IV) than in minimal/mild disease (stages I–II), whereas TGF-β1 and TGF-β3 did not reach statistical significance for a stage-dependent pattern in this pilot cohort (p = 0.42 and p = 0.41, respectively; Kruskal–Wallis), and a type II error cannot be excluded given the small sample size per rASRM (revised American Society of Reproductive Medicine)stage (n = 11–14). These findings suggest that TGF-β dysregulation is compartmentalized to the peritoneal environment rather than systemically imprinted in circulating immune cells. The stage-dependent elevation of TGF-β2 supports its role in progressive fibrogenesis and as a candidate severity biomarker, warranting confirmation in larger, stimulus-augmented studies. Full article

Leukocyte telomere length (LTL) is shortened in adults with type 1 diabetes (T1D), but less data is available concerning pediatric cases. Multiple factors affect LTL, namely genes, epigenetics, environmental factors, oxidation, and psychological stress. Children with T1D and their families experience chronic stress. This study aimed to investigate LTL in children with T1D (n = 35) aged 6–13 years old, in comparison to age-matched healthy counterparts (n = 35), and assess any correlation of LTL with perceived stress. Relative LTL (rLTL) was assessed through real-time qPCR. Morning serum cortisol, high-sensitivity C-Reactive Protein (hsCRP), and glycated hemoglobin (HbA1c) were measured. Children completed the validated questionnaires “Stress in Children” and “Pediatric Quality of Life”. Parents answered the “Perceived Stress Scale”. Children with T1D had a lower rLTL (p = 0.02) compared to age-matched healthy controls, higher hsCRP (p = 0.031), and a lower estimated quality of life (p = 0.01). RLTL was found to be lower in females with T1D (p < 0.001) and was positively related to the ‘gender–social support’ factor (p = 0.002) and diabetes duration (p = 0.045), adjusted for children’s age, parental age, and sociodemographic characteristics. These pilot findings indicate early emergence of shorter rLTL in T1D, pointing to a sexual dimorphism pattern. Insights into preventing LTL shortening in pediatric T1D can be gained from large-scale studies examining the impact of gender and social support. Full article