Search Results (10,276)

Per- and polyfluoroalkyl substances (PFAS) are highly stable and persistent environmental contaminants. Their exceptional chemical stability prevents natural breakdown, leading to global distribution and bioaccumulation in aquatic organisms. Long-chain PFAS, such as perfluorooctane sulfonic acid (PFOS), tend to accumulate in the liver, kidneys, and muscle tissues, whereas short-chain PFAS remain largely dissolved in water and show lower accumulation. Freshwater fish generally contain higher PFAS levels than marine fish, with concentrations varying according to species, habitat, trophic level, contamination site, and other factors. Human exposure primarily occurs through the consumption of contaminated fish and seafood, as well as through drinking water, inhalation, and skin contact. Such exposure is associated with immunosuppression, high cholesterol, hormonal disruption, cancer, and other health risks. Regulatory limits exist for four PFAS compounds, while many others, including emerging compounds, remain unregulated. This review synthesizes the current knowledge on the global distribution of PFAS across various fish species, analytical approaches including sample preparation (e.g., SPE, QuEChERS) and instrumental techniques (e.g., LC-MS/MS, HRMS), human dietary exposure, and the related health risks. By integrating environmental distribution, bioaccumulation, analytical challenges, and health issues, this review provides an up-to-date perspective on PFAS in fish and emphasizes the need for ongoing monitoring and stricter regulatory frameworks to ensure food safety and protect both human health and ecosystems. Full article

Functional pet food has grown rapidly, in line with the accelerated humanization of pets, growing attention to relations between diet and health, and mounting sustainability awareness. The article provides a critical overview of recent developments and new trends in functional pet food, combining data from published works, patents and market-driven innovative companies. The current trends depict a transition from single-nutrient fortification to integrated nutrition interventions through modulation of gastrointestinal health, immunity, metabolism, cognition and age-associated conditions. Special attention is dedicated to probiotics, prebiotics, postbiotics, polyphenols and novel protein sources, as well as innovations in processing and delivery technologies. The review highlights ongoing issues on the relevance of study design, available long-term safety information and our capacity to mechanistically underpin claims with respect to function. Because this review maps clusters of innovation and clusters of underdeveloped knowledge, it offers a roadmap for the translational pathway from scientific discovery to commercialization. The results highlight a call for harmonized methods, longer duration studies and integrative omics-based approaches in order to improve the evidence basis formulation and responsible marketing of future functional pet food products following credible, safe and sustainable strategies. Full article

Background: Hormone receptor-positive (HR+), Human Epidermal growth factor Receptor 2 (HER2-negative) metastatic breast cancer (MBC) represents a substantial proportion of breast cancer cases in Saudi Arabia. Despite the established efficacy of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, particularly Palbociclib, in randomized control trials, real-world data from local institutions in Saudi Arabia remain limited. Objectives: This study aimed to evaluate progression-free survival (PFS), overall survival (OS), and toxicity profile among HR+, HER2-negative MBC female patients treated with Palbociclib at King Fahad Medical City (KFMC). Methods: A retrospective study was conducted on female patients with HR+/HER2-negative MBC treated with oral palbociclib combined with endocrine therapy (ET) at KFMC between January 2021 and September 2024. Data were collected from electronic health records. Descriptive statistics were conducted using mean for continuous variables and frequency for categorical variables. Survival analyses were conducted using Cox regression, log-rank tests and Kaplan–Meier analysis. Results: A total of 169 female patients with HR+/HER2− MBC were included. In the first-line setting, the median PFS was 20.14 months (95% CI: 14.65–30.49), compared with 11.3 months (95% CI: 7.98–not estimable) in the second-line setting. For OS, the median OS values were 53.1 months (95% CI: 41.2–not estimable) in the first-line group and 23.7 months (95% CI: 18.5–not estimable) in the second-line group. Significant predictors of shorter PFS included age, Body Mass Index (BMI), type of ET, cancer type, line of therapy, family history of cancer, and history of VTE. Visceral metastasis (HR = 3.087; p = 0.0229) and ECOG performance status of 4 (HR = 13.86; p = 0.0156) were associated with significantly shorter OS. The most common hematological adverse events (AEs) were neutropenia (45.6%), followed by anemia (5.9%), leukopenia (5.3%), and back pain (5.3%). Most toxicities were managed with dose reduction, holding treatment, or supportive care. Conclusions: Palbociclib demonstrated favorable survival outcomes and a manageable safety profile, with neutropenia being the most common AE. This study provides region-specific real-world evidence supporting the use of Palbociclib in HR+/HER2− MBC. These findings align with global trial data and highlight the importance of individualized treatment in clinical practice. Full article

The increasing deployment of autonomous vehicles in port logistics requires safety assessment methods that remain valid in mixed traffic environments. This study evaluates the safety of mixed automated guided vehicle (AGV) and human-driven vehicle (HDV) traffic in a seaport terminal connected to an external urban road network. A microscopic traffic model was developed in AIMSUN Next to represent gate areas, internal roads, storage-yard access, berth interfaces, and external container-truck traffic. HDVs were modeled using a Gipps-based car-following model, whereas AGVs were represented through an Adaptive Cruise Control framework. Vehicle trajectories were exported to the Surrogate Safety Assessment Model (SSAM), where Time-to-Collision (TTC) and Post-Encroachment Time (PET) were used to detect and classify conflicts. Six staged fleet-composition scenarios were evaluated in 36 simulation runs, ranging from fully human-driven operation to full automation. Total conflicts decreased from 89 in the fully human-driven scenario to 43 in the fully automated scenario (−51.7%), while rear-end conflicts decreased from 70 to 30 (−57.1%). Crossing conflicts remained relatively stable across scenarios. At the same time, mean TTC decreased from 0.80 to 0.24 s and mean PET from 1.57 to 0.38 s, indicating tighter but more coordinated interactions under automated control. These results show that automation improves longitudinal safety performance in port traffic, but also that conventional TTC and PET thresholds calibrated for human-driven traffic may not be directly applicable to automated port operations. Automation-sensitive surrogate safety criteria are therefore needed for seaport mixed-traffic evaluation. Full article

Although tourism is increasingly seen as a key component of sustainable regional development and economic diversification, its extraordinary expansion raises governance and environmental issues at the local level. The current study assesses the influencing factors of inbound tourism demand to Saudi Arabia, a strategic empirical study due to its rapid and ambitious transformation under Vision 2030. This national strategy is designed to cultivate diverse tourist destinations, including coastal eco-resorts, mountain nature escapes, and urban cultural hubs. The unique sustainability hurdles in each area make the Kingdom a prime location for analyzing the development of regional tourism. This research focuses on the vibrant interfaces among sustainable practices, logistical efficiency, perceptions of safety and uncertainty, and macroeconomic environments that shape the Kingdom’s competitiveness as a tourism region. The study draws several beneficial findings using balanced panel data of 16 origin countries during the period of 2009–2023 and is assessed using a dynamic panel Generalized Method of Moments model. The findings state extensive perseverance within tourism flows, such that past arrivals significantly enable simultaneous inflows. Inbound tourism is strongly and favourably influenced by destination-side factors, particularly logistical performance, human rights conditions, and Saudi Arabia’s socioeconomic prosperity. In a similar vein, the demand for outward travel is strongly reinforced by origin-country prosperity. But travel expenses attenuate, environmental pressures and political risk reduce arrivals, and relative prices and pandemic uncertainty play a negligible role. The findings highlight the need to upgrade the country’s logistics infrastructure, enhance rights protection and governance, integrate sustainable practices, and capitalise on prosperity to make Saudi Arabia a desirable travel destination by Vision 2030. A key contribution of this study is to demonstrate how infrastructure, environmental stewardship, and institutional quality shape a region’s tourism attractiveness. The study illustrates how sustainability must be incorporated into regional-specific strategies to balance economic goals with ecological and social imperatives, providing a framework for other countries interested in sustainable tourism. Full article

Plant foods have been the cornerstone of human diets since ancient times, fueling civilization and shaping cultures. Plants became central to sustainable food systems, offering diverse and nutritious options for the future. Sea buckthorn (Hippophae rhamnoides L.) has attracted growing scientific interest due to the presence of bioactive compounds, polyphenols, fatty acids, phytosterols, carotenoids, vitamins, and minerals in its fruit, seeds, and leaves. Moreover, sea buckthorn exhibit antioxidant, anti-inflammatory, antimicrobial, antidiabetic, antihyperlipidemic, anticancer, hepatoprotective, neuroprotective, and metabolic regulatory properties supported by in vitro and in vivo models. The biological activity of these phytochemical compounds plays a crucial role in regulating the AMP-activated protein kinase (AMPK) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathways, as well as pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), cell proliferation, and apoptosis. Furthermore, its potential against microbial growth, including S. aureus, S. epidermidis, S. intermedius, and S. pyogenes, among others, not only expands its applications in the pharmaceutical industry but also attracts researchers to incorporate it into food products. This could lead to the discovery of plant-based therapeutic products without significant adverse effects. However, further exploration of each component’s potential side effects is necessary to support the commercialization of formulated products in either the pharmaceutical or food industries, ensuring the highest safety standards for consumers. Including studies on bioavailability and pharmacodynamics could further strengthen the scientific evidence supporting the specific phytochemicals in sea buckthorn and their mechanistic interactions. Full article

Chimeric antigen receptor–natural killer (CAR-NK) cell therapy is a promising immunotherapy for hematological malignancies. While engineered interleukin15 (IL15) variants like membrane-bound IL15 (mbIL15) and the IL15/IL15Rα heterodimer (RLI) can enhance NK cell activity, their relative efficacy and safety as armor for CAR-NK cells remain unclear. This study systematically evaluated primary human CAR-NK cells co-expressing an anti-CD19 CAR (19ζ) with soluble IL15, mbIL15, or RLI. We found that 19ζ-RLI CAR-NK cells exhibited superior IL15 secretion, proliferation, cytotoxicity, and migration in vitro, and effectively controlled tumors in vivo. However, all IL15-armored constructs, particularly 19ζ-RLI, induced lethal toxicity in mice, characterized by CAR-NK hyperproliferation and elevated systemic IL15. Transcriptomic analysis revealed that this toxicity correlated with a hyperactive molecular state driven by persistent IL15 signaling. In conclusion, this study suggests that constitutive IL15 armoring can be a potent but risky strategy for enhancing CAR-NK cells, with RLI being the most potent yet toxic exemplar of this general principle. Our findings highlight the necessity of incorporating safety-optimized strategies, such as inducible cytokine expression, into the design of cytokine-armored CAR-NK therapies for clinical translation. Full article

Maritime traffic complexity (MTC) is a term that has gained increased importance in the last decade in the maritime safety domain. It is a concept for understanding navigational safety and operational challenges in congested maritime environments. Although research interest in MTC has grown, it is a concept that remains fragmented, with various interpretations of definitions, indicators, and modeling approaches present in the literature. This study presents a comprehensive literature review and bibliometric analysis to synthesize the current state of research on MTC as a scientific construct and clarify its conceptual foundations from an analytical perspective. In accordance with PRISMA guidelines and systematic literature review (SLR) methodology, relevant studies were identified and screened across major scientific databases. A detailed analysis was conducted on 40 scientific publications. The findings indicate that most existing MTC models rely mainly on Automatic Identification System (AIS) data and corresponding derived metrics. MTC is primarily assessed through geometric vessel–vessel interactions, relative motion parameters, and collision-risk indicators. Bibliometric analysis demonstrates a rapid increase in scientific interest in this topic since 2015, with research concentrated in several leading journals. The study identifies a significant methodological limitation in current frameworks, which often overlook the heterogeneity of marine traffic, environmental conditions, vessel reliability, and human factors. Therefore, this study highlights the need for a more comprehensive MTC evaluation framework that incorporates operational, geographical constraint-based, environmental, and behavioral variables alongside traditional AIS-based metrics. Full article

Stable nanoemulsions with fine droplets reduce organic solvent use and improve the dispersion of hydrophobic pesticide. However, current studies on deltamethrin nanoemulsion lack systematic formula optimization, performance evaluation and biosafety assessment. This study developed a stable deltamethrin nanoemulsion (Del@Ne) and tested its physicochemical properties, insecticidal activity and non-target safety. In 2025, the effects of surfactant ratio, dosage, preparation temperature and emulsification method on emulsion stability was systematically investigated. The optimal formula contained an active ingredient (2.5% deltamethrin), a surfactant ratio of 8:1 (#601:#500), a 6% surfactant dosage, a 17.25% oil phase (S-100:DMF = 20:3), and deionised water filled to 100%, prepared by adding deionised water to an oil phase containing deltamethrin and surfactants at 40 °C. Del@Ne exhibited small droplet size and good storage stability (TSI ≈ 1), which had better wettability on peach leaves with contact angle falling from 40.4° to 21.6° in 120 s. Del@Ne also gave higher toxicity against Myzus persicae (LC₅₀ = 66.85 mg L⁻¹) than Del@EC (80.69 mg L⁻¹), while showing lower toxicity to zebrafish, earthworms and Harmonia axyridis, as well as better biocompatibility with human L02 hepatocytes. These results provide references for rapid screening of nanoemulsion formulation parameters and also offer insights for the efficient utilization of hydrophobic pesticides. Full article

Large Language Models (LLMs) have become foundational to modern Artificial Intelligence (AI), enabling advanced reasoning, multimodal understanding, and scalable human-AI interaction across diverse domains. This survey provides a comprehensive review of major proprietary and open-source LLM families, including GPT, LLaMA 2, Gemini, Claude, DeepSeek, Falcon, and Qwen. It systematically examines architectural advancements such as transformer refinements, mixture-of-experts paradigms, attention optimization, long-context modeling, and multimodal integration. The paper further analyzes alignment and safety mechanisms, encompassing instruction tuning, reinforcement learning from human feedback, and constitutional frameworks, and discusses their implications for controllability, reliability, and responsible deployment. Comparative analysis of training strategies, data curation practices, efficiency optimizations, and application settings highlights key trade-offs among scalability, performance, interpretability, and ethical considerations. Beyond synthesis, the survey introduces a structured taxonomy and a feature-driven comparative study of over 50 reconstructed LLM architectures, complemented by an interactive visualization interface and an open-source implementation to support transparency and reproducibility. Finally, it outlines open challenges and future research directions related to transparency, computational cost, data governance, and societal impact, offering a unified reference for researchers and practitioners developing large-scale AI systems. Full article

In this study, we propose a wearable fall detection system that combines wearable sensors, TinyML model, and IoT-based communication for real-time monitoring and detection of falls. The system is designed for resource-constrained IoT devices where memory, power, and processing capacity are limited. The system works by collecting body motion data using accelerometer sensors placed on the human body. The data is then processed using a feedforward neural network trained on preprocessed signals. The trained model is quantized so that it can run on low-power embedded hardware with small memory size. The model performs inference directly on the device. This reduces latency and avoids sending raw sensor data to the cloud. When a fall is detected, the result is sent through Bluetooth to a gateway. The gateway forwards the data to a cloud server using the MQTT protocol. The cloud stores the data and supports monitoring and analysis. The experimental results show that the quantized TinyML model achieves 98.40% accuracy with more than 80% F1-score and more than 99% recall. The deployed model uses only ∼5 KB of RAM and ∼40 KB of flash memory. The inference time is 7 ms per class. These results show that wearable sensing with quantized TinyML models and IoT communication can provide fast and reliable fall detection for real-world safety monitoring systems. Full article

Unmanned aerial vehicles (UAVs) are increasingly deployed in missions that require high autonomy and reliable decision-making; however, many operational concepts still assume access to GNSS and stable communication with a human operator. In contested environments, this assumption may no longer hold because GNSS degradation, radio-frequency interference, and intentional jamming can disrupt positioning and communication, thereby reducing mission effectiveness and safety. Recent surveys show that operation in GNSS-denied environments remains a major challenge and often requires alternative perception, localization, and control strategies. In response, this article investigates a reinforcement learning (RL)-based decision-support system for the autonomous control of a quadrotor UAV in a three-dimensional simulated environment. Rather than following pre-programmed waypoints, the UAV learns a control policy through interaction with the environment and reward-driven adaptation. The proposed system is designed for mission execution under uncertainty, limited external guidance, and partial observability. Two policy-gradient approaches are implemented and compared: classical REINFORCE and Proximal Policy Optimization (PPO) with an Actor–Critic architecture. The study presents the simulation environment, state and action representation, reward formulation, staged training procedure, and comparative evaluation. The results indicate that, within the considered unseen test scenario, the PPO-based configuration achieved higher mission effectiveness than REINFORCE in the final unseen test scenario, supporting the practical relevance of structured deep reinforcement learning for UAV operation in GPS-denied and communication-constrained environments. Full article

This study examined the toxicological, and bioaccumulative effects of dietary lead (Pb) on Tenebrio molitor larvae, increasingly considered for human and animal consumption within sustainable food and feed production systems. Larvae were exposed for 21 days to an oat-based diet contaminated with lead salts (125–2000 mg Pb/kg). Body mass, and Pb accumulation in the intestine, internal tissues, and cuticle were analyzed. Pb concentrations in larval compartments increased with increasing nominal Pb levels in feed, with concentrations in internal tissues and cuticle reaching 5–6 times higher than in the control. Estimated bioaccumulation factors (BAF) were below 1 in all cases, indicating no biomagnification. Despite high exposure levels, no significant effects on larval survival or biomass gain were observed. These findings indicate that growth-related parameters are not sensitive indicators of Pb exposure. At the same time, substantial Pb accumulation occurred, particularly in the gut and cuticle, highlighting a risk of “hidden” contamination in insect-based production systems. The results emphasize the need for substrate monitoring and the inclusion of sensitive chemical indicators in food safety risk assessment. Full article

Background: Erectile dysfunction (ED) and premature ejaculation (PE) are prevalent conditions affecting men’s sexual health, for which tadalafil and dapoxetine have shown promise in their treatment, respectively. Conventional oral dosage forms face limitations, including variable absorption and delayed onset of action. In this study, we developed electrospun nanofibers using polyvinylpyrrolidone for buccal drug delivery as an alternative dosage form to oral tablets. This route offers advantages such as easy administration, suitability for those with difficulty swallowing, particularly the elderly, and a rapid onset of action via the blood capillaries, which might improve bioavailability. Methods: PVP nanofibers loaded with tadalafil and dapoxetine were fabricated using a modified electrospinning procedure with the Spraybase system, where an 8% (w/v) PVP ethanol solution containing 1.5% dapoxetine and 0.5% tadalafil was electrospun under controlled conditions (800 µL/h flow rate, 15 cm distance, 0.55 mm needle, and 8–10 kV) to produce uniform fibers. Results: The morphology of the nanofibers was characterized using SEM, revealing smooth, uniform fibers with an average diameter of 218 ± 50 nm for drug-loaded nanofibers. This nanofibrous system also demonstrated ultra-rapid disintegration occurring within 4 ± 1 s and consistent drug loading and encapsulation efficiency for both drugs. The release profile showed a burst drug release after 15 min, which accounted for >45% for tadalafil and >50% for dapoxetine, followed by a sustained increment in the drug release that reached > 60% for tadalafil and >78% for dapoxetine after 30 min until a complete drug release (100%) for both drugs after 180 min. In vitro cytotoxicity studies on human dermal fibroblasts confirmed the safety of both medications, with cell viability exceeding 50%, at concentrations of 1.56 to 25 µg/mL for tadalafil and 4.69 to 9.38 µg/mL for dapoxetine after 24 and 48 h of incubation. Conclusions: These findings highlight the potential of PVP-based nanofibers as a novel buccal delivery system for the combined treatment of ED and PE. Full article

Background/Objectives: Meningococcal disease is primarily caused by serogroups A, B, C, W, and Y. Current US vaccination recommendations include routine serogroup A/C/W/Y (MenACWY) vaccination (ages 11–12 and 16 years) and a two-dose, 0-, 6-month MenB vaccination series (age 16–23 years) based on shared clinical decision-making. Administration of the first-in-class Pfizer pentavalent MenABCWY vaccine (Penbraya^TM), which received US licensure in 2023 as a two-dose, 0-, 6-month series, is endorsed when the MenACWY and MenB vaccines are recommended at the same visit. This study evaluated the immunogenicity and safety of two extended two-dose schedules of MenABCWY in healthy adolescents. Methods: In this observer-blinded, phase 2b study (ClinicalTrials.gov, NCT04440176; 19 June 2020), 309 healthy 11- to 14-year-olds were randomized 1:1 to receive a 0-, 36-month or 0-, 12-month Pfizer MenABCWY schedule, which more closely aligns with current US MenACWY vaccination recommendations. Endpoints included serum bactericidal assay using human complement seroprotection rates (titers ≥ 1:8 or ≥1:16, depending on strain), seroresponse rates (≥4-fold increase from baseline titer), and geometric mean titers (GMTs). Safety was also assessed. Results: One month after the second Pfizer MenABCWY dose, serogroup A/B/C/W/Y seroprotection rates were 100% for the 0-, 36-month schedule and 96.6–100% for the 0-, 12-month schedule; seroresponse rates were 100% and 92.9–100%, respectively. GMTs generally trended higher with the 0-, 36-month schedule. Seroprotection rates through 24 months after the second dose of the 0-, 12-month schedule were 44.0–75.0% for serogroup B and 88.9–100% for serogroup A/C/W/Y). No safety issues were identified. Conclusions: These data support Pfizer MenABCWY dosing flexibility and utility within the current or possible future US meningococcal vaccination framework. Full article