Search Results (950)

Malignant melanoma is a highly metastatic skin cancer, representing about 5% of all cancer diagnoses in the United States. Conventional chemotherapy often has limited effectiveness and severe systemic side effects. This study explores a localized, topical delivery system using cisplatin-loaded nanomembranes as a safer and more targeted alternative. Cell viability assays established the safe cisplatin concentrations for tissue culture. Gelatin-based nanomembranes incorporating cisplatin were fabricated via electrospinning. Biocompatibility and therapeutic efficacy were tested by applying the membranes to cultured melanoma and normal skin cells. Controlled drug release profiles were evaluated by adjusting cross-linking times. Cisplatin concentration between 3.125 and 12.5 µg/mL were found safe. Nanomembranes with these doses effectively eliminated melanoma cells with minimal harm to healthy skin cells. Drug-free membranes showed high biocompatibility. Cross-linking duration allowed tunable and stable drug release. Cisplatin-loaded gelatin nanomembranes offer a promising topical therapy for melanoma, enhancing drug targeting while reducing systemic toxicity. This approach may serve as a cost-effective alternative to systemic treatments like immunotherapy. Future research will focus on in vivo testing and clinical application. Full article

Scientific conferences are invaluable for knowledge exchange, yet pose growing environmental concerns, especially through long-distance travel. This work quantifies and compares the environmental burdens of a national conference (30 delegates, Pisa, Italy) and an international conference (50 delegates, Athens, Greece) using ISO 14040/44-compliant Life-Cycle Assessment (LCA). A cradle-to-grave inventory combined primary data on participant travel, venue utilities, catering materials and waste handling with secondary datasets from Ecoinvent 3.8. Sixteen midpoint impact categories were calculated with the Environmental Footprint 3.1 method and normalized per delegate. The international meeting incurred 130 kg CO_2eq per delegate, compared with 11 kg CO_2eq per delegate for the domestic event, reflecting a ten-fold rise in fossil energy demand and comparable multiples across acidification, eutrophication and toxicity categories. Participant travel explained >85% of every global indicator in both cases, while venue energy and material flows together accounted for ≤12%. Further developments require harmonized functional units, improved digital-infrastructure inventories and integration of social impact metrics. The findings provide preliminary input for evidence-based guidelines for organizers and contribute to the standardization of LCA in the emerging field of event sustainability. Full article

Social media empowers freedom of expression but is often misused for abuse and hate. The detection of such content is crucial, especially in under-resourced languages like Urdu. To address this challenge, this paper designed a comprehensive multilabel dataset, the Urdu toxicity corpus (UTC). Second, the Urdu toxicity detection model is developed, which detects toxic content from an Urdu dataset presented in Nastaliq Font. The proposed framework initially processed the gathered data and then applied feature engineering using term frequency-inverse document frequency, bag-of-words, and N-gram techniques. Subsequently, the synthetic minority over-sampling technique is used to address the data imbalance problem, and manual data annotation is performed to ensure label accuracy. Four machine learning models, namely logistic regression, support vector machine, random forest, and gradient boosting, are applied to preprocessed data. The results indicate that the RF outperformed all evaluation metrics. Deep learning algorithms, including long short-term memory (LSTM), Bidirectional LSTM, and gated recurrent unit, have also been applied to UTC for classification purposes. Random forest outperforms the other models, achieving a precision, recall, F1-score, and accuracy of 0.97, 0.99, 0.98, and 0.99, respectively. The proposed model demonstrates a strong potential to detect rude, offensive, abusive, and hate speech content from user comments in Urdu Nastaliq. Full article

Anthropomorphic CT phantoms are essential training tools for interventional radiology. Given the high technical demands and stringent safety requirements in this field, realistic CT phantoms are vital simulation tools that support effective hands-on training, procedural planning, and risk mitigation. However, commercially available phantom geometries are limited in their scope. This study investigates the use of polyvinyl alcohol (PVA) to fabricate customizable training phantoms. PVA, a non-toxic material, can be processed into PVA cryogels (PVA-C) with tissue-like mechanical properties. We modified PVA-C (10 wt.% PVA) by incorporating various additives to adjust X-ray attenuation and achieve Hounsfield units (HUs) similar to different soft tissues. HU values were measured at X-ray tube voltages of 70, 120, and 150 kV. The inclusion of barium sulfate (e.g., U = 120 kV; 0.1–2 wt.%: 33.29 ± 5.45–323.72 ± 12.64 HU) and iohexol (e.g., U = 120 kV; 0.1–2 wt.%: 26.05 ± 4.74–161.99 ± 5.69 HU) significantly increased HU values. Iohexol produced more homogeneous HU distributions than barium sulfate and cellulose derivatives, with the latter having air gaps and inconsistencies. The tested formulations encompassed a wide range of soft tissue densities, with HU values varying significantly across the energy range (p < 0.001). While cellulose derivatives showed variable HU modulation, their primary role appears to be in modifying phantom texture and morphology rather than precise attenuation control. In conclusion, PVA-C demonstrates strong potential for use in interventional radiology training phantoms. Further studies may enhance phantom realism by replicating tissue textures, for example, through the incorporation of cellulose-based substances. Full article

Background/Objectives: Acute liver failure (ALF) is a life-threatening condition with high mortality in nontransplant candidates. Therapeutic plasma exchange (TPE) has emerged as a promising intervention for removing inflammatory mediators and toxic metabolites. In Latin America, data on the efficacy of TPE in ALF patients are limited. This real-world study aimed to compare 30-day survival outcomes between patients receiving standard medical treatment (SMT) and those receiving SMT plus TPE. Methods: We analyzed 25 ALF patients admitted to the tertiary intensive care unit (ICU) of Hospital Juárez of Mexico City, Mexico, from 2018 to 2024. Patients received either standard medical treatment (SMT group, n = 12) or SMT with TPE (TPE group, n = 13), including high-volume TPE (n = 8) and standard-volume TPE (n = 5). Survival analysis was performed via Kaplan–Meier estimates, and binomial regression analysis was run to estimate the mortality probability stratified by the hepatic encephalopathy grade. Results: At 30 days, survival was significantly greater in the TPE group (92%) than in the SMT group (50%) (p = 0.02). The greatest survival benefit was observed in patients with Grade 4 encephalopathy. The ICU stay was longer in the TPE group, reflecting the complexity of ALF management. Conclusions: TPE significantly improves 30-day survival in ALF patients compared with SMT alone, supporting its role as an adjunct therapy. Further studies are needed to refine patient selection and optimize treatment protocols. Full article

Invasive fungal infections (IFIs) are one of the most significant public health challenges worldwide. Yet, research and communication thereof were left behind for a long time, until the WHO published a priority pathogens list to guide research, development, and public health action in October 2022. Indeed, due to the rising number of immunocompromised patients at risk and the high level of morbidity, mortality, and economic burden they entail, especially in low- and middle-income countries, IFIs are a serious public health threat. Fungal infections due to dimorphic fungi face additional challenges such as limited knowledge outside of endemic areas and restricted availability of antifungal molecules in areas affected by these infections. The number of related deaths per year is estimated at 2.5 million, but non-governmental organisations make a wider estimation, due to the difficulties in early in vitro diagnostic and troublesome collection and analysis of epidemiological data. Despite this fact, the therapeutic toolbox addressing these infections remains limited, with only four main families of molecules available so far. The antifungal therapeutic supply is composed of very toxic polyenes, the weakly selective and nearly unused 5-fluorocytosine, and azoles, some of which are becoming increasingly inefficient against IFIs. In the 2000–2020s, the fourth arising family consisted of safer semisynthetic echinocandins. Unfortunately, nowadays, more and more fungal isolates encountered in intensive care units exhibit a low susceptibility to echinocandins or are even multiresistant. In this review, we expose the current treatments available to fight against invasive fungal infections. We recall the discovery and physico-chemical aspects of these substances leading to structure/activity and structure/properties relationships. We particularly focus on the to-date resistances and their molecular mechanisms. We finally list some of the most relevant antifungal drug candidates, as they were freshly overviewed by the World Health Organization in April 2025, highlighting the importance of the molecular dimension of this pursuit toward the expansion of the antifungal therapeutic toolbox. Full article

This study delivers a pioneering, high-resolution hydrogeochemical assessment of surface waters in the Upper Velhas and Upper Paraopeba river basins within Brazil’s Iron Quadrangle—an area of critical socioeconomic importance marked by intensive mining and urbanization. Through a dense sampling network of 315 surface water points (one every 23 km²), the research generates an unprecedented spatial dataset, enabling the identification of contamination hotspots and the differentiation between lithogenic and anthropogenic sources of potentially toxic elements (PTEs). Statistical methods, including exploratory data analysis and cluster analysis, were applied to determine background and anomalous concentrations of potentially toxic elements (PTEs). Geospatial distribution maps were generated using GIS. The results revealed widespread contamination by As, Cd, Cr, Ni, Pb, and Zn, with many samples exceeding Brazilian, European, and global drinking water standards. Arsenic and cadmium anomalies in rural and peri-urban communities raise concerns due to the direct consumption of contaminated water. The innovative application of dense spatial sampling and integrated geostatistical methods offers new insights into the pathways and sources of PTE pollution, identifying specific lithological units (e.g., gold schists, mafic intrusions) and land uses (e.g., urban effluents, mining sites) associated with elevated contaminant levels. By establishing robust regional geochemical baselines and source attributions, this study sets a new standard for environmental monitoring in mining-impacted watersheds and provides a replicable framework for water governance, environmental licensing, and risk management in similar regions worldwide. Full article

Mercury (Hg) is a globally recognized toxic element, and the Minamata Convention on Mercury entered into force in 2017 to address its associated risks. Under the United Nations Environment Programme, international efforts to reduce Hg emissions and monitor its environmental presence are ongoing. In support of these initiatives, we developed a simple and rapid mercury detection device based on a quartz crystal microbalance (QCM-Hg sensor), which utilizes the direct amalgamation reaction between Hg and a gold (Au) electrode. The experimental results demonstrated a proportional relationship between Hg concentration and the resulting oscillation frequency shift. Increased flow rates and prolonged measurement durations enhanced detection sensitivity. The system achieved a detection limit of approximately 1 µg/m³, comparable to that of commercially available analyzers. Furthermore, a measurement configuration integrating the reduction-vaporization method with the QCM-Hg sensor enabled the detection of mercury in aqueous samples. Based on the experimental results and the gas-phase detection sensitivity achieved to date, concentrations as low as approximately 0.05 µg/L appear to be detectable. These findings highlight the potential of the QCM-Hg system for on-site mercury monitoring. This review aims to provide a comprehensive yet concise overview of QCM-Hg sensor development and its potential as a next-generation tool for environmental and occupational mercury monitoring. Full article

Certain environmental exposures are associated with COVID-19 incidence and mortality. To determine whether environmental context is associated with other COVID-19 experiences, we used data from the nationally representative Tufts Equity in Health, Wealth, and Civic Engagement Study data (n = 1785; three survey waves 2020–2022 for adults in the United States). Environmental context was assessed using self-reported climate stress and county-level air pollution, greenness, toxic release inventory site, and heatwave data. Self-reported COVID-19 experiences included willingness to vaccinate, health impacts, receiving assistance for COVID-19, and provisioning assistance for COVID-19. Self-reported climate stress in 2020 or 2021 was associated with increased COVID-19 vaccination willingness by 2022 (odds ratio [OR] = 2.35; 95% confidence interval [CI] = 1.47, 3.76), even after adjusting for political affiliation (OR = 1.79; 95% CI = 1.09, 2.93). Self-reported climate stress in 2020 was also associated with increased likelihood of receiving COVID-19 assistance by 2021 (OR = 1.89; 95% CI = 1.29, 2.78). County-level exposures (i.e., less greenness, more toxic release inventory sites, and more heatwaves) were associated with increased vaccination willingness. Air pollution exposure in 2020 was positively associated with the likelihood of provisioning COVID-19 assistance in 2020 (OR = 1.16 per µg/m³; 95% CI = 1.02, 1.32). Associations between certain environmental exposures and certain COVID-19 outcomes were stronger among those who identify as a race/ethnicity other than non-Hispanic White and among those who reported experiencing discrimination; however, these trends were not consistent. A latent variable representing a summary construct for environmental context was associated with COVID-19 vaccination willingness. Our results suggest that intersectional equity issues affecting the likelihood of exposure to adverse environmental conditions are also associated with health-related outcomes. Full article

This study evaluated dietary inclusion of tannin-based feed additives on heifer performance and physiological measures associated with fescue toxicosis and vaccine response. Forty-five yearling beef heifers (292.6 ± 29.0 kg) grazing toxic, endophyte-infected (E+) tall fescue pastures were assigned to 1 of 3 treatment groups: (1) soybean hulls (SH; n = 3 pastures), (2) SH and BX tannin-saponin additive (BX; 10.0 g heifer⁻¹ d⁻¹; n = 3 pastures), and (3) SH and ATX tannin-polyphenol additive (ATX; 5.0 g heifer⁻¹ d⁻¹; n = 3 pastures). Treatments were administered over an 84 d period. Data were analyzed using R and SAS 9.4 with treatment as a fixed effect, block as a random effect, and pasture as the experimental unit. Treatment effects were assessed at the pasture level. Average daily gain (ADG) of heifers receiving ATX (0.53 kg/d) and BX (0.49 kg/d) were increased relative to heifers receiving SH only (0.23 kg/d) between D56 and D84 (p = 0.07). There was no impact of treatment on other performance measures (p > 0.15) or on serum metabolite responses including bovine herpesvirus type 1 (BHV-1) titers (p > 0.15), prolactin (p = 0.97), haptoglobin (p = 0.26), and blood urea nitrogen (BUN; p = 0.38). Preliminary results show the potential for improved weight gain, suggesting further investigation with more experimental units is warranted. Full article

Contamination of food with heavy metals is an important factor leading to serious health concerns. Rapid identification of these heavy metals is of utmost priority. There are several methods to identify traces of heavy metals in food. Conventional methods for the detection of heavy metal residues have their limitations in terms of cost, analysis time, and complexity. In the last decade, voltammetric analysis has emerged as the most prominent electrochemical determination method for heavy metals. Voltammetry is a reliable, cost-effective, and rapid determination method. This review provides a detailed primer on recent advances in the development and application of graphene-based electrochemical sensors for heavy metal monitoring over the last decade. We critically examine aspects of graphene modification (fabrication process, stability, cost, reproducibility) and analytical properties (sensitivity, selectivity, rapid detection, lower detection, and matrix effects) of these sensors. Furthermore, to our knowledge, meta-analyses were performed for the first time for all investigated parameters, categorized based on graphene materials and heavy metal types. We also examined the pass–fail criteria according to the WHO drinking water guidelines. In addition, the effects of heavy metal toxicity on human health and the environment are discussed. Finally, the contribution of heavy metal contamination to the seventeen Sustainable Development Goals (SDGs) stated by the United Nations in 2015 is discussed in detail. The results confirm the significant impact of heavy metal contamination across twelve SDGs. This review critically examines the existing knowledge in this field and highlights significant research gaps and future opportunities. It is intended as a resource for researchers working on graphene-based electrochemical sensors for the detection of heavy metals in food safety, with the ultimate goal of improving consumer health protection. Full article

The rise in online communication platforms has significantly increased exposure to harmful discourse, presenting ongoing challenges for digital moderation and user well-being. This paper introduces the EsCorpiusBias corpus, designed to enhance the automated detection of sexism and racism within Spanish-language online dialogue, specifically sourced from the Mediavida forum. By means of a systematic, context-sensitive annotation protocol, approximately 1000 three-turn dialogue units per bias category are annotated, ensuring the nuanced recognition of pragmatic and conversational subtleties. Here, annotation guidelines are meticulously developed, covering explicit and implicit manifestations of sexism and racism. Annotations are performed using the Prodigy tool (v1. 16.0) resulting in moderate to substantial inter-annotator agreement (Cohen’s Kappa: 0.55 for sexism and 0.79 for racism). Models including logistic regression, SpaCy’s baseline n-gram bag-of-words model, and transformer-based BETO are trained and evaluated, demonstrating that contextualized transformer-based approaches significantly outperform baseline and general-purpose models. Notably, the single-turn BETO model achieves an ROC-AUC of 0.94 for racism detection, while the contextual BETO model reaches an ROC-AUC of 0.87 for sexism detection, highlighting BETO’s superior effectiveness in capturing nuanced bias in online dialogues. Additionally, lexical overlap analyses indicate a strong reliance on explicit lexical indicators, highlighting limitations in handling implicit biases. This research underscores the importance of contextually grounded, domain-specific fine-tuning for effective automated detection of toxicity, providing robust resources and methodologies to foster socially responsible NLP systems within Spanish-speaking online communities. Full article

The worldwide agriculture industry is facing increasing problems due to rapid population increase and increasingly unfavorable weather patterns. In order to reach the projected food production targets, which are essential for guaranteeing global food security, innovative and sustainable agricultural methods must be adopted. Conventional approaches, including traditional breeding procedures, often cannot handle the complex and simultaneous effects of biotic pressures such as pest infestations, disease attacks, and nutritional imbalances, as well as abiotic stresses including heat, salt, drought, and heavy metal toxicity. Applying phytohormonal approaches, particularly those involving hormonal crosstalk, presents a viable way to increase crop resilience in this context. Abscisic acid (ABA), gibberellins (GAs), auxin, cytokinins, salicylic acid (SA), jasmonic acid (JA), ethylene, and GA are among the plant hormones that control plant stress responses. In order to precisely respond to a range of environmental stimuli, these hormones allow plants to control gene expression, signal transduction, and physiological adaptation through intricate networks of antagonistic and constructive interactions. This review focuses on how the principal hormonal signaling pathways (in particular, ABA-ET, ABA-JA, JA-SA, and ABA-auxin) intricately interact and how they affect the plant stress response. For example, ABA-driven drought tolerance controls immunological responses and stomatal behavior through antagonistic interactions with ET and SA, while using SnRK2 kinases to activate genes that react to stress. Similarly, the transcription factor MYC2 is an essential node in ABA–JA crosstalk and mediates the integration of defense and drought signals. Plants’ complex hormonal crosstalk networks are an example of a precisely calibrated regulatory system that strikes a balance between growth and abiotic stress adaptation. ABA, JA, SA, ethylene, auxin, cytokinin, GA, and BR are examples of central nodes that interact dynamically and context-specifically to modify signal transduction, rewire gene expression, and change physiological outcomes. To engineer stress-resilient crops in the face of shifting environmental challenges, a systems-level view of these pathways is provided by a combination of enrichment analyses and STRING-based interaction mapping. These hormonal interactions are directly related to the United Nations Sustainable Development Goals (SDGs), particularly SDGs 2 (Zero Hunger), 12 (Responsible Consumption and Production), and 13 (Climate Action). This review emphasizes the potential of biotechnologies to use hormone signaling to improve agricultural performance and sustainability by uncovering the molecular foundations of hormonal crosstalk. Increasing our understanding of these pathways presents a strategic opportunity to increase crop resilience, reduce environmental degradation, and secure food systems in the face of increasing climate unpredictability. Full article

Ferrocene (Fc), a redox-active organometallic scaffold, has attracted significant attention in medicinal chemistry due to its favorable physicochemical and pharmacological properties. The present study explores the therapeutic potential of novel Fc-functionalized analogues of imatinib and nilotinib, aimed at targeting BCR-ABL1+ chronic myeloid leukemia (CML) cells. A series of Fc-based derivatives (compounds 6, 9, 14, and 18) were synthesized by systematically substituting key pharmacophoric regions of the parent tyrosine kinase inhibitors with Fc units. The antiproliferative activity of these compounds was evaluated against four BCR-ABL1-positive leukemia cell lines (K-562, BV-173, AR-230, and LAMA-84), with imatinib serving as a reference drug. Biological assays revealed distinct structure–activity relationships. Compounds 6 and 9 demonstrated superior activity against the K-562 cell line, while compounds 14 and 18 exhibited enhanced potency and higher ligand efficiencies (LEs) against BV-173 and AR-230 cells compared to imatinib. Selectivity assays further indicated favorable toxicity profiles of compounds 9 and 14 toward malignant versus non-malignant cells. Molecular docking studies supported these findings, showing that Fc substitution alters binding interactions within the c-Abl kinase ATP-binding site while retaining key stabilizing contacts. Computationally predicted LEs showed strong correlation with experimental data, especially for K-562 and LAMA-84 cells, confirming the kinase as a relevant target. Full article

The tarnished plant bug, Lygus lineolaris (TPB), (Palisot de Beauvois), and the western tarnished plant bug (WTPB), Lygus hesperus, Knight, are major agricultural pests that cause significant damage to a wide range of crops in the southeastern and southwestern United States. Flonicamid (commercial name: Carbine 50WG) is generally effective against various sap-feeding pests, including both L. hesperus and L. lineolaris. This study evaluated the toxicity of flonicamid on third-instar nymphs and adults of both Lygus species under laboratory conditions. Two bioassay methods were used: spray application to assess both contact and oral toxicity, and dipping to evaluate oral toxicity. Results showed that L. hesperus was significantly more susceptible to flonicamid than L. lineolaris across both bioassay methods. While no significant differences in toxicity were observed between spray and dipping assays, third-instar nymphs exhibited significantly higher sensitivity than adults in both species. The addition of piperonyl butoxide (PBO), a known inhibitor of cytochrome P450-monooxygenases (P450s), significantly enhanced the toxicity of flonicamid, suggesting that P450 enzyme plays a critical role in its detoxification. Sublethal exposure to flonicamid also induced increased P450 activity in both species. These findings provide valuable insights into the differences in susceptibility between L. lineolaris and L. hesperus to flonicamid and indicate that P450-mediated detoxification is critical for flonicamid metabolism. Such insights are valuable for early resistance monitoring and optimizing flonicamid application in integrated pest management programs. Full article