Search Results (184)

Background: Methotrexate-induced neurotoxicity (MTX-NTX) is a severe complication during childhood acute lymphoblastic leukemia (ALL) treatment, yet its underlying pharmacogenetic determinants remain incompletely understood. Methods: A multicenter retrospective nationwide case–control study was performed including 71 pediatric ALL patients (34 MTX-NTX cases and 37 controls). Targeted next-generation sequencing of 17 genes involved in MTX transport, intracellular metabolism and folate pathways was performed. Results: Transport-related genes accounted for 61.4% of all detected variants and showed the highest number of nominally significant variants. Pathway-level burden analysis demonstrated a significant enrichment of transporter-related variants in patients with MTX-NTX compared with controls (FDR-adjusted p = 0.004), whereas the analysis for folate/metabolism-related genes did not remain significant after multiple-testing (FDR-adjusted p = 0.096). Similar findings were observed in the stroke-like syndrome (SLS) subgroup (FDR-adjusted p = 0.014 and 0.108, respectively). Gene-level burden analysis identified ABCG2 and ABCC4 as the predominant contributors, harboring both 18.4% of significant variants in the overall MTX-NTX analysis and 20.6% and 17.6%, respectively in the SLS phenotype. Moreover, the distribution of significant variants was strongly correlated between the overall MTX-NTX and SLS analyses (Spearman’s ρ = 0.549, p = 0.022). Volcano plot analysis revealed ABCG2 as the gene showing the most prominent pattern of nominal associations, containing both the variants associated with a protective direction (e.g., c.1728-46G>A, p = 2.6 × 10⁻⁴) and variants associated with increased risk, including c.34G>A and c.203+36A>G (p = 0.002) and c.263+10A>G (p = 0.0097). Phenotype-specific analyses revealed distinct genetic signatures across neurological manifestations, with transporter genes predominating in focal neurological deficits. Conclusions: Our findings suggest that genetic variability in ABC transporter genes may contribute to susceptibility to MTX-NTX, whereas folate metabolism genes may represent complementary phenotype-modifying factors. These findings are exploratory and require validation in larger, independent cohorts and functional studies. Full article

Mycoviruses represent promising tools for the biological control of phytopathogenic fungi. However, their application is often constrained by host specificity and low natural prevalence in certain pathogens. Fusarium verticillioides, a major maize pathogen and fumonisin B1 (FB1) producer, harbors very few known mycoviruses, a circumstance that limits the development of virus-based control strategies. In this study, we explored a virocontrol approach for F. verticillioides based on the use of a heterologous mycovirus, Cryphonectria hypovirus 1 (CHV1). For the artificial transfection of F. verticillioides with CHV1, we used an infectious cDNA clone of the virus and protoplast-mediated transformation. Through RT-PCR and double-stranded RNA (dsRNA) purification by chromatography on cellulose, it was confirmed that the CHV1 infectious cDNA clone is stably integrated into the fungal genome, giving rise to autonomous virus replication in the cytoplasm of F. verticillioides cells. Characterization of four independent transformants harboring CHV1 showed a significant reduction in FB1 production compared to the parental uninfected strain and only moderate alterations in vegetative growth. The CHV1-associated reduction in FB1 was confirmed in maize grown under both greenhouse and field conditions. Our findings provide evidence that heterologous mycoviruses can modulate mycotoxin production in F. verticillioides, thus expanding the pool of viral species that can be explored as potential biocontrol agents in this pathogen. Further work will be required to elucidate the underlying mechanisms of CHV1-associated downregulation of FB1 production in F. verticillioides and assess its potential application in virocontrol strategies. Full article

The transition toward renewable energy in agricultural pumping requires robust decision-making tools capable of addressing multiple, often conflicting criteria. This study investigates the respective contributions of fuzzy weighting and fuzzy ranking within AHP–TOPSIS frameworks for photovoltaic (PV) self-consumption planning in agricultural pumping applications. Unlike conventional MCDM applications that focus on identifying a preferred alternative using a single classical or fuzzy formulation, this study systematically isolates the effects of fuzziness at the weighting and ranking stages. Four methodological configurations are comparatively analyzed: classical AHP–TOPSIS, fuzzy AHP–TOPSIS with fuzzy weighting, AHP–TOPSIS with fuzzy ranking, and a fully fuzzy AHP–TOPSIS approach incorporating both fuzzy weighting and fuzzy ranking. Triangular fuzzy numbers are employed to represent the vagueness and subjectivity inherent in expert judgments, which are commonly expressed using quantitative scales despite their imprecise nature. A real-world case study involving the planning of a self-consumption PV installation for an agricultural pumping system in southeastern Spain is used to assess and compare the four approaches. The results distinguish the effects of fuzzy weighting and fuzzy ranking on both criteria weights and alternative rankings, showing whether the differences between classical and fuzzy formulations arise primarily from the weighting stage, the ranking stage, or their combined application. Rather than assuming that fuzzy formulations provide universally superior results, the analysis identifies the specific circumstances and stages in which fuzzy modelling produces meaningful changes in the decision outcome. The findings contribute to sustainable energy planning by providing a systematic framework for PV self-consumption planning in agricultural pumping under uncertain and subjective decision environments. Full article

We present a brief review that highlights the importance of III-Nitride semiconductor compounds according to their structural, compositional, morphological, and optical properties, which have significant applications in new semiconductor devices and play a fundamental role in modern electronic and optoelectronic technologies. The importance of sputtering as a viable alternative for obtaining III-Nitride semiconductor compounds is discussed. This is due to its versatility, cost, ease of handling, and advantages provided by the physics of its operation in obtaining thin films compared to techniques such as metal–organic chemical vapor deposition (MOCVD), atomic layer deposition (ALD), and molecular beam epitaxy (MBE). The physics of the sputtering method is briefly and clearly described, including magnetron configurations, plasma generation, energy dependence of sputtering, reactive sputtering, hysteresis effects, target types, and the importance of temperature and working distance between the substrate and target. In addition, the review of the literature on the application of sputtering for obtaining III-Nitride semiconductor compounds is presented. Furthermore, this review also highlights the future of sputtering, which is moving towards high-power pulsation, atomic-level precision, and AI-driven automation due to the miniaturization of electronics, advances in green technology, and innovations in plasma control to increase film density and reduce target material loss. Full article

Patient-reported outcome measures (PROMs) in vision science are commonly evaluated using Cronbach’s alpha, yet Rasch-based statistics may provide different information about their reliability. This study compared Cronbach’s alpha, a Classical Test Theory (CTT) index, with Rasch person reliability and the person separation ratio across three vision-related questionnaires: the Symptom Questionnaire for Visual Dysfunctions (SQVD; n = 434), the Ocular Surface Disease Index (OSDI; n = 294), and the Quality of Vision questionnaire (QoV; n = 288), using retrospective data from unselected clinical populations. Cronbach’s alpha indicated acceptable internal consistency across all questionnaires (α = 0.80–0.87), whereas Rasch person reliability was lower (0.62–0.80) and person separation ratios ranged from 1.29 to 2.00, indicating more limited discrimination. Item reliability was generally high (0.90–0.97) overall but declined in subgroups with restricted score variability. Discrepancies were most pronounced in the OSDI, where estimates approached their theoretical floor when subgroups were defined by the questionnaire’s own scores. Cronbach’s alpha and Rasch-based statistics are not interchangeable and capture different aspects of measurement precision: alpha may overestimate internal consistency, whereas person reliability and the separation ratio provide complementary information about discriminatory capacity. These findings support reporting both CTT and Rasch-based reliability statistics when evaluating vision-related PROMs in clinical populations. Full article

Background: The timing of perceived exertion assessment within a resistance training set may influence physiological adaptation; this study aimed to directly compare first-repetition (RPE-1) and last-repetition (RPE-last) monitoring strategies applied to functional, neuromuscular, body composition, and cardiometabolic adaptations during elastic band resistance training in older adults. Methods: Forty sedentary older adults (n = twenty per group, sex-balanced) were randomly assigned to RPE-1 or RPE-last using the OMNI-RES elastic band scale during a 16-week, open-label high-intensity elastic band resistance training program, with blinded outcome assessment and data analysis; three withdrew during the intervention (RPE-1, n = 2; RPE-last, n = 1), and all forty randomized participants were retained in the intention-to-treat analysis via baseline carry-forward. Functional capacity, isokinetic knee and elbow strength (60 and 180°/s), DXA-assessed body composition, and fasting cardiometabolic biomarkers were evaluated pre- and post-intervention. Between-group effects were analyzed using ANCOVA with Benjamini–Hochberg false discovery rate (FDR) correction, whereas functional equivalence was assessed using Welch-corrected two one-sided tests (TOST) with percentile bootstrap against published minimum clinically important difference (MCID) margins. Results: Both groups improved significantly across most outcomes. For the primary outcomes, RPE-1 was associated with greater improvements across all eight isokinetic strength conditions after FDR correction, with adjusted between-group differences ranging from +7.86 to +18.38 Nm in favor of RPE-1, and all 95% CIs excluding zero (ηp² = 0.14–0.37). The Welch-corrected TOST demonstrated functional equivalence between monitoring strategies for all four functional outcomes in the primary intention-to-treat analysis. However, the pre-specified complete-case sensitivity did not confirm equivalence in the 30-Second Chair Stand Test, indicating that this outcome was sensitive to the handling of missing data. Among secondary exploratory outcomes, RPE-1 also was associated with greater improvements in DXA-assessed fat mass (adjusted difference—−1.33 kg; 95% CI—−2.02 to −0.63; ηp² = 0.29) and lean mass (+0.42 kg; 95% CI—0.02 to 0.83; ηp² = 0.11), high-density lipoprotein cholesterol (+5.11 mg/dL; 95% CI—1.52 to 8.69; ηp² = 0.18), and low-density lipoprotein cholesterol (−16.99 mg/dL; 95% CI—−23.22 to −10.76; ηp² = 0.45). Conclusion: RPE-1 appeared to confer greater benefits for maximizing neuromuscular strength, whereas RPE-last provides an equally valid alternative when preserving physical independence is the primary objective. Full article

Background/Objectives: Vegetation length is a guideline-endorsed criterion for surgery in left-sided infective endocarditis (LSIE). However, its measurement is highly variable with crucial implications for decision making. A standardized measurement system would not only facilitate decision making in these patients, but also cutoff-point optimization for improving clinical guidelines. For this purpose, this work introduces an Artificial Intelligence (AI)-based system capable of extracting vegetation length from standard transesophageal echocardiography (TEE). Methods: Five echocardiographers independently measured the vegetation length of 76 vegetations from 67 consecutive patients with LSIE using offline TEE images. The AI-based system was trained on a multicenter registry with 353 patients with LSIE, comprising 282,096 echocardiographic frames annotated by an independent expert. This system was applied to measure vegetation length as an independent observer. The variability and correlation between operators and the system were assessed. Results: Lin’s concordance correlation coefficient between the AI-based system and the mean of the measurements obtained by the echocardiographers was 0.74, comparable to the coefficient obtained between the echocardiographers themselves. Bland–Altman analysis showed a mean difference of −1.0 mm between the AI-based system and the mean of the measurements obtained by the echocardiographers. Conclusions: The AI-based system for vegetation measurement demonstrates a high level of correlation and agreement with experts, similar to the concordance between human operators themselves. This level of agreement suggests that the method has the potential to reduce inter-operator variability in the measurement process. Whether AI-based vegetation size improves embolism prediction has to be further investigated. Full article

This study systematically evaluates the impact of sensor configuration, body location, classification granularity, and model choice on inertial-based human activity recognition in a laboratory dataset aligned with the Spanish IMPaCT cohort design. Data were collected from 85 participants instrumented with thigh-, wrist-, and hip-mounted inertial measurement units over a structured protocol of 13 semi-structured daily activities, a resting phase and a structured activity. After manual correction of timestamp drift, signals were segmented into overlapping 10-s windows and analyzed using convolutional neural networks, Random Forest, and XGBoost classifiers.Two classification targets were defined: fine-grained recognition of 15 laboratory-controlled activities and coarse-grained classification into four MET-based intensity levels. Results showed that classification granularity is the primary determinant of performance ($F=224.85$, p-value = $2.304\times {10}^{-13}$ through the analysis of variance of the F1-score), with intensity-level classification substantially outperforming fine-grained activity recognition. Sensor configuration, model type, and body location also significantly influenced classification outcomes. Wrist-mounted sensors achieved the highest overall F1-scores. Incorporating gyroscope-derived features consistently improved performance across configurations, and feature importance analysis confirmed their substantial contribution. These findings, derived from models developed under controlled laboratory conditions, provide practical guidance for the design of wearable sensing protocols and modeling strategies in large-scale population-based studies, and support their extension to everyday physical activity, laying the foundation for future real-world applications. Full article

The increasing penetration of variable renewable energy sources requires flexible solutions to ensure system stability and economic efficiency. In this context, this study presents a comprehensive assessment of hybrid plants combining wind farms (WF) and photovoltaic (PV) systems integrated with battery energy storage systems (BESS), using the Casetona project in Spain as a real-world study. Three configurations (PV + WF + BESS, PV + BESS, and WF + BESS) are evaluated based on 2024 operational data combined with simulation tools. Under the assumptions of this study (2024 data, Spanish market), the results indicate that WF generation outperforms PV, mainly due to higher capacity factors and better alignment with high-price periods, while PV output is affected by price cannibalization. Under current Spanish market conditions and at the assumed BESS cost (236 €/kWh), energy arbitrage is not economically viable, yielding negative net present value across all configurations. In contrast, participation in automatic frequency restoration reserve services provides higher revenues under current Spanish market conditions, with the WF + BESS configuration achieving the best performance. From the perspective adopted in this study, the sustainability analysis reveals that the hybrid system enables annual greenhouse gas emissions reductions between 13,695 and 49,195 ${\mathrm{t}}_{C{O}_{2,eq}}$, depending on the displaced generation source. Although BESS does not directly reduce emissions, it enhances renewable integration, reduces curtailment, and improves grid flexibility. The results also highlight the importance of regulatory frameworks and market design in determining the economic viability of storage systems. While the quantitative results are specific to the case study and sensitive to regulatory parameters, this study provides a comprehensive and transferable methodology for evaluating hybrid renewable systems with storage, supporting informed decision-making in the transition toward low-carbon and resilient energy systems. Full article

The Petaquilla gold mine in Panama was abruptly closed without restoring the site. The objective of this study is to assess mine soils from a geochemical perspective, identify potential contaminants, and conduct a human health risk assessment (HHRA). Soil samples were analysed to determine pH, EC, OM, texture, hydrocarbons (TPHs), enzymatic activity (DHA), and the following potentially toxic elements (PTEs): As, Ba, Cd, Cu, Hg, Sb, Pb and Zn. The Igeo, PLI and HHRA indexes were evaluated. The Igeo indicates that the processing zone has atypical values of Cu (1.47), indicating moderate pollution (1 < Igeo ≤ 2), Zn (3.80), indicating strong pollution (3 < Igeo ≤ 4), and Pb (7.62), indicating extreme pollution (Igeo > 5), with enrichment due to mining activity. The PLI map shows that the affected areas are surrounding the Molejon River (1.62) and the processing zone (1.21), which are slightly contaminated (1 ≤ PLI < 2), and one site in the processing zone with moderate to considerable contamination (PLI ≥ 3) at the warehouse (6.07). Regarding TPHs, the processing area in front of transformer (54,844.47 mg kg⁻¹) and the workshop entrance (2045.26 mg kg⁻¹) have values above industrial use (620 mg kg⁻¹) due to visible hydrocarbon spills. In terms of HHRA, the non-carcinogenic risk associated with exposure to PTEs exceeds the reference threshold for both children and adults under a residential exposure scenario, whereas the non-carcinogenic risk for TPHs remains below the acceptable limit. Regarding carcinogenic risk, exposure to Pb and As remains within acceptable limits for both receptors. With a view to restoring the mine’s soil, the processing area and the workshop entrance are the first areas that need to be addressed. Full article

The common vole is one of the mammalian pests causing more agricultural damage in Europe. Since the late 1970s, this species has invaded the Duero valley in NW Spain, colonizing ca. 5 million ha of agricultural areas of the valley in about 20 years. Once settled in agricultural landscapes, the species experienced cyclic population outbreaks causing crop damages. The major vole population outbreak of 2006–2007 was managed by the Regional Government (Junta de Castilla y León, JCYL) mainly through large-scale application of anticoagulant rodenticides (ARs) and widespread destruction of field margins, natural vegetation patches, and crop stubbles by burning. These actions caused serious damage to regional agrarian biodiversity, including small game species. The coordinated action of scientific institutions and environmental NGOs, with the support of the main Spanish hunting association at a critical time, led to a progressive shift in pest management strategies during subsequent outbreaks, promoting the adoption of biological control and other management techniques causing less environmental damage. Finally, JCYL implemented an IPM program mainly based on biological control, good farming practices, and habitat management. This program has been increasingly adopted in recent years, leading to a marked reduction in chemical control and the complete elimination of burning as a tool of management. Over this period, the scientific knowledge of the species’ ecology has expanded substantially, providing key insights for the development and refinement of IPM strategies. Here, we synthesize this body of knowledge and provide additional recommendations to further improve the current IPM program, which may serve as a model for rodent pest management in other regions worldwide. Full article

This review, within the One Health framework, compiles information on plant-derived bioactive compounds and emphasises their multifunctional role in improving environmental, animal, and human health. These compounds support sustainable health and ecological stability by influencing biological and environmental processes. Data from literature research are combined to explain the mechanisms and potential uses of different key bioactive compounds. Mechanistic insights focus on their capacity to regulate oxidative stress, inflammation, and microbial balance, linking these effects to therapeutic benefits in human health, enhanced animal productivity, and environmental sustainability. These compounds show antioxidant, anti-inflammatory, antimicrobial, and metabolic activities, helping prevent chronic diseases, strengthen immunity, and reduce reliance on antibiotics and pollution. Examples like quercetin, resveratrol, and curcumin demonstrate their roles in modulating inflammatory and metabolic pathways to foster sustainable health and ecological balance. Bioactive compounds are linked to the One Health strategy, providing benefits across biological systems. Nonetheless, challenges such as variability, bioavailability, and standardization remain. Future directions should aim to develop sustainable extraction and formulation methods, leverage omics technologies and artificial intelligence for discovery and characterization, and foster industry partnerships to validate these compounds and secure global regulatory approval. Full article

Total electron scattering cross sections (TCSs) for NO₂ molecules have been measured with a magnetically confined electron beam transmission apparatus for impact energies ranging from 1 to 200 eV. The estimated total uncertainty limits are within ±5%. Moreover, integral elastic, ionization, electronic and rotational excitation cross sections in the (20–1000 eV) energy range have been calculated with our independent atom model-based screening corrected additivity rule including interference effects (IAM-SCAR+I) method. The cross-section data set derived from this study is critically compared with the recommended values available in the literature. Full article

Efficient and localized singlet oxygen (SO) generation is essential for improving antimicrobial photodynamic therapy (aPDT). In this study, a bis-imidazolium-based amphiphilic gelator is used, which self-assembles into a supramolecular gel in a water–ethanol medium and incorporates Rose Bengal (RB) as a photosensitizer. The gel network provides a confined environment that promotes SO formation under light irradiation. RB@Gel was characterized with respect to its morphology, degradation behavior, and swelling properties. Biopharmaceutical assessment included in vitro release, ex vivo permeation studies and Hen’s Egg Test–Chorioallantoic Membrane (HET-CAM) assay. Rheological measurements confirmed a viscoelastic profile, indicating structural stability and suitability for localized therapeutic applications. SO production within the gel was quantified using tetrasodium 9,10-anthracenediyl-bis(methylene)dimalonate (NaABMA), showing higher efficiency than that of RB in solution. The RB@Gel exhibited significant aPDT against E. coli in a direct-surface contact assay. Overall, the RB@Gel provides a stable, suitable platform capable of efficient SO generation and potent antibacterial activity, highlighting its promise for localized aPDT applications. Full article

The purpose of this work was to study water-soluble platinum complexes as potential therapeutic agents. We used water-soluble platinum(II) complexes containing sulfonated N-heterocyclic carbene ligands (NHC), applied on two human cell models: human NB4 acute promyelocytic leukemia and PC3 prostatic cancer cells. We studied the toxic effects on these two types of human tumor cells. We analyzed metabolic activity, membrane damage, cell cycle, DNA fragmentation and programmed cell death. In human NB4 leukemia cells, the water-soluble dimethyl NHC complex 5Me proved highly toxic. It extinguished cell metabolism at 1 mM for 24 h. This treatment gave rise to the presence of fragmented DNA (subdiploid DNA). This compound promoted programed cell death in 60% of the cells. At longer times, the treatments produced neither higher fragmentation of DNA nor augmented apoptosis. 5Me complex, at 100 µM, showed slight toxicity on NB4 cells. In PC3 cells, dimethyl complex 5Me (1 mM for 24 h) is less toxic (reduced DNA fragmentation and programmed cell death) than in NB4 cells. Mono-NHC complexes 4 and 5 treatments at a high concentration for 24 h on PC3 cells produced apoptosis (30% of the cells) but their damage on cell permeability and DNA fragmentation was weak. Thus, PC3 cells are more resistant to NHC platinum(II) complexes than NB4 cells. Full article