Search Results (11,075)

Stroke is a major global cause of death and disability and necessitates both quick diagnosis and treatment within narrow windows of opportunity. CT scanning is still the first-line imaging in the acute phase, but correct interpretation may not always be readily available and may not be resource-available in poor and rural health systems. Automated stroke classification systems can offer useful diagnostic assistance, but clinical application demands high accuracy and explainable decision-making to maintain physician trust and patient safety. In this paper, a ResNet-18 model was trained on 6653 CT brain scans (hemorrhagic stroke, ischemia, normal) with two-phase fine-tuning and transfer learning, XRAI explainability analysis, and web-based clinical decision support system integration. The model performed with 95% test accuracy with good performance across all classes. This system has great potential for emergency rooms and resource-poor environments, offering quick stroke evaluation when specialists are not available, particularly by rapidly excluding hemorrhagic stroke and assisting in the identification of ischemic stroke, which are critical steps in considering tissue plasminogen activator (tPA) administration within therapeutic windows in eligible patients. The combination of classification, explainability, and clinical interface offers a complete framework for medical AI implementation. Full article

Gestational complications, such as preeclampsia and gestational diabetes mellitus (GDM), pose significant risks to maternal and fetal health and increase long-term cardiovascular disease risk in offspring. This review aims to synthesize current knowledge on the roles of ferroptosis and neutrophil extracellular trap formation (NETosis)—two regulated cell death pathways—in these pregnancy-related conditions. We performed a comprehensive analysis of preclinical and clinical studies that investigate the involvement of dysregulated iron metabolism, oxidative stress, inflammation, and endothelial dysfunction mediated by ferroptosis and NETosis in gestational pathologies. Evidence indicates that disturbances in maternal iron homeostasis and enhanced formation of lipid peroxides and NETs contribute to placental dysfunction and systemic inflammation, exacerbating disease severity. Therapeutic strategies targeting these pathways are emerging but require further validation. Our review also identifies key gaps in mechanistic understanding, biomarker development, and translational research needs. We conclude that modulation of ferroptosis and NETosis offers promising avenues for improving diagnosis and treatment of pregnancy complications, though carefully designed clinical studies are essential to confirm their clinical utility and safety. Full article

The increasing use of reclaimed wastewater in agriculture raises growing concerns about the accumulation of priority organic micropollutants in edible crops. In this study, we developed and validated a novel QuEChERS–SPME–GC/MS method for the simultaneous determination of 15 polycyclic aromatic hydrocarbons (PAHs), 3 nitro-PAHs, and 14 polychlorinated biphenyls congeners in Eruca vesicaria (rocket) leaves. The method was optimized to address the matrix complexity of leafy vegetables and included a two-step dispersive solid-phase extraction (d-SPE) cleanup and aqueous dilution prior to SPME. Validation showed excellent performance, with MDLs between 0.1 and 6.7 µg/kg, recoveries generally between 70 and 120%, and precision (RSD%) below 20%. The greenness of the protocol was assessed using the AGREE metric, yielding a score of 0.60. Application to rocket samples irrigated with treated wastewater revealed no significant accumulation of target pollutants compared to commercial samples. All PCB and N-PAH congeners were below detection limits, and PAH concentrations were low and mostly limited to lighter compounds. Human health risk assessment based on toxic equivalent concentrations confirmed that estimated cancer risk (CR) values 10⁻⁹–10⁻⁸ were well below accepted safety thresholds. These findings support the safe use of reclaimed water for leafy crop irrigation under proper treatment conditions and highlight the suitability of the method for trace-level food safety monitoring. Full article

This paper presents an investigation into the mechanical performance of a subway station prefabricated assembly air duct (PAAD), constructed by assembling the prefabricated reinforced concrete segments. The study is implemented through numerical analysis, focusing on the impact from the grouting defects in the sleeve grouting connection and assembly error defects along the assembly direction. The results demonstrate that the assembly error defect has almost no impact on the mechanical performance of the PAAD, satisfying the safety requirements for use. However, the grouting defects in the sleeve grouting connection can influence the mechanical performance of the PAAD, in which the maximum tensile stress of concrete in the sleeve grouting connection with a 20 mm-long bottom grouting defect is greater than the tensile strength of that concrete, and strengthening treatment is thus required for ensuring the structure’s safety and reliability. This study provides the basis for applying a PAAD in subway station construction. Full article

Background: Autoimmune cholestatic liver diseases (AICLDs), including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), are characterized by progressive biliary injury and cholestasis, leading to an impaired quantity/quality of life. Pruritus affects 20–70% of patients and is often refractory to current treatments. Ileal bile acid transporter (IBAT) inhibitors reduce bile acid reabsorption and may alleviate cholestatic pruritus. This systematic review and meta-analysis evaluates their efficacy and safety in adults with AICLD. Methods: Following PRISMA guidelines, we systematically searched PubMed, Embase, and Cochrane-CENTRAL for studies assessing IBAT inhibitors in adult AICLD patients with pruritus for ≥12 weeks. The primary outcome was the change in the 5-D Pruritus Scale. Secondary outcomes included sleep quality, serum bile acids, liver biochemistry, and safety. Heterogeneity was assessed using Cochrane Q and I² statistics. Results: Three studies (n = 180) met inclusion criteria, including two RCTs and one single-arm study. Patients (78% female; 85% PBC; 77% linerixibat) showed a significant pruritus reduction (MD = −4.93, 95%CI [−6.26, −3.59], p < 0.0001), accompanied by improved sleep quality (MD = −8.12, 95%CI [−13.54, −2.70], p = 0.0033). Serum bile acids, FGF19, and autotaxin decreased significantly, with increased C4 levels. AST and GGT declined, while ALP, ALT, and bilirubin remained stable. Adverse events occurred in 89.7%, mainly diarrhea (22.7%), nausea (12.2%), and abdominal pain (18.2%); serious events were rare (2.2%). Conclusions: IBAT inhibitors significantly reduce pruritus and improve sleep in AICLD, with a favorable safety profile. These findings support their potential as a novel therapeutic option for cholestatic pruritus in adults with AICLD. Full article

Chimpanzees (Pan troglodytes) rescued from the illegal wildlife trade often suffer from chronic, traumatic injuries that require specialized and prolonged medical treatment in wildlife rehabilitation centers. We present the case report of a two-year-old male chimpanzee admitted at the Tchimpounga Chimpanzee Rehabilitation Center in the Republic of Congo with a chronic periorbital abscess, likely caused by a machete wound sustained during the poaching of his mother. Despite receiving extended antimicrobial therapy, his condition was never fully controlled and progressed to a chronic orbital infection, causing him discomfort and producing chronic purulent discharge. Enucleation was performed under general anesthesia using ketamine and medetomidine, with surgical approach adapted to the distinctive orbital anatomy of chimpanzees. During the procedure, ligation of the optic nerve and ophthalmic vessels was required due to the confined orbital apex and extensive vascularization, ensuring adequate haemostasias and procedural safety. The chimpanzee made an uneventful postoperative recovery, resuming normal feeding and social behavior within 48 h, with complete wound healing occurring within two weeks. This case report highlights the importance of prompt surgical intervention when conservative medical management fails to resolve refractory ocular infections in chimpanzees. It also emphasizes the importance of specific anesthetic protocols, refined surgical techniques and tailored postoperative care in wildlife rehabilitation centers. Documenting and sharing detailed case reports such as this contributes to the limited veterinary literature on great ape surgery and supports evidence-based clinical decision-making to improve the welfare and treatment outcomes of rescued chimpanzees. Full article

Background/Objectives: Toxoplasma gondii, an obligate intracellular parasite, poses a major global health concern owing to its potential for congenital transmission, particularly during pregnancy. Current pharmacological treatments, including spiramycin and pyrimethamine, exhibit limitations in both efficacy and safety, underscoring the need for novel therapeutic strategies. In this study, we investigated the antiparasitic potential of BthTX-II, an Asp49 phospholipase A₂ (PLA₂) isolated from Bothrops jararacussu venom, in human trophoblast cells (BeWo) and third-trimester human placental explants infected with T. gondii. Methods: In vitro assays were performed using BeWo cells infected with T. gondii tachyzoites and treated with non-cytotoxic concentrations of BthTX-II (3.125, 1.56, and 0.78 µg/mL). An ex vivo model employing third-trimester human placental villous explants was used under similar conditions. Parasite proliferation, adhesion, and invasion were assessed alongside host immune response modulation. Results: Our findings demonstrate that BthTX-II reduces T. gondii proliferation in BeWo cells at all tested non-cytotoxic concentrations. The toxin also significantly impaired parasite adhesion and invasion while modulating host immune response by upregulating interleukin (IL)-6, IL-8, and macrophage migration inhibitory factor (MIF), and downregulating vascular endothelial growth factor—potentially disrupting parasite proliferation. In placental villous explants, BthTX-II (1.56 μg/mL) reduced T. gondii proliferation and modulated IL-8, MIF, and tumour necrosis factor-alpha levels without compromising tissue viability. Conclusions: These findings highlight BthTX-II as a potential candidate in toxoplasmosis treatment. Further investigation should focus on its dual role in limiting parasite development and modulating immune responses at the maternal–fetal interface. Full article

Consumer demands for fresh and minimally processed liquid foods that support disease prevention and promote health emphasize the need for innovative processing technologies that ensure microbiological safety and preserve bioactive compounds. In addition, consumers are becoming more concerned about the presence of chemical additives in liquid foods. Non-thermal processing technologies, including high-pressure processing, high-pressure homogenization, pulsed electric field, pulsed magnetic field, high-pressure carbon dioxide, ultrasound treatment, radiation processing, ozone processing, cold plasma, and membrane processing, offer excellent prospects for the application in liquid foods. The given technologies aim to retain bioactive properties, deactivate enzymatic activity, and destroy microorganisms, thereby extending the shelf life of liquid foods. Thus, this current review, without a doubt, could be valuable to the liquid food industries and the scientific world by offering great insight into the latest developments in the use of innovative non-thermal processing technologies, which can be employed for shelf life extension and the retention of bioactive compounds in liquid foods. This paper also discusses the challenges faced by the liquid food industry that need to be addressed in future studies. Full article

Background: Hydrogen sulfide (H₂S) is an endogenously produced gaseous neurotransmitter. H₂S donors exhibited neuroprotection in oxidative-stress-related disorders in preclinical studies, but odor and short half-lives have limited their clinical use. However, endogenous H₂S stimulators with antioxidant properties have advantages over H₂S donors regarding safety and patient compliance. Empagliflozin (EMPA), a sodium–glucose cotransporter-2 (SGLT2) inhibitor widely used in the treatment of diabetes mellitus (DM), exerted similar neuroprotective and antioxidant effects as H₂S and shares common mechanisms. This study aimed to investigate the role of H₂S in the antioxidant effects of EMPA in the brain. Methods: The effects of EMPA on H₂S production and reactive oxygen species (ROS) formation were assessed ex vivo in mouse brain under normal conditions and pyrogallol-induced oxidative stress. Moreover, rats were divided into the following four groups: nondiabetic, EMPA-treated nondiabetic, streptozotocin (STZ)-induced diabetic, and EMPA-treated, STZ-induced diabetic. Endogenous H₂S and ROS levels in the brain were measured using methylene blue and chemiluminescence assays, respectively. Results: Ex vivo EMPA treatment significantly increased endogenous H₂S formation in both healthy and pyrogallol-induced oxidative stress, as well as reduced ROS formation in mouse brain; these effects were significantly reversed by the H₂S synthesis inhibitor aminooxyacetic acid (AOAA). Oral EMPA administration significantly elevated brain H₂S levels in both nondiabetic and diabetic rats and reduced ROS formation. These effects were inhibited by AOAA. Conclusions: Our study revealed a novel mechanism by which EMPA can reduce oxidative stress in neurodegenerative disorders by triggering H₂S synthesis in the brain. Full article

Objectives: This study aimed to evaluate the safety and efficacy of the eight-chop technique in cataract surgery in patients with pseudoexfoliation (PEX) syndrome and assess the intraoperative parameters, changes in corneal endothelial cells, intraocular pressure (IOP), and intraoperative complications. Methods: This technique was applied in patients with and without PEX syndrome. Preoperative and postoperative assessments were conducted on best-corrected visual acuity, IOP, corneal endothelial cell density (CECD), coefficient of variation, percentage of hexagonal cells, and central corneal thickness. Intraoperative recordings included operative time, phaco time, aspiration time, cumulative dissipated energy (CDE), and fluid of volume used. Results: We analyzed 150 eyes from 150 patients (mean age, 75.5 ± 5.7 years; 59 men, 91 women). In the PEX group, operative time, phaco time, aspiration time, CDE, and volume of fluid used were 6.7 min, 17.4 s, 85.2 s, 6.91 µJ, and 33.4 mL, respectively, demonstrating favorable surgical metrics. On the other hand, in the control group, operative time, phaco time, aspiration time, CDE, and volume of fluid used were 4.5 min, 14.3 s, 64.0 s, 5.83 µJ, and 25.5 mL, respectively. In addition, CECD losses were 3.7% at week 7 and 2.7% at week 19 in the PEX group and 2.7% and 1.6%, respectively, in the control group. Significant decreases were observed at 7 and 19 weeks postoperatively in the PEX and control groups. No eye in the PEX group required a capsular tension ring due to zonular dialysis. Conclusions: The eight-chop technique in cataract surgery demonstrates excellent intraoperative parameters in patients with PEX, is effective against zonular weakness, and does not require the use of a capsular tension ring. This technique will aid in establishing personalized treatment strategies and improve cataract management and treatment. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterised by cognitive decline, synaptic loss, and multifaceted pathology involving amyloid-β (Aβ) aggregation, tau hyperphosphorylation, neuroinflammation, and impaired proteostasis. In recent years, biologic therapies, such as monoclonal antibodies, vaccines, antisense oligonucleotides (ASOs), and gene therapies, have gained prominence as promising disease-modifying strategies. In this review, we provide a comprehensive synthesis of current biologic approaches under clinical evaluation for AD. Drawing on data curated from ClinicalTrials.gov (as of 2025), we systematically summarise the molecular targets, therapeutic modalities, mechanisms of action, trial phases, and sponsors of over 60 biologic agents. These include Aβ-directed antibodies targeting distinct conformers such as protofibrils, pyroglutamate-modified species, and soluble oligomers; tau-targeted immunotherapies and RNA-based interventions; and emerging platforms focused on neuroimmune modulation, peptide hormones, and microbiota-based strategies. Gene and RNA therapeutics, particularly ASOs and small interfering RNAs (siRNAs) delivered intrathecally or via lipid nanoparticles, are also reviewed for their potential to modulate intracellular targets with high specificity. We also analyse the historical landscape of biologic candidates that failed to reach approval, discussing key reasons for trial discontinuation, including lack of clinical efficacy, safety concerns (e.g., amyloid-related imaging abnormalities), or inadequate biomarker responses. These cases offer crucial insights for refining future drug design. Looking ahead, we highlight major challenges and evolving perspectives in AD biologic therapy: expanding therapeutic targets beyond Aβ and tau, overcoming delivery barriers to the brain, designing prevention-oriented and genetically stratified trials, and navigating regulatory and ethical considerations. Together, these efforts signal a paradigm shift in AD drug development, from symptomatic treatment to mechanism-based precision biologics. By integrating real-time clinical trial data with mechanistic insight, this review aims to inform both translational research and therapeutic innovation in AD. Full article

The reuse of treated wastewater (TWW) offers a sustainable solution for water management in agriculture, particularly in arid regions like Saudi Arabia. However, its success depends on farmers’ acceptance, influenced by perceptions of economic benefits, social acceptability, environmental impacts, and health risks. This study surveys 391 farmers across five regions in Saudi Arabia to assess their attitudes toward TWW reuse in irrigation, exploring how advanced wastewater treatment technologies can improve acceptance. Results show that 65% of farmers use TWW, with usage peaking at 72% in Al-Ahsa and Qatif, driven by water scarcity and lack of alternatives. While 78% are satisfied with TWW, concerns persist regarding pests, consumer acceptance, health risks, and soil quality. Advanced technologies can mitigate these issues by enhancing water quality and safety. The highest positive impact of the use of TWW in irrigation from was the impact on productivity, reduction in the cost of fertilizers and savings in the cost of water abstraction. With only 57% of farmers receiving extension services, integrating education on these technologies could further boost confidence. This study highlights key acceptance factors, underscoring the need for technological and educational interventions to promote sustainable TWW reuse in agriculture. Full article

Background/Objectives: Isotretinoin is a highly effective therapy for severe acne, but its potential neuropsychiatric adverse reactions (NPsRs) have been controversial. This study evaluated EudraVigilance data from 2005 to 2025 to better understand the frequency, typology, and predictors of such events. Methods: We conducted a retrospective analysis of 33,381 individual case safety reports (ICSRs) related to isotretinoin. Using descriptive statistics, chi-square tests, and logistic regression, we assessed associations between NPsRs and variables such as age, sex, geographic region, and reporter type. Results: A total of 9793 cases (29.3%) involved at least one NPsR. Depression (31%) and suicidal ideation (8.6%) were the most frequently reported symptoms. Adolescents (12–17 years) had the highest proportion of NPsR cases, while male patients and reports submitted by non-healthcare professionals were significantly overrepresented. Reports from non-European Economic Area countries also had slightly increased odds of including NPsRs. All predictors were statistically significant in the logistic regression model, though the explained variance was modest (Nagelkerke R² = 0.065). Conclusions: Neuropsychiatric reactions remain a prominent and persistent signal in isotretinoin pharmacovigilance, particularly among younger patients and non-professional reporters. Although causality cannot be inferred from spontaneous reporting data and confounding factors like acne-related depression cannot be excluded, these findings highlight the clinical value of pre-treatment psychiatric screening, patient-centered education, and proactive mental health monitoring throughout isotretinoin therapy. Full article

Background/Objectives: Sacituzumab govitecan (SG) is an antibody–drug conjugate targeting Trop-2 that has demonstrated clinical benefits in randomised trials for patients with metastatic triple-negative breast cancer (mTNBC) and metastatic hormone receptor-positive/HER2-negative (HR+/HER2− mBC) disease. However, real-world data on its effectiveness and safety are limited, especially in patients with poor performance status or central nervous system (CNS) involvement. This study aimed to evaluate the real-world outcomes of SG in these two subtypes. Methods: We conducted a retrospective, multicentre, observational study across three tertiary hospitals in Spain. Patients with mTNBC or HR+/HER2− mBC treated with SG between June 2022 and March 2025 were included. Clinical data, treatment history, adverse events (AEs), and survival outcomes were also recorded. The median progression-free survival (mPFS) and median overall survival (mOS) were estimated using Kaplan–Meier analysis. Univariate and multivariate analyses were performed to identify the factors influencing outcomes. The association between granulocyte colony-stimulating factor (G-CSF) prophylaxis and neutropenia was assessed using Fisher’s exact test. Results: A total of 56 patients were included in this study (33 with mTNBC and 23 with HR+/HER2− mBC). In the mTNBC group, mPFS was 4.0 months (95% CI: 1.94–5.98) and mOS was 11.0 months (95% CI: 4.80–17.12). In the HR+/HER2− mBC group, mPFS was 3.7 months (95% CI: 2.02–5.44) and mOS was 20.2 months (95% CI: 3.9–36.5). Fatigue, neutropenia, and gastrointestinal toxicity were the most common AEs. Primary G-CSF prophylaxis was not associated with a reduced incidence of neutropenia (p = 0.434). Conclusions: In routine practice, SG shows effectiveness comparable to that of randomised trials across both subtypes, with a safety profile consistent with pivotal studies. The observed toxicity profile was consistent with that described in pivotal clinical trials and other studies. The prophylactic use of G-CSF was not associated with an impact on the occurrence of neutropenia, but the incidence of neutropenia was lower than that in clinical trials and other studies that did not administer G-CSF prophylactically. Full article

Mastitis, an inflammatory disease caused by the invasion of various pathogenic microorganisms into mammary gland tissue, is a core health issue plaguing the global dairy industry. The consequences of this disease are manifold. In addition to directly compromising the health and welfare of dairy cows, it also precipitates a substantial decline in lactation function, a precipitous drop in raw milk production, and alterations in milk composition (e.g., increased somatic cell counts and imbalanced ratios of milk protein to fat). These changes result in a marked degradation of milk quality and safety, and in turn, engender significant economic losses for the livestock industry. Therefore, the establishment and implementation of a comprehensive prevention and control system is a key strategy to effectively curb the occurrence of mastitis, reduce its incidence rate, and minimise economic losses. This review systematically explores the complex etiological factors and pathogenic mechanisms of mastitis in dairy cows, and summarises various diagnostic methods, including milk apparent indicators monitoring, pathogen detection, physiological parameter monitoring, omics technologies, and emerging technologies. Furthermore, it undertakes an analysis of treatment protocols for mastitis in dairy cows, with a particular emphasis on the significance of rational antibiotic use and alternative therapies. Moreover, it delineates preventive measures encompassing both environmental and hygiene management, and dairy cow health management. The objective of this paper is to provide a comprehensive and scientific theoretical basis and practical guidance for dairy farming practices. This will help to improve the health of dairy cows, ensure a stable supply of high-quality dairy products, and promote the sustainable and healthy development of the dairy farming industry. Full article