Search Results (3,159)

Bone metastasis in breast cancer remains a major therapeutic challenge because current osteoclast-targeted therapies do not fully disrupt the tumor–bone vicious cycle. Osteocytes, the most abundant bone cells, are increasingly recognized as key regulators of bone–tumor crosstalk. Previous work has shown that osteocyte-specific overexpression of the Wnt co-receptor LRP5 inhibits breast cancer-induced osteolysis and generates conditioned medium (CM) with tumor-suppressive activity. Proteomic analysis identified LIM domain and actin-binding protein 1 (LIMA1) as a central mediator that interacts with Myosin Vb (MYO5B), suggesting the role of the LIMA1/MYO5B regulatory axis. This study demonstrates that CM derived from LRP5-overexpressing osteocytes suppresses EO771 breast cancer cell proliferation, migration, and invasion, and downregulates tumor-promoting proteins, including MMP9, Snail, IL-6, and TGF-β1, while upregulating the apoptosis-related protein cleaved caspase-3. These effects were largely reversed by knockdown of LIMA1 or MYO5B. In syngeneic mouse models of mammary tumors and bone metastasis, systemic administration of LRP5-overexpressing osteocyte-derived CM reduced tumor burden and osteolytic bone destruction, whereas genetic knockdown of LIMA1 in osteocytes or MYO5B in tumor cells abrogated these protective effects. Collectively, these findings indicate that LRP5 activation in osteocytes engages the LIMA1/MYO5B signaling axis that inhibits breast cancer progression and osteolysis, disrupts tumor–stromal interactions, and restores bone–tumor homeostasis, thereby providing a potential therapeutic strategy to break the vicious cycle of bone metastasis in breast cancer. Full article

Pulmonary drug delivery represents a promising approach in the treatment of respiratory diseases, allowing for passive targeting and enhanced drug efficacy. Background/Objectives: The aim of the present study was to develop inhalable dry powders from lyophilized sildenafil citrate (SC)-loaded liposomes made from phosphatidylcholine and either cholesterol (CH) or resveratrol (RSV). Methods: Liposomes were prepared via a pH gradient method to increase drug entrapment efficiency and drug loading, and then the liposomes were lyophilized using different proportions of ethanol, mannitol, and lactose as excipients. The resulting dry cakes were converted into powders and evaluated for aerodynamic performance using a custom-designed air-blowing device. Notably, this is the first time that resveratrol has been used as a substitute for cholesterol in SC-loaded liposomes. Results: Our results demonstrate that RSV is a suitable liposome bilayer component and improves drug loading. Our findings prove that lyophilized cakes containing liposomes produce a dry powder that is suitable for aerosolization with potential application to pulmonary delivery of sildenafil citrate. The results suggest that RSV represents a potential alternative to traditional cholesterol-based liposomal formulations. Conclusions: This work presents a novel strategy for the pulmonary delivery of sildenafil, using biocompatible and FDA-approved mannitol and lactose for this administration route. Full article

This study examines the behavioral intention of Muslims in Bosnia and Herzegovina to adopt blockchain-based zakat systems. It offers novel insights from a European Islamic context. Prior studies have primarily focused on Southeast Asia and the Middle East. The research develops an SEM model on an extended Unified Theory of Acceptance and Use of Technology framework. Data were collected through a survey of Bosnian Muslims. The aim was to investigate how these factors influence the acceptance of digital zakat platforms. The findings highlight the potential of blockchain to address inefficiencies and trust issues in traditional zakat management. The study shows that performance expectancy, intrinsic religiosity, and trust are significant determinants of adopting blockchain-based zakat platforms. These results emphasize both technological and faith-based drivers of acceptance. Technology can enhance the trustworthiness and inclusivity of zakat administration for a broader group of Muslims in Bosnia and Herzegovina and similar contexts. This work contributes to broader international discussions on the intersection of technology, religion and finance. The article is laying a foundation for the future development of blockchain-based zakat platforms in Muslim societies. Full article

Due to the complexity of blood glucose dynamics and the high variability of the physiological structure of diabetic patients, implementing a safe and effective insulin dosage control algorithm to keep the blood glucose of diabetic patients within the normal range (70–180 mg/dL) is currently a challenging task in the field of diabetes treatment. Deep reinforcement learning (DRL) has proven its potential in diabetes treatment in previous work, thanks to its strong advantages in solving complex dynamic and uncertain problems. It can address the challenges faced by traditional control algorithms, such as the need for patients to manually estimate carbohydrate intake before meals, the requirement to establish complex dynamic models, and the need for professional prior knowledge. However, reinforcement learning is essentially a highly exploratory trial-and-error learning strategy, which is contrary to the high-safety requirements of clinical practice. Therefore, achieving safer control has always been a major challenge for the clinical application of DRL. This paper addresses this challenge by combining the advantages of DRL and the traditional control algorithm—model predictive control (MPC). Specifically, by using the blood glucose and insulin data generated during the interaction between DRL and patients in the learning process to learn a blood glucose prediction model, the problem of MPC needing to establish a patient’s blood glucose dynamic model is solved. Then, MPC is used for forward-looking prediction and simulation of blood glucose, and a safety controller is introduced to avoid unsafe actions, thus restricting DRL control to a safer range. Experiments on the UVA/Padova glucose kinetics simulator approved by the US Food and Drug Administration (FDA) show that the time proportion of adult patients within the healthy blood glucose range under the control of the model proposed in this paper reaches 72.51%, an increase of 2.54% compared with the baseline model, and the proportion of severe hyperglycemia and hypoglycemia events is not increased, taking an important step towards the safe control of blood glucose. Full article

On 1 November 2024, the Federal Highway Administration issued a final rule updating the 23 CFR Part 630 Subpart J on Work Zone Safety and Mobility, detailing performance measures and reporting requirements. The rule suggests that state agencies should define formal performance measures that can be tracked consistently for the continuity of work zone program management across states. The objective is to help identify work zones needing mobility or safety improvements, as well as provide quantitative feedback on the best practices. The emergence of connected vehicle data over the past few years provides a scalable approach for agencies to calculate and monitor the performance measures defined in the CFR, covering, but not limited to, speed, travel time, queue length and duration, hard braking events and speed differentials. This paper describes techniques that use connected vehicle data to estimate different measures that map into the performance measures defined in this rule. A 2024 work zone in Illinois along I-24 was chosen to demonstrate the utility of the measures. The paper concludes with a discussion of ongoing work applying these derived measures to 101 work zones across 9 states in 2025 to demonstrate scalability. Full article

This study investigates workplace stress-management practices and their relationships with employees’ well-being and productivity in accordance with Tayma University College’s goals in Saudi Vision 2030. Although stress-relief programs have been studied in detail in Western cultural environments, efficacy in the context of Saudi higher education institutions has proven to be limited, particularly as employee reactions are shaped by cultural, organizational, and institutional factors. This paper aims to explore the relationships between various other indicators, namely, mindfulness, time management, scheduling autonomy, and coworker support, and stress, job performance, and work–life balance. A convergent mixed-methods design was utilized, based on survey responses from 104 academic and administrative employees and semi-structured interviews with 20 respondents. The presentation of data demonstrated that time management was most consistently and significantly effective using SEM. In conclusion, time management was positively and significantly associated with increased schedule control, coworker support, and job performance, resulting in a more balanced work–life experience. Mindfulness had no significant or meaningful influence on perceived stress levels, while the influence of coworker support was more variable, and job performance experienced greater variation. Qualitative results confirmed this trend, as evidenced by the fact that time-management-oriented activities were incorporated into the daily routine, while mindfulness-related exercises were not well integrated with the cultural norms and work requirements. Within the university context of Saudi Arabia and with reference to the Job Demands–Resources (JDs–Rs) framework and the Transactional Model of Stress and Coping, the study also reveals that situational influences constitute a significant contribution to the development and use of stress-relief resources. Ultimately, the findings highlight the value of culturally relevant stress-management practices to facilitate the well-being, performance, and stability of employees with the backdrop of Saudi Vision 2030. Full article

How does digital technology mediate decision-making and shape our understanding of disaster recovery? I address this question by examining both the administrative and cinematic uses of digital images in the reconstruction process following the 2011 Great East Japan Earthquake. Post-disaster digital mediation is characterized by the administrative use of what has been termed “operational images,” designed not for interpretation but for action, particularly in disaster response and prevention. I connect the social and ethical dimensions of post-disaster recovery with the ontological dimensions of the technological characteristics of digital photography. By comparing Japanese independent filmmaker Haruka Komori’s digital filmmaking practice with the operational images utilized by administrative and research bodies, I aim to demonstrate how her particular digital aesthetics elicit the latent capacity of the “digital unconscious” and offer new modes of perceiving post-disaster recovery, in contrast to both other forms of post-disaster digital mediation and to analog photography. Through close analyses, I argue that her work articulates an alternative vision of recovery—one rooted not in spatial management or predictive planning, but in physical attachment to place, trust in the future, and imaginative engagement with survivors and the dead. Full article

Huntington’s Disease (HD) is characterized by prominent degeneration of the principal neurons of the striatum and by progressive motor and cognitive deterioration. Striatal neurons degenerate in HD due to multiple cell-autonomous and non-autonomous factors. Impaired neurotrophin signaling by brain-derived neurotrophic factor (BDNF) and its cognate receptor Tropomyosin receptor kinase B (TrkB) is an important mechanism underlying neuronal loss in HD. Fingolimod, a clinically approved oral drug for Multiple Sclerosis, was originally developed based on its anti-inflammatory properties. Recent work suggests that fingolimod can also promote BDNF expression and enhance neurotrophic support in the brain. We hypothesized that fingolimod treatment initiated during the presymptomatic phase would increase striatal BDNF levels and protect against motor dysfunction in HD. In wild-type mice, fingolimod treatment increases striatal BDNF levels and enhances BDNF-TrkB signaling. However, chronic fingolimod therapy (0.1 mg/kg, i.p., twice per week, over 7 weeks) initiated at age 4 weeks in the R6/2 mouse model of HD failed to improve behavioral locomotor deficits and exacerbated limb clasping. Furthermore, fingolimod treatment in these presymptomatic R6/2 mice acutely decreased BDNF-TrkB signaling in the striatum in a dose-dependent manner. In contrast, acute administration of fingolimod in symptomatic 7-week-old R6/2 mice increased striatal BDNF-TrkB signaling in a dose-dependent manner, consistent with previous work suggesting that chronic fingolimod can improve motor behavior when given during the symptomatic phase. Thus, the effects of fingolimod striatal BDNF-TrkB signaling and motor behavior in HD are complex and vary with disease stage. Addressing this variability is critical for the design of neuroprotective drug trials in HD, including those utilizing sphingosine-1-phosphate receptor (S1P) modulators. Full article

The increasing complexity and digitization of scientific research require Electronic Laboratory Notebooks (ELNs) that are adaptable, sustainable, and compliant across heterogeneous laboratory environments. In response to the limitations of proprietary, inflexible, and cost-intensive ELN solutions, this study systematically derives comprehensive requirements and proposes a modular solution concept for self-configurable ELNs that is explicitly platform-agnostic and broadly accessible. The methodological approach combines a structured requirements analysis with a modular architectural design, followed by theoretical validation through stepwise implementation walkthroughs on Microsoft SharePoint and Google Workspace. These walkthroughs demonstrate the feasibility of deploying self-configurable ELN modules using widely available low-code/no-code tools and native platform extensibility mechanisms. Based on a rigorous literature-driven analysis, key requirements, including modularity, usability, regulatory compliance, interoperability, scalability, auditability, and cost efficiency, are explicitly mapped to concrete architectural features within the proposed framework. The results show that essential ELN functionalities can, in principle, be realized across diverse digital platforms, enabling researchers and local administrators to independently assemble, configure, and adapt ELNs to their specific operational and regulatory contexts. Beyond technical feasibility, the proposed approach fundamentally democratizes ELN deployment and substantially mitigates vendor lock-in by leveraging existing digital infrastructures. Identified limitations, particularly with respect to advanced workflow orchestration and real-time data integration, delineate clear directions for future development. Overall, this work provides a systematic theoretical validation of a modular, self-configurable ELN concept, establishing it as a robust, scalable, and future-ready foundation for digital laboratory infrastructures. Full article

The increasing integration of Artificial Intelligence (AI) in education (AIEd) and its dependence on contemporary communication infrastructures (5G/6G, the Internet of Things (IoT), and Multi-Access Edge Computing (MEC)) has prompted a surge of research into applications, infrastructural dependencies, and deployment constraints. This is giving rise to a new paradigm termed AI-Enabled Telecommunication-Based Education (AITE). This review synthesises the recent literature (2022–2025) to examine how telecommunications and AI technologies converge to enhance educational ecosystems through adaptive learning systems, intelligent tutoring systems, AI-driven assessment, and administration. The findings reveal that low-latency, high-bandwidth connectivity, combined with edge-deployed analytics, enables real-time personalisation, continuous feedback, and scalable learning models that extend beyond traditional classrooms. In addition, persistent critical challenges are also reported, including issues with ethical governance, data privacy, algorithmic fairness, and uneven access to digital infrastructure, all affecting equitable adoption. By linking pedagogical transformation with telecom performance metrics—namely, latency, Quality of Service (QoS), and device interconnectivity—this work outlines a unified cross-layer framework for AITE. This review concludes by identifying future research avenues in ethical AI deployment, resilient architectures, and inclusive policy design to ensure transparent, secure, and human-centred educational transformation. Full article

Historic city centers are characterized by dense and heterogeneous built environments, making them particularly vulnerable to the compound effects of seismic, flood, and landslide hazards. In this context, information required for vulnerability and risk assessment is often fragmented, limiting the effectiveness of preventive planning and mitigation strategies. This reveals an operational gap in current practice; therefore, this work aims to support decision-oriented, multi-level assessment in historic centers through a replicable approach, even in low-resource contexts. A GIS workflow integrates territorial multi-hazard screening with building-scale overlay mapping of literature-based vulnerability, exposure, and risk classes. Applied to Montalbano Jonico (Italy), the screening analyzed 15 census sections and identified three hotspot areas within the historic center for detailed assessment. Within these critical areas, building-scale mapping yields intervention priorities: 42.8% of building aggregates show High–Very High seismic vulnerability (44.4% in Very High–Maximum Priority risk classes) and 50% show Very High landslide vulnerability (63.2% in Very High–Maximum Priority risk classes), mostly affecting masonry and residential buildings. Overall, the framework provides a practical decision tool to support municipal administrations, technical offices, civil protection agencies, and built heritage management institutions, and is designed for GIS–BIM interoperability. Full article

This article provides a detailed comparative analysis of the transposition and implementation of the Renewable Energy Directives II and III (RED II and RED III), REPowerEU Plan, and the ‘Fit for 55’ package in France, Italy, and Germany. The analysis highlights the objectives, key legislative provisions, and national-scale achievements, challenges, advantages, and disadvantages—including implications for investment conditions and renewable energy financing mechanisms—associated with these pivotal European Union legislative frameworks, which, to a certain extent, induced a paradigm shift with varying degrees of impact in every Member State. The work is divided into four parts that follow this brief introductory outline of the problem. The introduction presents legal developments in renewable energy law in the European Union. The second part offers a comprehensive and in-depth examination of the European Union’s renewable energy regulatory framework and research gaps that hinder doctrinal tensions within the EU’s renewable energy legislative framework. In the third part, we analyze the transposition and implementation of each mentioned directive in the selected countries. The last part highlights commonalities, divergences, challenges, best practices, and lessons learned from each nation’s approach. This comparative analysis predicts that implementation success is inversely linked to administrative divergence, with France’s centralized legal system facilitating effective bureaucratic streamlining and higher predicted deployment, while the fragmented governance structures of Germany and Italy serve as structural impediments that critically undermine the EU’s acceleration mandate. Full article

In recent years, the convergence of advanced technologies has enabled real-time data access and sharing across diverse devices and networks, significantly amplifying cybersecurity risks. For organizations with digital infrastructures, network security is crucial for mitigating potential cyber-attacks. They establish security policies to protect systems and data, but employees may intentionally or unintentionally bypass these policies, rendering the network vulnerable to internal and external threats. Detecting these policy violations is challenging, requiring frequent manual system checks for compliance. This paper addresses key challenges in safeguarding digital assets against evolving threats, including rogue access points, man-in-the-middle attacks, denial-of-service (DoS) incidents, unpatched vulnerabilities, and AI-driven automated exploits. We propose a Blockchain-Enhanced Network Scanning and Monitoring (BENSAM) Framework, a multi-layered system that integrates advanced network scanning with a structured database for asset management, policy-driven vulnerability detection, and remediation planning. Key enhancements include device profiling, user activity monitoring, network forensics, intrusion detection capabilities, and multi-format report generation. By incorporating blockchain technology, and leveraging immutable ledgers and smart contracts, the framework ensures tamper-proof audit trails, decentralized verification of policy compliance, and automated real-time responses to violations such as alerts; actual device isolation is performed by external controllers like SDN or NAC systems. The research provides a detailed literature review on blockchain applications in domains like IoT, healthcare, and vehicular networks. A working prototype of the proposed BENSAM framework was developed that demonstrates end-to-end network scanning, device profiling, traffic monitoring, policy enforcement, and blockchain-based immutable logging. This implementation is publicly released and is available on GitHub. It analyzes common network vulnerabilities (e.g., open ports, remote access, and disabled firewalls), attacks (including spoofing, flooding, and DDoS), and outlines policy enforcement methods. Moreover, the framework anticipates emerging challenges from AI-driven attacks such as adversarial evasion, data poisoning, and transformer-based threats, positioning the system for the future integration of adaptive mechanisms to counter these advanced intrusions. This blockchain-enhanced approach streamlines security analysis, extends the framework for AI threat detection with improved accuracy, and reduces administrative overhead by integrating multiple security tools into a cohesive, trustworthy, reliable solution. Full article

High-flow nasal cannula (HFNC) therapy is frequently described as a positive pressure modality, yet this classification lacks mechanistic support. This critical narrative review integrates experimental, computational, and clinical evidence to examine the established physiological mechanisms underlying HFNC, with emphasis on precise terminology. The study clarifies that labeling HFNC as “positive pressure” is conceptually inaccurate, as the system delivers transient, flow-dependent pressures characteristic of open-circuit administration. Evidence is synthesized to quantify the relative contributions of nasopharyngeal dead-space clearance versus emergent pressure generation. Unlike CPAP, HFNC produces pressures ranging from 0.2 to 13.5 cmH₂O, determined by airway geometry, leak magnitude, and mouth position. Fluid dynamic modeling using Bernoulli and Darcy–Weisbach equations demonstrates oscillatory rather than sustained pressures, with magnitudes linked to nasopharyngeal Reynolds numbers (2400–6000) and turbulent energy dissipation (30–60%). Clinical efficacy persists despite variable pressures, reflecting synergistic mechanisms: inspiratory flow matching (40–50% reduction in work of breathing), dead-space clearance (CO₂ reduction, r = −0.77, p < 0.05), emergent pressure effects (10–20%), and thermal humidification (10–20%). Electrical impedance tomography reveals heterogeneous alveolar recruitment, with high-potential (54%) and low-potential (46%) phenotypes. Based on these mechanistic insights, this review proposes the term “emergent hydrodynamic pressure” to accurately describe HFNC’s transient, flow-dependent pressures. This terminology differentiates HFNC from conventional positive pressure systems and aligns language with the principles of fluid dynamics and respiratory physiology. Full article

The TV series Architecture School depicts entanglements between design (education), urban development, and the complexities of everyday life through its presentation of students in a program of “public-interest” design–build education (wherein students plan and construct homes for low-income families in post-Hurricane Katrina New Orleans). The series offers a nuanced presentation of the situated difficulties of critical design thinking in the context of creating contemporary homes: starting from the initial stages of sketching and model making, through construction, and finally to managing the occupation of the homes by persons who are typically underserved by contemporary architecture. We provide an analysis of the series through outlining how the show presents its participants (student designer-builders, non-profit housing administrators, potential homeowners). We focus on discussing instances of talk on the TV series to illustrate some of the specific concerns and contexts of these participants. Our aim is to explore Architecture School as a relevant case study in designing and building that reflects a dilemma underpinning much contemporary, urban, and public-interest design: how can socially and economically marginalized individuals acquire innovative, well-designed homes when structural conditions of government policies, financial protocols, and administrative complexity offer sustained constraint? We detail how the series depicts the students, administrators, and potential occupants to consider how stereotypes of architects, bureaucrats, and the working poor are reinforced or challenged. Accordingly, we argue that Architecture School is a cultural text that remains timely and important today for its presentation and critique of both the inside world of design’s aims to design and build for others and also the outside-world challenges that limit design’s capacities to create inclusive and equitable material conditions. Full article