Search Results (678)

Background: Various predisposing factors contribute to the emergence and dissemination of the multidrug-resistant (MDR) phenotype in Escherichia coli and Klebsiella pneumoniae. Understanding these factors is crucial for guiding appropriate antimicrobial therapy and infection control strategies. This study investigated the predisposing factors contributing to the MDR characteristics of E. coli and K. pneumoniae isolated in a community hospital in northeastern Thailand. Methods: This case–control study utilized retrospective data from bacterial culture, as well as demographic, clinical, and antibiotic susceptibility records collected during 5 years (January 2016–December 2020). E. coli and K. pneumoniae isolates were analyzed from various clinical samples, including blood, urine, pus, sputum, and other body fluids. Data were analyzed using descriptive statistics and univariate logistic regression. Results: In total, 660 clinical isolates were analyzed (421 E. coli and 239 K. pneumoniae). Blood was the most common source of the detection of E. coli (63.0%) and sputum was the most common source of K. pneumoniae (51.0%). The median ages of patients were 67 and 63 years for E. coli and K. pneumoniae, respectively. E. coli cases were significantly associated with prior antibiotic use (OR = 1.79, 95% CI: 1.17–2.74 p = 0.008). MDR was observed in 50.1% of E. coli and 29.7% of K. pneumoniae (p < 0.001). E. coli compared to K. pneumoniae had lower resistance to third-gen cephalosporins (64.9% versus 95.8%) and carbapenems (8.0% versus 6.9%). ICU admission was the only factor significantly associated with MDR E. coli (OR = 2.40, 95% CI: 1.11–5.20 p = 0.026). No significant differences were observed in gender, age, or comorbidities between MDR cases. Antibiotic usage patterns also differed, with E. coli more likely to receive third-gen cephalosporins compared to carbapenems (OR = 3.02, 95% CI:1.18–7.74 p = 0.021). Conclusions: The use of third-generation cephalosporin may drive MDR E. coli more than K. pneumoniae. Prior antibiotic exposure was linked to E. coli bloodstream infections, while MDR E. coli showed greater clinical severity. These findings highlighted the need for improved antibiotic stewardship in rural hospitals. Full article

Nanofertilizers (NFs) and engineered nanoparticles (NPs) are increasingly used in agriculture, yet their environmental safety remains poorly understood. This study evaluated the comparative phytotoxicity of zinc oxide (ZnO), titanium dioxide (TiO₂), and clinoptilolite nanoparticles, three commercial nanofertilizers, and potassium dichromate (K₂Cr₂O₇) using Lactuca sativa seeds under adapted OECD-208 protocol conditions. Seeds were exposed to varying concentrations of each xenobiotic material (0.5–3% for NFs; 10–50% for NPs), with systematic assessment of seedling survival, root and hypocotyl length, dry biomass, germination index (GI), and median effective concentration (EC₅₀) values. Nanofertilizers demonstrated significantly greater phytotoxicity than engineered nanoparticles despite lower application concentrations. The toxicity ranking was established as NF1 > NF3 > NF2 > NM2 > NM1 > NM3, with NF1 being most toxic (EC₅₀ = 1.2%). Nanofertilizers caused 45–78% reductions in root length and 30–65% decreases in dry biomass compared with controls. GI values dropped to ≤70% in NF1 and NF3 treatments, indicating concentration-dependent growth inhibition. While nanofertilizers offer agricultural benefits, their elevated phytotoxicity compared with conventional nanoparticles necessitates rigorous pre-application safety assessment. These findings emphasize the critical need for standardized evaluation protocols incorporating both physiological and ecotoxicological endpoints to ensure safe xenobiotic nanomaterial deployment in agricultural systems. Full article

Purpose: To present the findings of our preliminary experience using daily image-guided radiotherapy (IGRT) supported by implanted fiducial markers (FMs) in the radiotherapy of the vaginal cuff, in a cohort of post-surgery endometrial cancer patients. Methods: Patients with vaginal cuff cancer requiring adjuvant radiation with external beams were enrolled. Five patients underwent radiation therapy targeting the pelvic disease and positive lymph nodes, with doses of 50.4 Gy in twenty-eight fractions and a subsequent stereotactic boost on the vaginal vault at a dose of 5 Gy in a single fraction. One patient was administered 30 Gy in five fractions to the vaginal vault. These patients underwent external beam RT following the implantation of three 0.40 × 10 mm gold fiducial markers (FMs). Our IGRT strategy involved real-time 2D kV image-based monitoring of the fiducial markers during the treatment delivery as a surrogate of the vaginal cuff. To explore the potential role of FMs throughout the treatment process, we analyzed cine movies of the 2D kV-triggered images during delivery, as well as the image registration between pre- and post-treatment CBCT scans and the planning CT (pCT). Each CBCT used to trigger fraction delivery was segmented to define the rectum, bladder, and vaginal cuff. We calculated a standard metric to assess the similarity among the images (Dice index). Results: All the patients completed radiotherapy and experienced good tolerance without any reported acute or long-term toxicity. We did not observe any loss of FMs during or before treatment. A total of twenty CBCTs were analyzed across ten fractions. The observed trend showed a relatively emptier bladder compared to the simulation phase, with the bladder filling during the delivery. This resulted in a final median Dice similarity coefficient (DSC) of 0.90, indicating strong performance. The rectum reproducibility revealed greater variability, negatively affecting the quality of the delivery. Only in two patients, FMs showed intrafractional shift > 5 mm, probably associated with considerable rectal volume changes. Target coverage was preserved due to a safe CTV-to-PTV margin (10 mm). Conclusions: In our preliminary study, CBCT in combination with the use of fiducial markers to guide the delivery proved to be a feasible method for IGRT both before and during the treatment of post-operative gynecological cancer. In particular, this approach seems to be promising in selected patients to facilitate the use of SBRT instead of BRT (brachytherapy), thanks to margin reduction and adaptive strategies to optimize dose delivery while minimizing toxicity. A larger sample of patients is needed to confirm our results. Full article

Phosphatidylinositol-3-kinase (PI3K) inhibition has emerged as a therapeutic option against indolent lymphoma, including relapsed follicular lymphoma (FL). While inhibition of active signaling in the lymphoma cell represents the primary mode of action, PI3K inhibition also exerts immunomodulatory effects. Here we have analyzed 17 consecutive advanced treatment line FL patients treated with the delta-selective PI3K inhibitor idelalisib in a retrospective single-center observational study, with a specific focus on response and immune effects. Eleven patients achieved complete remission (CR) or partial remission (PR) with median response duration of 22 (11–88) months following a median idelalisib exposure of 15 (4–88) months. Disease response persisted in three patients for a median of 37 (21–63) months following cessation of idelalisib without another therapy being initiated. Autoimmune side effects occurred in eight of the eleven patients who responded, compared to none in six patients whose disease did not respond. In conclusion, a time-limited exposure to idelalisib may induce sustained remissions in a portion of patients with recurrent and/or refractory (r/r) FL, suggesting immunomodulatory effects of PI3K inhibition to be involved in the control of the disease. Full article

Water infiltration into soil is a key process in regulating the hydrological cycle and sustaining ecosystem services in high-Andean environments. However, limited information is available regarding its dynamics in these ecosystems. This study evaluated the influence of three types of vegetation cover and soil properties on water infiltration in a high-Andean environment. A double-ring infiltrometer, the Water Drop Penetration Time (WDPT, s) method, and laboratory physicochemical characterization were employed. Soils under forest cover exhibited significantly higher quasi-steady infiltration rates (i_s, 0.248 ± 0.028 cm·min⁻¹) compared to grazing areas (0.051 ± 0.016 cm·min⁻¹) and agricultural lands (0.032 ± 0.013 cm·min⁻¹). Soil organic matter content was positively correlated with i_s. The modified Kostiakov infiltration model provided the best overall fit, while the Horton model better described infiltration rates approaching i_s. Sand and clay fractions, along with K⁺, Ca²⁺, and Mg²⁺, were particularly significant during the soil’s wet stages. In drier stages, increased Na⁺ concentrations and decreased silt content were associated with higher water repellency. Based on WDPT, agricultural soils exhibited persistent hydrophilic behavior even after drying (median [IQR] from 0.61 [0.38] s to 1.24 [0.46] s), whereas forest (from 2.84 [3.73] s to 3.53 [24.17] s) and grazing soils (from 4.37 [1.95] s to 19.83 [109.33] s) transitioned to weakly or moderately hydrophobic patterns. These findings demonstrate that native Andean forest soils exhibit a higher infiltration capacity than soils under anthropogenic management (agriculture and grazing), highlighting the need to conserve and restore native vegetation cover to strengthen water resilience and mitigate the impacts of land-use change. Full article

The article is focused on the quantitative assessment of the thermal impact of polar mesospheric clouds (PMCs) on the mesopause caused by the emission of absorbed solar and terrestrial infrared (IR) radiation by cloud particles. For this purpose, a parameterization of mesopause heating by PMC crystals has been developed, the main feature of which is to incorporate the thermal properties of ice and the interaction of cloud particles with the environment. Parametrization is based on PMCs zero-dimensional (0-D) model and uses temperature, pressure, and water vapor data in the 80–90 km altitude range retrieved from Solar Occultation for Ice Experiment (SOFIE) measurements. The calculations are made for 14 PMC seasons in both hemispheres with the summer solstice as the central date. The obtained results show that PMCs can make a significant contribution to the heat balance of the upper atmosphere, comparable to the heating caused, for example, by the dissipation of atmospheric gravity waves (GWs). The interhemispheric differences in heating are manifested mainly in the altitude structure: in the Southern Hemisphere (SH), the area of maximum heating values is 1–2 km higher than in the Northern Hemisphere (NH), while quantitatively they are of the same order. The most intensive heating is observed at the lower boundary of the minimum temperature layer (below 150 K) and gradually weakens with altitude. The NH heating median value is 5.86 K/day, while in the SH it is 5.24 K/day. The lowest values of heating are located above the maximum of cloud ice concentration in both hemispheres. The calculated heating rates are also examined in the context of the various factors of temperature variation in the observed atmospheric layers. It is shown in particular that the thermal impact of PMC is commensurate with the influence of dissipating gravity waves at heights of the mesosphere and lower thermosphere (MLT), which parameterizations are included in all modern numerical models of atmospheric circulation. Hence, the developed parameterization can be used in global atmospheric circulation models for further study of the peculiarities of the thermodynamic regime of the MLT. Full article

Over 40% of freshwater fish species in Europe are currently at risk of extinction, highlighting the need for improved conservation planning. This study examines whether the threat status is associated with life-history and ecological traits across 580 autochthonous (native and endemic) freshwater fish species in European inland waters. Using data from FishBase and the IUCN Red List, we assessed associations between threat level and both categorical (e.g., migratory behavior, commercial importance, reproductive guild, and body shape) and numerical traits (e.g., maximum length, weight, age, growth parameters, and maturity traits). Significant, though modest, associations were identified between species threat level and migratory behavior and reproductive guild. Non-migratory species exhibited higher median threat levels, while amphidromous species showed a non-significant trend toward higher threat, suggesting that limited dispersal ability and dependence on fragmented freshwater networks may increase extinction vulnerability. Species with unclassified reproductive strategies also showed elevated threat levels, possibly reflecting both actual risk and underlying data gaps. In contrast, body shape and trophic level were not significantly associated with threat status. Critically Endangered species tend to be larger, heavier, and mature later—traits characteristic of slow life history strategies that limit population recovery. Although length at maturity and maximum age did not differ significantly among IUCN categories, age at maturity was significantly higher in more threatened species, and growth rate (K) was negatively correlated with threat level. Together, these patterns suggest that slower-growing, later-maturing species face elevated extinction risk. Overall, the findings underscore that the threat level in European freshwater fish is shaped by complex interactions between intrinsic biological traits and external pressures. Trait-based approaches can enhance extinction risk assessments and conservation prioritization, especially in data-deficient freshwater ecosystems facing multifaceted environmental challenges. Full article

Background/Objectives: Recent Japanese guidelines recommend using the average sodium-to-potassium (Na/K) ratio from casual urine samples to assess hypertension and cardiovascular risk, suggesting cutoffs of 2 (optimal) and 4 (feasible). We aimed to evaluate the proportion of Korean individuals who would be classified as having elevated Na/K ratios using these cutoffs, based on random urine Na/K measurements obtained from the nationally representative Korea National Health and Nutrition Examination Survey (KNHANES) dataset. Methods: We analyzed 50,440 participants from the KNHANES 2016–2023 with available random urine Na and K results. Annual urinary Na/K ratios were calculated, and the prevalence of ratios ≥2 and ≥4 was assessed by age and sex using sampling weights. Results: The weighted median Na/K ratios were consistently lower than the weighted means, indicating skewed distributions. From 2016 to 2023, the weighted median and mean values increased from 2.3 and 2.7 to 2.8 and 3.3, respectively. The prevalence of a Na/K ratio ≥2 increased from 60.5% to 72.0%, and that of a ratio ≥4 increased from 16.9% to 28.3%. A U-shaped trend in Na/K ≥4 prevalence was observed by age, highest among those <20 and ≥70 years. Males had a higher prevalence than females in all age groups except 20–29. Conclusions: A growing proportion of Koreans exceeded Na/K cutoffs of 2 and 4 over time. Age- and sex-specific variation suggests tailored interpretation may be necessary when applying these thresholds in population health monitoring. Full article

Objectives: Cefideroccol (FDC) is a siderophore cephalosporin with potent antibacterial activity against a wide range of Gram-negative multidrug-resistant (MDR) microorganisms. We investigated the anti-biofilm capacity of FDC against clinical strains. Methods: This multicenter study was conducted on 28 selected strains of MDR Gram-negative bacilli isolated from clinical samples of Pseudomonas aeruginosa (n = 5), Acinetobacter baumannii (n = 11), and Klebsiella pneumoniae (n = 12). We first determined the minimum inhibitory concentration (MIC) of each strain using the microdilution method. We also defined the minimum biofilm inhibitory concentration (MBIC) as a ≥50% reduction in tetrazolium salt (XTT) (as recommended in the 2017 Spanish Microbiology Protocols [SEIMC] for the microbiological diagnosis of infections related to the formation of biofilms). We also analyzed the reduction in the following biofilm variables after an 8 mg/mL FDC treatment: the CFU count, the cell viability, the biomass, the metabolic activity, and extracellular α or β polysaccharides. Results: The MIC₅₀ and MBIC₅₀ of FDC were 0.5 mg/L and 64 mg/L, respectively. We observed a mean (SD) fold increase in the susceptibility to FDC between planktonic and sessile cells for P. aeruginosa, A. baumannii, and K. pneumoniae of 9.60 (0.55), 6.27 (2.28), and 6.25 (2.80), respectively. When 8 mg/mL of FDC was tested, we observed that the best median (IQR) percentage reductions were obtained for cell viability and the extracellular matrix (73.1 [12.4–86.5] and 79.5 [37.3–95.5], respectively), particularly for P. aeruginosa. The lowest percentage reduction rates were those obtained for biomass. Conclusions: We demonstrated that the susceptibility to FDC was significantly reduced when strains were in a biofilm state. The best percentage reduction rates for all biofilm-defining variables were observed for P. aeruginosa. Our results need to be validated using a larger collection of clinical samples. Full article

Glioblastoma multiforme (GBM) is an aggressive and molecularly heterogeneous brain cancer with a poor prognosis. Despite advancements in standard-of-care therapies, including surgery, radiotherapy, and temozolomide (TMZ), the median survival remains approximately 15 months, with a 5-year survival rate of less than 10%. We and others have demonstrated that FOXM1 is a critical oncogenic driver of GBM cell proliferation. However, the role of FOXM1 and its interaction with other oncogenic signaling pathways in GBM remains incompletely understood. In this study, we identified FOXM1, AXL, and eEF2K as highly upregulated oncogenes in GBM patient tumors. We demonstrated, for the first time, that FOXM1 directly interacts with AXL and eEF2K, regulating their expression and promoting GBM cell proliferation, migration, and invasion. Knockdown of these genes disrupted cell proliferation, spheroid formation, migration, and invasion, and induced apoptosis and ferroptosis. Additionally, inhibiting the FOXM1–AXL/eEF2K signaling axis sensitized GBM cells to TMZ, further enhancing apoptotic and ferroptotic responses. These findings highlight the critical role of the FOXM1–AXL/eEF2K signaling pathway in GBM progression and suggest that targeting this axis may offer a novel multitargeted therapeutic strategy in GBM. Full article

Background: Multidrug-resistant (MDR) Gram-negative infections, particularly those caused by carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), present a growing global healthcare challenge, especially in critically ill populations. Imipenem–relebactam (I/R), a novel β-lactam/β-lactamase inhibitor combination, has shown efficacy in clinical trials, but real-world data remain limited. Methods: We conducted a multicenter, retrospective–prospective observational study across tertiary-care hospitals in Italy between January 2020 and May 2025. Adult patients (≥18 years) treated with I/R for ≥48 h for suspected or confirmed MDR Gram-negative infections were included. Primary endpoints were clinical success at the end of therapy and 30-day all-cause mortality. Secondary endpoints included microbiological eradication, recurrence, safety, and predictors of treatment failure. Statistical analysis involved descriptive methods and correlation analysis for mortality predictors. Results: Twenty-nine patients were included (median age 66 years; 58.6% ICU admission; 71.4% mechanical ventilation). Clinical success was achieved in 22/29 patients (75.9%), while 30-day mortality was 24.1% (7/29). The most common pathogen was Klebsiella pneumoniae (62.1%), with 41.4% of infections being polymicrobial. Microbiological eradication was confirmed in all the BSIs. Parenteral nutrition (p = 0.016), sepsis at presentation (p = 0.04), candidemia (p = 0.036), and arterial catheter use (p = 0.029) were significantly more frequent in non-survivors. Survivors showed significant reductions in CRP, PCT, and bilirubin at 48 h, while non-survivors did not. Parenteral nutrition (rho = 0.427, p = 0.023), sepsis (rho = 0.378, p = 0.043), and arterial catheter use (rho = 0.384, p = 0.04) were significantly correlated with mortality. Conclusions: In this Italian multicenter cohort of critically ill patients, imipenem–relebactam demonstrated high clinical success and acceptable mortality rates in the treatment of severe MDR Gram-negative infections, particularly those caused by KPC-producing K. pneumoniae. Early biomarker dynamics may aid in monitoring treatment response. Larger prospective studies are needed to confirm these findings and define optimal treatment strategies. Full article

To address the technical problems of broad droplet size spectrum, insufficient atomization uniformity, and spray drift in plant protection unmanned aerial vehicle (UAV) applications, this study developed a novel two-stage aerial electrostatic spraying device based on the coupled mechanisms of hydraulic atomization and electrostatic induction, and, through the integration of three-dimensional numerical simulation and additive manufacturing technology, a new two-stage inductive charging device was designed on the basis of the traditional hydrodynamic nozzle structure, and a synergistic optimization study of the charging effect and atomization characteristics was carried out systematically. With the help of a charge ratio detection system and Malvern laser particle sizer, spray pressure (0.25–0.35 MPa), charging voltage (0–16 kV), and spray height (100–1000 mm) were selected as the key parameters, and the interaction mechanism of each parameter on the droplet charge ratio (C/m) and the particle size distribution (Dv50) was analyzed through the Box–Behnken response surface experimental design. The experimental data showed that when the charge voltage was increased to 12 kV, the droplet charge-to-mass ratio reached a peak value of 1.62 mC/kg (p < 0.01), which was 83.6% higher than that of the base condition; the concentration of the particle size distribution of the charged droplets was significantly improved; charged droplets exhibited a 23.6% reduction in Dv50 (p < 0.05) within the 0–200 mm core atomization zone below the nozzle, with the coefficient of variation of volume median diameter decreasing from 28.4% to 16.7%. This study confirms that the two-stage induction structure can effectively break through the charge saturation threshold of traditional electrostatic spraying, which provides a theoretical basis and technical support for the optimal design of electrostatic spraying systems for plant protection UAVs. This technology holds broad application prospects in agricultural settings such as orchards and farmlands. It can significantly enhance the targeted deposition efficiency of pesticides, reducing drift losses and chemical usage, thereby enabling agricultural enterprises to achieve practical economic benefits, including reduced operational costs, improved pest control efficacy, and minimized environmental pollution, while generating environmental benefits. Full article

Gender recognition from pedestrian imagery is acknowledged by many as a quasi-solved problem, yet most existing approaches evaluate performance in a within-domain setting, i.e., when the test and training data, though disjoint, closely resemble each other. This work provides the first exhaustive cross-domain assessment of six architectures considered to represent the state of the art: ALM, VAC, Rethinking, LML, YinYang-Net, and MAMBA, across three widely known benchmarks: PA-100K, PETA, and RAP. All train/test combinations between datasets were evaluated, yielding 54 comparable experiments. The results revealed a performance split: median in-domain F1 approached 90% in most models, while the average drop under domain shift was up to 16.4 percentage points, with the most recent approaches degrading the most. The adaptive-masking ALM achieved an F1 above 80% in most transfer scenarios, particularly those involving high-resolution or pose-stable domains, highlighting the importance of strong inductive biases over architectural novelty alone. Further, to characterize robustness quantitatively, we introduced the Unified Robustness Metric (URM), which integrates the average cross-domain degradation performance into a single score. A qualitative saliency analysis also corroborated the numerical findings by exposing over-confidence and contextual bias in misclassifications. Overall, this study suggests that challenges in gender recognition are much more evident in cross-domain settings than under the commonly reported within-domain context. Finally, we formalize an open evaluation protocol that can serve as a baseline for future works of this kind. Full article

To investigate the impact of sand-laden flow on energy loss in Francis turbines, this study integrates entropy generation theory with numerical simulations conducted using ANSYS CFX. The mixture multiphase flow model and the SST k-ω turbulence model are employed to simulate the solid–liquid two-phase flow throughout the entire flow passage of the turbine at the Gengda Hydropower Station (Minjiang River Basin section, 103°17′ E and 31°06′ N). The energy loss characteristics under different off-design conditions are analyzed on the basis of the average sediment concentration during the flood season (2.9 kg/m³) and a median particle diameter of 0.058 mm. The results indicate that indirect entropy generation and wall entropy generation are the primary contributors to total energy loss, while direct entropy generation accounts for less than 1%. As the guide vane opening increases, the proportion of wall entropy generation initially rises and then decreases, while the total indirect entropy generation exhibits a non-monotonic trend dominated by the flow pattern in the draft tube. Entropy generation on the runner walls increases steadily with larger openings, whereas entropy generation on the draft tube walls first decreases and then increases. The variation in entropy generation on the guide vanes remains relatively small. These findings provide technical support for the optimal design and operation of turbines in sediment-rich rivers. Full article

Declining kidney function contributes to the accumulation of uraemic toxins produced by gut microbiota, leading to the uraemic syndrome. This study aimed to identify associations between uraemic toxins, diet quality, symptoms and the gut microbiota in individuals initiating peritoneal dialysis. A cross-sectional analysis of baseline data from participants in a longitudinal study was conducted. Symptom scores using the Integrated Palliative Care Outcomes Scale-Renal were recorded. Plasma p-Cresyl sulfate, indoxyl sulfate and trimethylamine N-oxide were measured using liquid chromatography-mass spectrometry. Gut microbiota was determined using 16S rRNA sequencing. Multivariate linear models examined associations across the cohort. Data from 43 participants (mean age 61 ± 13 years; 70% male; median eGFR 7 mL/min/1.73 m²) were analysed. Diabetes was the primary cause of kidney disease (51.2%). Patients were classified into ‘high’ (n = 18) and ‘low’ (n = 26) uraemic toxin groups using K-means clustering. The ‘high’ group had a lower eGFR (p < 0.05) but no differences in diet quality or symptom scores. Significant differences in alpha and beta diversity were observed between the groups (p = 0.01). The ‘high’ group had increased Catenibacterium, Prevotella, Clostridia, and decreased Ruminococcus gnavus abundances. Multivariate models identified 32 genera associated with uraemic toxins, including positive associations of Oscillospiraceae UCG-002 and UCG-005 with p-cresyl sulfate, and negative associations with Actinomyces and Enterococcus. Patients with kidney failure initiating peritoneal dialysis have distinct uraemic toxin profiles, associated with differences in microbial diversity. This phenotype was also associated with differences in residual kidney function but not with diet or symptom severity. Longitudinal studies are required to determine causality and guide therapeutic interventions. Full article