Search Results (5,644)

The pharmaceutical industry faces significant challenges when promising drug candidates fail during development due to suboptimal ADME (absorption, distribution, metabolism, excretion) properties or toxicity concerns. Natural compounds are subject to the same pharmacokinetic considerations. In silico approaches offer a compelling advantage—they eliminate the need for physical samples and laboratory facilities, while providing rapid and cost-effective alternatives to expensive and time-consuming experimental testing. Computational methods can often effectively address common challenges associated with natural compounds, such as chemical instability and poor solubility. Through a review of the relevant scientific literature, we present a comprehensive analysis of in silico methods and tools used for ADME prediction, specifically examining their application to natural compounds. Whereas we focus on identifying the predominant computational approaches applicable to natural compounds, these tools were developed for conventional drug discovery and are of general use. We examine an array of computational approaches for evaluating natural compounds, including fundamental methods like quantum mechanics calculations, molecular docking, and pharmacophore modeling, as well as more complex techniques such as QSAR analysis, molecular dynamics simulations, and PBPK modeling. Full article

Accurate estimation of biomass higher heating value (HHV) is crucial for designing efficient bioenergy systems. In this study, we developed a Backpropagation artificial neural network (ANN) that predicts HHV from routine proximate/ultimate composition data. The network (9-6-6-1 architecture, trained for 15,000 epochs with learning rate 0.3 and momentum 0.4) was calibrated on 99 diverse Spanish biomass samples (inputs: moisture, ash, volatile matter, fixed carbon, C, H, O, N, S). The optimized ANN achieved strong predictive accuracy (validation R² ≈ 0.81; mean squared error ≈ 1.33 MJ/kg; MAE ≈ 0.77 MJ/kg), representing a substantial improvement over 54 analytical models despite the known complexity and variability of biomass composition. Importantly, in direct comparisons it significantly outperformed 54 published analytical HHV correlations—the ANN achieved substantially higher R² and lower prediction error than any fixed-form formula in the literature. A sensitivity analysis confirmed chemically intuitive trends (higher C/H/FC increase HHV; higher moisture/ash/O reduce it), indicating the model learned meaningful fuel-property relationships. The ANN thus provided a computationally efficient and robust tool for rapid, accurate HHV estimation from compositional data. Future work will expand the dataset, incorporate thermal pretreatment effects, and integrate the model into a user-friendly decision-support platform for bioenergy applications. Full article

The rapid emergence of generative AI technologies has sparked significant transformation across educational landscapes worldwide. This study presents a comprehensive bibliometric analysis of GAI in education, mapping scholarly trends from 2022 to 2025. Drawing on 3808 peer-reviewed journal articles indexed in Scopus, the analysis reveals exponential growth in publications, with dominant contributions from the United States, China, and Hong Kong. Using VOSviewer, the study identifies six major thematic clusters, including GAI in higher education, ethics, technological foundations, writing support, and assessment. Prominent tools, especially ChatGPT, are shown to influence pedagogical design, academic integrity, and learner engagement. The study highlights interdisciplinary integration, regional research ecosystems, and evolving keyword patterns reflecting the field’s transition from tool-based inquiry to learner-centered concerns. This review offers strategic insights for educators, researchers, and policymakers navigating AI’s transformative role in education. Full article

Background/Objectives: Borderline Personality Disorder (BPD) involves emotional dysregulation, interpersonal instability and impulsivity. Although treatments have advanced, evaluating the latest innovations remains essential. This rapid review aimed to (1) identify and classify recent therapeutic innovations for BPD, (2) assess their effects on clinical and functional outcomes, and (3) highlight research gaps to inform future priorities. Methods: Employing a rapid review design, we searched PubMed/MEDLINE, PsycINFO, and Embase for publications from 1 January 2019 to 28 March 2025. Eligible studies addressed adult or adolescent BPD populations and novel interventions—psychotherapies, pharmacological agents, digital tools, and neuromodulation. Two independent reviewers conducted screening, full-text review, and data extraction using a standardised form. Results: Sixty-nine studies—predominantly from Europe and North America—were included. Psychotherapeutic programmes dominated, ranging from entirely novel models to adaptations of established treatments (for example, extended or modified Dialectical Behavior Therapy). Pharmacological research offered fresh insights, particularly into ketamine, while holistic approaches such as adventure therapy and digital interventions also emerged. Most investigations centred on symptom reduction; far fewer examined psychosocial functioning, mortality, or social inclusion. Conclusions: Recent innovations show promise in BPD treatment but underserve the needs of mortality and societal-level outcomes. Future research should adopt inclusive, equity-focused agendas that align with patient-centred and recovery-oriented goals, supported by a coordinated, integrated research strategy. Full article

One concern in the yearly re-formulation of influenza vaccines is the time-consuming manufacturing of vaccine potency reagents, particularly for emergency responses. The continuous evaluation of modern techniques such as reversed-phase (RP) chromatography is an asset for streamlining this process. One challenge with RP methods, however, is the need to re-optimize methods for antigens that show poor separation, which can be highly dependent on analyst experience and available data. In this study, we leveraged a large RP dataset of influenza antigens to explore machine learning (ML) approaches of classifying challenging separations for computer-assisted method re-optimization across years, products, and analysts. Methods: To address recurring chromatographic issues—such as poor resolution, strain co-elution, and signal absence—we applied data augmentation techniques to correct class imbalance and trained multiple supervised ML classifiers to distinguish between these peak profiles. Results: With data augmentation, several ML models demonstrated promising accuracy in classifying chromatographic profiles according to the provided labels. These models effectively distinguished patterns indicative of separation issues in real-world data. Conclusions Our findings highlight the potential of ML as a computer assisted tool in the evaluation of vaccine quality, offering a scalable and objective approach to chromatogram classification. By reducing reliance on manual interpretation, ML can expedite the optimization of analytical methods, which is particularly needed for rapid responses. Future research involving larger, inter-laboratory datasets will further elucidate the utility of ML in vaccine analysis. Full article

Tocopherols, major lipid-soluble components of vitamin E, are essential natural products with significant nutritional and pharmacological value. Their structural diversity and uneven distribution across vegetable oils require accurate analytical strategies for compositional profiling, quality control, and authenticity verification, amid concerns over food fraud and regulatory demands. Analytical challenges, such as matrix effects in complex oils and the cost trade-offs of green extraction methods, complicate these processes. This review examines recent advances in tocopherol analysis, focusing on extraction and detection techniques. Green methods like supercritical fluid extraction and deep eutectic solvents offer selectivity and sustainability, though they are costlier than traditional approaches. On the analytical side, hyphenated techniques such as supercritical fluid chromatography-mass spectrometry (SFC-MS) achieve detection limits as low as 0.05 ng/mL, improving sensitivity in complex matrices. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) provides robust analysis, while spectroscopic and electrochemical sensors offer rapid, cost-effective alternatives for high-throughput screening. The integration of chemometric tools and miniaturized systems supports scalable workflows. Looking ahead, the incorporation of Artificial Intelligence (AI) in oil authentication has the potential to enhance the accuracy and efficiency of future analyses. These innovations could improve our understanding of tocopherol compositions in vegetable oils, supporting more reliable assessments of nutritional value and product authenticity. Full article

This study evaluated and compared two encapsulation techniques—co-crystallization and ionic gelation—for stabilizing bioactive components derived from lavender distillation residues. Utilizing aqueous ethanol extraction (solid residues) and concentration (liquid residues), phenolic-rich extracts were incorporated into encapsulation matrices and processed under controlled conditions. Comprehensive characterization included encapsulation efficiency (Ef), antioxidant activity (AA), moisture content, hygroscopicity, dissolution time, bulk density, and color parameters (L*, a*, b*). Co-crystallization outperformed ionic gelation across most criteria, achieving significantly higher Ef (>150%) and superior functional properties such as lower moisture content (<0.5%), negative hygroscopicity (−6%), and faster dissolution (<60 s). These features suggested enhanced physicochemical stability and suitability for applications requiring long shelf life and rapid solubility. In contrast, extruded beads exhibited high moisture levels (94.0–95.4%) but allowed better control over morphological features. The work introduced a mild-processing approach applied innovatively to the valorization of lavender distillation waste through structurally stable phenolic delivery systems. By systematically benchmarking two distinct encapsulation strategies under equivalent formulation conditions, this study advanced current understanding in bioactive microencapsulation and offers new tools for developing functional ingredients from aromatic plant by-products. Full article

Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis and is primarily transmitted via contaminated water and food. Groundwater may also serve as a potential vector for HEV transmission. This study aimed to optimize real-time polymerase chain reaction (rtPCR) for the detection of HEV, employing both TaqMan probe- and SYBR Green-based methods. A total of 12 primer sets for the TaqMan probe-based method and 41 primer sets for the SYBR Green-based method were evaluated in order to identify the optimal combinations. Primer sets #4 (TaqMan probe-based) and #21 (SYBR Green-based) demonstrated the highest sensitivity and specificity, successfully detecting HEV in artificially spiked samples at 1 fg/μL. The TaqMan probe-based method facilitated rapid detection with minimized non-specific amplification, whereas the SYBR Green-based method allowed for broader primer exploration by leveraging melting curve analysis. Despite the absence of HEV detection in 123 groundwater samples, this study underscores the value of real-time PCR for environmental monitoring and paves the way for enhanced diagnostic tools for public health applications. Full article

This study addresses the understanding of fungal diversity and their bioremediation roles in an integrated aquaculture wastewater bioremediation system, an area less explored compared to bacteria, viruses, and protozoa. Despite the rapid advancement and affordability of molecular tools, insights into fungal communities remain vague, and interpreting environmental studies in an ecologically meaningful manner continues to pose challenges. To bridge this knowledge gap, we developed an integrated aquaculture wastewater bioremediation system, incorporating photosynthetic bacteria, and utilizing internal transcribed spacer (ITS) sequencing to analyze fungal community composition. Our findings indicate that the fungal community in aquaculture wastewater is predominantly composed of the phyla Ascomycota and Chytridiomycota, with dominant genera including Aspergillus, Hortea, and Ciliphora. FUNGuild, a user-friendly trait and character database operating at the genus level, facilitated the ecological interpretation of fungal functional groups. The analysis revealed significant negative correlations between nutrient levels (COD_mn, NH₄⁺-N, NO₃⁻-N, NO₂⁻-N, and PO₄⁻³-P) and specific fungal functional groups, including epiphytes, animal pathogens, dung saprotrophs, plant pathogens, and ectomycorrhizal fungi. The removal rate for the COD_mn, NH₄⁺-N, NO₃⁻-N, NO₂⁻-N, and PO₄⁻³-P were 71.42, 91.37, 88.80, 87.20, and 91.72% respectively. This study highlights the potential role of fungal communities in bioremediation processes and provides a framework for further ecological interpretation in aquaculture wastewater treatment systems. Full article

The rapid increase in the global population of older adults presents a significant challenge, but also a unique opportunity to leverage technological advancements for promoting independent living and well-being. This study introduces the CIREI framework, which is a comprehensive model designed to enhance the integration of smart home and assistive technologies specifically for pre-frail older adults. Developed through a systematic literature review and innovative and comprehensive co-design activities, the CIREI framework captures the nuanced needs, preferences, and challenges faced by older adults, caregivers, and experts. Key findings from the co-design workshop highlight critical factors such as usability, privacy, and personalised learning preferences, which directly influence technology adoption. These insights informed the creation of an intelligent middleware prototype named WISE-WARE, which seamlessly integrates commercial off-the-shelf (COTS) devices to support health management and improve the quality of life for older adults. The CIREI framework’s adaptability ensures it can be extended and refined to meet the ever-changing needs of the ageing population, providing a robust foundation for future research and development in user-centred technology design. All workshop materials, including tools and methodologies, are made available to encourage the further exploration and adaptation of the CIREI framework, ensuring its relevance and effectiveness in the dynamic landscape of ageing and technology. This research contributes significantly to the discourse on ageing in place, digital inclusion, and the role of technology in empowering older adults to maintain independence. Full article

In recent years, the persistent emergence of novel infectious pathogens (epitomized by the global coronavirus disease-2019 (COVID-2019) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) has propelled nucleic acid testing (NAT) into an unprecedented phase of rapid development. As a key technology in modern molecular diagnostics, NAT achieves precise pathogen identification through specific nucleic acid sequence recognition, establishing itself as an indispensable diagnostic tool across diverse scenarios, including public health surveillance, clinical decision-making, and food safety control. The reliability of NAT systems fundamentally depends on reference materials (RMs) that authentically mimic the biological characteristics of natural viruses. This critical requirement reveals significant limitations of current RMs in the NAT area: naked nucleic acids lack the structural authenticity of viral particles and exhibit restricted applicability due to stability deficiencies, while inactivated viruses have biosafety risks and inter-batch heterogeneity. Notably, pseudovirus has emerged as a novel RM that integrates non-replicative viral vectors with target nucleic acid sequences. Demonstrating superior performance in mimicking authentic viral structure, biosafety, and stability compared to conventional RMs, the pseudovirus has garnered substantial attention. In this comprehensive review, we critically summarize the engineering strategies of pseudovirus platforms and their emerging role in ensuring the reliability of NAT systems. We also discuss future prospects for standardized pseudovirus RMs, addressing key challenges in scalability, stability, and clinical validation, aiming to provide guidance for optimizing pseudovirus design and practical implementation, thereby facilitating the continuous improvement and innovation of NAT technologies. Full article

Conventional methods for generating knock-out or knock-in mammalian cell models using CRISPR-Cas9 genome editing often require tedious single-cell clone selection and expansion. In this study, we develop and optimise rapid and robust strategies to engineer homozygous fluorescent reporter knock-in cell pools with precise genome editing, circumventing clonal variability inherent to traditional approaches. To reduce false-positive cells associated with random integration, we optimise the design of donor DNA by removing the start codon of the fluorescent reporter and incorporating a self-cleaving T2A peptide system. Using fluorescence-assisted cell sorting (FACS), we efficiently identify and isolate the desired homozygous fluorescent knock-in clones, establishing stable cell pools that preserve parental cell line heterogeneity and faithfully reflect endogenous transcriptional regulation of the target gene. We evaluate the knock-in efficiency and rate of undesired random integration in the electroporation method with either a dual-plasmid system (sgRNA and donor DNA in two separate vectors) or a single-plasmid system (sgRNA and donor DNA combined in one vector). We further demonstrate that coupling our single-plasmid construct with an integrase-deficient lentivirus vector (IDLV) packaging system efficiently generates fluorescent knock-in reporter cell pools, offering flexibility between electroporation and lentivirus transduction methods. Notably, compared to the electroporation methods, the IDLV system significantly minimises random integration. Moreover, the resulting reporter cell lines are compatible with most of the available genome-wide sgRNA libraries, enabling unbiased CRISPR screens to identify key transcriptional regulators of a gene of interest. Overall, our methodologies provide a powerful genetic tool for rapid and robust generation of fluorescent reporter knock-in cell pools with precise genome editing by CRISPR-Cas9 for various research purposes. Full article

The rapid proliferation of electronic waste, driven by the short lifecycle of smartphones and planned obsolescence strategies, presents escalating global environmental challenges. To address these issues from a systems perspective, this study develops an agent-based modeling (ABM) framework that simulates consumer decisions and stakeholder interactions within the smartphone reuse and recycling ecosystem. The model incorporates key behavioral drivers—privacy concerns, moral norms, and financial incentives—to examine how social and economic factors shape consumer behavior. Four primary agent types—consumers, manufacturers, recyclers, and second-hand retailers—are modeled to capture complex feedback and market dynamics. Calibrated using empirical data from Jiangsu Province, China, the simulation reveals a dominant consumer tendency to store obsolete smartphones rather than engage in reuse or formal recycling. However, the introduction of government subsidies significantly shifts behavior, doubling participation in second-hand markets and markedly improving recycling rates. These results highlight the value of integrating behavioral insights into environmental modeling to inform circular economy strategies. By offering a flexible and behaviorally grounded simulation tool, this study supports the design of more effective policies for promoting responsible smartphone disposal and lifecycle extension. Full article

Background: Nemaline myopathy is a rare congenital neuromuscular disease associated with progressive weakness and frequent respiratory complications. In emergency situations, families often serve as the first and only responders. The aim of this study is to explore how parents in Spain care for children with nemaline myopathy during emergency situations, focusing on the clinical responses performed at home and the organizational challenges encountered when interacting with healthcare systems. Methods: A qualitative phenomenological study was conducted with 17 parents from 10 families belonging to the Asociación Yo Nemalínica. Semi-structured interviews were performed via video calls, transcribed verbatim, and analyzed using Giorgi’s descriptive method and ATLAS.ti software (version 24). Methodological rigor was ensured through triangulation, reflexivity, and member validation. Results: Four themes were identified. First, families were described as acting under extreme pressure and in isolation during acute home emergencies, often providing cardiopulmonary resuscitation and respiratory support without professional backup. Second, families managed ambiguous signs of deterioration using clinical judgment and home monitoring tools, often preventing fatal outcomes. Third, parents frequently assumed guiding roles in emergency departments due to a lack of clinician familiarity with the disease, leading to delays or errors. Finally, the transition to the Pediatric Intensive Care Unit was marked by emotional distress and rapid decision-making, with families often participating in critical choices about invasive procedures. These findings underscore the complex, multidisciplinary nature of caregiving. Conclusions: Parents play an active clinical role during emergencies and episodes of deterioration. Their lived experience should be formally integrated into emergency protocols and the continuity of care strategies to improve safety and outcomes. Full article

Predicting the blow-off (BO) is critical for characterising the operability limits of gas turbine engines. In this study, the applicability of a low-order extinction prediction modelling, which is based on a stochastic variant of the Imperfectly Stirred Reactor (ISR) approach, to predict the lean blow-off (LBO) curve and the extinction conditions in a hydrogen Rich-Quench-Lean (RQL)-like swirl combustor is investigated. The model predicts the blow-off scalar dissipation rate (SDR), which is then extrapolated using Reynolds-Averaged Navier–Stokes (RANS) cold-flow simulations and simple scaling laws, to determine the critical blow-off conditions. It has been found that the sISR modelling framework can predict the BO flow split ratio at different global equivalence ratios, showing a reasonable agreement with the experimental data. This further validates sISR as an efficient low-order modelling flame extinction tool, which can significantly contribute to the development of robust hydrogen RQL combustors by enabling the rapid exploration of combustor operability during the preliminary design phases. Full article