Search Results (7,402)

Objectives: The current work aimed to formulate and optimize a self-emulsifying microemulsion drug delivery system (SEME) for acemetacin (ACM) to increase ACM’s aqueous solubility, improve oral bioavailability, and reduce gastrointestinal complications. Methods: Screening of components capable of enhancing ACM solubility was performed. Pseudo-ternary phase diagrams were performed to choose the optimal formulation ratio. The ACM-SEME formulation’s composition was optimized using D-optimal design. Oil, S_mix, and water percentages were used as independent variables, while globule size, polydispersity index, ACM content, and in vitro ACM release after 90 min were used as dependent variables. Also, thermodynamic stability and transmittance percentage tests were studied. Zeta potential was assessed for the optimized ACM-SEME formulation, which was then subjected to spray drying. The dried ACM-SEME was characterized using field-emission scanning electron microscope, Fourier-transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The dried ACM-SEME formulation was filled into hard gelatin capsules and coated with Eudragit L100 to achieve pH-dependent release. Results: The antinociceptive activity of ACM-SEME was evaluated in vivo using Eddy’s hot plate test in rats, revealing a significant prolongation of the noxious time threshold compared to control groups. Ex vivo permeation studies across rat intestinal tissue confirmed the enhanced permeation potential of the ACM-SEME. Conclusions: It was concluded that the developed ACM-SEME system demonstrated improved physicochemical properties, enhanced release behavior, and superior therapeutic performance, highlighting its potential as a safer and more effective oral delivery platform for ACM. Full article

At the international level, new measures, policies, and technologies are being developed to reduce greenhouse gas emissions and, more broadly, air pollutants. Road transportation is one of the main contributors to such emissions, as vehicles are extensively used in logistics operations, and many fleet owners of fossil-fueled trucks are adopting new technologies such as electric, hybrid, and hydrogen-based vehicles. This paper addresses the Hybrid Fleet Capacitated Vehicle Routing Problem with Time Windows (HF-CVRPTW), with the objectives of minimizing costs and mitigating environmental impacts. A mixed-integer linear programming model is developed, incorporating split deliveries, scheduled arrival times at stores, and a carbon cap-and-trade mechanism. The model is tested on a real case study provided by Decathlon, evaluating the performance of internal combustion engine (ICE), electric (EV), and hydrogen fuel cell (HV) vehicles. Results show that when considering economic and emission trading costs, the optimal fleet deployment priority is to use ICE vehicles first, followed by EVs and then HVs, but considering only total emissions, the result is the reverse. Further analysis explores the conditions under which alternative fuel, electricity, or hydrogen prices can achieve competitiveness, and a further analysis investigates the impact of different electricity generation and hydrogen production pathways on overall indirect emissions. Full article

Conventional projection systems typically require a fixed spatial configuration relative to the projection surface, with strict control over distance and angle. In contrast, UAV-mounted projectors overcome these constraints, enabling dynamic, large-scale projections onto non-planar and complex environments. However, such flexible scenarios introduce a key challenge: severe geometric distortions caused by intricate surface geometry and continuous camera–projector motion. To address this, we propose a novel image registration method based on global dense matching, which estimates the real-time optical flow field between the input projection image and the target surface. The estimated flow is used to pre-warp the image, ensuring that the projected content appears geometrically consistent across arbitrary, deformable surfaces. The core idea of our method lies in reformulating the geometric distortion correction task as a global feature matching problem, effectively reducing 3D spatial deformation into a 2D dense correspondence learning process. To support learning and evaluation, we construct a hybrid dataset that covers a wide range of projection scenarios, including diverse lighting conditions, object geometries, and projection contents. Extensive simulation and real-world experiments show that our method achieves superior accuracy and robustness in correcting geometric distortions in dynamic UAV projection, significantly enhancing visual fidelity in complex environments. This approach provides a practical solution for real-time, high-quality projection in UAV-based augmented reality, outdoor display, and aerial information delivery systems. Full article

This study reports the development and optimization of a Melissa officinalis oil-based nanoemulgel for transdermal delivery using a Design-of-Experiments (DoE) approach. A Central Composite Design (CCD) was applied to optimize Tween 80 concentration and homogenization time, resulting in a nanoemulsion with a droplet size of 127.31 nm, PDI of 17.7%, and zeta potential of −25.0 mV, indicating good colloidal stability. FTIR analysis confirmed the presence of functional groups such as O–H, C=O, and C–O–C, supporting the oil’s phytochemical richness and therapeutic potential. DSC analysis revealed enhanced thermal stability and successful encapsulation, while SEM imaging showed a uniform and spherical microstructure. The drug release followed Higuchi kinetics (R² = 0.900), indicating diffusion-driven release, with the Korsmeyer–Peppas model (n = 0.88) suggesting anomalous transport. Antibacterial studies showed inhibition of Staphylococcus aureus (MIC = 250 µg/mL) and Escherichia coli (MIC = 500 µg/mL). In vivo anti-inflammatory testing demonstrated significant edema reduction (p < 0.05) using a carrageenan-induced rat paw model. These results support the potential of Melissa nanoemulgel as a stable and effective topical therapeutic for inflammatory and microbial skin disorders. Full article

Background/Objectives: This study developed a targeted drug delivery nanoplatform for treating HER2-positive breast cancer. The nanoplatform encapsulated two hydrophobic anticancer agents, neratinib (NTB) and docetaxel (DTX), within nanoparticles (DTX+NTB−NP) functionalized for conjugation to trastuzumab to form trastuzumab-tagged nanoparticles (TRZ−NP). Trastuzumab is a HER2-specific monoclo-nal antibody that binds to HER2 receptors, blocking signal transduction and inducing an-tibody-dependent cellular cytotoxicity (ADCC). Upon receptor-mediated endocytosis, neratinib inhibits cytosolic HER2 signaling, while docetaxel disrupts mitotic cell division, collectively leading to tumor cell death. Methods: Nanoparticles were fabricated by the nanoprecipitation technique, followed by surface modification with a crosslinker and a targeting moiety. DTX+NTB−NP, TRZ−NP, and singly loaded nanoparticles (NTB−NP and DTX−NP) were characterized and their effects evaluated in HER2-positive cancer cell line and xenograft model. Results: In vitro antiproliferation assay in SKBR-3 cell line re-veals a dose and time-dependent cytotoxicity. There was no significant difference in cyto-toxicity observed between DTX+NTB−NP and its free form (DTX+NTB) [p = 0.9172], and between TRZ−NP and its free form (TRZ+DTX+NTB) [p = 0.6750]. However, TRZ−NP, at half the concentration of the singly loaded nanoparticles, significantly reduced the viabil-ity of SKBR-3 cells compared to pure trastuzumab (TRZ) [p < 0.001], NTB−NP [p = 0.0019], and DTX−NP [p = 0.0002]. In vivo evaluation in female athymic nude mice showed sig-nificant log relative tumor volume (%) reduction in groups treated with TRZ−NP and DTX+NTB−NP compared to PBS (phosphate-buffered saline) controls (p ≤ 0.001 and p ≤ 0.001), respectively. Notably, TRZ−NP demonstrated a statistically significant regression in the log relative tumor volume (%) compared to DTX+NTB−NP (p = 0.001). Conclusions: These findings underscore the therapeutic potential and suitability of these nanoplatforms for the precise and controlled targeting of HER2-positive tumors. This study is the first to synchronize the delivery of multiple agents-docetaxel, neratinib, and trastuzumab-within a nanoparticle system for treating HER2-positive tumors, offering a promising strategy to enhance treatment outcomes for HER2 positive breast cancer patients. Full article

Background: Sustained-release (SR) formulations of non-steroidal anti-inflammatory drugs (NSAIDs) aim to prolong therapeutic activity, reduce dosing frequency, and improve patient adherence. However, currently marketed SR NSAIDs exhibit persistent limitations, including incomplete control over release kinetics, high interpatient variability in bioavailability, limited reduction in gastrointestinal adverse effects, and insufficient dose flexibility for individualized therapy. In many cases, conventional excipients and release mechanisms remain predominant, leaving drug-specific physicochemical and pharmacokinetic constraints only partially addressed. These gaps highlight the need for a comprehensive synthesis of recent technological advances to guide the development of more effective, patient-centered delivery systems. Methods: A narrative literature review was conducted using Web of Science and PubMed databases to identify original research articles and comprehensive technological studies on oral SR formulations of NSAIDs and paracetamol published between January 2020 and March 2025. Inclusion criteria focused on preclinical and technological research addressing formulation design, excipient innovations, and manufacturing approaches. Results: Sixty-four studies met the inclusion criteria, encompassing polymeric matrices (31%), lipid-based carriers (18%), microspheres/hydrogel beads/interpenetrating polymer networks (30%), nanostructured systems (11%), and hybrid platforms (10%). The most common strategies involved pH-dependent release, mucoadhesive systems, and floating drug delivery, aiming to optimize release kinetics, minimize mucosal irritation, and sustain therapeutic plasma levels. Advances in manufacturing—such as hot-melt extrusion, 3D printing, electrospinning, and spray drying—enabled enhanced control of drug release profiles, improved stability, and in some cases up to 30–50% prolongation of release time or reduction in Cmax fluctuations compared with conventional formulations. Conclusions: Recent formulation strategies show substantial potential to overcome long-standing limitations of SR NSAID delivery, with expected benefits for patient compliance and quality of life through reduced dosing frequency, better tolerability, and more predictable therapeutic effects. Nevertheless, integration of in vitro performance with pharmacokinetic and clinical safety outcomes remains limited, and the translation to clinical practice is still in its early stages. This review provides a comprehensive overview of current technological trends, identifies persisting gaps, and proposes future research directions to advance SR NSAID systems toward safer, more effective, and patient-focused therapy. Full article

Intraoperative radiotherapy (IORT) is a radiation technique that allows for the delivery of a high radiation dose to the target while preserving the surrounding structures, which can be displaced during the surgical procedure. An important limitation of this technique is the lack of real-time image guidance, which is one of the main achievements of modern radiation therapy because it allows for treatment optimization. IORT can be delivered by low-energy X-rays or by accelerated electrons. The present review describes the most relevant clinical applications for IORT and discusses the potential advantages of using artificial intelligence (AI) to overcome some of the current limitations of IORT. In recent decades, IORT has proven to be an effective treatment in several cancer types. In breast cancer, IORT can be used to deliver a single dose of radiation (partial breast irradiation) or as a boost in high-risk patients. In locally advanced rectal cancer, a single dose to the tumor bed can improve local control and prevent pelvic relapse in primary and recurrent tumors. In sarcomas, IORT enables the delivery of high doses, achieving good functional outcomes with low toxicity in tumors located in the retroperitoneum and extremities. In pancreatic cancer, IORT shows promising results in borderline resectable and unresectable cases. Ongoing technological advances are addressing current challenges in imaging and radiation planning, paving the way for personalized, image-guided IORT. Recent innovations such as CT- and MRI-equipped hybrid operating theaters allow for real-time imaging, which could be used for AI-assisted segmentation and planning. Moreover, the implementation of AI in terms of machine learning, deep learning, and radiomics can improve the interpretation of imaging, predict treatment outcomes, and optimize workflow efficiency. Full article

Timely and accurate traffic information is crucial for maintaining safety and efficiency on motorway networks. This research examines time delays in traffic information transmission through intelligent transport systems (ITSs) and cooperative intelligent transport systems (C-ITSs) on the Slovenian motorway network. The aim of the research is to assess the effectiveness of existing notification systems and the impact of time delays on the timely informing of drivers in the event of an accident in a tunnel. Using real-world data from Regional Traffic Center (RCC) in Vransko, manual and automated activations of traffic portals and different update frequencies of the Promet+ mobile application were analyzed during peak hours. Results show that automated activation reduces delays from 34 to 25 s at portals and from 27 to 18 s in the Promet+ app. Continuous updates in the app provided the highest driver coverage, leaving only 15 uninformed drivers in the morning peak and 8 in the afternoon, whereas 60 s update intervals left up to 71 drivers uninformed. These findings highlight the effectiveness of automation and continuous updates in minimizing delays and improving driver awareness. The research contributes by quantifying latency in ITSs and C-ITSs and demonstrating that their combined use offers the most reliable information delivery. Future improvements should focus on hybrid integration of ITS and C-ITS, dynamic update intervals, and infrastructure upgrades to ensure consistent real-time communication, shorter response times, and enhanced motorway safety. Full article

Background/Objectives: Fetuin-A is a multifunctional glycoprotein involved in metabolic and inflammatory regulation. Although its role in insulin resistance, type 2 diabetes, and cardiovascular disease is well recognized, its relationship with pregnancy-related body mass changes remains unclear. This study aimed to explore associations between maternal BMI dynamics during and shortly after pregnancy and serum fetuin-A concentrations. Methods: Fifty-five healthy Caucasian women with term singleton pregnancies were enrolled. BMI was recorded at three time points: pre-pregnancy, before delivery, and 48 h postpartum. Based on ΔBMI (postpartum minus pre-pregnancy BMI), participants were divided into two groups: ΔBMI ≤ 1 kg/m² (n = 32) and ΔBMI > 1 kg/m² (n = 23). Serum fetuin-A levels were measured before delivery and postpartum using ELISA. Additional laboratory parameters and body composition were assessed postpartum via standard tests and bioelectrical impedance analysis (BIA). Results: No significant differences were found between groups in BMI at any single time point or in laboratory or BIA-derived parameters. However, all three BMI change indices (ΔBMI_gestational, ΔBMI_puerperal, and ΔBMI) differed significantly between groups. Fetuin-A concentrations did not differ significantly between groups. Importantly, fetuin-A levels decreased significantly after delivery in both groups, suggesting a potential role of the placenta in its regulation. A significant correlation was observed between pre-delivery fetuin-A and postpartum uric acid in Group ΔBMI > 1 kg/m² (p = 0.016), indicating a possible link in women with greater gestational weight gain. Conclusions: While fetuin-A was not directly associated with BMI changes, its peripartum dynamics and correlation with uric acid may reflect underlying metabolic-inflammation pathways. ΔBMI indices may offer a more individualized measure of weight dynamics in pregnancy research. Full article

This paper presents an advanced, adaptive model for designing and optimizing agile and sustainable supply chains by integrating fuzzy multi-objective programming, Internet of Things (IoT), digital twin (DT) technologies, and reinforcement learning. Unlike conventional static models, the proposed framework utilizes real-time data and dynamically updates fuzzy parameters through a deep deterministic policy gradient (DDPG) algorithm. The model simultaneously addresses three conflicting objectives: minimizing cost, delivery time, and carbon emissions, while maximizing agility. To validate the model’s effectiveness, various optimization strategies including NSGA-II, MOPSO, and the Whale Optimization Algorithm are applied across small- to large-scale scenarios. Results demonstrate that the integration of IoT and DT, alongside adaptive learning, significantly improves decision accuracy, responsiveness, and sustainability. The model is particularly suited for high-volatility environments, offering decision-makers an intelligent, real-time support tool. Case study simulations further illustrate the model’s value in sectors such as urban logistics and humanitarian aid supply chains. Full article

Pregnancy in women with type 1 diabetes mellitus (T1DM) is associated with a high risk of maternal and perinatal complications, and achieving optimal glycaemic control remains a clinical challenge. This article presents a narrative review of the evidence on advanced hybrid closed loop (AHCL) insulin delivery systems in pregnancy, with a focus on maternal glycaemic outcomes, neonatal outcomes, and psychosocial aspects. The relevant literature was identified through a structured search of PubMed, Scopus, and Web of Science (2010–2025), supplemented by guideline documents and reference screening. Eligible studies included randomised controlled trials, observational studies, and qualitative investigations. Data were synthesised thematically. Findings from key trials, including CONCEPTT, AiDAPT, and CRISTAL, demonstrate that AHCL systems improve time in range, lower mean glucose, and reduce hyperglycaemia without increasing hypoglycaemia. Some evidence also suggests improved neonatal outcomes, though statistical significance varies. Qualitative studies highlight reduced anxiety, improved sleep, and enhanced quality of life for women using AHCL during pregnancy. In conclusion, AHCL systems show strong promise in optimising maternal glycaemic control and potentially improving perinatal outcomes. However, larger, unbiased studies and real-world evaluations are needed to confirm their benefits and support broader clinical implementation. Full article

Exosomes are lipid bilayer vesicles approximately 30–150 nm in diameter that serve as key mediators of intercellular communication. By transporting diverse bioactive molecules, including proteins and nucleic acids, they play a crucial role in tumor initiation and progression. Among their functional cargo, exosomal microRNAs (miRNAs) are central to epigenetic regulation and intercellular signaling, significantly influencing tumor biology. This review provides a comprehensive overview of the multifaceted roles of exosomal miRNAs in remodeling the tumor microenvironment (TME) and regulating cancer stem cells (CSCs). Specifically, exosomal miRNAs modulate various immune cells (such as macrophages, T cells, and NK cells) as well as cancer-associated fibroblasts (CAFs), thereby promoting immune evasion, angiogenesis, epithelial–mesenchymal transition (EMT), and metastatic progression. At the same time, they enhance CSC stemness, self-renewal, and therapeutic resistance, ultimately driving tumor recurrence and dissemination. Furthermore, exosome-mediated miRNA signaling acts as a critical force in malignant progression. Finally, we discuss the clinical potential of exosomal miRNAs as diagnostic and prognostic biomarkers, therapeutic targets, and vehicles for targeted drug delivery, highlighting their translational value and future directions in cancer research. Full article

Palliative radiotherapy (PRT) is central to symptom control in advanced cancer, yet referrals are often late, and patients and clinicians frequently hold misconceptions about intent, benefits, and logistics. Patient education may address these gaps, but the PRT-specific evidence base has not been consolidated. We conducted a narrative review following SANRA guidance. We searched PubMed, Scopus, and the Cochrane Library for English-language studies from 1 January 2000 to 18 July 2025. Eligible articles evaluated structured patient-education interventions or characterized education or communication content, information needs, or decision processes among adults referred to or receiving PRT. Two reviewers independently screened and extracted data. Owing to heterogeneity of designs and endpoints, we performed a narrative synthesis without meta-analysis. Six studies met criteria: two randomized controlled trials, two prospective pre–post studies, one qualitative interview study, and one observational communication study, conducted in the Netherlands, the United States, Canada, and Hong Kong. Education at referral or consultation improved knowledge, reduced decisional uncertainty, and increased readiness to proceed with PRT. Education integrated with treatment improved symptom outcomes, including higher rates of pain control at 12 weeks and faster time to pain control when a nurse-led pain-education program accompanied PRT for painful bone metastases, and improvements in dyspnea, fatigue, anxiety, and function in advanced lung cancer. Observational and qualitative work showed low patient question-asking and persistent curative expectations; overall quality of life generally did not change. Although the evidence is limited and heterogeneous, targeted, standardized education appears to improve decision quality and selected symptoms in PRT pathways. Pragmatic multi-site trials and implementation studies are needed to define content, timing, personnel, and delivery models that are scalable in routine care. Full article

Objectives: Ketamine has demonstrated rapid and sustained antidepressant effects; however, its clinical utility is limited by the risk of addiction and systemic side effects. This study aimed to develop ketamine-loaded nanodroplets (Ket-NDs) with high encapsulation efficiency (EE) and stability for targeted low-dose intravenous (IV) administration in a mice model of depression. Low-intensity focused ultrasound (LIFU) was employed to induce transcranial, region-specific drug release in the lateral habenula (LHb). Methods: Ket-NDs were synthesized using a thin-film hydration method with sonication and emulsification, incorporating perfluoropentane as the core material. Characterization was performed using light microscopy, cryogenic scanning electron microscopy (cryo-SEM), transmission electron microscopy, and dynamic light scattering (DLS). Drug EE and loading efficiency (LE) were quantified by reversed-phase high-performance liquid chromatography. A chronic restraint stress model was established, and Ket-NDs were administered intravenously followed by LIFU targeting the LHb. Antidepressant efficacy and biosafety were systematically evaluated. Results: (1) Ket-NDs exhibited uniform spherical morphology and a narrow size distribution, as confirmed by DLS (particle size: 139.75 ± 9.43 nm; Polydispersity index: 0.225 ± 0.025) and cryo-SEM analysis (number-average diameter: 109.5 ± 10.4 nm). The zeta potential was −15.93 ± 5.906 mV, and the formulation remained stable under 4 °C storage. (2) Ket-NDs demonstrated high EE (78.25 ± 16.13%) and LE (15.55 ± 4.49%). (3) In depressive mice, IV administration of Ket-NDs followed by LIFU targeting the LHb significantly improved behavioral outcomes: increased locomotor activity in the open field test, elevated sucrose preference index, and reduced immobility time in the tail suspension test. (4) Safety assessments revealed no significant organ toxicity or brain tissue damage in ultrasound-exposed regions. Conclusions: In summary, this study developed stable Ket-NDs. When combined with LIFU, they enable precise regional drug delivery to the brain, showcasing a promising treatment strategy for depression with reduced systemic side effects. Full article

Registered Respiratory Therapists (RRTs) have unique skills in managing chronic obstructive pulmonary disease (COPD) in primary care settings. With an 82% increase in COPD diagnoses between 2000 and 2010 in Canada, the fact that over 10% of Canadians aged 35 and older are living with COPD, and primary care reform in Ontario and Manitoba, we would expect an increasing number of RRTs working in this setting. However, this is not happening. Through the concept of job satisfaction, we want to investigate the barriers of integrating this allied healthcare professional into primary care settings. Using a pragmatic approach, we examined RRT job satisfaction in primary care via semi-structured interviews of 19 RRTs in Manitoba and Ontario in 2018 and 2019. A combined inductive and deductive (Mottaz framework) analysis approach allowed us to cross reference work context with job satisfaction. The context in which primary care is operationalized impacts RRT job satisfaction. In Ontario, retention of RRTs in primary care was the main issue due to lower salaries and benefits. In Manitoba, recruitment of RRTs in primary care was the main issue due to lack of human resources and funding. Efforts should be made to address gaps in job satisfaction of RRTs in primary care. To improve retention in Ontario, RRTs should be compensated similarly to their counterparts in acute care. In Manitoba, there should be increased positions for RRTs in primary care. Developing strategies for enhancing job satisfaction will ensure the delivery of high-quality, patient-centered care. This study provides both theoretical and practical contributions to primary care workforce research. Theoretically, our findings demonstrate how contextual factors moderate job satisfaction, showing that the primary care context produces various work situations and heavily impacts work satisfaction. Practically, our results offer specific guidance for healthcare policymakers and administrators, including standardizing compensation across care settings, converting part-time positions to full-time roles, and developing targeted educational initiatives to improve workforce recruitment and retention in underserved areas. Full article