Search Results (1,596)

Background/Objectives: Stroke often results in lasting upper limb deficits. Mirror visual feedback (MVF) supports motor recovery, and electromyography-triggered electrical stimulation (ES) could enhance engagement. However, the effects in healthy older adults, age-matched to typical patient cohorts, remain insufficiently understood. We tested MVF and MVF + ES using functional near-infrared spectroscopy. Methods: Seventeen right-handed older adults performed left-wrist flexion under three visual conditions: circle fixation, viewing the right hand at rest, and mirror viewing, with/without electrical stimulation to the right-wrist flexors time-locked to left-forearm electromyography. Oxygenated hemoglobin (oxy-Hb) was recorded over the bilateral inferior frontal gyrus (IFG), precentral gyrus (PrG), postcentral gyrus (PoG), supramarginal gyrus (SMG), superior parietal lobule (SPL), and supplementary motor area. Effects were assessed with linear mixed-effects models (stimulation × visual condition); pairwise comparisons of estimated marginal means used Fisher’s least significant difference. Left-forearm electromyography verified comparable effort across conditions. Results: Linear mixed-effects models revealed left-lateralized increases in oxy-Hb, most prominently under mirror viewing with stimulation. Post hoc tests showed high oxy-Hb in the left IFG, PrG, PoG, SMG, and SMA. The left EMG did not differ. Conclusions: In healthy older adults, MVF paired with EMG-triggered ES enhances frontoparietal–motor engagement beyond MVF alone, with recruitment shaped by visuo–proprioceptive congruence. These findings support mechanistic plausibility and motivate dose–response optimization and patient-focused trials testing behavioral transfer in stroke. Full article

Omni-channel retailers arise to address the deficiencies in consumers’ online shopping experiences; the resulting competition between such retailers and traditional online platforms presents substantial challenges for green product manufacturers. A three-level game model is established to examine a manufacturer’s green contract design (product pricing and greenness determination) and mode selection under the competition between an online platform and a new retailer providing omni-channel services to end customers. The manufacturer can select between two modes: supplying a green product to the online platform and new retailer (mode RR) or selling it directly through the online platform and reselling it to the new retailer (mode PR). Our findings indicate that, first, even if the relationship between the manufacturer and new retailer has changed from cooperation under mode RR to competition and cooperation under mode PR, the manufacturer still favors two-channel sales over single-channel sales and affects consumer channel choices to adjust market shares through mode selection. Second, regarding the impacts of the key parameters on the manufacturer, downstream e-commerce platform retailers and environment are intricate and nuanced. While raising the omni-channel service level enhances profitability in the new retailer across both modes, its environmental impacts differ significantly between them. Additionally, it can harm the online platform in some cases. Nevertheless, when the parameters fall within suitable ranges, the manufacturer and both downstream retailers have a consistent preference for improved omni-channel services under both modes. Finally, there is a significant divergence in mode preferences among the manufacturer and both downstream platform retailers. Due to the first-mover advantage, the manufacturer opts for mode RR over mode PR in most cases. Notably, within a specific range of parameters, they consistently prefer mode RR, which also proves beneficial for the environment, resulting in a Pareto optimal outcome. This proposes a concrete cooperation mechanism among the manufacturer, retailers, and consumers from quantitative insights, which can promote green products to achieve the objective of low-carbon environmental protection. Full article

Background/Objectives: Wilson’s disease (WD) is an autosomal recessive disorder characterized by pathological copper accumulation, primarily in the liver and brain. Severe hepatic involvement can be effectively treated with liver transplantation (LT). Geographic variation in ATP7B mutations suggests the presence of regional patterns that may impact disease presentation and management. This study aims to investigate the genetic basis of WD in patients from a major LT center in Iran. Methods: A retrospective analysis was conducted on clinical, biochemical, and pathological data from patients suspected of WD who underwent evaluation for LT between May 2020 and June 2025 at Shiraz University of Medical Sciences. Genetic testing was carried out on 20 patients at the Shiraz Transplant Research Center (STRC). Direct mutation analysis of ATP7B was performed for all patients, and the results correlated with clinical and demographic information. Results: In total, 20 WD patients who underwent liver transplantation (15 males, 5 females) carried 25 pathogenic or likely pathogenic ATP7B variants, 21 of which were previously unreported. Fifteen patients were homozygous, and five were compound-heterozygous; all heterozygous combinations occurred in the offspring of second-degree consanguineous unions. Recurrent changes included p.L549V, p.V872E, and p.P992S/L, while two nonsense variants (p.E1293X, p.R1319X) predicted truncated proteins. Variants were distributed across copper-binding, transmembrane, phosphorylation, and ATP-binding domains, and in silico AlphaMissense scores indicate damaging effects for most novel substitutions. Post-LT follow-up showed biochemical normalization in the majority of recipients, with five deaths recorded during the study period. Conclusions: This single-center Iranian study reveals a highly heterogeneous ATP7B mutational landscape with a large proportion of novel population-specific variants and underscores the benefit of comprehensive gene sequencing for timely WD diagnosis and family counseling, particularly in regions with prevalent consanguinity. Full article

Background: attention-deficit/hyperactivity disorder (ADHD) and Alzheimer’s disease (AD) are distinct neurological conditions that may share genetic and molecular underpinnings. ADHD, a neurodevelopmental disorder, affects approximately 5% of children and 3% of adults globally, while AD, a neurodegenerative disorder, is the leading cause of dementia in older adults. Emerging evidence suggests potential overlapping contributors, including pathways related to synaptic plasticity, neuroinflammation, and oxidative stress. Methods: this systematic review investigated potential genetic predispositions linking Attention-Deficit/Hyperactivity Disorder (ADHD) and Alzheimer’s Disease (AD). Following PRISMA guidelines, a search was conducted in Web of Science, Embase, PsycINFO, and PubMed using keywords related to ADHD, AD, and genetic factors. Studies included were original human studies utilizing genetic analyses and ADHD polygenic risk scores (PRS), with AD confirmed using established diagnostic criteria. Exclusion criteria comprised non-original studies, animal research, and articles not addressing genetic links between ADHD and AD. Screening was conducted with Rayyan software, assessing relevance based on titles, abstracts, and full texts. Results:. The search identified 1450 records, of which 1092 were screened after duplicates were removed. Following exclusions, two studies met inclusion criteria. One study analyzed ADHD-PRS in 212 cognitively unimpaired older adults using amyloid-beta (Aβ) PET imaging and tau biomarkers. The findings revealed that ADHD-PRS was associated with progressive cognitive decline, increased tau pathology, and frontoparietal atrophy in Aβ-positive individuals, suggesting that ADHD genetic liability may exacerbate AD pathology. Another study assessed ADHD-PRS in a cohort of 10,645 Swedish twins, examining its association with 16 somatic conditions. The results showed modest risk increases for cardiometabolic, autoimmune, and neurological conditions, with mediation effects through BMI, education, tobacco use, and alcohol misuse, but no direct link between ADHD-PRS and dementia. Discussion and conclusion: this review highlights preliminary but conflicting evidence for a genetic intersection between ADHD and AD. One study suggests that ADHD genetic liability may exacerbate AD-related pathology in Aβ-positive individuals, whereas another large registry-based study finds no direct link to dementia, with associations largely mediated by lifestyle factors. The potential ADHD–AD relationship is likely complex and context-dependent, influenced by biomarker status and environmental confounders. Longitudinal studies integrating genetics, biomarkers, and detailed lifestyle data are needed to clarify this relationship. Full article

Tuberculosis (TB) is one of the leading infectious causes of mortality worldwide. Although a significant proportion of the population (up to 36%, depending on the region) is infected with the latent form of TB, only about one in ten of these people will develop an active form of the disease in their lifetime. This is due to a complex interaction between the host’s genetic predisposition and environment. However, the genetic determinants of TB are not well established and have been insufficiently explored in previous genome-wide association studies (GWAS) with sparse and incongruent results. We reviewed recent evidence on host genetic susceptibility to TB, highlighting population-specific characteristics, host–pathogen coevolution, and the limitations of conventional GWAS approaches in terms of clinical and genetic heterogeneity. While rare variants with high penetrance, such as TYK2 P1104A, lead to monogenic susceptibility, most heritable risk results from the cumulative effect of numerous common variants. This cumulative effect may be summarized using polygenic risk scores (PRSs). Although their use has been proven for non-communicable diseases, PRSs are not applied to infectious disease susceptibility. To date, no PRS model for susceptibility to tuberculosis has been consistently validated. The development of PRSs for TB susceptibility is limited by phenotypic heterogeneity, population structure, and co-adaptation between host and pathogen. Another major challenge is to take into account the considerable influence of environmental factors. This difficulty in modeling environmental influences probably explains the current lack of a clinically applicable PRS for TB susceptibility. However, taking these caveats into account, polygenic models could improve risk stratification at the individual level compared to single-variant association and allow for earlier targeted treatment and prophylaxis. Full article

Background/Objectives: The interaction between brain-metastasizing melanoma cells and surrounding microglia shapes the immune tumor microenvironment and influences tumor progression. Gene expression analysis revealed that sphingosine-1-phosphate receptor 1 (S1PR1), encoding the S1P1 receptor, is upregulated in microglia upon interaction with melanoma cells. Here, we investigated the functions of S1P1 in microglia and its contribution to melanoma–microglia crosstalk. Methods: We examined the effects of S1P1 inhibition on microglia and four brain-metastasizing human melanoma cell lines in monocultures and co-cultures using the selective S1P1 antagonist NIBR0213 and S1PR1 gene knockdown. Results: We found that melanoma-secreted IL-6 upregulated S1PR1 expression in microglia. S1P1 inhibition increased expression of CD32, CD150, and CD163 in microglia; however, CD150 and CD163 upregulation was abolished in the presence of melanoma cells. S1P1 inhibition downregulated immunosuppressive and anti-inflammatory factors in microglia, including CD274, SOCS3, TGFBR1, TGFBR2, and JunB, promoting a pro-inflammatory phenotype. It also reduced viability of both melanoma and microglia cells, inducing apoptosis in melanoma-associated microglia, possibly via downregulation of CH25H, an upstream regulator of SREBPs. In co-cultures, melanoma cells were more sensitive than microglia to NIBR0213-induced growth arrest. In 3D spheroid cultures, NIBR0213 delayed melanoma–microglia aggregation. Combined treatment with the BRAF inhibitor Vemurafenib and NIBR0213 enhanced Vemurafenib efficacy in three of four melanoma lines. Conclusions: S1P1 contributes to the immunosuppressive phenotype of microglia. Inhibiting the S1P/S1P1 axis impairs viability and crosstalk between melanoma cells and tumor-activated microglia, offering a potential therapeutic strategy for melanoma brain metastases. Full article

Sodium metal batteries (SMBs) with ceramic solid electrolytes offer a promising route to improve the energy density of conventional Na-ion batteries (SIBs). Silicate-based ceramics have recently gained attention for their favourable properties, including better ionic conduction and wider stability windows. In this study, 10% Pr³⁺ and Nd³⁺ were doped into sodium gadolinium silicate ceramics to examine the effects on phase purity, ionic conductivity, and interfacial compatibility with sodium metal anodes. The materials were synthesized via solid-state methods and sintered at 950–1075 °C to study the impact of sintering temperature on densification and microstructure. Na₅Gd_0.9Pr_0.1Si₄O₁₂ (NGPS) and Na₅Gd_0.9Nd_0.1Si₄O₁₂ (NGNS) sintered at 1075 °C showed the highest room temperature total ionic conductivities of 1.64 and 1.74 mS cm⁻¹, respectively. The highest critical current density of 0.5 mA cm⁻² is achieved with a low interfacial area-specific resistance of 29.47 Ω cm² for NGPS and 22.88 Ω cm² for NGNS after Na plating/stripping experiments. These results highlight how doping enhances phase purity, ionic conductivity, and interfacial stability of silicates with Na metal anodes. Full article

Ischemic stroke remains a leading cause of mortality and disability worldwide, with current therapies such as intravenous thrombolysis and mechanical thrombectomy benefiting only a limited proportion of patients. Neuroinflammation is a key contributor to secondary brain injury, creating a strong rationale for adjunctive therapies targeting immune modulation. Fingolimod, a sphingosine-1-phosphate receptor (S1PR) modulator originally approved for multiple sclerosis, has shown promising effects in both preclinical and early clinical studies of acute ischemic stroke. Methods: We conducted a structured narrative review of preclinical and clinical studies published between 2015 and 2024, using PubMed, Scopus, and Web of Science databases. Inclusion criteria were original studies evaluating fingolimod in ischemic stroke models or human patients, either as monotherapy or in combination with reperfusion therapies. Exclusion criteria included conference abstracts without peer review, studies lacking mechanistic insight, and non-English publications. Results: Preclinical evidence demonstrates that fingolimod reduces infarct size, preserves blood–brain barrier integrity, and modulates neuroinflammation through multiple mechanisms, including T cell sequestration, microglial polarization, and mitochondrial protection. Clinical trials, though limited in size, suggest improved short- and long-term outcomes when fingolimod is used in combination with intravenous thrombolysis or endovascular therapy, with a manageable safety profile. Novel nanotechnology-based delivery systems further enhance central nervous system (CNS) targeting and reduce systemic side effects. Conclusions: Fingolimod represents a promising multi-targeted adjunctive strategy for ischemic stroke, acting at the intersection of immune modulation, vascular protection, and neuroprotection. While current findings are encouraging, larger randomized controlled trials and biomarker-driven patient selection are needed to validate its clinical utility. This review highlights the translational potential of fingolimod and outlines key directions for future research. Full article

Background: A range of cancer cells are significantly inhibited by FTY720. It is unknown, nevertheless, how FTY720 influences the onset of non-small cell lung cancer (NSCLC). Using bioinformatics techniques, we analyzed and the possible molecular mechanisms and targets of FTY720 for the treatment of NSCLC. Methods: DEGs (Differentially expressed genes) were acquired by differential analysis of the dataset GSE10072. Obtained FTY720 target genes and NSCLC disease genes from databases such as Swiss-TargetPrediction and GeneCard. Subsequently, target and disease genes, as well as DEGs, were merged for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, gene ontology (GO), and protein interaction analysis. The overlapping genes of DEGs and target genes, and disease genes were also obtained separately and subjected to survival as well as expression analyses. We constructed the regulatory network of miRNAs and transcription factors (TFs) on hub genes. Finally, the immune cell association of hub genes was evaluated using the ssGSEA method, molecular docking of FTY720 to hub genes was carried out utilizing Autodock, and molecular dynamics simulations were conducted. Results: In this study, 444 DEGs, 232 target genes of FTY720, and 466 disease genes were obtained. Moreover, a total of 1062 genes were obtained by removing duplicate values after merging, among which PIK3R1, Akt1, and S1PR1 had the highest DEGREE values in the protein interactions network, and these genes were primarily enriched in MAPK, PI3K-Akt signaling pathways, with the PI3K-Akt signaling pathway being the most prominent. Among the overlapping genes, three potential targets of FTY720 for NSCLC treatment were found: S1PR1, ZEB2, and HBEGF. ZEB2 and S1PR1 were determined to be hub genes and to significantly affect NSCLC prognosis by survival analysis. Furthermore, hsa-miR-132-3p, hsa-miR-192-5p, and hsa-miR-6845-3p were strongly associated with FTY720 for the treatment of NSCLC; CTBP1 (carboxy-terminal binding protein 1), EZH2 (protein lysine N-methyltransferase), and ZNF610 (zinc-finger protein 610) may all influence the expression of ZEB2 and S1PR1. Hub genes had a substantial negative link with memory B cells and a significant positive correlation with memory CD8 T cells and Th17 helper T cells. The molecular docking and kinetic simulation results of FTY720 with the two hub genes indicate that the protein-ligand complex has good stability. Conclusion: Our research indicates that FTY720 may inhibit NSCLC via possible targets ZEB2 and S1PR1, further laying the theoretical foundation for the utilization of FTY720 in NSCLC treatment. Full article

Accurate estimation of daily reference evapotranspiration (ET_o) is crucial for sustainable water resource management and irrigation scheduling, especially in water-scarce regions like Arizona. The standardized Penman–Monteith (PM) method is costly and requires specialized instruments and expertise, making it generally impractical for commercial growers. This study developed 35 ET_o models to predict daily ET_o across Coolidge, Maricopa, and Queen Creek in Pinal County, Arizona. Seven input combinations of daily meteorological variables were used for training and testing five machine learning (ML) models: Artificial Neural Network (ANN), Random Forest (RF), Extreme Gradient Boosting (XGBoost), Categorical Boosting (CatBoost), and Support Vector Machine (SVM). Four statistical indicators, coefficient of determination (R²), the normalized root-mean-squared error (RMSE_n), mean absolute error (MAE), and simulation error (S_e), were used to evaluate the ML models’ performance in comparison with the FAO-56 PM standardized method. The SHapley Additive exPlanations (SHAP) method was used to interpret each meteorological variable’s contribution to the model predictions. Overall, the 35 ET_o-developed models showed an excellent to fair performance in predicting daily ET_o over the three weather stations. Employing ANN10, RF10, XGBoost10, CatBoost10, and SVM10, incorporating all ten meteorological variables, yielded the highest accuracies during training and testing periods (0.994 ≤ R² ≤ 1.0, 0.729 ≤ RMSE_n ≤ 3.662, 0.030 ≤ MAE ≤ 0.181 mm·day⁻¹, and 0.833 ≤ S_e ≤ 2.295). Excluding meteorological variables caused a gradual decline in ET-developed models’ performance across the stations. However, 3-variable models using only maximum, minimum, and average temperatures (T_max, T_min, and T_ave) predicted ET_o well across the three stations during testing (17.655 ≤ RMSE_n ≤ 13.469 and S_e ≤ 15.45%). Results highlighted that T_max, solar radiation (R_s), and wind speed at 2 m height (U₂) are the most influential factors affecting ET_o at the central Arizona sites, followed by extraterrestrial solar radiation (R_a) and T_ave. In contrast, humidity-related variables (RH_min, RH_max, and RH_ave), along with T_min and precipitation (P_r), had minimal impact on the model’s predictions. The results are informative for assisting growers and policymakers in developing effective water management strategies, especially for arid regions like central Arizona. Full article

The molten salt reactor (MSR) is a prominent Generation IV nuclear reactor concept that offers substantial advantages over conventional solid-fueled systems, including enhanced fuel utilization, inherent passive safety features, and significant reductions in long-lived radioactive waste. Central to its safety strategy is a reliance on natural circulation (NC) mechanisms, which eliminate the need for active pumping systems and enhance system reliability during normal and off-normal conditions. However, the challenges associated with molten salts, such as their high melting points, corrosivity, and material compatibility issues, render experimental investigations inherently complex and demanding. Therefore, the use of high-Pr-number surrogate fluids represents a practical alternative for studying molten salt behavior under safer and more accessible experimental conditions. In this study, a single-phase natural circulation loop setup at the University of Idaho’s Thermal–Hydraulics Laboratory was employed to investigate NC behavior under various operating conditions. The RELAP5-3D code was initially validated against water-based experiments before employing Therminol-66, a high-Prandtl-number surrogate for molten salts, in the natural circulation loop for the first time. The RELAP5-3D results demonstrated good agreement with both steady-state and transient experimental results, thereby confirming the code’s ability to model NC behavior in a single-phase flow regime. The results also highlighted certain experimental limitations that should be addressed to enhance the NC loop’s performance. These include increasing the insulation thickness to reduce heat losses, incorporating a dedicated mass flow measurement device for improved accuracy, and replacing the current heater with a higher-capacity unit to enable testing at elevated power levels. By identifying and addressing the main causes of these limitations and uncertainties during water-based experiments, targeted improvements can be implemented in both the RELAP5 model and the experimental setup, thereby ensuring that tests using a surrogate fluid for MSR analyses are conducted with higher accuracy and minimal uncertainty. Full article

Accurate long-term tracking of individual cattle is essential for precision livestock farming but remains challenging due to occlusions, posture variability, and identity drift in free-range environments. We propose a multi-camera tracking framework that combines bird’s-eye-view (BEV) trajectory matching with cattle face recognition to ensure identity preservation across long video sequences. A large-scale dataset was collected from five synchronized 4K cameras in a commercial barn, capturing both full-body movements and frontal facial views. The system employs center point detection and BEV projection for cross-view trajectory association, while periodic face recognition during feeding refreshes identity assignments and corrects errors. Evaluations on a two-day dataset of more than 600,000 images demonstrate robust performance, with an AssPr of 84.481% and a LocA score of 78.836%. The framework outperforms baseline trajectory matching methods, maintaining identity consistency under dense crowding and noisy labels. These results demonstrate a practical and scalable solution for automated cattle monitoring, advancing data-driven livestock management and welfare. Full article

Introduction: Nasopharyngeal carcinoma (NPC) is a distinct malignancy of the head and neck with high prevalence in endemic regions and a strong association with Epstein–Barr virus (EBV). In locally advanced stages, neoadjuvant chemotherapy (NAC) followed by chemoradiotherapy improves outcomes, but response rates vary. Identifying early predictors of NAC response is essential for guiding personalized treatment strategies. This study aims to assess whether baseline [¹⁸F]FDG PET/CT parameters can predict NAC response in NPC patients. Methods: In this retrospective study, 27 patients with histologically confirmed, locally advanced (stage III) NPC underwent baseline [¹⁸F]FDG PET/CT prior to NAC between 2015 and 2023. Quantitative PET parameters including SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were extracted from the primary tumor. NAC response was assessed using RECIST 1.1 criteria and classified as responders (CR + PR) or non-responders (SD + PD). Group comparisons were performed using Student’s t-test. ROC analysis was used to identify optimal cut-off values. A p-value < 0.05 was considered significant. Results: The cohort included 20 males and 7 females (mean age: 60.8 ± 15.2 years). The predominant histotype was undifferentiated non-keratinizing carcinoma (92.6%). A total of 19 patients (70.4%) responded to NAC. Responders had significantly lower baseline SUVmax (10.9 ± 4.8 vs. 15.8 ± 4.1, p = 0.021), MTV (16.2 ± 12.4 vs. 27.8 ± 19.5 cm³, p = 0.045), and TLG (128.6 ± 98.2 vs. 218.7 ± 152.4, p = 0.038). SUVmean was also lower in responders (6.1 ± 2.1 vs. 9.3 ± 2.8), although not statistically reported. ROC analysis identified SUVmax > 12.5 and MTV > 20.0 cm³ as thresholds associated with poor NAC response. Conclusions: Baseline metabolic parameters from [¹⁸F]FDG PET/CT, particularly SUVmax and MTV, may assist stratification of NAC response in nasopharyngeal carcinoma. These biomarkers may facilitate pre-treatment stratification and guide more personalized therapeutic approaches. However, the limited sample size may affect the generalizability of these findings, and larger prospective studies are needed to confirm the results. Full article

Coffee demand continues to rise, while producing countries face increasing challenges and yield losses due to climate change. In response, farmers are adopting agricultural practices capable of boosting productivity. However, these practices increase intercrop variability, making coffee mapping more challenging. In this study, a novel approach is proposed to identify coffee cultivation considering four phenological stages: planting (PL), producing (PR), skeleton pruning (SK), and renovation with stumping (ST). A hierarchical classification framework was designed to isolate coffee pixels and identify their respective stages in one of Brazil’s most important coffee-producing regions. A dense time series of multispectral bands, spectral indices, and texture metrics derived from Harmonized Landsat Sentinel-2 (HLS) imagery, with an average revisit time of ~3 days, was employed. This data was combined with an ensemble learning approach based on decision-tree algorithms, specifically Random Forest (RF) and Extreme Gradient Boosting (XGBoost). The results achieved unprecedented sensitivity and specificity for coffee plantation detection with RF, consistently exceeding 95%. The classification of coffee phenological stages showed balanced accuracies of 77% (ST) and from 93% to 95% for the other classes. These findings are promising and provide a scalable framework to monitor climate-resilient coffee management practices. Full article

Background: Physical frailty is a prevalent and clinically important manifestation of COPD. While the ERS/ATS recommends the Short Physical Performance Battery (SPPB), handgrip strength (HGS), 30 s sit-to-stand (30secSTS), and Timed-Up-and-Go (TUG) as frailty screening tools, their agreement and predictive performance remain unclear. Furthermore, the trajectory of frailty is poorly understood in patients who decline pulmonary rehabilitation (PR). Objective: To assess the prevalence of and change in physical frailty and its association with 12-month all-cause hospitalizations and mortality. Secondarily, to assess the agreement and predictive value (positive; PPV/negative; NPV) of recommended screening tests in COPD patients declining PR. Methods: In this prospective cohort study, 102 patients with COPD (61 females, mean ± SD age 70 ± 9 years, FEV₁ 34 ± 11%, SPPB 8.0 ± 3.2 points, CAT 19 ± 7) underwent repeated frailty assessments at baseline and after 12 months using the SPPB (reference), TUG, 30secSTS, and HGS. Results: At baseline, 39% were physically frail (SPPB ≤ 7). Frailty persisted in 86%, and 23% had died at 12 months. Baseline age-adjusted physical frailty was not statistically associated with 12-month all-cause hospitalization (OR 1.79 [0.61–5.24]) or mortality (OR 3.54 [0.95–13.16]). Agreement with SPPB was moderate for TUG (κ = 0.53) and fair for 30secSTS (κ = 0.38) and HGS (κ = 0.26), with similar findings at 12 months. TUG had the highest PPV/NPV (0.85/0.71). Conclusions: Physical frailty is prevalent and persistent in patients with severe COPD who decline PR. ERS/ATS-recommended tools showed fair to moderate agreement and predictive value. TUG was the most robust proxy, though tool selection should be guided by clinical context and purpose. Full article