Search Results (18,550)

Many commercially available medications are often unapproved or unavailable in suitable dosage forms for specific patient populations, particularly infants and children. This necessitates the use of extemporaneously compounded formulations to deliver individualized doses based on body weight or body surface area, and when a medication is unavailable at an appropriate concentration or contains excipients potentially unsafe for certain patients. Extemporaneous compounding is required for oral liquids when patients are unable to swallow tablets or capsules. It is also needed for topical preparations and sterile dosage forms when commercial products are unavailable. Across regions, practices follow national pharmacopeial standards for both sterile and non-sterile compounding. Stability factors influencing the safety and efficacy of compounded formulations must be carefully considered when assigning appropriate beyond-use dates. While stability information is available for some medications in monographs, peer-reviewed literature, prescribing information, and investigator’s brochures, such data is often lacking for many compounded preparations. Emerging extemporaneous formulations—such as orodispersible films, nanoparticle systems, and 3D-printed compounds—offer potential advantages over traditional compounded formulations but present unique challenges to widespread implementation. Despite the justified clinical need for extemporaneous compounding, significant barriers remain, including limited access to medications, insufficient compounding expertise or resources, gaps in pharmacokinetic and safety data, and regulatory constraints. This review critically appraises the current state of extemporaneous compounding—drawing primarily on the United States of America frameworks—and highlights its continued necessity, associated challenges, and pragmatic solutions for advancing personalized pharmacotherapy across pediatric age groups worldwide. Full article

The integration of artificial intelligence (AI) into marketing and sales has significantly reshaped the European digital economy, altering how companies engage with consumers and create online value. This research examines the impact of AI adoption on e-commerce performance across the 27 EU member states. Drawing on Eurostat data, it applies advanced statistical methods, including factor analysis, structural equation modeling (SEM), and cluster analysis, to examine the links among AI-powered business practices, digital engagement, and e-commerce outcomes. The results reveal a strong positive association between AI use in marketing and e-commerce sales, underscoring the mediating role of consumer digital behavior. Regional disparities are also evident: Northern and Western European economies lead in AI adoption and digital maturity, while Southern and Eastern nations show emerging potential for rapid growth. Overall, the study emphasizes that AI-driven marketing boosts e-commerce growth and digital competitiveness, aligning with the European Union’s broader goals of fostering innovation and technological integration. Full article

Cyanobacteria harbor sophisticated molecular defense systems that have evolved over billions of years to protect against viral invasion and foreign genetic elements. These ancient photosynthetic organisms possess a diverse array of restriction-modification (R-M) systems and CRISPR-Cas arrays that present challenges for genetic engineering, but also offer unique opportunities for cancer-targeted biotechnological applications. These systems exist in prokaryotes mainly as defense mechanisms but they are currently used in molecular applications as gene editing tools. Moreover, latest developments in nucleases such as zinc finger nucleases (ZFNs), TALENs (transcription-activator-like effector nucleases) are discussed. A comprehensive genomic analysis of 126 cyanobacterial species found 89% encode multiple R-M systems, averaging 3.2 systems per genome, creating formidable barriers to transformation but also providing molecular machinery that could be harnessed for precise recognition and targeting of cancer cells. This review critically examines the dual nature of these defense systems, their ecological functions, and the emerging strategies to translate their molecular precision into advanced anticancer therapeutics. Hence, the review main objectives are to explore the recent understanding of these mechanisms and to exploit the knowledge gained in opening new avenues for cancer-focused targeted interventions, while acknowledging the significant challenges to translate these systems from laboratory curiosities to practical applications. Full article

Background/Objectives: Epithelial ovarian cancer (EOC) is often diagnosed at advanced stages, with metastasis driven by spheroid dissemination within the peritoneal cavity. We previously demonstrated that autophagy supports spheroid cell survival and suggest that it contributes to chemoresistance. Unc-51-like autophagy activating kinase 1 (ULK1), a key regulator of autophagy, has emerged as a promising therapeutic target. Here, we evaluated the effects of ULK1 inhibition via MRT68921, alone and in combination with afatinib—a tyrosine kinase inhibitor (TKI) known to induce pro-survival autophagy—in EOC. Methods: High-grade serous (HGSOC) and ovarian clear cell carcinoma (OCCC) cell lines were cultured under adherent and spheroid conditions. Immunoblotting confirmed on-target effects and modulation of autophagy. Autophagic flux was assessed using mCherry-eGFP-LC3 reporter assays. We assessed 96 dose combinations of MRT68921 and afatinib using drug combination matrices, with synergy evaluated via Synergy Finder. Promising combinations were evaluated across multiple EOC spheroid models and patient ascites-derived organoids. Results: MRT68921 inhibited ULK1 activity and reduced autophagic flux in a context-dependent manner while afatinib alone induced autophagy. Their combination produced synergistic effects at select concentrations, impairing spheroid reattachment and viability. However, MRT68921 alone significantly reduced viability across multiple EOC models, including patient ascites-derived organoids. Conclusions: This study is the first to evaluate the combined effects of MRT68921 and afatinib in epithelial ovarian cancer. Our findings demonstrate that ULK1 inhibition via MRT68921 consistently reduces cell viability across multiple ovarian cancer models, supporting ULK1 as a promising therapeutic target. In contrast, combination with afatinib produced limited and context-dependent effects, indicating that further investigation is needed to identify optimal combination strategies for ULK1-targeted therapies. Full article

Lipopeptides (LPs) have evolved from naturally occurring compounds to key therapeutic agents against multidrug-resistant (MDR) bacterial infections. However, their expanding clinical use has triggered emerging resistance mechanisms, posing serious challenges to anti-infective therapy. This systematic review outlines the development of LP resistance and highlights innovative strategies to counteract it. To overcome these evolving barriers, the field has transitioned from traditional empirical optimization to multidimensional rational design. Moving beyond conventional structure–activity relationship (SAR)-guided chemical synthesis, current approaches integrate diverse innovative methodologies. Based on these advances, this review provides the first systematic summary of contemporary strategies for developing novel LPs, offering new perspectives and methodological support to combat resistant bacterial infections and accelerate the development of next-generation LP-based therapeutics. Full article

Alzheimer’s disease (AD) involves a constellation of molecular processes that extend well beyond amyloid-β (Aβ) accumulation. Recent anti-amyloid antibodies provide limited clinical benefits, highlighting the need for additional strategies due to their modest efficacy and safety concerns. Increasing proteomic evidence reveals that proteins such as midkine (MDK), pleiotrophin (PTN) and clusterin (CLU) accumulate within amyloid plaques and may shape disease progression, although their precise contributions—protective, pathogenic, or both—remain unknown. In this Perspective, we examine how emerging targeted protein degradation (TPD) technologies, including Proteolysis-Targeting Chimeras (PROTACs), Lysosome-Targeting Chimeras (LYTACs) and molecular glues (MGs), could provide a means to selectively eliminate these co-aggregating proteins. We also discuss advances in degrader design, artificial intelligence (AI)-assisted screening, and strategies aimed at enhancing Central Nervous System (CNS) delivery. We finally outline how integrating TPD modalities with antibody-based and multi-target therapeutic approaches may promote more effective, systems-level interventions for AD. Full article

The aviation industry, responsible for approximately 2.5–3.5% of global greenhouse gas emissions, faces increasing pressure to adopt sustainable energy solutions. Hydrogen, with its high gravimetric energy density and zero carbon emissions during use, has emerged as a promising alternative fuel to support aviation decarbonization. However, its large-scale implementation remains hindered by cryogenic storage requirements, safety risks, infrastructure adaptation, and economic constraints. This study aims to identify and evaluate the primary technical and operational risks associated with hydrogen utilization in aviation through a comprehensive Monte Carlo Simulation-based risk assessment. The analysis specifically focuses on four key domains—hydrogen leakage, cryogenic storage, explosion hazards, and infrastructure challenges—while excluding economic and lifecycle aspects to maintain a technical scope only. A 10,000-iteration simulation was conducted to quantify the probability and impact of each risk factor. Results indicate that hydrogen leakage and explosion hazards represent the most critical risks, with mean risk scores exceeding 20 on a 25-point scale, whereas investment costs and technical expertise were ranked as comparatively low-level risks. Based on these findings, strategic mitigation measures—including real-time leak detection systems, composite cryotank technologies, and standardized safety protocols—are proposed to enhance system reliability and support the safe integration of hydrogen-powered aviation. This study contributes to a data-driven understanding of hydrogen-related risks and provides a technological roadmap for advancing carbon-neutral air transport. Full article

Glioblastoma (GB) is one of the most aggressive and invasive cancers. Current treatment protocols for GB include surgical resection, radiotherapy, and chemotherapy with temozolomide. However, despite these treatments, physicians still struggle to effectively image, diagnose, and treat GB. As such, patients frequently experience recurrence of GB, demanding innovative strategies for early detection and effective therapy. Bioconjugated quantum dots (QDs) have emerged as powerful nanoplatforms for precision imaging and targeted drug delivery due to their unique optical properties, tunable size, and surface versatility. Due to their extremely small size, QDs can cross the blood–brain barrier and be used for precision imaging of GB. This review explores the integration of QDs with click chemistry for robust bioconjugation, focusing on artificial intelligence (AI) to advance GB therapy, mechanistic insights into cellular uptake and signaling, and strategies for mitigating toxicity. Click chemistry enables site-specific and stable conjugation of targeting ligands, peptides, and therapeutic agents to QDs, enhancing selectivity and functionalization. Algorithms driven by AI may facilitate predictive modeling, image reconstruction, and personalized treatment planning, optimizing QD design and therapeutic outcomes. We discuss molecular mechanisms underlying interactions of QDs with GB, including receptor-mediated endocytosis and intracellular trafficking, which influence biodistribution and therapeutic efficacy. Use of QDs in photodynamic therapy, which uses reactive oxygen species to induce apoptotic cell death in GB cells, is an innovative therapy that is covered in this review. Finally, this review addresses concerns associated with the toxicity of metal-based QDs and highlights how QDs can be coupled with AI to develop new methods for precision imaging for detecting and treating GB for induction of apoptosis. By converging nanotechnology and computational intelligence, bioconjugated QDs represent a transformative platform for paving a safer path to smarter and more effective clinical interventions of GB. Full article

Objective: We analyzed nanoparticle regulation research to examine the evolution of regulatory frameworks, identify major thematic structures, and evaluate current challenges in the governance of rapidly advancing nanotechnologies. By drawing parallels with the historical development of radiation regulation, the study aimed to contextualize emerging regulatory strategies and derive lessons for future governance. Methods: A total of 9095 PubMed-indexed articles published between January 2015 and October 2025 were analyzed using text mining, keyword frequency analysis, and topic modeling. Preprocessed titles and abstracts were transformed into a TF-IDF (Term Frequency–Inverse Document Frequency) document–term matrix, and NMF (Non-negative Matrix Factorization) was applied to extract semantically coherent topics. Candidate topic numbers (K = 1–12) were evaluated using UMass coherence scores and qualitative interpretability criteria to determine the optimal topic structure. Results: Six major research topics were identified, spanning energy and sensor applications, metal oxide toxicity, antibacterial silver nanoparticles, cancer nano-therapy, and nanoparticle-enabled drug and mRNA delivery. Publication output increased markedly after 2019 with interdisciplinary journals driving much of the growth. Regulatory considerations were increasingly embedded within experimental and biomedical research, particularly in safety assessment and environmental impact analyses. Conclusions: Nanoparticle regulation matured into a dynamic multidisciplinary field. Regulatory efforts should prioritize adaptive, data-informed, and internationally harmonized frameworks that support innovation while ensuring human and environmental safety. These findings provide a data-driven overview of how regulatory thinking was evolved alongside scientific development and highlight areas where future governance efforts were most urgently needed. Full article

Treponeme-associated hoof disease (TAHD) is an emerging disease of free-ranging elk (Cervus canadensis) in the northwestern United States. Affected elk develop chronic foot lesions, lameness, debilitation, and an apparent increase in mortality, but the onset of lameness and associated changes in activity are not fully understood. We evaluated the accuracy of a newly developed leg-mounted tri-axial accelerometer monitor (Advanced Telemetry Systems) on captive elk and collected monitor-derived data to assess activity before and during an experimental TAHD challenge. Monitors provided reliable data with 85% overall accuracy of the continuous onboard classification of activity as standing, moving, or bedded against direct visual observation using seven healthy elk. Further, following TAHD challenge, monitor-derived data were able to detect that treatment elk exhibiting abnormal locomotion spent more time bedded and less time moving or standing. During the challenge period, treatment elk spent roughly 10% more of the day bedded than control elk. These findings suggest that leg-mounted activity monitors can detect changes in elk activity and may serve as a useful tool for future wildlife disease monitoring efforts. Full article

Cross-laminated bamboo (CLB) has gained increasing attention as an emerging structural material combining high mechanical performance with remarkable sustainability potential. This comprehensive review summarizes and critically discusses the main advances and trends in CLB research, drawing on experimental, analytical, and numerical approaches reported in the literature. The review highlights that the mechanical performance of CLB depends on panel architecture, bamboo product type, and adhesive systems. Reported experimental results indicate that CLB panels can achieve competitive or higher mechanical performance than selected cross-laminated timber (CLT) configurations made from specific wood species, particularly in bending, compression, tension, and rolling shear. At the same time, the literature reveals variability associated with manufacturing parameters, adhesive types, and lamella orientation, which affects the comparability of results and highlights current challenges for standardization. Structural applications investigated include floor and wall panels, beams, and rocking walls, especially for seismic-resilient building systems. Despite growing experimental evidence, most investigations remain limited to laboratory-scale elements, with modelling simplifications that constrain predictive accuracy. This review identifies the main challenges and research opportunities towards industrial scalability, standardized testing procedures, and design models adapted to the specific behavior of CLB, paving the way for its consolidation as a reliable and sustainable construction material. Full article

Licorice (Glycyrrhiza glabra) is a perennial herb traditionally valued for its aromatic and therapeutic properties. In recent years, however, growing attention has shifted toward the technical and environmental potential of the plant’s industrial by-products, particularly the fibrous material left after extraction. This review integrates botanical knowledge with engineering and industrial perspectives, highlighting the role of licorice fiber in advancing sustainable innovation. The natural fiber obtained from licorice roots exhibits notable physical and mechanical qualities, including lightness, biodegradability, and compatibility with bio-based polymer matrices. These attributes make it a promising candidate for biocomposites used in green building and other sectors of the circular economy. Developing efficient recovery processes requires collaboration across disciplines, combining expertise in plant science, materials engineering, and industrial technology. The article also examines the economic and regulatory context driving the transition toward more circular and traceable production models. Increasing interest from companies, research institutions, and public bodies in valorizing licorice fiber and its derivatives is opening new market opportunities. Potential applications extend to agroindustry, eco-friendly cosmetics, bioeconomy, and sustainable construction. By linking botanical insights with innovative waste management strategies, licorice emerges as a resource capable of supporting integrated, competitive, and environmentally responsible industrial practices. Full article

The “Neuroimaging and Pathology Biomarkers in Parkinson’s Disease” course held on 12–13 September 2025 in Milan, Italy, convened an international faculty to review state-of-the-art biomarkers spanning neurotransmitter dysfunction, protein pathology and clinical translation. Here, we synthesize the four themed sessions and highlights convergent messages for diagnosis, stratification and trial design. The first session focused on neuroimaging markers of neurotransmitter dysfunction, highlighting how positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) provided complementary insights into dopaminergic, noradrenergic, cholinergic and serotonergic dysfunction. The second session addressed in vivo imaging of protein pathology, presenting recent advances in PET ligands targeting α-synuclein, progress in four-repeat tau imaging for progressive supranuclear palsy and corticobasal syndromes, and the prognostic relevance of amyloid imaging in the context of mixed pathologies. Imaging of neuroinflammation captures inflammatory processes in vivo and helps study pathophysiological effects. The third session bridged pathology and disease mechanisms, covering the biology of α-synuclein and emerging therapeutic strategies, the clinical potential of seed amplification assays and skin biopsy, the impact of co-pathologies on disease expression, and the “brain-first” versus “body-first” model of pathological spread. Finally, the fourth session addressed disease progression and clinical translation, focusing on imaging predictors of phenoconversion from prodromal to clinically overt stages of synucleinopathies, concepts of neural reserve and compensation, imaging correlates of cognitive impairment, and MRI approaches for atypical parkinsonism. Biomarker-informed pharmacological, infusion-based, and surgical strategies, including network-guided and adaptive deep brain stimulation, were discussed as examples of how multimodal biomarkers may inform personalized management. Across all sessions, the need for harmonization, longitudinal validation, and pathology-confirmed outcome measures was consistently emphasized as essential for advancing biomarker qualification in multicentre research and clinical practice. Full article

Pipelines, as critical carriers for energy transportation, are prone to defects such as cracks and corrosion during long-term operation. Traditional testing methods exhibit limitations in various aspects, while electromagnetic ultrasonic testing technology, leveraging its advantages of non-contact operation and couplant-free application, has emerged as a significant direction for pipeline integrity assessment. This paper analyzes the advantages of EMAT guided wave testing technology in achieving long-distance and rapid screening of pipelines, as well as the strengths of bulk wave testing technology in high-precision quantitative evaluation. It also examines the unique value of obliquely incident SV waves in the directional identification of weld defects. Furthermore, the paper discusses the potential of integrating EMAT with multiple technologies, demonstrating how multi-physical field synergy enhances detection reliability. Finally, it summarizes the remaining challenges in practical engineering applications, providing references for advancing the field toward intelligent and high-precision development. Full article

Offshore wind energy is a strategic pillar for achieving European climate neutrality targets, yet its deployment faces geographical and technological constraints. Fixed-bottom offshore wind (FBOW) has reached industrial maturity in shallow waters but is limited by depth. Floating offshore wind (FOW) emerges as a solution for deep-water contexts, unlocking vast resources and enabling integration with advanced energy systems such as power-to-X. This analysis conducts a systematic comparative analysis of FBOW and FOW technologies through a techno-economic framework based on six key parameters: installation depth, turbine power, capacity factor (CF), CAPEX, OPEX, and levelized cost of energy (LCOE). A review of 313 sources, reduced to 61 after applying selection criteria, reveals that FOW operates at depths up to 1550 m, with higher average turbine capacities (16 MW vs. 11 MW for FBOW) and superior CF (38% vs. 22%). Economic results show combined averages CAPEX of 2.43 M$/MW, OPEX of 22.7 k$/MW/year, and LCOE around 120 $/MWh, with significant variability. While FOW currently exhibits higher initial costs, its scalability and operational advantages, such as tow-to-shore maintenance, suggest strong potential for cost reduction. These findings highlight FOW as essential for exploiting deep-water wind resources and achieving long-term decarbonization goals in regions like the Mediterranean. Full article