Search Results (5,006)

Sporotrichosis is a zoonotic fungal infection with increasing incidence in the Brazilian Amazon, primarily affecting domestic cats and posing risks to human health. This study characterized the clinical and epidemiological profiles of 29 feline sporotrichosis cases in Manaus and optimized molecular diagnostic methods for Sporothrix species identification. Most affected cats were young (86.2% aged 1–3 years), male (82.7%), and free-roaming or semi-indoor (44.8% each), frequently presenting cutaneous lesions localized at the nasal planum (23.3%), ears (7%), eyes (2.3%) and other facial areas (18.6%). Three DNA extraction methods were compared; the phenol–chloroform protocol yielded the highest DNA concentration and purity, and ITS1–ITS4 primers showed an adequate sensibility for PCR detection. In silico RFLP profiles using common restriction enzymes showed limited discriminatory power among Sporothrix species. ITS sequencing of four high-quality amplicons confirmed all isolates as Sporothrix brasiliensis. Antifungal susceptibility testing of all isolates revealed geometric mean MICs of 0.25 µg/mL for ketoconazole, 0.57 µg/mL for itraconazole, 7.27 µg/mL for amphotericin B, and 64 µg/mL for fluconazole, respectively. These findings provide clinical, molecular, and therapeutic information supporting the diagnosis and surveillance of feline sporotrichosis in the Amazon, reinforcing the need for ongoing veterinary and public health monitoring. Full article

Protecting threatened elasmobranch species despite limited data on their distribution and abundance is a critical challenge, particularly in the context of increasing human impacts on marine ecosystems. In the northeastern Atlantic, species such as the leafscale gulper shark, Portuguese dogfish, spurdog, and spotted ray are facing pressures from overfishing, bycatch, habitat degradation, and climate change. The OSPAR Commission has listed these species as threatened and/or declining and aims to protect them by reliably identifying suitable habitats and integrating these areas into Marine Protected Areas (MPAs). In this study, we present a spatial modelling framework using regression-based approaches to identify suitable habitats for these four species. Results show that suitable habitats of the spotted ray (25.8%) and spurdog (18.8%) are relatively well represented within existing MPAs, while those of the deep-water sharks are underrepresented (6.0% for leafscale gulper shark, and 6.8% for Portuguese dogfish). Our findings highlight the need for additional MPAs in deep-sea continental slope areas, particularly west and northwest of Scotland and Ireland. Such expansions would support OSPAR’s goal to protect 30% of its maritime area by 2030 and could benefit broader deep-sea biodiversity, including other vulnerable demersal species and benthic communities. Full article

Objective: Visceral leishmaniasis (VL), a Neglected Tropical Disease caused by Leishmania donovani, remains insufficiently addressed by current therapies due to high toxicity, poor efficacy, and immunosuppressive complications. This study aimed to identify and characterize repurposed drugs that simultaneously target parasite-encoded and host-associated mechanisms essential for VL pathogenesis. Methods: Two complementary in silico drug repurposing strategies were employed. The first method utilized electron–ion interaction potential (EIIP) screening followed by molecular docking and molecular dynamics (MD) simulations targeting two L. donovani proteins: Rab5a and pteridine reductase 1 (PTR1). The second approach employed network-based drug repurposing using the Drugst.One platform, prioritizing candidates via STAT3-associated gene networks. Predicted drug–target complexes were validated by 100 ns MD simulations, and pharmacokinetic parameters were assessed via ADMET profiling using QikProp v7.0 and SwissADME web server. Results: Entecavir and valganciclovir showed strong binding to Rab5a and PTR1, respectively, with Glide Scores of −9.36 and −9.10 kcal/mol, and corresponding MM-GBSA ΔG_bind values of −14.00 and −13.25 kcal/mol, confirming their stable interactions and repurposing potential. Network-based analysis identified nifuroxazide as the top candidate targeting the host JAK2/TYK2–STAT3 axis, with high stability confirmed in MD simulations. Nifuroxazide also displayed the most favorable ADMET profile, including oral bioavailability, membrane permeability, and absence of PAINS alerts. Conclusions: This study highlights the potential of guanine analogs such as entecavir and valganciclovir, and the nitrofuran derivative nifuroxazide, as promising multi-target drug repurposing candidates for VL. Their mechanisms support a dual strategy targeting both parasite biology and host immunoregulation, warranting further preclinical investigation. Full article

Background/Objectives: Aberrant expression of high-mobility group protein B1 (HMGB1) has been linked to cancer development and progression. Methods: To better comprehend the role of HMGB1 expression in cancer, a tissue microarray containing 14,966 samples from 134 different tumor entities and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Results: Strong HMGB1 staining occurred in almost all normal cell types and in most cancers. Of 11,808 evaluable cancers, only 7.8% showed complete absence of HMGB1 staining (HMGB1 deficiency) while 9.9% showed 1+, 25.0% showed 2+, and 57.2% showed 3+ HMGB1 positivity. Absence of HMGB1 staining mostly occurred in pheochromocytoma (90.0%), seminoma (72.4%), gastrointestinal stromal tumor (28.6%), adrenal cortical carcinoma (25.0%), and Hodgkin’s lymphoma (25.0%). Low HMGB1 staining was linked to poor histologic grade (p < 0.0001), advanced pT stage (p < 0.0001), high UICC stage (p < 0.0001), and distant metastasis (p = 0.0413) in clear cell renal cell carcinoma, invasive tumor growth in urothelial carcinoma (pTa vs. pT2–4, p < 0.0001), mismatch repair deficiency (p = 0.0167) in colorectal cancers, and advanced pT stage in invasive breast carcinoma of no special type (p = 0.0038). Strong HMGB1 staining was linked to nodal metastases in high-grade serous ovarian carcinomas (p = 0.0213) and colorectal adenocarcinomas (p = 0.0137), as well as to poor histological grade in squamous cell carcinomas (p = 0.0010). Conclusions: HMGB1 deficiency and reduced HMGB1 expression occur in a broad range of different tumor entities. Low rather than strong HMGB1 staining is often linked to an aggressive tumor phenotype. Whether HMGB1 deficiency renders cells susceptible to specific drugs remains to be determined. Full article

Background: A dilated main pancreatic duct (MPD) ≥ 5 mm can be observed in main-duct IPMNs (MD-IPMN) and chronic pancreatitis (CP); however, distinguishing between the two differently treated diseases can be difficult. Cell-free (cf) DNA in MPD fluid obtained by EUS-guided FNA might help to distinguish MD-IPMN from CP. Methods: All patients with a dilated MPD ≥ 5 mm on EUS during the period of 1 June 2017 to 30 April 2024 were prospectively analysed in this single-centre study, with EUS-guided MPD fluid aspiration performed for suspected MD-IPMN or CP in patients who were suitable for surgery. Twenty-two known gastrointestinal cancer genes, including GNAS and KRAS, were analysed by deep targeted (dt) NGS. The results were correlated with resected tissue, biopsy, and long-term follow-up. Results: A total of 164 patients with a dilated MPD were identified, of which 30 (18.3%) underwent EUS-guided FNA, with 1 patient having a minor complication (3.3%). Twenty-two patients (mean MPD diameter of 12.4 (7–31) mm) with a definitive, mostly surgically confirmed diagnosis were included in the analysis. Only a fish-mouth papilla, which was present in 3 of 12 (25%) MD-IPMNs, could reliably differentiate between the two diseases, with history, symptoms, diffuse or segmental MPD dilation, presence of calcifications on imaging, cytology, and CEA in the ductal fluid failing to achieve differentiation. However, GNAS mutations were found exclusively in 11 of the 12 (91.6%) patients with MD-IPMN (p < 0.01), whereas KRAS mutations were identified in both diseases. Conclusions: GNAS testing by dtNGS in aspirated fluid from dilated MPD obtained by EUS-guided FNA may help differentiate MD-IPMN from CP for surgical resection. Full article

With rising global temperatures and increasing sustainability demands, the need for advanced pavement solutions has never been greater. This study breaks new ground by integrating phase change materials (PCMs), including paraffin-based wax (Rubitherm RT55), hydrated salt (Climator Salt S10), and fatty acid (lauric acid), as binder modifiers within warm mix asphalt (WMA) mixtures. Moving beyond the traditional focus on binder-only modifications, this research utilizes recycled cigarette filters (CFs) as a dual-purpose fiber additive, directly reinforcing the asphalt mixture while simultaneously transforming a major urban waste stream into valuable infrastructure. The performance of the developed WMA mixture has been evaluated in terms of stiffness behavior using an Indirect Tensile Strength Modulus (ITSM) test, permanent deformation using a static creep strain test, and rutting resistance using the Hamburg wheel-track test. Laboratory tests demonstrated that the incorporation of PCMs and recycled CFs into WMA mixtures led to remarkable improvements in stiffness, deformation resistance, and rutting performance. Modified mixes consistently outperformed the control, achieving up to 15% higher stiffness after 7 days of curing, 36% lower creep strain after 4000 s, and 64% reduction in rut depth at 20,000 passes. Cost–benefit analysis and service life prediction show that, despite costing USD 0.71 more per square meter with 5 cm thickness, the modified WMA mixture delivers much greater durability and rutting resistance, extending service life to 19–29 years compared to 10–15 years for the control. This highlights the value of these modifications for durable, sustainable pavements. Full article

Background: Breast and hematological cancer treatments, especially with anthracyclines, have been shown to be associated with an increased risk of cardiotoxicity (CTX). An accurate prediction of cardiotoxicity risk and early detection of myocardial injury may allow for effective cardioprotection to be instituted and tailored to reverse cardiac dysfunction and prevent the discontinuation of essential cancer treatments. Objectives: The PRoactive Evaluation of Function to Evade Cardio Toxicity (PREFECT) study sought to evaluate the ability of fast-strain-encoded (F-SENC) cardiac magnetic resonance imaging (CMR) and 2D echocardiography (2D Echo) to stratify patients at risk of CTX prior to initiating cancer treatment, detect early signs of cardiac dysfunction, including subclinical CTX (sub-CTX) and CTX, and monitor for recovery (REC) during cardioprotective therapy. Methods: Fifty-nine patients with breast cancer or lymphoma were prospectively monitored for CTX with F-SENC CMR and 2D Echo over at least 1 year for evidence of cardiac dysfunction during anthracycline based chemotherapy. F-SENC CMR also monitored myocardial deformation in 37 left ventricular (LV) segments to obtain a MyoHealth risk score based on both longitudinal and circumferential strain. Sub-CTX and CTX were classified based on pre-specified cardiotoxicity definitions. Results: CTX was observed in 9/59 (15%) and sub-CTX in 24/59 (41%) patients undergoing chemotherapy. F-SENC CMR parameters at baseline predicted CTX with a lower LVEF (57 ± 5% vs. 61 ± 5% for all, p = 0.05), as well as a lower MyoHealth (70 ± 9 vs. 79 ± 11 for all, p = 0.004) and a worse global circumferential strain (GCS) (−18 ± 1 vs. −20 ± 1 for all, p < 0.001). Pre-chemotherapy MyoHealth had a higher accuracy in predicting the development of CTX compared to CMR LVEF and 2D Echo LVEF (AUC = 0.85, 0.69, and 0.57, respectively). The 2D Echo parameters on baseline imaging did not stratify CTX risk. F-SENC CMR obtained good or excellent images in 320/322 (99.4%) scans. During cancer treatment, MyoHealth had a high accuracy of detecting sub-CTX or CTX (AUC = 0.950), and the highest log likelihood ratio (indicating a higher probability of detecting CTX) followed by F-SENC GLS and F-SENC GCS. CMR LVEF and CMR LV stroke volume index (LVSVI) also significantly worsened in patients developing CTX during cancer treatment. Conclusions: F-SENC CMR provided a reliable and accurate assessment of myocardial function during anthracycline-based chemotherapy, and demonstrated accurate early detection of CTX. In addition, MyoHealth allows for the robust identification of patients at risk for CTX prior to treatment with higher accuracy than LVEF. Full article

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, largely due to its profound intratumoral heterogeneity and immunosuppressive microenvironment. Various classifications of GBM subtypes were created based on transcriptional and methylation profiles. This effort, followed by the development of new technology such as single-nuclei sequencing (snRNAseq) and spatial transcriptomics, led to a better understanding of the glioma cells’ plasticity and their ability to transition between diverse cellular states. GBM cells can mimic neurodevelopmental programs to resemble oligodendrocyte or neural progenitor behavior and hitchhike the local neuronal network to support their growth. The tumor microenvironment, especially under hypoxic conditions, drives the tumor cell clonal selection, which then reshapes the immune cells’ functions. These adaptations contribute to immune evasion by progressively disabling T cell and myeloid cell functions, ultimately establishing a highly immunosuppressive tumor milieu. This complex and metabolically constrained environment poses a major barrier to effective antitumor immunity and limits the success of conventional therapies. Understanding the dynamic interactions between glioma cells and their microenvironment is essential for the development of more effective immunotherapies and rational combination strategies aimed at overcoming resistance and improving patient outcomes. Full article

The growing global demand for electricity, driven by the development of electromobility, data centers, and smart technologies, necessitates innovative approaches to energy generation. Wind power, as a clean and renewable energy source, plays a pivotal role in the global transition towards low-carbon power systems. This paper presents a comprehensive review of generator technologies used in wind turbine applications, ranging from conventional synchronous and asynchronous machines to advanced concepts such as low-speed direct-drive (DD) generators, axial-flux topologies, and superconducting generators utilizing low-temperature superconductors (LTS) and high-temperature superconductors (HTS). The advantages and limitations of each design are discussed in the context of efficiency, weight, reliability, scalability, and suitability for offshore deployment. Special attention is given to HTS-based generator systems, which offer superior power density and reduced losses, along with challenges related to cryogenic cooling and materials engineering. Furthermore, the paper analyzes selected modern generator designs to provide references for enhancing the performance of grid-synchronized hybrid microgrids integrating solar PV, wind, battery energy storage, and HTS-enhanced generators. This review serves as a valuable resource for researchers and engineers developing next-generation wind energy technologies with improved efficiency and integration potential. Full article

Heavy metal pollution from human activities is an increasing environmental concern. This study investigates the concentrations of Cu, Pb, Zn, Cd, Hg, and As in the coastal seawater offshore of Beihai, Guangxi, in April 2021, and explores their relationships with dissolved inorganic nitrogen, phosphate, and salinity. Our results reveal higher heavy metal concentrations in the northern nearshore waters and lower levels in southern offshore areas, with surface waters generally exhibiting greater enrichment than bottom waters. Surface concentrations show a decreasing trend from the northeast to the southwest, likely influenced by prevailing northeast monsoon winds. While bottom water concentrations decline from the northwest to the southeast, which indicates the influence of riverine runoff, particularly from the Qinzhou Bay estuary. Heavy metal levels in southern Beihai waters are comparable to those in the Beibu Gulf, except for Hg and Zn, which are significantly higher in the water of the Beibu Gulf. Notably, heavy metal concentrations in both Beihai and Beibu Gulf remain considerably lower than those observed in the coastal waters of Guangdong. Overall, Beihai’s coastal seawater meets China’s Class I quality standards. Nonetheless, continued monitoring is essential, especially of the potential ecological impacts of Hg and Zn on marine life. Full article

Background: Polyparasitic infections remain widespread in endemic regions, yet its contributing factors and health impact are not well understood. This study aims to estimate the prevalence and associated factors and examines the effect of polyparasitic infection on haemoglobin levels among children. Methods: A cross-sectional study was conducted in Lambaréné, Gabon, among children aged 2–17 years from November 2019 to December 2020. Haemoglobin levels, environmental conditions, and sociodemographic data were collected. Stool, urine, and blood samples were analysed using light microscopy for parasite detection. Factors associated with polyparasitism were explored. Results: Out of 656 participants, 65.4% had at least one infection, with intestinal protozoa species (21.3%), Trichuris trichiura (33%), Ascaris lumbricoides (22%), Schistosoma haematobium (20%), and Plasmodium falciparum (10%) being the most common. Polyparasitic infection was identified in 26% of children, mostly as bi-infections (69.2%), and was negatively associated with haemoglobin levels (β = −0.06). Conclusions: These findings emphasise the burden of polyparasitic infections and adverse health effects in Lambaréné, Gabon. Full article

In high-dynamic bipedal locomotion control, robotic systems are often constrained by motor torque limitations, particularly during explosive tasks such as jumping. One of the key challenges in reinforcement learning lies in bridging the sim-to-real gap, which mainly stems from both inaccuracies in simulation models and the limitations of motor torque output, ultimately leading to the failure of deploying learned policies in real-world systems. Traditional RL methods usually focus on peak torque limits but ignore that motor torque changes with speed. By only limiting peak torque, they prevent the torque from adjusting dynamically based on velocity, which can reduce the system’s efficiency and performance in high-speed tasks. To address these issues, this paper proposes a reinforcement learning jump-control framework tailored for tendon-driven bipedal robots, which integrates dynamic torque boundary constraints and torque error-compensation modeling. First, we developed a torque transmission coefficient model based on the tendon-driven mechanism, taking into account tendon elasticity and motor-control errors, which significantly improves the modeling accuracy. Building on this, we derived a dynamic joint torque limit that adapts to joint velocity, and designed a torque-aware reward function within the reinforcement learning environment, aimed at encouraging the policy to implicitly learn and comply with physical constraints during training, effectively bridging the gap between simulation and real-world performance. Hardware experimental results demonstrate that the proposed method effectively satisfies actuator safety limits while achieving more efficient and stable jumping behavior. This work provides a general and scalable modeling and control framework for learning high-dynamic bipedal motion under complex physical constraints. Full article

Apples are one of the most popular fruits in Germany, valued for their regional availability and health benefits. When deciding which apple to buy, several characteristics are important to consumers, including the taxonomic variety, organic cultivation and regional production. To verify that these characteristics are correctly declared, powerful analytical methods are required. In this study, ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-ToF-MS) is applied in combination with random forest to 193 apple samples for the analysis of various authentication issues. Accuracies of 93.3, 85.5, 85.6 and 90% were achieved for distinguishing between German and non-German, North and South German, organic and conventional apples and for six different taxonomic varieties. Since the classification models largely use different parts of the data, which is shown by variable selection, this method is very well suited to answer different authentication issues with one analytical approach. Full article

The contamination of drinking water sources with selenium (Se) oxyanions, including selenite (Se(IV)) and selenate (Se(VI)), contains serious health hazards with an oral intake exceeding 400 µg/day and therefore requires urgent attention. Various natural and anthropogenic sources are responsible for high Se concentrations in aquatic environments. In addition, the chemical behavior and speciation of selenium can vary noticeably depending on the origin of the source water. The Se(VI) oxyanion is more soluble and therefore more abundant in surface water. Se levels in contaminated waters often exceed 50 µg/L and may reach several hundred µg/L, well above drinking water limits set by the World Health Organization (40 µg/L) and Germany (10 µg/L), as well as typical industrial discharge limits (5–10 µg/L). Overall, Se is difficult to remove using conventionally available physical, chemical, and biological treatment technologies. The recent literature has therefore highlighted promising advancements in Se removal using emerging technologies. These include advanced physical separation methods such as membrane-based treatment systems and engineered nanomaterials for selective Se decontamination. Additionally, other integrated approaches incorporating photocatalysis coupled adsorption processes, and bio-electrochemical systems have also demonstrated high efficiency in redox transformation and capturing of Se from contaminated water bodies. These innovative strategies may offer enhanced selectivity, removal, and recovery potential for Se-containing species. Here, a current review outlines the sources, distribution, and chemical behavior of Se in natural waters, along with its toxicity and associated health risks. It also provides a broad and multi-perspective assessment of conventional as well as emerging physical, chemical, and biological approaches for Se removal and/or recovery with further prospects for integrated and sustainable strategies. Full article