Search Results (875)

Chagas disease and trichomoniasis are two neglected parasitic infections (NPIs) in need for new therapies that address both the toxicity and limited bioavailability impacting on the effectiveness of benznidazole (BZ) and nifurtimox, the only drugs available for treating the infection caused by Trypanosoma cruzi, as well as the resistance that Trichomonas vaginalis has developed to 5-nitroimidazoles. Herein, we report the outcomes of the primary screening of a series of eighteen quinoxaline-1,4-di-N-oxides (QdNOs) carried out against both protozoan parasites. Computational approaches revealed that these derivatives have adequate oral bioavailability and do not pose toxicity risks associated with their chemical structures. Meanwhile, biological studies disclosed that compounds 4b and 4m exhibit considerable activity against T. cruzi at the highest concentration tested, showing 4m a trypanocidal profile (IC₅₀ = 23.66 µM) similar to that of BZ (IC₅₀ = 21.66 µM), and a selectivity index (SI) > 5.32. Regarding the activity on T. vaginalis, derivative 4n stands out with an IC₅₀ value of 9.85 µM, showing no cytotoxicity towards mammalian cells. However, their potency decreases when tested over resistant parasites. Alterations in either the hydrogenosomal membrane potential or the production of reactive oxygen species (ROS) were also explored. The findings suggest that the trichomonacidal activity of compound 4n is not mediated by a direct disruption of hydrogenosomal bioenergetics or a pro-oxidant effect. Altogether, these preliminary results support that the QdNO scaffold could be introduced as a proper template for developing novel trypanocidal and trichomonacidal agents. Full article

The holm oak (Quercus ilex) is a keystone species in Mediterranean ecosystems due to its ecological relevance and economic value. However, its forests are experiencing increasing decline driven by poor regeneration, prolonged drought, diseases, and wood-boring insect infestations. This study evaluates the impact of Coraebus florentinus on the mechanical properties of holm oak wood. Laboratory bending tests on healthy and insect-damaged branches assessed resistance in relation to applied load, diameter, and length until maximum deflection and breakage. Results showed that C. florentinus damage (considered as a categorical variable, it was not quantified based on the presence or absence of visible symptoms and characteristic larval galleries, and we acknowledge this as a limitation of the study) altered the bending behavior of holm oak branches, mainly by reducing deformation capacity before failure. However, bending strength showed a site-dependent response, indicating that the mechanical effect of infestation may vary according to local branch characteristics and damage distribution. Infestations of C. florentinus in Q. ilex stands, whether used for timber production or pasture systems, may contribute to the loss of photosynthetically active branches and potentially affect tree productivity. Full article

Primary succession following glacier retreat provides a natural system for testing whether soil development simply shifts fine roots along a single acquisitive–conservative axis orinstead changes the nutrient-acquisition pathway that dominates at the community level. We hypothesized a stage-dependent sequence, from substrate-limited exploration, to transient morphological capture, and finally to rhizosphere-mediated biochemical mobilization. To test this idea, we quantified fine-root morphology, absorptive-transport partitioning, anatomy, phosphatase activity, exudation, community-scale belowground structure, and soil and rhizosphere properties across woody communities representing approximately 20, 40, and 90 years since deglaciation in the Hailuogou Glacier foreland. Across succession stages, bulk density and pH declined, whereas field capacity, soil carbon, and soil nitrogen increased, indicating rapid development of the belowground resource environment. Fine-root strategies did not fall along a single acquisitive–conservative continuum. Instead, morphological nutrient capture peaked at intermediate succession: the 40-year stage had the highest specific root length, specific root area, absorptive-to-transport root length ratio, and root nitrogen concentration. In contrast, the 90-year stage showed lower specific root length but higher dry matter content, thicker cortex, greater standing fine-root biomass, larger rhizosphere volume, higher phosphatase activity, and greater area-based carbon exudation. This late-successional syndrome coincided with stronger extracellular enzyme activity, larger dissolved organic carbon and nitrogen pools, and higher microbial biomass, despite negative net nitrogen mineralization. Species-level analyses showed that biochemical-input traits were jointly shaped by successional stage, species identity, and their interaction. Together, these results show that primary succession did not simply increase or decrease root acquisitiveness. Instead, as soils developed, it changed the nutrient-acquisition pathway that dominated, with direct implications for nutrient cycling and vegetation dynamics in rapidly developing glacier-foreland ecosystems. Full article

Background: Fibromyalgia is a chronic condition characterized by a complex array of symptoms that impact multiple domains, including physical, psychological, and social aspects of an individual’s well-being. Although home-based adapted physical activity (HAP) interventions represent a promising strategy to improve health-related physical fitness (PF), studies on the topic are still lacking and further research is required. The objective of the present study was to evaluate the impact of participation in a 12-week HAP intervention on health-related PF in adult women with fibromyalgia syndrome (FS). Methods: Participants were women with fibromyalgia (n = 29; 47.1 ± 9.5 yrs) assigned to the 12-week HAP program (n = 17) or wait-list control group (n = 12). Participants completed two weekly circuit-training sessions delivered through an online platform. PF components were assessed through a standardized test battery: 30-s chair stand (lower-body strength), arm curl (upper-body strength), 2-min step (cardiorespiratory fitness), back scratch (flexibility) and 8-foot up-and-go test (agility and balance). Three time-point evaluations were planned: at baseline (T0), after 6 weeks (T1), and after 12 weeks (T2). Linear mixed models were used, and partial eta-squared (η²p) effect sizes were calculated. Results: A significant time × group interaction emerged for upper body strength (p = 0.001; η²p = 0.404), agility (p < 0.001; η²p = 0.569) and cardiorespiratory fitness (p = 0.009, η²p = 0.292). Specifically, from baseline to 12 weeks, the experimental group improved in the arm-curl test (from 15.8 ± 4.5 to 18.9 ± 5.0 repetitions), agility (from 6.6 ± 1.5 to 5.2 ± 1.1 s), and cardiorespiratory fitness (from 69.1 ± 18.8 to 77.2 ± 21.1 repetitions), while the control group showed no meaningful changes. Conclusions: The participation in a 12-week HAP intervention had a positive impact on different components of PF in women with FS, which may have implications for greater physical autonomy and well-being. Full article

Background and Clinical Significance: Alpha-1 antitrypsin deficiency (AATD) is an autosomal codominant disorder caused by pathogenic variants in the SERPINA1 gene, resulting in reduced circulating alpha-1 antitrypsin (AAT) or production of dysfunctional protein. AAT is the principal inhibitor of neutrophil elastase, and its deficiency leads to unchecked proteolytic activity, progressive destruction of lung parenchyma, and increased susceptibility to infections. Severe deficiency, particularly in individuals homozygous for the Z allele (PI*ZZ), predisposes to early-onset panacinar emphysema, chronic airflow obstruction, and liver disease. Despite its clinical relevance, AATD remains markedly underdiagnosed and is frequently misclassified as smoking-related chronic obstructive pulmonary disease (COPD), delaying access to disease-modifying therapy, genetic counselling, and preventive strategies. Early recognition is therefore essential to improve outcomes. Case Presentation: We report the case of a 68-year-old ex-smoker with a long-standing diagnosis of “COPD” who presented with acute-on-chronic type 2 respiratory failure and community-acquired pneumonia. Spirometry revealed severe airflow obstruction, and high-resolution computed tomography demonstrated extensive basilar panlobular emphysema, raising suspicion for AATD. Serum AAT concentration was critically low at 26.8 mg·dL⁻¹, and isoelectric focusing confirmed a PI*ZZ phenotype. Next-generation sequencing identified homozygosity for the SERPINA1 c.1096G>A (Z) variant, with no additional pathogenic alleles. Cascade family screening revealed multiple heterozygous PI*MZ relatives. Before augmentation therapy could be initiated, the patient developed severe Legionella pneumophila pneumonia with secondary bacterial superinfection, progressing to refractory septic shock and death. Conclusions: This case illustrates how AATD can masquerade as smoking-related COPD for years, leading to missed opportunities for timely intervention. It underscores the importance of testing all adults with COPD or refractory asthma at least once, regardless of age or smoking history. Early diagnosis enables initiation of augmentation therapy, targeted vaccination, lifestyle modification, and genetic counselling, ultimately improving prognosis and reducing preventable morbidity and mortality. Full article

Cattle behavior constitutes important phenotypic information reflecting animals’ health status, activity level, and welfare condition, and is therefore of considerable significance for automated monitoring and precision management in smart livestock farming. However, under complex barn conditions, cattle behavior recognition is easily affected by factors such as illumination variation, partial occlusion, background interference, and individual differences, thereby reducing recognition stability and generalization capability. To address these challenges, this study proposes a pose-driven method for cattle behavior recognition in complex barn environments. First, a 16-keypoint annotation scheme suitable for describing bovine posture, termed cow16, was constructed. Based on this scheme, OpenPose was employed to extract heatmaps (HMs) and part affinity fields (PAFs), which were then used to build an intermediate HM/PAF posture representation. Subsequently, this representation was taken as the input to a lightweight convolutional neural network for classifying three behavioral categories: stand, walk, and lying. On this basis, class-imbalance correction during training and a multi-random-seed logits ensemble strategy during inference were further introduced. In addition, knowledge distillation was adopted to transfer knowledge from a high-performance teacher model to a lightweight student model. Experimental results demonstrate that training-stage class-imbalance correction and inference-stage multi-random-seed logits ensembling exhibit strong complementarity; when combined, the AB configuration improves the test-set Macro-F1 by 3.83 percentage points. Moreover, the distilled student model still achieves competitive recognition performance while maintaining 1× inference cost, indicating a favorable trade-off between accuracy and efficiency. This study provides a useful reference for deployment-oriented cattle behavior recognition in smart farming scenarios and offers a lightweight technical basis for subsequent practical applications. Full article

Background: This study aimed to examine whether a physical education program based on the ecological dynamics approach, implemented through small-sided games (SSG), produces greater improvements in motor skills, daily physical activity levels, and perceived physical fitness in middle school students. Methods: Forty-eight students were assigned to an SSG group (ecological dynamics lessons including small-sided games, n = 26) or a Control group (traditional lessons based on teacher-centered instruction and analytical exercises, n = 22). The intervention lasted 12 weeks, with two sessions per week. Motor performance was assessed using the standing broad jump, 5-standing broad jump, 20 m sprint, 10 × 5 m shuttle run, 5-0-5 agility test, and sit-and-reach test. Daily physical activity was evaluated using the International Physical Activity Questionnaire—Short Form (IPAQ-SF), and perceived physical fitness was assessed using the Visual Analogue Fitness Perception Scale for Adolescents (FPVASA). Results: Significant group-by-time interactions were found in all motor tests. IPAQ-SF data revealed significant group-by-time interactions for vigorous and moderate physical activity. Perceived physical fitness showed significant group-by-time interactions for all items except flexibility. Conclusions: Physical education lessons structured according to the ecological dynamics approach and implemented through SSG-based protocols led to greater improvements than traditional methods. The dynamic and variable nature of SSG likely enhances neuromuscular stimulation, motor engagement, and motivation during physical education lessons. Full article

Urban trees are increasingly deployed as nature-based infrastructure to mitigate heat and manage stormwater, yet quantitative guidance on how species traits and site context shape transpiration remains fragmented. We conducted a systematic metadata analysis of seven field studies that measured daily transpiration rate in urban settings using heat-pulse methods. The units and spatial scales reported were harmonized with the sap flow density across active sapwood (J_s, g H₂O/${\mathrm{cm}}^2$/day) by converting reported stand transpiration and the outer 2 cm of sapwood sap flux using established Gaussian radial distribution functions for angiosperms and gymnosperms, which account for the non-linear decline in sap flux from the vascular cambium to the heartwood boundary. We then summarized distributions and tested group differences with Kruskal–Wallis and Dunn post hoc comparisons across wood anatomy, climate, soil texture, and planting configuration. Conifers exhibited significantly lower median $J_s$ (39.76 g/${\mathrm{cm}}^2$/day) than angiosperms, while the ring-porous group (median $J_s$ = 92.25 g/${\mathrm{cm}}^2$/day) and diffuse-porous groups (median $J_s$ = 96.70 g/${\mathrm{cm}}^2$/day) had similar distributions overall. Climate-modulated responses within wood anatomy groups differed, with diffuse-porous species exhibiting the highest median $J_s$ (152.59 g/${\mathrm{cm}}^2$/day) in semi-arid regions, ring-porous species maintaining comparatively stable median $J_s$ across climates (varying slightly between 80.72 and 99.32 g/${\mathrm{cm}}^2$/day), and conifers reaching their highest median $J_s$ (69.90 g/${\mathrm{cm}}^2$/day) in humid continental sites. Soil texture effects were consistent with moisture availability: sandy loam generally reduced $J_s$ relative to loam or silt loam for conifers and diffuse-porous species. Across anatomies, single trees transpired more than clustered trees or closed canopies. For example, planting as single trees increased median $J_s$ by 86% in conifers (from 33.01 to 61.37 g/${\mathrm{cm}}^2$/day) and by 45% in diffuse-porous species (from 81.31 to 118.25 g/${\mathrm{cm}}^2$/day). These results provide actionable ranges and contrasts to inform species selection and planting design for urban greening and runoff reduction, while highlighting data gaps for future research. Ultimately, by matching specific wood anatomies and planting configurations to local soil and climatic conditions, urban planners and ecohydrologists can strategically optimize urban forests to maximize targeted ecosystem services. Full article

Welders constitute an occupational group that is particularly exposed to high-risk hazards arising from harmful radiation emitted during welding, including ultraviolet (UV) and infrared (IR) radiation, as well as visible (VIS) radiation, whose high intensity causes glare. Effective protection of the eyes and face is provided by welding shields equipped with automatic welding filters (AWFs), which activate automatically upon arc ignition. Their switching time is the most important protective parameter, as it has a direct impact on the user’s visual health. The objective of the work is to present a novel test stand for determining AWFs switching and holding times, which provides advanced possibilities for evaluating all types of AWFs. Until now, performance and safety levels have been determined based on numerical values: switching time and hold time. For the first time, it is possible to analyze the darkening and clearing phenomena over time with an interpretation of graphical results. Importantly, it is possible to analyze the symmetry of filter properties, using two measurement channels, which is crucial for binocular and curved (panoramic) AWFs. The results obtained for two types of AWFs mounted in goggles with a one-piece and a binocular visor differ from each other. Switching time differences between the left and right measurement channels were about 6–7% for the one-piece visor goggles (G1) and about 3–4% for the binocular goggles (G2). The dispersion of results confirmed the importance of the two measurement channels, which was not previously practiced. The test stand, designed in accordance with the requirements of the new European standards (EN ISO 18526-2:2020, EN ISO 16321-2:2021), can be used for prototyping and for AWF certification purposes. Full article

Background and Clinical Significance: Isolated prolongation of activated partial thromboplastin time (aPTT) without a bleeding tendency presents a frequent diagnostic challenge and often leads to prolonged, inconclusive evaluations. Case Presentation: We report the case of a pregnant woman with long-standing isolated aPTT prolongation in whom clinical exome sequencing enabled a definitive diagnosis. Two compound heterozygous variants in F12 were identified: NM_000505.4:c.1561G>A, p.(Glu521Lys), previously reported in Factor XII deficiency, and a novel in-frame insertion, NM_000505.4:c.1423_1425dup, p.(Cys475dup), absent from population databases and the prior literature. Familial genetic testing confirmed a trans configuration. Factor XII activity was markedly reduced to 1%, and mixing studies showed complete correction, consistent with coagulation factor deficiency without inhibitors. Variant interpretation using ClinGen specifications within a Bayesian framework classified both variants as likely pathogenic. Despite significant laboratory abnormalities, the patient experienced no bleeding or thrombotic complications and underwent cesarean delivery without adverse events. Conclusions: This case highlights that early integration of next-generation sequencing and quantitative variant interpretation frameworks can facilitate timely diagnosis, clarify clinical significance, and support appropriate management in patients with unexplained isolated aPTT prolongation. Full article

Wind energy stands as one of the most technologically mature renewable sources, playing a pivotal role in the mitigation of greenhouse gas emissions. However, wind farms and associated infrastructures increase collision risk for flying organisms. Implementing higher cut-in speeds is a proven mitigation strategy to significantly decrease wildlife mortality rates, particularly for bat species, by preventing turbine operation during low-wind periods of high activity. The suggested, non-standard, increased cut-in speed for wind turbines is generally 5.0 m/s. To test the effectiveness of cut-in speed increase, bat activity was monitored at three wind farms in northern Portugal (Gevancas, Azinheira, and Lagoa de Dom João e Feirão), to characterize spatial and temporal activity patterns and assess the potential associated risk. Ultrasonic acoustic detection was carried out at fixed stations, at heights of 55 m above ground level from March to October. Wind speed data were recorded concurrently using anemometers mounted on meteorological towers. Contradicting recommendations, the results show that significant bat activity might occur at wind speeds above the current curtailment values. Since turbine operation coincides with peak bat activity, it is imperative to implement site-specific mitigation strategies, such as optimized cut-in speeds, to minimize mortality risk. Full article

This study examines the relationship between house prices and the factors driving their growth during the transition from a long-standing currency board regime to Eurozone membership. The main objective is to identify and quantify the key factors explaining the variation in house price growth in Bulgaria under conditions of prolonged currency convergence. The study applies a set of econometric techniques, including stationarity tests (ADF and KPSS), diagnostic checks for normality, serial correlation and heteroscedasticity, and robustness checks. The study is based on 40 quarterly observations covering the period 2015Q4–2025Q3 and 48 selected predictors of the General house price index. The final ARIMAX(0,2,1) model is estimated using second-differenced data. The model includes a first-order moving average component and three exogenous regressors: the owner-occupiers’ housing expenditures, the actual rentals for housing in Bulgaria and the homeowners’ utility expenses. The model explains 87% of the variation in house price acceleration, with a comparatively low mean squared error. The diagnostic analysis confirms model adequacy. The three exogenous regressors are statistically significant at the 1% level with strong and stable effects on house price dynamics. No statistically significant relationship is found for the set of traditional macroeconomic, demographic, financial, and sectoral factors. The results show that during Bulgaria’s transition from a currency board to the Eurozone, the sustained house price growth was driven by country-specific factors. The three statistically significant determinants of the house price acceleration in Bulgaria reflect, respectively, the active investment behaviour of homeowners in improving existing properties, the rational assessment by housing market participants of the balance between mortgage and rental payments, and the burden of utility and maintenance costs borne by owners and tenants, depending on property size and energy efficiency. The first factor is most influential for homeowners, the second for tenants, and the third has a similarly significant impact on both groups. Full article

Among the naturally abundant clays in the Earth’s crust, montmorillonite (MMT), a member of the smectite group, stands out for its versatility. Its interesting properties can be further improved by chemical processing with inorganic acids and reaction temperatures close to boiling. In this study, a Brazilian polycationic MMT was treated with a low-concentration (2M) aqueous solution of hydrochloric acid at 60 and 70 °C for 5 h. The resulting modified clay was then employed in the purification of post-consumption oil (PCO), specifically soybean oil. The effect of the modification variables of the clay and also the purification parameters (time and temperature) were investigated, comparing the adsorptive and purification capacities of the modified MMT with those of the natural and a commercial clay sample. The characterization of the MMT (raw and modified) was carried out by bulk density, moisture content, plasticity limit, BET, SEM/EDS, XRD, and FTIR, whereas the characterization of the PCO, as-received and after purification, involved the analyses of apparent density, relative flow time, UV-Vis spectrophotometry, and acid value. The results show that light acid activation, especially at 70 °C, promoted a significant increase in the surface area up to 96% and the adsorption capacity of the clay. The oil purification showed good results in all tests, with the best condition being 70 °C for 24 h with the C70 clay. Thus, the satisfactory results represent an economy of time and energy. Full article

Amid the accelerating spread of antibiotic resistance, medicinal and aromatic plants stand out as powerful natural reservoirs of bioactive compounds, offering innovative prospects for next-generation antimicrobial therapies. To explore its therapeutic potential, this study evaluated the antimicrobial and antioxidant activities of Matricaria pubescens from Southeastern Morocco, supported by a thorough chemical profiling of its essential oils. The oils were obtained by steam distillation and analyzed using gas chromatography–mass spectrometry (GC–MS). The results revealed two distinct chemotypes, with isochrysanthemic ethyl ester (32.7%) as the dominant compound in chemotype EO1 and α-ocimene (19.62%) as the major constituent in chemotype EO2. Antioxidant activities were assessed using DPPH, ABTS, and reducing power assays, while antimicrobial activities were evaluated against bacteria, fungi, and yeasts using both disc diffusion and broth microdilution methods. Both oils exhibited notable antioxidant activities. Significant antimicrobial effects were observed, with Bacillus subtilis, Escherichia coli, and Staphylococcus aureus being the most sensitive strains, whereas Pseudomonas aeruginosa exhibited the highest resistance among all tested microorganisms, with the lowest MIC recorded for B. subtilis (0.612 mg/mL). These findings emphasize that M. pubescens could serve as a valuable source of biologically active compounds, particularly in the development of agents to combat microbial resistance, and further support its potential applications in pharmaceutical, cosmetic, and food industries. Full article

Background: Type 2 diabetes mellitus (T2DM) is characterized by chronic low-grade inflammation that contributes to cardiometabolic complications. While diabetes duration reflects cumulative metabolic exposure, its relationship with systemic inflammatory burden remains insufficiently defined. We aimed to investigate inflammatory patterns across diabetes duration and to explore their metabolic and cardio–renal correlates. Methods: This real-world cross-sectional study included 250 adults with T2DM. Diabetes duration was analyzed both continuously and across four predefined strata (0–4, 5–9, 10–14, and ≥15 years). Inflammatory burden was assessed using C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Given the skewed distribution of CRP, log-transformed CRP was used in regression analyses. Nonlinear associations were evaluated using quadratic regression models. This approach was selected because preliminary descriptive analyses suggested a non-monotonic relationship between diabetes duration and CRP levels. Inclusion of a quadratic term allowed formal testing of a potential curvilinear association between diabetes duration and inflammatory burden. Spearman correlations were performed to assess associations with metabolic, renal, and cardiovascular variables. Results: CRP showed a nonlinear cross-sectional association across diabetes duration strata. Median CRP values were higher in early (0–4 years: 0.62 mg/L) and long-standing diabetes (≥15 years: 0.77 mg/L) compared with intermediate-duration groups (p = 0.063). Quadratic regression confirmed a U-shaped relationship (adjusted β_duration = −0.079, p < 0.001; β_duration² = 0.0027, p < 0.001; R² = 0.326). ESR differed significantly across duration strata (p = 0.002), with the highest levels observed in long-standing diabetes. CRP correlated positively with BMI (ρ = 0.151; p = 0.017) and triglyceride-to-HDL ratio (ρ = 0.215; p < 0.001), but not with HbA1c. Both CRP and ESR were more strongly associated with functional CKD (ρ = 0.350 and 0.429, respectively; p < 0.001) than with ASCVD. Conclusions: Inflammatory burden in T2DM shows a nonlinear cross-sectional pattern across diabetes duration, characterized by elevated levels in early and long-standing disease. Systemic inflammation appears more closely linked to renal dysfunction than to established cardiovascular disease. These findings support a cardio–renal–inflammatory axis in which prolonged diabetes exposure contributes to renal decline, which in turn amplifies systemic inflammatory activation. Full article