Search Results (42,390)

Background/Objectives: RELA encodes the p65 subunit of NF-κB and plays a critical role in immune regulation, epithelial protection, and anti-apoptotic signaling. Pathogenic RELA variants cause monogenic immune dysregulation with heterogeneous clinical manifestations. However, genotype–phenotype relationships and optimal treatment strategies remain incompletely defined. Methods: We conducted a comprehensive literature-based analysis of reported individuals with RELA variants and additionally described a family carrying a RELA c.706C>T (p.R236*) variant, including a clinically affected proband and his variant-positive father with isolated vitiligo. Clinical, immunological, genetic, endoscopic, and therapeutic data were extracted and summarized using a module-based phenotypic framework. Exploratory analyses were performed to examine potential genotype–phenotype patterns and reported treatment responses. Results: A total of 72 individuals with RELA variants, including the proband and his variant-positive father from the present family, were analyzed. RELA-associated disease exhibited marked clinical heterogeneity, encompassing mucocutaneous, systemic inflammatory, autoimmune, gastrointestinal, hematologic, allergic/eosinophilic, and infection-related manifestations. Exploratory analyses suggested that truncating or splice-site variants were more frequently observed among individuals with mucocutaneous lesions, whereas missense variants appeared to be more common among those with autoimmune manifestations. Tumor necrosis factor (TNF) inhibitors were among the therapies associated with favorable reported responses. In the present family, the proband presented with early-onset Behçet-like intestinal inflammation and achieved clinical and endoscopic remission after thalidomide and dose-escalated infliximab treatment. Conclusions: This study expands the clinical spectrum of RELA-associated disease and highlights preliminary variant-related clinical patterns that require confirmation in larger independent cohorts. The available treatment experience suggests that TNF blockade may be considered as a therapeutic option in selected patients, although comparative efficacy cannot be established from the available data. Full article

Tracheal intubation in patients at risk of acute hypoxemic respiratory failure (AHRF) carries a high risk of life-threatening desaturation, and the choice of peri-intubation oxygenation strategy critically influences patient safety. This narrative review synthesizes current evidence on non-invasive oxygenation techniques—high-flow nasal oxygen (HFNO), non-invasive ventilation (NIV), and their combination—across the pre-oxygenation, apneic, and awake-intubation phases of airway management. We examine the physiological mechanisms underlying each modality, appraise landmark randomized trials and meta-analyses (including PREOXI, OPTINIV, and OPTIMASK), and address disease-specific considerations in chronic obstructive pulmonary disease, heart failure, interstitial lung disease, severe obesity, obstructive sleep apnea, and obstetric, pediatric, and trauma populations. The evidence supports a phenotype-driven hierarchy rather than a single dominant technique: NIV—optionally combined with HFNO for apneic oxygenation—is preferred in severely hypoxemic critically ill patients, whereas HFNO alone is adequate for many moderately hypoxemic or non-hypoxemic patients. Progressive hypercapnia limits apneic oxygenation, particularly in chronic CO₂ retainers, underscoring the value of continuous CO₂ monitoring. Persistent under-implementation of NIV-based pre-oxygenation reveals a gap between evidence and practice. Individualized, physiology-guided oxygenation—aligned with the goals of personalized peri-procedural medicine—offers the greatest potential to reduce peri-intubation morbidity. Full article

Passenger car waste tires (PCWTs) are difficult to recycle as asphalt modifiers due to their high styrene-butadiene rubber (SBR) content and poor compatibility with asphalt. This study investigates whether hexadecylamine (HDA)-assisted thermo-mechanical devulcanization can transform PCWT rubber into an effective modifier for styrene-butadiene-styrene (SBS)-composite-modified asphalt, and how rubber dosage influences the performance balance. PCWT rubber was devulcanized using HDA-assisted twin-screw extrusion and incorporated into 90# asphalt with 3 wt% SBS at 20 wt% and 30 wt% dosages, alongside non-devulcanized PCWT and truck tire rubber for comparison. Comprehensive characterization, including sol fraction, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS), dynamic shear rheometer (DSR), multiple stress creep recovery (MSCR), and bending beam rheometer (BBR), was conducted. The results demonstrate that HDA-assisted devulcanization effectively breaks sulfur crosslinks while preserving the rubber backbone, significantly improving compatibility and low-temperature performance. Increasing the devulcanized rubber dosage from 20 wt% to 30 wt% compensates for the reduced high-temperature stiffness, achieving a balanced performance profile comparable to truck tire rubber. The novelty of this work lies in establishing HDA-assisted thermo-mechanical devulcanization as a viable pathway for converting otherwise underutilized PCWT rubber into a high-performance asphalt modifier, thereby expanding the feedstock options for crumb rubber-modified asphalt. Full article

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers worldwide, with limited treatment options and a high prevalence of oncogenic KRAS mutations. Piper betle contains numerous bioactive phytochemicals with reported anticancer activities, although its activity against pancreatic cancer remains incompletely characterized. This study evaluated the phytochemical composition of P. betle leaf extracts and the cell viability effects of ethanolic extracts against human KRAS G12D-mutant pancreatic cancer cell lines (PANC-1, AsPC-1, Panc 02.03, Panc 04.03, Panc 08.13 and Panc 10.05). Phytochemical screening, total phenolic content (TPC), total flavonoid content (TFC) and gas chromatography–mass spectrometry (GC-MS) analyses were performed to characterize the extracts. The ethanolic extracts exhibited higher extraction yield (17.26%), TPC (395.94 ± 0.010 mg GAE/g) and TFC (121.28 ± 0.009 mg QE/g) than aqueous extracts. GC-MS analysis tentatively identified phenylpropanoid compounds, including chavicol, chavibetol, and eugenol. Based on these findings, the ethanolic extract was selected for biological evaluation. Treatment significantly reduced cell viability in a concentration-dependent manner across all pancreatic cancer cell lines, with estimated IC₅₀ values ranging from 21.54 to 54.91 µg/mL. These findings suggest that ethanolic P. betle leaf extract possesses promising biological activity and support further studies to identify its active constituents and elucidate their mechanisms of action. Full article

The spectrum of diseases in individuals with human immunodeficiency virus (HIV) receiving successful antiretroviral therapy has evolved over time. In the past, they developed opportunistic infections and malignancies, whereas today, cardiovascular disease is among the most common causes of illness and premature death. Traditional risk factors for atherosclerosis (hypertension, hyperlipidemia, smoking, diabetes, family history of heart disease) are more prevalent in people with HIV than in the general population. However, it is well established that HIV itself causes increased immune activation, chronic inflammation, vascular dysfunction, and a cluster of metabolic abnormalities that contribute to a faster-than-usual rate of biological aging and a higher risk of developing atherosclerosis, a risk not fully captured by current risk models. In the REPRIEVE study, treatment with pitavastatin was shown to reduce the rate of first cardiovascular events among individuals with HIV receiving antiretroviral therapy. Importantly, the beneficial effects of statins on atherosclerosis likely extend beyond lowering cholesterol to include effects on vascular function and on immune and metabolic systems altered by HIV. Even among individuals on statins, a considerable risk of cardiovascular disease remains. Here, We provide a narrative review of current evidence and an expert perspective on emerging approaches to residual cardiovascular risk after REPRIEVE. We review the current understanding of atherosclerosis pathogenesis in individuals with HIV, focusing on recent findings from the REPRIEVE trial. We outline current approaches to improving cardiovascular risk assessment across clinical, biological, and computational levels. We also examine a growing number of therapeutic options that address residual inflammation and atherogenic metabolic disturbance in individuals with HIV on long-term, effective antiretroviral therapy. Significantly, after REPRIEVE, we must move from prescribing statins to all individuals with HIV toward more individualized cardiovascular disease prevention strategies, integrating clinical information, a variety of biomarkers, imaging studies, and even molecular information to generate optimal individualized cardiovascular disease prevention regimens that reflect the complexity of this outcome in naturally diverse individuals. Full article

Coal-resource-exhausted cities face severe spatial conflicts between mining land redevelopment, urban sprawl, agricultural expansion, and ecological restoration, necessitating optimized spatial planning of forest-dominated ecological landscapes. This study constructs an ecology-prioritized identification and multi-scenario optimization framework for forest landscapes in resource-depleted urban fringes, taking Xinqiu District, Fuxin City, China, as a representative case. Coupling the Analytic Hierarchy Process and Entropy Weight Method, a mining-adapted Ecological Protection Importance (EPI) evaluation system was established. Results indicated that geological hazard sensitivity exerted the highest weighting dominance ($w_6=0.2322$) in EPI, establishing an Ecological Priority Control Zone covering 47.86% (6782.04 ha) of the district. Spatial dual-conflict mapping revealed a conflict footprint of 1493.82 ha, heavily dominated by Ecological-Urban/Mining Conflicts (1156.95 ha). Multi-scenario simulation via Fragstats 4.2 demonstrated that Option A (ecology priority-agriculture secondary) achieved the highest landscape score (0.8870), effectively maximizing network cohesion (COHESION = 99.3911) and restoring natural fractal boundary geometry (PAFRAC = 1.4760). The “southern conservation, central remediation, and river corridor connectivity” zonal strategy provides a science-based decision tool for forest network reconstruction in resource-exhausted cities. Full article

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by typical heart failure symptoms, left ventricular ejection fraction (LVEF) ≥50%, elevated natriuretic peptides, and impaired diastolic function. HFpEF constitutes a heterogeneous clinical syndrome with increasing prevalence worldwide and limited therapeutic options. Short-chain fatty acids (SCFAs), generated by gut microbial fermentation of dietary fibers, have recently been implicated as modulators of cardiovascular physiology and pathology. In this narrative review, we synthesize evidence linking SCFAs and SCFA-related signaling to HFpEF pathophysiology, with attention to the distinction between direct HFpEF evidence and findings extrapolated from broader cardiovascular and metabolic models. Although HFpEF-specific data remain limited, available evidence suggests that SCFAs may be relevant to several disease-associated processes, including systemic inflammation, adipokine dysregulation, endothelial dysfunction, myocardial stiffness, and metabolic derangement. We further discuss receptor-mediated and histone deacetylase-dependent mechanisms, consider differences among acetate, propionate, and butyrate, and evaluate the current limitations and therapeutic implications of SCFA-related pathways in HFpEF. At present, SCFA-directed interventions should be viewed as investigational rather than established therapeutic strategies for HFpEF. Full article

Background: Total trapeziometacarpal (TMC) joint arthroplasty has emerged as a surgical option for selected patients with TMC osteoarthritis. The HORUS^® prosthesis (Evolutis, France) is a novel uncemented modular implant featuring a threaded screw-in trapezial cup coated with porous titanium and a PEXEL-E liner (vitamin E-infused cross-linked polyethylene) with a semi-retentive articulation. The purpose of this study was to report preliminary clinical and radiographic outcomes of total TMC joint arthroplasty using the uncemented HORUS^® prosthesis at 6-month follow-up. Methods: Eleven patients (8 women, 3 men; mean age 63.6 ± 10.1 years) with Eaton-Littler stage II–III TMC osteoarthritis and at least 6 months of unsuccessful conservative treatment underwent total TMC joint arthroplasty using the HORUS^® prosthesis. All procedures were performed by a single surgeon through a dorso-radial approach. Clinical outcomes were assessed preoperatively and at 15 days, 1, 3, and 6 months postoperatively using the Visual Analogue Scale (VAS), QuickDASH questionnaire, and Kapandji opposition score. Standardized radiographs were assessed at 1, 3, and 6 months for component position, periprosthetic radiolucency, cup migration/loosening, and stem subsidence. Results: One intraoperative trapezial fracture (1/11; 9.1%) required conversion to trapeziectomy with suspension arthroplasty; this patient was excluded from the prosthetic outcome analysis. In the remaining 10 patients, mean VAS decreased from 8.7 ± 1.1 preoperatively to 0.3 ± 0.7 at 6 months, mean QuickDASH decreased from 66.2 ± 11.3 to 14.5 ± 7.6, and mean Kapandji score increased from 5.8 ± 0.8 to 9.2 ± 0.6. One minor postoperative complication occurred (flexor tendinopathy of the third and fourth digits at 4 weeks). No dislocation, infection, or radiographic evidence of component migration, stem subsidence, or periprosthetic radiolucency was detected during the 6-month observation period. Conclusions: In this small preliminary series, the HORUS^® prosthesis was associated with marked short-term improvements in pain, disability, and thumb opposition. These data should not be interpreted as evidence of long-term implant survival or a reduced risk of loosening because the cohort was small and follow-up was limited to 6 months. Larger comparative studies with longer follow-up are required to assess durability, implant-related complications, and revision risk. Full article

The choice of suitable color palettes is a central task in thematic cartography. Established palette libraries such as ColorBrewer 2.0 provide cartographically proven color schemes, but they account only to a limited extent for the specific visual context of a background map. Particularly in web-based mapping environments, basemaps vary widely in lightness, colorfulness, texture, and semantic density. This paper introduces CartoPalette v4.2, a basemap-dependent tool for generating thematic color palettes. The system combines a trained Conditional Variational Autoencoder model (CVAE) with explicit scoring, minimum domain checks, constrained reranking, and optional CIELAB-color-space-based repair. The goal is not the automation of cartographic design, but a transparent, traceable decision aid. The benchmark comprised 40 basemaps from held-out test locations, drawn from the ten map styles included in the training data, together with two palette types and four class counts. In this setting, 90% of CartoPalette’s suggestions scored higher than the corresponding best available ColorBrewer palette. In about 83% of cases, the visual contrast to the background map was greater than with ColorBrewer. The results show that explicitly incorporating the basemap context offers a clear added value over classical palette libraries. These findings therefore refer to previously unseen locations within basemap styles represented during training. Transfer to entirely new styles has not yet been evaluated. Full article

The detection of elevated corruption risk in public procurement, where risk is measured by objective procedural indicators rather than by confirmed corruption, is typically constrained by the fragmentation of the underlying records: each national authority holds its own, and legal obligations prevent them from being pooled. The current study examines whether authorities can improve detection by collaborating without exchanging data records. To this end, a federated framework is developed in which each authority trains locally and publishes only model parameters and anonymized class-conditional statistics to a coordination layer. It is evaluated on real procurement records from three European Union member states, using a predictor set audited to exclude attributes that determine the label. Collaboration improved detection substantially over independent operation across the federation, recovering most of the performance achievable by centralized training, with the largest improvements at the operating points relevant to bounded audit capacity. A model trained on two authorities and applied to a third performed near the local base rate, so participation is a condition of benefit rather than an optional route to it. Perturbing the exchanged quantities carries a measurable cost that grows with model size, so that beyond a modest noise level, an interpretable linear model outperforms a higher-capacity network. Full article

Nucleus pulposus cells (NPCs) age mainly because reactive oxygen species (ROS) build up too much. Excess ROS is associated with intervertebral disc degeneration (IVDD). In this study, we prepared ergothioneine-derived carbon dots (EGT-Fe-CDs) as an antioxidant nanozyme. EGT-Fe-CDs showed good biocompatibility, superoxide dismutase-like and catalase-like activities, and high total antioxidant capacity. In H₂O₂-treated NPCs, EGT-Fe-CDs reduced cell damage. Local EGT-Fe-CDs treatment also reduced degeneration in the animal model, based on imaging, disc height index (DHI), and Pfirrmann grade. EGT-Fe-CDs also reduced mitochondrial damage associated with excess ROS. They slow down NPC ageing and help control IVDD. Based on these characteristics, the nanozyme could be a useful option for clinical therapy in the future. Full article

Background/Objectives: Veterinarians are exposed to substantial psychological strain, including burnout, depressive symptoms, and increased suicide risk. Emotional and ethical challenges, such as managing animal suffering, making difficult treatment decisions, and handling conflicts with animal owners, may compound the pressures associated with demanding working conditions. This study aimed to investigate occupational stressors, working conditions, job satisfaction, and self-reported mental health among veterinarians working in Germany. Methods: An exploratory, quantitative, cross-sectional online survey was conducted among veterinarians working in Germany between August and October 2025. A total of 126 veterinarians completed the questionnaire. Associations between demographic and professional characteristics, working conditions, occupational stressors, and self-reported mental health indicators were analyzed using Pearson’s chi-square tests, Mann–Whitney U tests and Kruskal–Wallis tests. Results: The greatest perceived occupational stress was associated with work–life balance and working hours (mean ± SD: 3.67 ± 1.14), followed by the management of complex medical cases and communication with animal owners. Younger veterinary respondents reported greater stress related to selection of treatment options, whereas older and more experienced veterinary respondents reported greater stress related to administrative workload. Women reported higher stress levels across several domains, including communication with animal owners and the management of difficult medical cases. Veterinarians working more than 40 h per week reported lower satisfaction with work–life balance, while those with more than 28 days of annual leave reported greater workplace comfort. Self-reported stress-related symptoms were frequently indicated in the symptom checklist: 63.5% reported sleep disturbances, 31.7% burnout symptoms, and 26.2% anxiety. Only 19.0% had sought psychological help for work-related stress, and workplace psychological support was available and used by only 3.2% of respondents. Conclusions: The exploratory findings indicate substantial perceived work-related, emotional, and ethical burdens among veterinarians working in Germany. Improved working-time arrangements, administrative support, accessible psychological support, and broader organizational measures may help protect veterinarians’ well-being and long-term job satisfaction. Full article

This narrative review summarizes the published literature on robotic coronary revascularization, encompassing robotic-assisted minimally invasive direct coronary artery bypass (RA-MIDCAB), totally endoscopic coronary artery bypass (TECAB), and hybrid coronary revascularization (HCR). These are distinct procedures that differ in operative access, conduit harvesting, use of cardiopulmonary bypass (CPB), and typical patient selection, and are treated as such throughout this review rather than as interchangeable techniques. A structured, non-systematic literature search of PubMed/MEDLINE and major cardiothoracic surgical journals was performed. Articles were selected by the authors based on relevance, methodological quality, and recency. This is explicitly a narrative rather than a systematic review, and no PRISMA methodology was applied. In observational series from experienced centers, RA-MIDCAB and TECAB are associated with low perioperative mortality (0–2.8%), high early left internal thoracic artery (LITA)-to-left anterior descending (LAD) graft patency (>95%), and shorter hospital stay than conventional sternotomy coronary artery bypass grafting (CABG) in selected patients. HCR extends robotic revascularization to selected patients with multivessel and left main disease. However, nearly all of this evidence derives from retrospective, single-center, or registry-based observational studies performed at high-volume expert centers in selected patient populations, and comparative claims against conventional CABG are vulnerable to selection bias and residual confounding. Robotic coronary revascularization is a feasible option that has been reproduced across a growing number of high-volume centers for carefully selected patients, but current evidence does not support broad claims of superiority over conventional CABG, and outcome data remain concentrated among a limited number of expert programs. Prospective multicenter and randomized data, standardized outcome definitions, and structured training pathways are needed to define its long-term role in coronary revascularization. Full article

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, and internal radionuclide therapy is an important locoregional option for unresectable disease. This review summarizes the current landscape of transarterial radionuclide therapy for HCC and, as a translational perspective, considers how the carrier, radionuclide, and dosimetry concepts established in HCC may extend to secondary liver tumors (liver metastases). It begins with established transarterial radioembolization (TARE/selective internal radiation therapy, SIRT) using yttrium-90 (⁹⁰Y) microspheres and the shift toward personalized dosimetry and combination with systemic and immune-based therapies. It then examines alternative radionuclides and carrier systems—including holmium-166 (¹⁶⁶Ho) microspheres, iodine-131 (¹³¹I) lipiodol, rhenium-188 (¹⁸⁸Re) lipiodol, and lutetium-177 emulsified in lipiodol (¹⁷⁷Lu-lipiodol)—from the standpoint of their physical properties, radiochemistry, theranostic potential, and preclinical and clinical evidence. Particular attention is given to ¹⁷⁷Lu-based approaches, including their favorable beta energy, the concurrent imageable gamma emission that enables single-photon emission computed tomography (SPECT)-based dosimetry, and the potential to address post-embolization hypoxia-related radioresistance, while noting that the clinical evidence for ¹⁷⁷Lu-lipiodol remains preclinical. The application of these platforms to colorectal and neuroendocrine liver metastases is then outlined. Finally, regulatory, radiation safety, and waste management considerations and the principal challenges to clinical translation are discussed. Full article

Distributed offloading systems rely on periodic broadcasts to disseminate server state, yet propagation delays inevitably leave agents operating with stale information at decision time. Staleness is typically viewed as a performance limitation that should be minimized. This work revisits this assumption by studying its role in a distributed asynchronous offloading framework that operates under delayed and potentially stale load information. Players make independent server-selection decisions using locally available information and may optionally compensate for staleness through lightweight load-prediction mechanisms. A central finding is that staleness can act as an implicit coordination mechanism. By inducing heterogeneous and desynchronized perceptions of system state, it naturally diversifies agent decisions and mitigates collective migration oscillations that arise under perfect information sharing. These oscillations are shown to significantly delay convergence and can lead to unstable behavior in lightly loaded regimes. In contrast, stale yet diverse views prevent synchronized reactions and promote faster stabilization. The results further show that the value of prediction increases with communication staleness. As broadcast intervals grow and server-state information becomes increasingly outdated, prediction-based approaches substantially reduce performance degradation, improve load-balancing fairness, and lower migration activity relative to stale-information decisions. The numerical results show that increasing the broadcast interval from 0.5 s to 4 s causes a performance deterioration of approximately 95% for stale-information decisions, whereas prediction-based approaches limit this degradation to less than 15% over the same range. These findings suggest that the objective of distributed offloading should not be to eliminate staleness entirely, but rather to combine its stabilizing effects with lightweight predictive mechanisms that mitigate its negative impact on decision quality. Full article