Search Results (250,953)

According to the World Health Organization, cancer is still the leading cause of death for humans worldwide. Although over 100 chemotherapeutic agents are currently available for the treatment of cancer patients, the overall long term clinical benefit is disappointing due to the lack of effectiveness or severe side effects from these drugs. The use of complementary and alternative medicinal products from plants has continued to increase in past decades, due to fewer side effects of bioactive compounds from medicinal plants of which pentacyclic triterpenoids have been identified as one class of secondary metabolites that could play an important role in the treatment and management of a number of non-communicable diseases. The main aim of this study is to extract, isolate, identify, and elucidate pentacyclic triterpenoid (ursolic acid, UA (1), and oleanolic acid, OA (2)) from Mimusops caffra. Semi-synthesis of UA was carried out to obtain some triterpenoid derivatives (3-O-acetyl ursolic acid, AUA (3), ursolic-28-methylate, UM (4), and 3-acetylursolic-methylate, AUM (5)), and we evaluated these compounds as anti-cancer therapeutic agents. Isolation of ursolic acid (UA) (1) from M. caffra is always accompanied by its isomer oleanolic acid (OA) (2) due to their similar retention factors (Rf) values. Acetylation and deacetylation techniques were used to isolate compounds 1 and 2. In vitro cytotoxicity activities of UA, AUA UM, and AUM were evaluated against various cancer cell lines, such as human breast adenocarcinoma cancer cell lines (MDA), human liver cancer cell lines (HepG2), human prostate cancer cell lines (PC3) and non-cancerous human fibroblast cell lines (KMST-6) using MTT assays. The UM exhibited remarkable cytotoxic activities against cancer cells, while little or no activities were observed on non-cancerous cell lines, which indicates that the addition of methyl at C-28 of UA is essential to enhance its activity as a therapeutic agent for cancer. The AUA showed moderate or no cytotoxicity against the different cancer cell lines, which is less than that of the UA parent compound. Moreover, these results suggest that ursolic acid and UA derivatives are potential therapeutic drugs for human breast, liver, and prostate cancers. Full article

Background: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by poor prognosis and limited therapeutic options. Chemotherapy regimens are associated with significant adverse effects negatively impacting patients’ quality of life (QoL). This systematic review aims to evaluate and compare QoL outcomes of patients with TNBC receiving novel therapies—including immunotherapy, antibody–drug conjugates, and targeted therapies—versus standard chemotherapy. Methods: We systematically reviewed randomized controlled trials (RCTs) published within the past 15 years, identified through comprehensive searches in PubMed, Google Scholar, Research4Life, and Elicit. Included studies involved FDA-approved novel therapies (pembrolizumab, atezolizumab, sacituzumab-govitecan, olaparib, and talazoparib) administered to TNBC patients, and assessed QoL using validated tools such as EORTC QLQ-C30. Observational studies, case reports, and non-standardized assessments were excluded. Results: Eight RCTs comprising 3929 patients met the inclusion criteria. Sacituzumab govitecan and PARP inhibitors (olaparib and talazoparib) significantly improved QoL, notably delaying deterioration across physical, emotional, and functional domains compared to standard chemotherapy. Conversely, immunotherapies (pembrolizumab, atezolizumab) showed non-significant trends toward QoL improvement, with effects varying by patient subgroup and disease stage. Interpretation was limited by study design differences, inconsistent compliance, and incomplete data reporting. Conclusions: Immunotherapy showed a neutral effect on quality of life, providing neither significant improvement nor additional decline. Olaparib was associated with a delayed deterioration in quality of life, showing a more favorable tolerability profile compared to chemotherapy. Talazoparib leads to clinically meaningful enhancements in quality of life, while sacituzumab govitecan effectively improves patient-reported outcomes relative to standard chemotherapy. Full article

This study examines the impact of varying pulse conditions on the properties of titanium diboride (TiB₂) coatings deposited by high-power impulse magnetron sputtering (HiPIMS). The coatings were prepared on steel substrates using an industrial-scale system. During the experiments, the HiPIMS frequency and pulse width were systematically varied to examine their influence on the coating’s microstructural, mechanical, and tribological properties. The obtained results show a correlation between process parameters and coating performance. A maximum hardness of 39.7 GPa and a coefficient of friction (CoF) as low as 0.68 were achieved. The best combination of mechanical properties was observed for coatings prepared in a frequency range of 600–1000 Hz and with a pulse width of 50 µs. Notably, the optimal tribological properties and surface roughness were obtained at 800 Hz and a 50 µs pulse width. This work demonstrates that fine-tuning HiPIMS pulse conditions is crucial for achieving high-quality TiB₂ coatings with enhanced functional performance. Full article

Feline lymphoma, a common neoplasm in cats, presents across diverse anatomical sites and is influenced by genetic, immune, environmental, and viral factors. This 15-year retrospective study analyzed feline lymphoma cases from the University of Zagreb’s Department of Veterinary Pathology, focusing on epidemiology, anatomical distribution, and immunophenotype. A bimodal age distribution was observed, with peaks at 2–3 and 10–12 years, and breed predispositions were noted in British and European Shorthairs after adjusting for referral frequency. Multicentric lymphoma was the most frequent type observed, followed by alimentary and mediastinal forms. Mediastinal lymphoma predominated in younger cats, whereas alimentary lymphoma was more common in older individuals. Male cats were overrepresented among renal lymphoma cases. Feline leukemia virus/feline immunodeficiency virus (FeLV/FIV) infection showed a strong correlation with mediastinal lymphoma. Overall, B-cell lymphomas were predominant; however, T-cell types were more frequently observed in European Shorthairs. In our study, mediastinal forms were uniformly T-cell, while alimentary and multicentric lymphomas were predominantly B-cell. Temporal trends showed surges in 2016–2017 and 2022–2023, and a decline during the COVID-19 pandemic. These findings highlight the complexity of feline lymphoma and underscore the need for tailored diagnostic and therapeutic strategies. Full article

Cholesterol, triglycerides, high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), and very-low-density lipoproteins (VLDLs) were evaluated in chimpanzees at Tacugama Chimpanzee Sanctuary, Sierra Leone. Blood from 75 visually healthy chimpanzees was collected, centrifuged within one hour of collection, and analyzed at Choithram Hospital within 24 h. Statistical analyses assessed differences and interactions based on age, body condition score (BCS), housing group, and sex. HDLs varied widely by housing group; HDLs and LDLs were higher in males than in females. Cholesterol and LDLs were higher in prepubertal individuals while VLDLs and triglycerides were higher in postpubertal individuals. Lipid biomarker differences by age and age * sex statistical interactions were not observed. These data represent a novel compilation of serum lipid biomarkers from a large population of sanctuary-housed Western chimpanzees (Pan troglodytes verus) within a range country, a population not previously studied with regard to serum lipid biomarkers. This study has documented significant differences compared to known values from managed chimpanzees and human reference ranges. The relationship of serum lipid biomarkers with health and disease in great apes remains understudied, but the present data set provides a basis for future studies to ascertain whether these differences are healthy biomarker variations or represent an elevated risk factor for disease. Full article

Consumer choices are largely influenced by sustainability, necessitating SMEs from the agri-food sector to strategically address sustainability and innovate their business models. Nonetheless, the challenge for such sustainable leadership lies in maintaining an equilibrium between innovation, sustainability, and financial performance. This study examined how strategic leadership fosters sustainability-oriented innovation within SMEs exemplified by the wine industry. A survey involving 354 German wineries served to analyze a multi-dimensional concept of innovation clusters (early adopters, pragmatists, pioneers, skeptics, conservatives), type of innovation, sustainability orientation, strategic ambitions, and business performance. Exploring the adoption of fungus-resistant grape varieties (FRV) allowed investigating how sustainability transitions to meet EU Green Deal targets are shaped by strategic groups involving strategic positioning and innovation clusters. There was a correlation between stronger sustainability orientation with greater innovation (Means up to 4.39). As per the findings, it was observed that high scores (p < 0.001, η² = 0.144–0.160) in market and process innovation were obtained by early adopters and pioneers. These innovation champions excel in economic and social sustainability (p < 0.001) but nonetheless were found to be financially underperforming (Means 1.97–2.18). Innovations that were applied enhanced innovation scores (η² = 0.128) but did not improve immediate performance. The strongest performance (Mean 2.60) was reported by skeptics though they fared poor in terms of sustainability and innovation. It was also noted that early adopters and pioneers (44–45%) were leading in FRV adoption, while a lag was observed within premium-oriented organizations. These insights may motivate SMEs in their quest for strategic sustainability and allow fine-tuning political and societal measures to achieve a sustainable transition and quantified Green Deal ambitions. It was concluded that long-term positioning was improved by sustainability-driven innovation, however, it would involve short-term performance trade-offs for SMEs. Political support should motivate the sustainable leadership champions to also safeguard profitability. Full article

The indiscriminate use of antibiotics in food-producing animals serves as a major catalyst for the emergence of antibiotic-resistant infections. This study aimed to assess the genetic diversity and antibiotic resistance of Enterobacterales in animal-derived foods. A total of 905 animal-derived food samples, including meat, dairy, poultry, fish, and environmental sources, were collected from various locations in Pakistan. Isolates were confirmed through selective subculturing, morphological, biochemical, and MALDI-TOF analysis, followed by antibiotic susceptibility testing. Subsequently, PCR-based detection of antibiotic resistance genes and virulence-associated genes. Overall, a total of 263 (29.06%) Enterobacterales were identified, as follows: 58.55% (154/263) E. coli, 6.84% (18/263) K. pneumoniae, 21.29% (56/263) P. mirabilis, and 13.30% (35/263) Salmonella spp. Isolates showed a varying resistance pattern against different studied antibiotics, e.g., beta-lactams and inhibitors, ciprofloxacin, and tetracycline, while colistin and tigecycline remained most effective. All the isolates displayed an array of antibiotic resistance and virulence-associated genes. Particularly significant (<0.05) co-existence of bla_NDM and mcr-1 was observed among the Enterobacterales isolated from various animal-derived foods. This study underscores the need to monitor Enterobacterales in animal-derived foods, especially in developing countries, to curb the spread of resistant pathogens and ensure effective food safety measures. Full article

Rising ocean temperatures due to climate change, combined with the intensification of anthropogenic activity, may lead to changes in the physiology and distribution of native species. Compounding climate stress, microplastic particles (MPs) enter the oceans through wastewater and the breakdown of macroplastics. Depending on their composition, they can be harmful and act as a vehicle for toxic substances, although their effects on native Antarctic and subantarctic species are unknown. Notothenioid fish are members of this group and are found inside and outside Antarctica, such as the Harpagifer, which has adapted to the cold and is particularly sensitive to thermal increases. Here, we aimed to evaluate the innate immune response in the head kidney, spleen, and foregut of two notothenoid fish, Harpagifer antarcticus and Harpagifer bispinis, exposed to elevated temperatures and PVC (polyvinyl chloride) microplastics. Adults from both species were collected on King George Island (Antarctica) and Punta Arenas (Chile), respectively. Specimens were assigned to a control group or exposed to a temperature increase (TI) or PVC microplastics (MPs), separately or in combination (MPs + TI). MP exposures were oral (gavage) for 24 h or aqueous (in a bath) for 24 and 48 h. Using real-time qPCR, we evaluated the relative gene expression of markers involved in the innate immune response, including tlr2 (toll-like receptor 2), tlr4 (toll-like receptor 4), myd88 (myeloid differentiation factor 88), nfkb (nuclear factor kb), il6 (interleukin 6), and il8 (irterleukin 8). We found differences between treatments when H. antarcticus and H. bispinis were exposed independently to MPs or thermal increase (TI) in the experiment with a cannula, showing an up-regulation in transcripts. In contrast, a down-regulation was observed when exposed in combination to MP + TI, which looked to be tissue-dependent. However, transcripts related to innate immunity in the bath experiment increased when exposure to both stressors was combined, mostly at 48 h. These results highlight the importance of evaluating the effects of multiple stressors, both independently and in combination, and whether these species will have the capacity to adapt or survive under these conditions, especially in waters where temperature is increasing and pollution is also rising, primarily from MP-PVC, a plastic widely used in various industries and among the population. Full article

Accurate automatic sleep stage classification from single-channel EEG remains challenging due to the need for effective extraction of multiscale neurophysiological features and modeling of long-range temporal dependencies. This study aims to address these limitations by developing an efficient and compact deep learning architecture tailored for wearable and edge device applications. We propose MultiScaleSleepNet, a hybrid convolutional neural network–bidirectional long short-term memory–transformer architecture that extracts multiscale temporal and spectral features through parallel convolutional branches, followed by sequential modeling using a BiLSTM memory network and transformer-based attention mechanisms. The model obtained an accuracy, macro-averaged F1 score, and kappa coefficient of 88.6%, 0.833, and 0.84 on the Sleep-EDF dataset; 85.6%, 0.811, and 0.80 on the Sleep-EDF Expanded dataset; and 84.6%, 0.745, and 0.79 on the SHHS dataset. Ablation studies indicate that attention mechanisms and spectral fusion consistently improve performance, with the most notable gains observed for stages N1, N3, and rapid eye movement. MultiScaleSleepNet demonstrates competitive performance across multiple benchmark datasets while maintaining a compact size of 1.9 million parameters, suggesting robustness to variations in dataset size and class distribution. The study supports the feasibility of real-time, accurate sleep staging from single-channel EEG using parameter-efficient deep models suitable for portable systems. Full article

Coastal upwelling off La Guajira, Colombia, is an atypical system where persistent easterly winds drive upwelling along a zonally oriented coastline. To characterize its seasonal cycle and variability, the ROMS AGRIF hydrodynamic model was implemented under climatological forcing. Three indicators were analyzed: the 25 °C isotherm, the 36.5 isohaline, and sea-level anomalies. The simulations showed that upwelling initiates in December, reaches maximum intensity during February–April, and weakens from September to November. At maturity, vertical velocities up to 8.5 m·day⁻¹ and the shoaling of Subtropical Underwater (T = 22–25 °C; S = 36.5–37.0) dominate the coastal domain, producing widespread surface cooling (23–24 °C) and salinity enhancement. During relaxation, weaker winds and the influence of the Caribbean Coastal Undercurrent displace the upwelled waters to below 80–100 m in depth, with surface temperatures above 27 °C. Model performance against MODIS Aqua SST was high (d > 0.99; RMSE < 1.7 °C), confirming its reliability to reproduce the observed thermal cycle. The multiparametric approach reveals that upwelling persistence depends on both seasonal trade wind forcing and regional circulation. This framework provides a more integrated description of the Guajira upwelling system than previous studies and supports applications in fisheries management, ecosystem monitoring, and maritime operations. Full article

Background: Goalkeeper actions directly influence match outcomes and overall team performance. Neuromuscular determinants (e.g., perception–action coupling, reaction speed, rate of force development (RFD), balance, etc.) translate into higher save probability, faster second actions, and more accurate distribution. Objectives: This systematic review analysed neuromuscular performance factors in 11-a-side football goalkeepers and examined how these factors evolve across age and sex groups. Methods: The review adhered to the PRISMA 2020 Statement guidelines. A systematic search was conducted using the PubMed, Web of Science, SPORTDiscus, PsycINFO, Dialnet, LILACS, and Scopus databases. Studies that assessed any aspect of goalkeepers’ neuromuscular performance except for aerobic endurance and VO₂ max (due to the short duration of goalkeeping actions) were included, regardless of the type of observational design. Results: Thirty-five studies were finally included in the synthesis, encompassing neuromuscular performance factors such as agility, speed, anaerobic power, strength, flexibility, and dynamic balance and coordination. The findings underscore the need for neuromuscular training for goalkeepers, particularly agility training. Neuromuscular performance improves with age, especially in linear speed, agility, change-of-direction speed, strength, and power; however, flexibility shows no significant progression. This review identifies key tests for evaluating goalkeepers’ neuromuscular capacities across major performance domains. Conclusions: Although sex differences are apparent, the main limitation is the lack of research on neuromuscular performance in male and female goalkeepers, making it difficult to define indicators for different age and sex categories. Full article

Objectives: Few studies have examined maternal dietary intakes in relation to children’s malnutrition status. We examined variations in children stunting status and their association with maternal and child dietary intakes. Methods: This one-year prospective study (conducted from November 2021 to December 2022) consisted of up to four surveys carried out in rural Kenya. It included 135 pairs of children aged 12–59 months and their non-pregnant mothers, all of whom had received nutrition guidance during the study. Dietary intakes were assessed in four non-consecutive 24 h dietary recalls during the first two surveys. Anthropometric measurements were taken at most four times, and variations in children stunting status (not-stunted, recovered-from-stunting, or persistent/worsened stunting) were assessed. Maternal and child dietary intakes, based on variations in stunting status, were compared using one-way analysis of covariance adjusted for socio-demographic variables. Results: Of the 135 children studied, 40 (29.6%) were stunted at baseline, whereas 85, 20, and 30 had no stunting, recovered from stunting, or had persistent/worsened stunting. Children with persistent/worsened stunting had a significantly lower energy intake than other children; however, maternal energy intake did not differ by children’s stunting status. Milk intake was significantly lower among children with persistent/worsening stunting than other children. A similar difference based on variations in stunting was also observed for maternal milk intake. Conclusions for Practice: The mothers of rural Kenyan children who had recovered from stunting consumed the most milk, while the mothers of children with persistent/worsening consumed the least milk. Further research is needed to confirm the factors behind the observed intake differences. Full article

The National Water Model (NWM)’s streamflow forecasts are widely used by stakeholders to make critical water management decisions. This study evaluates the performance of the NWM v2.1 in simulating streamflow across the Alabama Black Belt Region (ABBR), in the southeastern United States. Using retrospective NWM and USGS observed streamflow data, model performance was assessed across four-time scales—hourly, daily, weekly, and monthly—using three metrics: Nash-Sutcliffe Efficiency (NSE), Root Mean Square Error Ratio (RSR), and Percent Bias (PBIAS). The results demonstrate that the NWM accuracy improves significantly with longer-term forecasts. At the monthly scale, 89% of evaluated stations reached above “Good” classification based on NSE (>0.75), and 85% based on RSR (<0.5). However, consistent negative bias was observed across all time scales, particularly in the underestimating flows. The results highlight the influence of environmental factors, including land use, topography, and soil characteristics, on model performance, as well as potential sources of systematic bias within the model’s processes. Although the NWM does not incorporate regulated protocols, its ability to capture flow variability improves at aggregated scales, suggesting its suitability for long-term planning applications. These findings underscore the need for further model structure refinement and regional calibration to enhance predictive reliability Full article

Nitrogen dioxide (NO₂) poses severe risks to human health and the environment, especially in densely populated megacities. Ground-based air quality monitoring stations provide high-temporal-resolution data but are spatially limited, while satellite observations offer broad coverage but measure column densities rather than surface concentrations. To overcome these limitations, this study integrates ground-based observations with satellite-derived NO₂ from Sentinel-5P TROPOMI and GEOS-CF products to estimate ground-level NO₂ in Istanbul using machine learning (ML) approaches. Three ML algorithms (RF, XGB, and CB) were tested on two datasets spanning 2019–2024 at ~1 km resolution, incorporating 20 features, including topographic, meteorological, environmental, and demographic variables. Among models, CB achieved the best performance (R: 0.686, RMSE: 16.23 µg/m³, and MAE: 11.75 µg/m³ in the test dataset) with the Sentinel-5P dataset, successfully capturing spatial and seasonal variations in ground-level NO₂ both quantitatively and qualitatively. SHAP analysis revealed that regarding satellite-derived NO₂, anthropogenic indicators such as population density, road length, and digital elevation model were the most influential features, while meteorological factors contributed secondarily. Despite the lower spatial resolution of GEOS-CF data, both Sentinel-5P and GEOS-CF datasets supported reliable model outputs. This study provides the first ML-based ground-level NO₂ estimation framework for the Istanbul Metropolitan City. Full article

Obesity is a risk factor for numerous complications, including atherosclerosis, the pathogenesis of which is complex. The aim of our study is to evaluate serum levels of E-selectin and hs-CRP and pulse wave velocity (PWV) as atherosclerosis risk factors and to explore their relationship with advanced glycation end products (AGEs), methylgioxal (MG) and skin autofluorescence (sAF). We evaluated 125 children aged 8–18 years with simple obesity, stratified into two subgroups based on SDS BMI (Group I: 2–4; Group II:> 4), and compared them with 33 age-matched peers of normal weight. Children with obesity exhibited significantly elevated serum concentrations of AGEs, MG, E-selectin, and hs-CRP relative to the control group. Additionally, both height-normalized pulse wave velocity (SDS PWV) and sAF values were significantly higher in the children with obesity compared to their normal-weight counterparts. Except for sAF, which was elevated in children with obesity with a higher SDS BMI, no significant differences were observed among the subgroups of children. Positive correlations were observed between E-selectin and AGEs, MG and SDS PWV, as well as sAF and SDS BMI. Our findings indicate that children with obesity exhibit early signs of atherosclerotic changes, regardless of the degree of obesity. Moreover, circulating AGEs may represent a more reliable biomarker of atherosclerosis risk than sAF, as suggested by the strong positive correlation between AGEs and E-selectin. Further studies are warranted to validate these findings. Full article