Search Results (187)

Background: Atezolizumab plus bevacizumab is the standard first-line therapy for unresectable hepatocellular carcinoma (uHCC). Immune-related liver injury (IrLI) is common; however, the association between IrLI severity and patient outcomes remains unknown. This study aimed to investigate the prognostic value of irLI in such patients. Methods: One hundred and sixteen patients who fulfilled the IMBrave150 inclusion criteria were enrolled. IrLI was defined as an increase in serum ALT and/or AST levels attributed to treatment and was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Results: A total of 61 patients (52.6%) developed any grade of irLI, with a median onset time of 1.7 months. Multivariate analysis revealed that grade II ALBI (hazard ratio [HR] = 2.003, p = 0.028) and BCLC stage C (HR = 3.876, p = 0.016) were associated with worse OS and PFS (HR = 1.327, p = 0.044 and HR = 1.790, p = 0.039, respectively), whereas grade 2 irLI was associated with better OS (HR = 0.223, p = 0.046) and PFS (HR = 0.244, p = 0.011). Patients with grade 2 irLI showed better median OS (not reached) than those without irLI (16.7 months), those with grade 1 (17.5 months), and those with grade ≥ 3 (7.3 months) (overall log-rank p = 0.037). Furthermore, patients with grade 2 irLI demonstrated significantly enhanced PFS (not reached) compared to those without irLI (5.7 months), grade 1 (4.6 months), or grade ≥ 3 (2.3 months), with an overall log-rank p = 0.010. In addition, patients with grade 2 irLI had the highest disease control rate (overall p = 0.053). Conclusion: In patients with uHCC treated with Ate/Bev, moderate elevation of liver enzymes (grade 2 irLI) was associated with significantly improved survival and tumor control. Full article

Background: Biliary tract cancer (BTC) management has undergone tremendous changes, benefiting from the identification of highly actionable molecular alterations. Among these, IDH1 mutations and FGFR2 fusions are the most common alterations detected and are classified as ESCAT tier 1 in BTC. However, their prognostic value in real-world settings remains uncertain. Objective: To explore overall survival (OS) in patients harbouring locally advanced or metastatic BTC (mBTC) with IDH1 or FGFR2 alterations, compared to those with wild-type tumours. Methods: This retrospective, multicentre study included patients with mBTC treated between 2020 and 2023 across five French centres. Patients were categorized into two cohorts based on molecular profiling: those with IDH1 or FGFR2 alterations, and those with wild-type tumours (WT-mBTC). Results: 119 consecutive patients were included. 18 were classified as altered (IDH1 = 13; FGFR2 = 5). Sixty-four pts underwent no molecular testing. The median OS of the entire cohort was 11.9 months (10.3–14.3). The median OS was 24.2 months (12.3–NA) versus 10.8 months (7.9–12.9), p = 0.02, in the altered and WT-mBTC cohorts, respectively. The Cox regression model conducted depicted an HR for death of 0.46 (CI95%, 0.2–0.9) for IDH1 or FGFR2 alterations. There were no diffence in PFS for first-line. Conclusions: Our cohort suggests that IDH1 or FGFR2 alterations may be associated with prognostic differences in patients with metastatic BTC, although they do not appear to influence outcomes under first-line treatment. These findings are consistent with trends observed in clinical trials. Whether improved survival is solely attributable to targeted therapies remains questionable. In line with ESMO recommendations, systematic molecular profiling should be considered in patients with mBTC. Full article

This study investigates the comparative applicability of Somaloy 700HR 5P and Fe-5.0 wt.%Si powders for axial flux permanent magnet (AFPM) motor cores in low-speed electric vehicles. Optimal forming conditions were derived through Taguchi-based simulations, considering corner radius, forming temperature, and forming speed, followed by prototype fabrication and validation. Simulation and SEM-EDS analyses confirmed consistent density distribution trends, and XRD verified phase stability during forming. While Fe-5.0 wt.%Si exhibited ~10% ± 2 superior electromagnetic performance in the powder state, its motor dynamo performance decreased by 19–25% (n = 1) compared to Somaloy 700HR 5P. This discrepancy was attributed to its ~4% lower target density (7.19 ± 0.02 g/cm³ vs. 7.51 ± 0.01 g/cm³, n = 3), assembly-induced mechanical losses, and non-uniform insulation layer caused by residual H₃PO₄ and Mo segregation. Somaloy 700HR 5P, despite a higher relative density variation (0.084 ± 0.002 g/cm³ vs. 0.063 ± 0.003 g/cm³ for Fe-5.0 wt.%Si), achieved an average density close to 7.5 g/cm³ and delivered more stable motor performance. Overall, Somaloy 700HR 5P was identified as a more suitable candidate for AFPM motor cores in low-speed EV applications, balancing formability and electromagnetic performance. Full article

Precision and real-time detection of hydrogen peroxide (H₂O₂) are essential in pharmaceutical, industrial, and defence sectors due to its strong oxidizing nature. In this study, silver (Ag)-doped CeO₂/Ag₂O-modified glassy carbon electrode (Ag-CeO₂/Ag₂O/GCE) has been developed as a non-enzymatic electrochemical sensor for the sensitive and selective detection of H₂O₂. The synthesized Ag-doped CeO₂/Ag₂O nanocomposite was characterized using various advanced techniques, including X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), field-emission scanning electron microscopy (FE-SEM), and high-resolution transmission electron microscopy (HR-TEM). Their optical, magnetic, thermal, and chemical properties were further analyzed using UV–vis spectroscopy, electron paramagnetic resonance (EPR), thermogravimetric-differential thermal analysis (TG-DTA), and X-ray photoelectron spectroscopy (XPS). Electrochemical sensing performance was evaluated using cyclic voltammetry and amperometry. The Ag-CeO₂/Ag₂O/GCE exhibited superior electrocatalytic activity for H₂O₂, attributed to the increased number of active sites and enhanced electron transfer. The sensor displayed a high sensitivity of 2.728 µA cm⁻² µM⁻¹, significantly outperforming the undoped CeO₂/GCE (0.0404 µA cm⁻² µM⁻¹). The limit of detection (LOD) and limit of quantification (LOQ) were found to be 6.34 µM and 21.1 µM, respectively, within a broad linear detection range of 1 × 10⁻⁸ to 0.5 × 10⁻³ M. The sensor also demonstrated excellent selectivity with minimal interference from common analytes, along with outstanding storage stability, reproducibility, and repeatability. Owing to these attributes, the Ag-CeO₂/Ag₂O/GCE sensor proved effective for real sample analysis, showcasing its potential as a reliable, non-enzymatic platform for H₂O₂ detection. Full article

Traditional book recommendation methods predominantly rely on collaborative filtering and context-based approaches. However, existing methods fail to account for the order of users’ book borrowings and the duration they hold them, both of which are crucial indicators reflecting users’ book preferences. To address this challenge, we propose a book recommendation framework called DPBD, which disentangles preferences based on borrowing duration, thereby explicitly modeling temporal patterns in library borrowing behaviors. The DPBD model adopts a dual-path neural architecture comprising the following: (1) The item-level path utilizes self-attention networks to encode historical borrowing sequences while incorporating borrowing duration as an adaptive weighting mechanism for attention score refinement. (2) The feature-level path employs gated fusion modules to effectively aggregate multi-source item attributes (e.g., category and title), followed by self-attention networks to model feature transition patterns. The framework subsequently combines both path representations through fully connected layers to generate user preference embeddings for next-book recommendation. Extensive experiments conducted on two real-world university library datasets demonstrate the superior performance of the proposed DPBD model compared with baseline methods. Specifically, the model achieved 13.67% and 15.75% on HR@1 and 15.75% and 12.90% on NDCG@1 across the two datasets. Full article

Background/Objectives: Ceftaroline (CPT) is a broad-spectrum, fifth-generation cephalosporin with in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA) and drug-resistant Streptococcus pneumoniae. Real-world data on its use in pediatric patients remain limited. This study aimed to the describe clinical characteristics and outcomes associated with CPT use in pediatric patients at a pediatric academic medical center. Methods: This retrospective case series evaluated patients under 18 years of age who received CPT between November 2016 and August 2023. The primary outcome was clinical success, defined as a composite of 30-day survival, absence of microbiological recurrence within 30 days, and/or resolution of acute infection signs and symptoms without therapy modification due to clinical failure. The secondary outcomes included adverse effects potentially attributable to CPT and the clinical rationale guiding its use. Results: Among 25 patients, most were male (68%) with a median (IQR) age of 3.4 (1.4–14.3) years. The indications for use commonly included respiratory infections (48%), bacteremia (16%), and/or skin and soft tissue (12%) infections. The frequently used dosing regimens included 12 mg/kg (36%) and 8 mg/kg (28%) q8hr, with a median (IQR) duration of therapy of 4.6 (1.7–10.0) days. Clinical success was achieved in 96% of patients. No adverse effects attributable to CPT were observed and CPT was commonly used for escalation (40%) and/or issues with alternative therapies (36%). Conclusions: CPT use was associated with high clinical success rates and no observed adverse effects in this pediatric report. These findings support its use as a therapeutic option when the alternatives are limited. Larger multicenter studies are needed to further evaluate the clinical outcomes and safety of CPT use in pediatric patients. Full article

Little is known about the manifestation of cardiovascular diseases (CVD) among individuals with ocular cancer (OC), a population for whom reports on sex-based differences in survival remain inconsistent. We evaluated the occurrence of CVD mortality after the diagnosis of OC in the United States. We used data from 11,460 adults diagnosed with OC from 2000 to 2021 who were ≥18 years and were enrolled in the Surveillance, Epidemiology, and End Results program. We used competing risk models to estimate hazard ratios (HR) and 95% confidence intervals (CI). About 55% of adults were male, with uveal melanoma being the most common OC (72.1%). During a median follow-up of 5.4 years, 4561 deaths occurred, with 15% attributable to CVD. In models adjusted for sociodemographic and clinico-pathophysiological factors, male adults had elevated risk for CVD mortality (HR: 1.54, 95%CI: 1.31–1.81). The sex difference in CVD mortality was more prominent for adults diagnosed with OC before 65 years of age (HR: 2.15; 95%CI: 1.48–3.11). These associations remained largely unchanged in propensity score analysis. In this study of adults with OC, CVD deaths were higher among young and middle-aged males. Implementation of optimal cardiovascular health interventions after diagnosis of OC, especially among men, holds promise in enhancing survival in this population. Full article

The European Union Council’s zero vision aims to eliminate workplace fatalities, while Industry 4.0 presents new challenges for occupational safety. Despite HR professionals assessing managers’ and employees’ competencies, no system currently exists to evaluate the competencies of workers’ representatives in occupational safety and health (OSH). It is crucial to establish the necessary competencies for these representatives to avoid their selection based on personal bias, ambition, or coercion. The main objective of the study is to identify the competencies and their components required for workers’ representatives in the field of occupational safety and health by following the steps of the DACUM method with the assistance of OSH professionals. First, tasks were identified through semi-structured interviews conducted with eight occupational safety experts. In the second step, a focus group consisting of 34 OSH professionals (2 invited guests and 32 volunteers) determined the competencies and their components necessary to perform those tasks. Finally, the results were validated through an online questionnaire sent to the 32 volunteer participants of the focus group, from which 11 responses (34%) were received. The research categorized the competencies into the following three groups: core competencies (occupational safety and professional knowledge) and distinguishing competencies (personal attributes). Within occupational safety knowledge, 10 components were defined; for professional expertise, 7 components; and for personal attributes, 16 components. Based on the results, it was confirmed that all participants of the tripartite system have an important role in the training and development of workers’ representatives in the field of occupational safety and health. The results indicate that although OSH representation is not yet a priority in Hungary, there is a willingness to collaborate with competent, well-prepared representatives. The study emphasizes the importance of clearly defining and assessing the required competencies. Full article

The global prevalence of hypertension continues to rise, affecting an estimated one billion worldwide. Regular exercise is well recognized as a non-pharmacological approach for individuals with hypertension due to its blood pressure (BP)-lowering effect, largely attributed to repeated exposure to post-exercise hypotension (PEH). Recent evidence also indicates that aromatherapy can contribute to BP reduction, indicating that combining aromatherapy with exercise may enhance the overall BP-lowering effects. Therefore, this pilot study aimed to investigate the effects of aromatherapy on PEH during the recovery phase following exercise. Fourteen healthy young males (22.7 ± 0.7 yrs) participated in this randomized crossover-designed study. All participants completed two exercise sessions per week, each lasting 30 min, at a target heart rate (HR) of 60–65%. The individuals inhaled either aroma oil or water vapor at 5, 35, 65, and 95 min after exercise. The HR, BP, blood lactate level, and arterial stiffness index were measured before and after the exercise. Our findings revealed the following. (1) PEH occurred in both groups. (2) In the aroma group, PEH was augmented compared with the control group, with the maximum reduction in BP being greater in the aroma group. (3) The reduction in arterial stiffness was greater and longer in the aroma group than in the control group. (4) The changes in the lactate levels after exercise did not differ between the groups. Our findings indicate that aromatherapy can amplify PEH, suggesting that its use after exercise may help maximize the positive effects of exercise on BP reduction. Full article

Background: Employee turnover poses a multi-faceted challenge to organizations by undermining productivity, morale, and financial stability while rendering recruitment, onboarding, and training investments wasteful. Traditional machine learning approaches often struggle with class imbalance and lack transparency, limiting actionable insights. This study introduces an Explainable AI (XAI) framework to achieve both high predictive accuracy and interpretability in turnover forecasting. Methods: Two publicly available HR datasets (IBM HR Analytics, Kaggle HR Analytics) were preprocessed with label encoding and MinMax scaling. Class imbalance was addressed via GAN-based synthetic data generation. A three-layer Transformer encoder performed binary classification, and SHapley Additive exPlanations (SHAP) analysis provided both global and local feature attributions. Model performance was evaluated using accuracy, precision, recall, F1 score, and ROC AUC metrics. Results: On the IBM dataset, the Generative Adversarial Network (GAN) Transformer model achieved 92.00% accuracy, 96.67% precision, 87.00% recall, 91.58% F1, and 96.32% ROC AUC. On the Kaggle dataset, it reached 96.95% accuracy, 97.28% precision, 96.60% recall, 96.94% F1, and 99.15% ROC AUC, substantially outperforming classical resampling methods (ROS, SMOTE, ADASYN) and recent literature benchmarks. SHAP explanations highlighted JobSatisfaction, Age, and YearsWithCurrManager as top predictors in IBM and number project, satisfaction level, and time spend company in Kaggle. Conclusion: The proposed GAN Transformer SHAP pipeline delivers state-of-the-art turnover prediction while furnishing transparent, actionable insights for HR decision-makers. Future work should validate generalizability across diverse industries and develop lightweight, real-time implementations. Full article

Background/Objectives: Patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) exhibit increased cardiovascular risk, partly attributed to persistent systemic inflammation. Janus kinase inhibitors (JAKi) effectively reduce inflammation, but their impact on cardiovascular risk remains unclear. This pilot study aimed to evaluate the effect of JAKi therapy on systemic inflammation and lipid markers, correlate traditional cardiovascular risk factors with biological parameters, and quantify subclinical atherosclerosis progression. Methods: We conducted a prospective, single-center study including 48 patients receiving JAKi. Clinical, inflammatory, lipid, and vascular parameters were assessed at baseline (T0) and after 12 months (T1). Primary endpoints included changes in carotid intima-media thickness (cIMT), ankle-brachial index (ABI), and carotid plaque presence. Results: Mean cIMT significantly decreased from 0.29 mm to 0.125 mm (p = 0.019), while ABI improved modestly, but not significantly (0.125 to 0.04, p = 0.103). Carotid plaque prevalence increased slightly from 39.6% to 47.9%, p = 0.159. C-reactive protein (CRP) levels declined significantly, while interleukin (IL)-1β levels increased. Lipoprotein(a) [Lp(a)] levels decreased significantly (mean reduction −7.96 mmol/L, p = 0.001). Multivariate regression identified Lp(a) as an independent predictor of carotid plaque at both T0 (p = 0.011) and T1 (p = 0.005). Baseline ABI was a significant predictor of acute cardiovascular events [hazard ratio (HR): 4.614, 95% CI: 1.034–20.596, p = 0.045]. Conclusions: JAKi therapy significantly reduced systemic inflammation and cIMT in patients with autoimmune rheumatic diseases, suggesting a potential benefit in attenuating early vascular changes. However, residual cardiovascular risk remains in patients with low ABI and elevated Lp(a), warranting close monitoring. Full article

Background: A significant proportion of post-myocardial infarction (MI) patients do not reach target low-density lipoprotein cholesterol (LDL-C) levels. Suboptimal LDL-C reduction is often attributed to poor adherence to pharmacological therapy and lifestyle recommendations. Methods: In a prospective registry of 179 post-MI patients who completed a Phase 2 Cardiac Rehabilitation Program (CRP), we evaluated the characteristics and predictors of suboptimal LDL-C reduction. Key indicators were assessed before and after CRP: adherence to the Mediterranean diet (using the PREDIMED questionnaire), weekly physical activity (via the IPAQ questionnaire), therapeutic adherence (using the Morisky–Green questionnaire), and peak oxygen consumption (VO₂) on exercise testing. Lipid-lowering therapy (LLT) and LDL-C were recorded prior to MI and both before and after Phase 2 CRP. At the end of Phase 2, we analyzed the difference between measured and theoretical LDL-C (basal LDL-C minus expected LDL-C reduction by LLT), which was defined as “residual difference in LDL-C” (RD-LDL-C). We analyzed the predictors of positive RD-LDL-C (lower than theoretically expected). Results: After CRP, 54 (30.2%) patients exhibited positive RD-LDL-C. Within this subgroup, LLT was uptitrated, and patients received more potent LLT at the conclusion of CRP (theoretical potency: 69.81 ± 7.07 vs. 66.41 ± 7.48%, p = 0.005). However, they were less likely to reach the target LDL-C level <55 mg/dL (66.7% vs. 93.6%, p < 0.001). Male sex (HR 17.96 [2.15, 149.92], p = 0.008) and higher lipoprotein (a) levels (HR 1.02 [1.01, 1.03] per mg/dL, p = 0.001) were associated with a positive RD-LDL-C. Conversely, diabetes mellitus (HR 0.17 [0.06, 0.51], p = 0.002), higher corrected basal LDL-C levels (HR 0.98 [0.97, 0.99] per mg/dL, p = 0.001), and supervised in-hospital training during CRP (HR 0.28 [0.09, 0.86], p = 0.03) were associated with a reduced probability of positive RD-LDL-C. No association was found with adherence to the Mediterranean diet (88.1%), therapeutic adherence (89.1%), reported weekly physical activity (median 3545 [1980, 6132] metabolic equivalents per week), or change in peak VO₂. Conclusions: More than one-third of post-MI patients demonstrated lower than expected LDL-C reduction (positive RD-LDL-C) following CRP, a finding that could not be attributed to poor adherence to pharmacological therapy or lifestyle recommendations. These findings suggest that a personalized approach to prescribing and uptitrating LLT may help achieve LDL-C targets, particularly in MI patients with healthy lifestyle habits who exhibit a lower response to LLT. Full article

Background: The gut microbiome plays a pivotal role in shaping systemic immunity and modulating anti-tumor responses. Preclinical and clinical studies have shown that higher gut microbial diversity and the presence of specific commensal taxa correlate with improved responses to immune checkpoint inhibitors (ICI) in melanoma. Conversely, broad-spectrum antibiotics can induce dysbiosis, reducing T cell activation and cytokine production, and have been linked to diminished ICI efficacy in several cancer types. Methods: We conducted a systematic review and meta-analysis of seven retrospective cohorts (total n = 5213) comparing overall survival in cutaneous melanoma (CM) patients who did or did not receive systemic antibiotics within six weeks before ICI initiation. From each study, we extracted hazard ratios (HRs) for death, antibiotic-to-ICI interval, ICI regimen (PD-1 monotherapy vs. PD-1 + CTLA-4 combination), cohort size, and country. Pooled log-HRs were estimated under fixed-effect and random-effects (REML) models. Statistical heterogeneity was quantified by Cochran’s Q and I² statistics, and τ². We performed leave-one-out sensitivity analyses, generated a Baujat plot to identify influential studies, applied trim-and-fill to assess publication bias, and ran meta-regressions for regimen, antibiotic timing, sample size, and geography. Results: Under the fixed-effect model, antibiotic exposure corresponded to a pooled HR of 1.26 (95% CI 1.13–1.41; p < 0.001). The random-effects model yielded a pooled HR of 1.55 (95% CI 1.21–1.98; p = 0.0005) with substantial heterogeneity (Q = 25.1; I² = 76%). Prediction intervals (0.78–3.06) underscored between-study variability. Leave-one-out analyses produced HRs from 1.50 to 1.75, confirming robustness, and the Baujat plot highlighted two cohorts as primary heterogeneity drivers. Trim-and-fill adjusted the HR to 1.46 (95% CI 1.08–1.97). In subgroup analyses, combination therapy studies (k = 4) showed a pooled HR of ~1.9 (I² = 58%) versus ~1.3 (I² = 79%) for monotherapy. Meta-regression attributed the largest variance to the regimen (R² = 32%; β(monotherapy) = −0.35; p = 0.13). Conclusions: Pre-ICI antibiotic use in CM is consistently associated with a 26–55% increase in mortality risk, particularly with PD-1 + CTLA-4 combinations, reinforcing the mechanistic link between microbiome integrity and ICI success. Looking ahead, integrating prospective microbiome profiling into clinical trials will be critical to personalize ICI therapy, clarify causality, and identify microbial biomarkers for optimal treatment selection. Prospective, microbiome-integrated trials promise to refine melanoma immunotherapy by tailoring antibiotic stewardship and microbial interventions to enhance patient outcomes. Full article

Background/objectives: Second primary lung cancer frequently manifests in individuals who have survived head and neck cancer, with this occurrence often being attributed to shared risk factors. The objective of the present study is to compare the prognosis, in terms of survival rate, of patients who presented isolated bronchogenic carcinoma (BC) with that of patients who presented with a personal history of BC and associated oropharyngeal and oral cancer (OAOC). Methods: A retrospective longitudinal study was conducted, including all consecutive patients who underwent surgical resection with curative intent for BC in Hospital Clínico San Carlos (HCSC), Madrid, Spain, between December 1989 and December 2024. The survival rate was calculated and compared in two groups of patients: Group 1: 1594 patients with isolated BC and Group 2: 97 patients with BC and OAOC. Results: Group 2 did not show a significant difference in their 60-month survival rate in comparison to Group 1 (HR = 1.23, CI 95% 0.9–1.6) p = 0.14. But when comparing the 120-month survival rate, Group 1 showed a significantly higher survival rate (36.4%, CI 95% 33.9–39%) compared to Group 2, (25.54%, CI 95% 17.78–36.7%) HR= 1.28 (CI 95% 1–1.6), p = 0.04. Disease-free survival showed a non-significant trend of greater severity among patients with a previous history of OAOC. Conclusions: Lung cancer patients who presented with OAOC had worse overall survival compared to patients who presented with isolated lung cancer, and a significant difference was observed at 120 months of follow-up. Full article

The Eastern Tibetan Plateau (ETP), characterized by its intricate topography and pronounced altitudinal gradient, presents significant challenges for climate model simulations. This study assesses precipitation over the ETP using high-resolution (HR) and low-resolution (LR) models from CMIP6 HighResMIP. Both HR and LR models successfully reproduce the spatial distribution of annual precipitation, capturing the northwest-to-southeast increasing gradient. However, HR models significantly outperform LR models, reducing the annual mean precipitation bias from 1.09 mm/day to 1.00 mm/day (9% reduction, p < 0.05, two-tailed Student’s t-test) and decreasing RMSE by 12% (p < 0.05) in the ETP for the 1985–2014 period. Furthermore, HR models exhibit superior skill in simulating extreme precipitation events, particularly over the Sichuan Basin. For the 1985–2014 period, HR models show markedly smaller biases in representing extreme precipitation and accurately reflect observed trends. Projections for the future suggest a pronounced intensification of extreme precipitation events across the region. Process-based scaling diagnostics attribute these changes predominantly to dynamical components, which account for approximately 85% of the total scaling change in HR models and 89% in LR models. These findings underscore the pivotal role of dynamical processes in shaping extreme precipitation and highlight the advantages of HR models in enhancing simulation fidelity. This study provides critical insights into climate model performance, offering robust information to inform climate mitigation and adaptation strategies tailored for the ETP. Full article