Search Results (11,561)

This study investigates the long-term variability and evolution of particulate matter with an aerodynamic diameter of <2.5 µm (PM_2.5) sources in Vilnius, Lithuania, during the period 2013–2021. Source apportionment was performed using Positive Matrix Factorization (PMF) based on elemental composition data obtained through particle-induced X-ray emission (PIXE) analysis. The results revealed substantial year-to-year variability in the chemical profiles of the identified sources. Crustal/mineral dust was characterized by high contributions of lithogenic elements, including Si, Ca, Ti, and Fe, while soil dust exhibited elevated proportions of Al, Ca, and Fe. Traffic non-exhaust emissions were marked by elevated Cu, Zn, and Pb in 2013–2015, whereas exhaust emissions in 2019–2021 were characterized by sulfur-rich aerosols. Industrial and oil combustion sources showed enhanced contributions of Ni, V, and Cr, particularly in 2016, 2018, and 2020. Biomass/wood burning represented a major seasonal source, reaching peak intensity in 2018–2019 and characterized by elevated K and Zn contributions. A notable long-term trend was the increasing importance of soil-derived particles, as reflected by Al contributions rising to 91.2% by 2021. Overall, the major PM₂.₅ source categories remained relatively stable, while their chemical fingerprints and relative importance exhibited substantial temporal variability. Full article

The valorization of vegetable-oil biomass into bio-based functional fluids offers a sustainable route for replacing petroleum-derived insulating liquids in power equipment. In this study, soybean and canola oils were used as renewable lipid feedstocks and converted into biomass-derived ester fluids through acid-catalyzed transesterification with methanol, ethanol, 1-propanol, and 1-butanol. The obtained ester-rich products were subjected to a combined physicochemical, dielectric, and thermal screening workflow, including kinematic viscosity at 40 °C (ν₄₀), acid value, breakdown voltage (BDV), differential scanning calorimetry (DSC; 2–8 °C min⁻¹ under N₂), and oxygen bomb calorimetry. Transesterification effectively upgraded the vegetable oils into low-viscosity ester-rich product fluids for most alcohol routes, with soybean methyl ester (SME) reaching 4.41 ± 0.02 mm² s⁻¹ and selected canola-derived esters showing viscosities of 5.81–6.81 mm² s⁻¹. However, the functional performance of the biomass-derived fluids was strongly governed by the alcohol route. SME exhibited the most favorable balance between dielectric and physicochemical properties, delivering the highest BDV of 64.90 ± 9.74 kV, exceeding the IEC 60156 threshold of 30 kV, while maintaining a low acid value of 0.0103 ± 0.0006 mg KOH g⁻¹. In contrast, propyl- and butyl-derived esters showed substantially lower BDV values of ≤14.98 kV, whereas ethanol-derived products retained near-neat-oil viscosities and were unsuitable for BDV testing under the applied conditions. Although propyl- and butyl-derived ester-rich products reduced kinematic viscosity, their markedly lower BDV values were likely associated with route-dependent product heterogeneity, lower alcohol–oil miscibility, possible residual polar impurities, and moisture sensitivity; therefore, they were regarded as non-optimized screening outcomes rather than IEC-compliant transformer-fluid candidates. DSC analysis provided comparative thermal-response descriptors under nitrogen, with methylation producing more coherent endothermic features. The combustion heats of the ester-rich products were concentrated at approximately 39–41 MJ kg⁻¹, lower than that of the mineral-oil reference in this dataset, suggesting combustion heat was used only as a preliminary energy-density descriptor and was not interpreted as direct evidence of improved fire safety. From an engineering-safety perspective, the lower combustion heat of the bio-esters may reduce the potential fire-load contribution during fault-related fire scenarios, although full fire-safety qualification requires additional flash-point, fire-point, and aging evaluations. Overall, this work demonstrates that alcohol route selection is a critical factor in converting vegetable oil biomass into high-value bio-based insulating fluids. Among the tested formulations, soybean methyl ester is the most promising baseline candidate for further development as a biodegradable, sustainable transformer fluid. Full article

Background: Moyamoya disease (MMD) is a progressive cerebrovascular disorder and an important cause of ischemic stroke in children. Surgical revascularization is the mainstay of treatment; however, data on functional and angiographic outcomes in pediatric populations, particularly from Central Asia, remain limited. Methods: We conducted a retrospective single-centre cohort study of 45 pediatric patients with MMD who underwent surgical revascularization between 2013 and 2025. Clinical outcomes were assessed using the modified Rankin Scale (mRS), and angiographic outcomes were evaluated using the Matsushima grading system. Associations between clinical, surgical, and radiological factors and functional outcomes were analysed. Results: The mean age at diagnosis was 9.5 ± 3.8 years, with a mean follow-up of 20.6 ± 17.5 months. Headache was the most common presenting symptom (77.8%), while ischemic stroke was the predominant cerebrovascular presentation, occurring in more than 70% of patients. More than 75% of patients had advanced angiographic disease (Suzuki stages IV–V). Functional outcomes improved significantly following surgery, with mean mRS decreasing from 2.09 ± 1.26 to 1.64 ± 1.00 (p = 0.004). At follow-up, 82.2% of patients achieved favorable outcomes (mRS 1–2). Bilateral revascularization was performed in 64.4% of cases. No significant differences were observed between direct, indirect, and combined techniques, although a trend toward improved outcomes with direct and combined approaches was noted. Postoperative collateral formation was strongly associated with functional outcome (p = 0.005). Conclusions: Surgical revascularization is associated with significant functional improvement and low recurrence rates in pediatric MMD. The quality of collateral formation, rather than the surgical technique itself, appears to be the primary determinant of outcome. Full article

Tobacco leaf extract (TLE) exposure can induce liver injury-associated responses involving cell death, inflammatory signaling, and extracellular matrix (ECM)-related changes. This study examined whether apple seed extract (ASE) post-treatment changes apoptosis-, inflammation-, ECM-, and insulin-like growth factor (IGF)-related markers after TLE exposure. Primary mouse hepatocytes were exposed to TLE, ASE alone, or TLE followed by ASE, and mouse liver tissues were examined after TLE exposure with or without ASE post-treatment. TLE reduced hepatocyte viability in a concentration-dependent manner, with an IC₅₀ of 4.4 mg/mL. Annexin V/propidium iodide analysis showed that early apoptosis increased from 2.20% in untreated cells to 5.50% after 2 mg/mL TLE and 85.65% after 4 mg/mL TLE. ASE alone at 40 µg/mL increased the early apoptotic fraction to 53.65%, indicating that this concentration was not biologically neutral under basal culture conditions. After TLE exposure followed by ASE post-treatment, the live-cell fraction remained high in T2HA and T4HA, whereas T5HA retained a high early apoptotic fraction. In mice, TLE exposure was accompanied by visible liver appearance changes and histological alterations. ASE post-treatment changed Alcian blue staining, gelatinase activity, TIMP-associated signals, and IGF-related signals. These findings indicate treatment-dependent changes in selected injury-associated markers rather than a consistently protective effect of ASE. The study does not assign these effects to a specific ASE constituent because compound-level chemical standardization was not performed. Full article

Accurate prediction of protein–protein interaction (PPI) interface residues is essential for understanding molecular recognition and supporting structure-guided design. To integrate contextual sequence representations with structure-related physicochemical information, we propose a multimodal framework termed MD-Transformer. The model combines residue-level ProtBERT embeddings with physicochemical descriptors, including B-factor, solvent-accessible surface area (SASA), and hydrophobicity. A hybrid fusion module first aligns heterogeneous features, followed by Transformer encoding and cross-modal attention for multimodal integration. Using the DB5.5 benchmark, physicochemical descriptors were Z-score normalized exclusively with training-set statistics. Under the complex-level split protocol (Official A), MD-Transformer achieved an AUPRC of 0.564, outperforming the ablation model without physicochemical descriptors by 0.159 and reducing false-positive predictions on exposed non-interface residues. Under the homology-aware split protocol (Official B v1), the model maintained an AUPRC of 0.480 and an MCC of 0.242, indicating retained predictive capability under reduced sequence similarity constraints. Under the same aligned evaluation workflow, PeSTo achieved an AUPRC of 0.264. Further SASA-stratified analyses identified SASA as a major contributor to suppressing false-positive predictions across residue exposure environments, while also revealing a precision-recall trade-off in highly exposed residues. These results suggest that contextual sequence representations and residue-level physicochemical descriptors provide complementary predictive signals. Full article

Canada played a pivotal role in the establishment of the International Criminal Court (ICC) and it was the first country in the world to incorporate the Rome Statute in its domestic law when it passed the Crimes Against Humanity and War Crimes Act (CAHWCA) on 24 June 2000. The CAHWCA allows the application of universal jurisdiction for the prosecution of those persons responsible for “atrocity crimes” who are present in Canada. Yet, Canada’s record for the prosecution and conviction of those who are responsible for “atrocity crimes” under CAHWCA is far from enviable. Rather than taking a leadership role in the prosecution of those responsible for “atrocity crimes,” Canada has avoided doing so. Thus far, Canada has prosecuted only two atrocity crimes cases under universal jurisdiction: R. v. Munyaneza 2009 QCCS 2201 [2009] QJ No 4913 conviction and the denial of its appeal in R. v. Munyaneza 2201. (Quebec Court of Appeal, 7 May 2014); and an acquittal in the R. v. Mungwarere (Superior Court of Ontario, 5 July 2013) case. This article will analyze the ratio decidendi in these two precedent-setting cases that rest on the credibility and trustworthiness of the testimonial evidence presented. It also considers other factors that militate against the criminal investigation and prosecution of those who are allegedly responsible for atrocity crimes. This raises the fundamental question of whether it will be possible to “end impunity for international crimes” and advance international justice when States, such as Canada, are failing to prosecute and convict those who are responsible for atrocity crimes through universal jurisdiction. It calls on States to allocate adequate funding for criminal investigations and prosecutions under universal jurisdiction and to develop more rigorous, detailed, and refined methods for gathering and adducing credible and trustworthy testimonial evidence for the prosecution of cases involving these serious international crimes. Full article

Host microRNAs (miRNAs) are widely proposed as innate antiviral effectors against SARS-CoV-2, yet whether they actually restrict infection in lung epithelial cells remains unresolved. Two of the most-cited candidates, miR-29a-3p and miR-15b-5p, are predicted to bind both the viral genome and key entry/trafficking factors such as Furin and ATG9A, but functional evidence is fragmented and often contradictory. Here, we put both miRNAs to the test in human Calu-3 cells infected with the SARS-CoV-2 Beta and Omicron BA.1 variants, using parallel gain- and loss-of-function strategies coupled to RT-qPCR of viral and cellular transcripts and back-titration of infectious progeny on VeroE6/TMPRSS2 cells. Both miRNAs transiently suppressed viral gene expression at 6 hpi, but this early dampening was followed by a marked transcript rebound at 24 hpi, especially for Omicron, with virtually no impact on total extracellular viral RNA. More strikingly, miR-15b modulation enhanced infectious virus output during Beta infection, and miR-29a overexpression boosted Omicron BA.1 infectivity, while Furin, ATG9A, AKT3, and TFEB showed only modest, condition-dependent shifts. Rather than acting as clean antiviral effectors, miR-29a and miR-15b emerge as context-dependent modulators that can paradoxically favor SARS-CoV-2 replication—a cautionary signal for miRNA-based antiviral strategies. Full article

Cystic echinococcosis (CE), a neglected zoonotic disease caused by Echinococcus granulosus sensu lato, poses a persistent public health burden in agro-pastoral regions worldwide. This study provides a large-scale epidemiological assessment of CE, highlighting sustained zoonotic transmission driven by agro-pastoral practices and human–animal interactions, and supporting the urgent implementation of One Health strategies. This ten-year retrospective study (2015–2024) analyzed 326 surgically confirmed cases from five hospitals in Djelfa. The cumulative surgical incidence was 2.04 cases per 100,000 person-years, classifying the region as hypoendemic. Females predominated (61.96%), and individuals aged 31–60 years represented 47.24% of cases. Rural residence (73.62%) and dog contact (94.17%) were major risk factors, with hepatic localization dominating (88.96%). Correlation analysis showed moderate associations between rural habitat and dog contact (V = 0.46, p < 0.001) and between sex and habitat (V = 0.34, p < 0.001), as well as weaker but significant associations for age and cyst location (V = 0.28, p < 0.001) and dog contact and cyst location (V = 0.20, p < 0.05). No postoperative mortality was recorded. These findings confirm active transmission linked to agro-pastoral practices and emphasize the need for coordinated One Health control strategies. Full article

Background/Objectives: The efficacy of lenvatinib after different first-line immune checkpoint inhibitor (ICI)-based regimens for hepatocellular carcinoma (HCC) remains unclear. Materials and Methods: In this retrospective single-center study, we analyzed 56 patients with unresectable HCC who received lenvatinib as second-line therapy after atezolizumab plus bevacizumab (Atz/Bev; n = 41) or durvalumab plus tremelimumab (Dur/Tre; n = 15). Antitumor response was evaluated using RECIST v1.1 and modified RECIST (mRECIST). Results: Patients in the Dur/Tre group demonstrated significantly lower disease control rates (46.7% vs. 82.9%, p = 0.014) and shorter progression-free survival (PFS) (median, 56 vs. 210 days; p = 0.015) during prior ICI therapy, indicating more refractory disease. Despite this, lenvatinib demonstrated clinically meaningful antitumor activity after both Atz/Bev and Dur/Tre. Objective response rates were 12.2% vs. 26.7% by RECIST v1.1 and 41.5% vs. 60.0% by mRECIST in the Atz/Bev and Dur/Tre groups, respectively. Similar findings were observed in the Child–Pugh class A subgroup, in which mRECIST response rates were numerically higher in the Dur/Tre group. PFS and overall survival (OS) after lenvatinib initiation were comparable between groups. Objective responses were observed even in patients with progressive disease during prior ICI therapy. Multivariate analysis identified ECOG performance status and mALBI grade, but not prior ICI regimen or antitumor response, as independent prognostic factors for OS. Conclusions: Lenvatinib demonstrated clinically meaningful efficacy after both Atz/Bev and Dur/Tre, and no significant association was observed between prior ICI response and subsequent lenvatinib efficacy. These findings suggest that resistance to immunotherapy does not necessarily confer resistance to lenvatinib in patients with unresectable HCC. The observed differences in response patterns according to prior treatment exposure warrant further investigation and may have implications for treatment sequencing in the current ICI era. However, these findings should be considered hypothesis-generating and require validation in larger multicenter studies. Full article

Background: While vaccines are designed to elicit targeted immune responses, in some cases, the immunogenic molecules employed can inherently interact with broader host cellular pathways as a secondary consequence. This phenomenon can be exemplified by COVID-19 vaccines. COVID-19 vaccines, including mRNA platforms, use the SARS-CoV-2 spike protein as an immunogen to induce the production of neutralizing antibodies. The spike protein binds the ACE2 (angiotensin-converting enzyme 2) receptor on human cells, mediating viral entry and infection. ACE2 is widely expressed across multiple tissues and is a key component of the renin–angiotensin–aldosterone system (RAAS) that acts as a homeostatic regulator of systemic and local blood flow, blood pressure, cardiac function, fluid balance and immunity. Some studies have proposed the interaction between the spike protein and ACE2 as a possible contributing factor to rare adverse effects observed following COVID-19 vaccination, including myocarditis, pericarditis, thrombosis, and reported alterations in blood pressure, though these mechanisms remain to be fully elucidated. Objectives: As a proof-of-concept approach in vaccine antigen development, we engineered SARS-CoV-2 spike mutants with impaired binding to the host receptor ACE2. Methods: By rational design, we produced and validated in vitro and in vivo spike point mutants that do not effectively bind ACE2. Results: The engineered spike mutants do not effectively bind the human entry receptor ACE2 while retaining the immunogenic properties equal to or better than the wild type spike and thus generate a protective response in animals when used as a vaccination agent. Conclusions: By establishing a straightforward molecular strategy for rational vaccine design, this work demonstrates the feasibility of limiting specific antigen–host receptor interactions while maintaining immunogenicity. This approach may be applicable to future vaccination strategies where antigen interaction with host cells could potentially interfere with physiological pathways. Full article

Background/Objectives: Adalimumab (ADM) is a recombinant, fully human monoclonal antibody that exhibits pronounced inter- and intra-individual pharmacokinetic variability attributed to several factors. This study aims to externally evaluate the published ADM population pharmacokinetic models and their potential use in clinical practice, as well as to develop novel population pharmacokinetic model. Methods: Literature search was conducted using PubMed to identify ADM population pharmacokinetic models. Data from 195 patients with Crohn’s disease treated at the University Medical Center “Zvezdara”, Serbia, were used for the external evaluation of previously published models. In addition, the development of the new population pharmacokinetic model incorporated informative priors derived from the best-performing published model. Nonlinear mixed-effects modeling was performed in NONMEM^® (versions 7.6) for both prediction- and simulation-based diagnostics of existing models, as well as for the development of a new model. Results: Eight published pharmacokinetic models of ADM were included in the external evaluation. Although none of the models satisfied both population-level and normalized prediction distribution error (NPDE) diagnostic criteria, individual-level performance was acceptable: median prediction errors (MDPEs) were within ±20% across all studies, and median absolute prediction errors (MDAPEs) were below 30% in most cases (7 of 8 studies). The best-performing model was identified and implemented as a priori information in subsequent model development. A one-compartment model using with first-order absorption and elimination best described the data. The apparent clearance (CL/F) was estimated at 0.334 L/day, while informative priors were used for V/F and the effect of anti-drug antibodies (ADAs) on CL/F. Covariate analysis on CL/F identified C-reactive protein (CRP) and dosing regimen as statistically significant predictors (p < 0.01). Conclusions: The previous pharmacokinetic models of ADM exhibited suboptimal performance in population-level metrics and simulation-based diagnostics, while individual-level metrics showed substantial improvement. The newly developed model of ADM highlights associations among immunogenicity, drug pharmacokinetics, and inflammatory burden. Full article

Interfacial defect passivation has emerged as a critical strategy for mitigating non-radiative recombination losses in inorganic perovskite solar cells (PSCs). However, the distinct chemical environments at the bottom (hole-transport layer) and top (electron-transport layer) interfaces demand passivation agents with tailored functionalities—a principle that remains largely underexplored. Herein, we systematically employed two organic ammonium iodide salts, phenylethylammonium iodide (PEAI) and 2-thiophenemethylammonium iodide (ThMI), to separately modulate the bottom NiO_x/CsPbI₂Br and top CsPbI₂Br/PCBM interfaces of inverted PSCs with a configuration of ITO/NiO_x/CsPbI₂Br/PCBM/BCP/Ag. We reveal different interfacial modulation effects: bottom-interface modification by both PEAI and ThMI dramatically improves the fill factor (FF), with PEAI delivering a more pronounced enhancement due to improved interfacial contact and reduced series resistance. However, top-interface passivation effectively boosts the open-circuit voltage (V_oc), where ThMI exhibits superior voltage elevation capability over PEAI by neutralizing undercoordinated Pb²⁺ defects via its thiophene moiety. Capitalizing on this complementary selectivity, we construct an asymmetric dual-interface passivation architecture with PEAI at the bottom and ThMI at the top (ITO/NiO_x/PEAI/CsPbI₂Br/ThMI/PCBM/BCP/Ag), which synergistically enhances both FF and V_oc. Consequently, the optimized PEAI/ThMI device achieves a champion power conversion efficiency (PCE) of 15.44%, with a V_oc of 1.15 V, a J_sc of 16.34 mA/cm², and an FF of 82.15%, significantly outperforming the control device (11.79%). This work establishes a rational design paradigm for interface-specific passivation in inverted inorganic PSCs, highlighting the importance of molecular functionality in addressing distinct interfacial recombination pathways. Full article

Background/Objectives: Undergraduate nursing students consider bioscience courses essential to their education and clinical practice, yet they often find them challenging. This study explored the associations among achievement goal orientations, perceived stress, and self-esteem to examine factors associated with bioscience learning in nursing education. Methods: A quantitative cross-sectional study was conducted with undergraduate nursing students enrolled in the first-year courses “Biology–Clinical Biochemistry” and “Genetics”. Data were gathered using the Perceived Stress Scale-14 (PSS14); the Achievement Goal Questionnaire-Revised (AGQ-R), divided into four subscales, each representing a goal type (mastery-approach or AGQ MA, mastery-avoidance or AGQ MAV, performance-approach or AGQ PA, performance-avoidance or AGQ PAV); and the Rosenberg Self-Esteem Scale (RSES). Univariate and multiple regression analyses were conducted using SPSS v26.0, with significance set at p < 0.05. Results: Perceived stress was negatively associated with self-esteem in both Biology–Clinical Biochemistry and Genetics (p < 0.001). The assessment of potential links between quantitative variables and the study topic using univariate analysis showed an association of course category with the PSS14 score (p= 0.008). This finding remained significant in the regression analysis (p = 0.004), which also identified an effect of gender on the same scale (p = 0.029). Multiple regression further revealed associations between AGQ MA and the subject of study (p = 0.047), AGQ MAV and gender (p = 0.001), AGQ PAV and gender (p = 0.016), and RSES Total and type of secondary education (p = 0.007). Conclusions: Psychological factors interact dynamically with the demands of bioscience education within tertiary nursing curricula, varying according to demographic and academic traits. Full article

Background/Objectives: Healthcare workers (HCWs) were the most exposed job category to SARS-CoV-2, due to patient care, HCW-to-HCW transmission, and community exposure. However, the relative relevance of each source is still debated. To address this issue, this study investigated the dynamics of the professional and extra-professional determinants of infection across the pandemic among a large, multicenter cohort of HCWs. Methods: The study included 5576 HCWs from four Italian University Hospitals within a European Project, called ORCHESTRA. Socio-demographic and clinical data were collected retrospectively via online surveys from March 2020 to September 2022. Factors associated with SARS-CoV-2 infection during different pandemic periods were evaluated by a multinomial logistic regression model. Results were expressed as Relative Risk Ratios (RRR). Results: The cumulative incidence was 46.2%. The highest incidence period was the Omicron phase (OVP) (69.7%). The extra-professional source was the most reported (34.3%), followed by the occupational (26.8%). However, in almost 40%, the source was undetected. The RRR for occupational exposures was 0.39 (95% CI 0.25–0.61) during the Pre-Omicron variant Period (POP) and even lower (0.22, 95% CI 0.16–0.29) in the OVP, as compared to extra-professional exposures, using the Pre-Vaccination Period (PVP) as reference. Conclusions: The dominant source of infection among HCWs changed over time. While occupational contacts were more frequent during PVP, it significantly waned over the subsequent pandemic phases. Implementing procedures and guidelines to prevent infection, even outside the workplace during pandemics, would reduce the spread of infection among HCWs and patients. Full article

Oral manifestations are common in people living with HIV (PLWH) and may affect oral health-related quality of life (OHRQoL), while data from Greece remain limited. This multicenter prospective cohort study evaluated oral health status and OHRQoL among PLWH and explored associations with antiretroviral therapy (ART) and clinical factors. Overall, 370 PLWH from seven referral centers were included. Participants underwent oral examination, with oral hygiene assessed using the Simplified Oral Hygiene Index (OHI-S), and completed the Oral Health Impact Profile-14 (OHIP-14). Statistical analyses were performed using IBM SPSS Statistics v29.0, while multinomial and binary logistic regression identified predictors of oral hygiene status and OHRQoL, respectively. Most participants were male (76.5%), had CD4 counts ≥ 200 cells/μL (95.4%), and were receiving ART (98.6%). Annual dental check-ups, daily tooth brushing, mouthwash use, and dental floss use were reported by 54.1%, 69.5%, 31.9%, and 23.8%, respectively. The median OHI-S score was 2.0 (IQR:1.5–2.7), with 16.9% having poor OHI-S; the median OHIP-14 score was 11 (IQR: 7–15), with 64.4% reporting poor OHRQoL. Male sex was associated with lower odds of poor OHRQoL (OR = 0.377; p = 0.006), whereas ART regimen independently predicted poor OHRQoL. These findings support patient-centered oral healthcare within HIV care. Full article