Search Results (96,850)

Background: Population aging has increased the prevalence of cognitive impairment and dementia, highlighting the need for personalized non-pharmacological interventions. Although socially assistive robots have shown therapeutic benefits, most rely on predefined interactions with limited adaptability. This study proposes an AI-enabled framework integrating continuous self-monitoring and explainable multicriteria decision-making to personalize robot-assisted interventions. Methods: A 12-week longitudinal quasi-experimental study was conducted involving 78 older adults with mild-to-moderate cognitive impairment allocated to three groups: an adaptive AI-based robot (n = 26), a sensor-based robot (n = 26), and a control group receiving conventional care (n = 26). The proposed framework combined continous self-monitoring, AI-based emotional-state estimation, and an Analytic Hierarchy Process (AHP) model to adapt robot behaviour according to participants’ clinical and behavioural profiles. Results: The AI-based robot achieved the greatest improvements in emotional status, social interaction, and functional performance. Depressive symptoms decreased by 42.9%, anxiety decreased by 39.1%, social interaction increased by 60.7%, and functional independence improved by 20.1%. Although the sensor-based robot showed slightly higher adherence (97.2% vs. 95.6%), the AI-based intervention achieved the highest overall effectiveness (AHP global score = 0.90). Conclusions: Integrating continuous self-monitoring, AI-based emotional-state estimation, and explainable multicriteria decision-making enables personalized robot-assisted interventions that improve emotional well-being, social engagement, and functional independence. These findings support the potential of adaptive socially assistive robots as AI-driven clinical decision-support systems for dementia care. Full article

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a progressive condition predisposing to cirrhosis and hepatocellular carcinoma, with prevalence rising globally. Yet effective therapies remain limited. Wuzhi Dripping Pills (WZDP), derived from Schisandra sphenanthera, possess hepatoprotective and anti-inflammatory properties, though their efficacy against MASLD remains unexplored. Methods: Network pharmacology predicted active ingredients and targets, followed by KEGG enrichment analysis. A high-fat diet MASLD rat model was established to evaluate WZDP effects on weight, liver index, and serum markers. Serum metabolomic profiling via UPLC-MS/MS, combined with multivariate statistics and KEGG annotation, identified perturbed pathways. Results: Twelve bioactive compounds and 434 WZDP targets were retrieved, of which 74 intersected with 838 MASLD-associated genes. Enrichment implicated AGE-RAGE, insulin resistance, and HIF-1 signaling. In vivo, WZDP significantly improved anthropometric and biochemical parameters. Metabolomic analysis distinctly separated WZDP-treated from model groups, highlighting phospholipase D signaling as a key differential pathway. Conclusions: This integrative approach confirms that WZDP confers therapeutic benefits in MASLD through coordinated regulation of neuroactive ligand–receptor interaction, bile acid biosynthesis, phospholipase D signaling, and arginine–proline metabolism. Our findings furnish a molecular and metabolic rationale for further mechanistic studies and drug discovery efforts. Full article

Background/Objectives: Chimeric antigen receptor (CAR)-T cell therapy has achieved substantial clinical success in haematological malignancies but has shown limited efficacy against solid tumours. Key barriers include inadequate tumour trafficking, immunosuppressive tumour microenvironments, poor selectivity and heterogeneity of antigen expression, and challenges related to safety and manufacturing. Biomaterial-based technologies have emerged as a potential strategy to address many of these limitations. This review aims to critically evaluate biomaterial approaches designed to enhance CAR-T cell therapy of solid tumours and assess their translational potential. Methods: A narrative review of recent pre-clinical translational studies was conducted, focussing on biomaterial platforms developed to improve CAR-T cell delivery, persistence, functionality, safety control, and manufacturing efficiency in solid-tumour settings. Approaches were analysed according to their mechanisms of action, therapeutic benefits, and stage of translational readiness. Results: Biomaterial strategies, including nanoparticles, injectable and implantable hydrogels, scaffolds, and hybrid delivery systems, have improved CAR-T infiltration, survival, and therapeutic efficacy in several solid-tumour models. Localised delivery of cytokines and other immunomodulatory cues enabled improved spatio-temporal control of CAR-T activation, reducing systemic toxicity, and increasing persistence. Additional applications include amplified ex vivo CAR-T expansion and support for non-viral or in vivo CAR-T generation. However, increased material complexity was frequently associated with challenges in scalability, regulatory approval, and long-term safety. Conclusions: Biomaterial-enabled approaches offer a versatile toolkit to address key biological and translational barriers limiting CAR-T cell therapy of solid tumours. Strategies based on clinically familiar materials and simplified designs appear most suitable for near-term clinical translation, emphasising the need to balance engineering innovation with safety, scalability, and integration into existing clinical workflows. Full article

Polygonatum cyrtonema Hua polysaccharides (PCPs) are bioactive components with antioxidant and immunomodulatory properties. However, whether the polysaccharides derived from elder Polygonatum cyrtonema exhibit superior health benefits remains unclear. This study systematically compared the in vitro fermentation characteristics, gut microbiota-modulating effects, and short-chain fatty acid (SCFA) production of PCPs extracted from three-year-old (TPP), five-year-old (FPP), and eight-year-old (EPP) plants using a human fecal fermentation model. The fermentation dynamics were evaluated by monitoring pH, OD₆₀₀, and the consumption of total and reducing sugars, while the structural degradation and compositional differences in PCPs were tracked via molecular weight distribution and monosaccharide composition analysis. The results showed that all three PCPs were degraded and utilized by gut microbiota, accompanied by decreased pH, increased OD₆₀₀, and enhanced antioxidant activities. High-throughput 16S rDNA sequencing revealed that, at the phylum level, all PCPs increased the Firmicutes/Bacteroidetes ratio. At the genus level, they reduced the abundance of harmful bacteria such as Sutterella and increased beneficial bacteria including Bifidobacterium and Megasphaera. Furthermore, gas chromatography (GC) analysis demonstrated that, compared with FPP, TPP and EPP significantly promoted the production of SCFAs. In summary, this study indicates that the in vitro fermentation characteristics and prebiotic properties of PCPs vary with growth years, and a comprehensive evaluation suggests that three-year-old Polygonatum cyrtonema Hua represents a promising raw material for the development of functional foods. Full article

This single-institution case study examined faculty acceptance and instructional use of social media at the United Arab Emirates University (UAEU), with emphasis on individual-level demographic associations and faculty perceptions of technology-enhanced learning. A cross-sectional survey of 246 faculty members was analyzed using descriptive statistics and contingency-table methods. Female faculty reported higher instructional use than male faculty (88.0% vs. 75.3%; χ²(1, N = 246) = 5.07, p = 0.024; Φ = 0.144; OR = 2.41, 95% CI [1.16, 5.00]), indicating a small association. For age, the omnibus 5 × 2 chi-square test was not statistically significant (χ²(4, N = 246) = 8.17, p = 0.085), although an ordered trend test suggested increasing non-use with age (z = 2.34, p = 0.019); descriptively, this pattern was driven mainly by the 61–70 group rather than a steady increase across all age categories. Academic rank differed overall (χ²(3, N = 246) = 8.70, p = 0.034), but the pattern was non-monotonic, and the prespecified junior-versus-senior comparison was not significant (χ²(1, N = 246) = 2.00, p = 0.157). Faculty reported benefits related to communication, collaboration, audiovisual learning, mobile access, and academic networking, alongside concerns about distraction and reduced interpersonal interaction. Because the study was conducted at one university with a 26.25% response rate, the findings are context-specific and should not be generalized to all UAE or Gulf higher-education institutions. Full article

Protease-activated receptor-2 (PAR-2; encoded by F2RL1) is emerging as a context-dependent driver of gastrointestinal cancer. Activated by irreversible N-terminal cleavage, its signalling output is not fixed but is calibrated by the identity and source of the activating protease, the receptor cleavage state, cellular context and biased coupling to G-protein αq (Gαq), G-protein α12/13 (Gα12/13) and β-arrestin. PAR-2 is best understood not as a simple inflammatory receptor but as a proteolytic rheostat that converts diverse coagulation, inflammatory, microbial and stromal protease inputs into distinct oncogenic programmes. Colorectal cancer and pancreatic ductal adenocarcinoma provide complementary models: in colorectal cancer, PAR-2 links mucosal inflammation and coagulation to proliferation, metastatic competence and resistance to epidermal growth factor receptor (EGFR)-targeted therapy, whereas in pancreatic cancer, it is embedded in a tissue-factor-rich desmoplastic microenvironment that promotes invasion, immune exclusion and chemoresistance. Therapeutic strategies suggested by this framework include direct and biased PAR-2 modulators, upstream protease and factor Xa (FXa) inhibition, statin repurposing and activated-fragment biomarkers such as the PAR-2 activation neoepitope (PRO-PAR2). These strategies must be applied under biomarker guidance, since PAR-2 blockade may benefit inflammation-dominant tumours yet prove counterproductive where PAR-2 sustains antitumour immunity. Full article

Wearable assistive exoskeletons require lightweight, compact, and backdrivable transmission systems with low output impedance to ensure safe and comfortable human–robot interaction. These efficient, modular actuators benefit from reduction mechanisms that minimize axial bulk while providing high motion regularity. While existing transmissions perform well on some of these metrics, their practical implementation is often constrained by geometric complexity, low backdrivability, limited reduction ratios, or standard component sizes. This paper presents a novel combination of a Rolling Element Eccentric (REE) stage and a planetary gearbox, specifically designed for wearable exoskeleton actuation. The proposed architecture integrates a bearing-based REE drive concentrically within the sun gear of a planetary transmission, reducing mechanical complexity and friction and improving regularity. Moreover, the design exploits additively manufactured bearings, enabling substantial weight reduction, reduced encumbrance, and increased design freedom without reliance on standard bearing dimensions. A prototype reducer has been designed and fabricated using additive manufacturing techniques. It was experimentally evaluated and compared with state-of-the-art transmission designs. These investigations demonstrated low friction, minimal backlash, good torsional stiffness, and sufficient backdrivability, despite the high reduction ratio, while maintaining a compact, flat form factor. The experimental results indicate that the proposed rolling element eccentric planetary transmission is a viable and effective solution for lightweight, efficient, axially compact (independently of the implemented reduction ratio), and backdrivable actuators in assistive wearable robotics. Full article

The addition of hydrogen to diesel engines is increasingly being seen as a promising interim solution to reduce fossil fuel consumption and carbon emissions without changing the basic architecture of the compression-ignition engine. This study experimentally evaluated the effect of hydrogen addition on the combustion, performance and emissions characteristics of a single-cylinder AVL 5402 Common Rail diesel engine when hydrogen was supplied via the intake manifold and diesel injection parameters were kept constant. The tests were performed at engine speeds of 1200, 1500, 2000 and 2500 min⁻¹ and loads of 5, 10, 15, 20 and 25 Nm, using a hydrogen mass replacement level of up to 10%. It was found that the addition of hydrogen in many modes increased the maximum cylinder pressure, accelerated the pressure rise, brought the pressure peak earlier and increased engine power, especially at higher loads and speeds. At the same time, fuel consumption decreased in all modes, and CO₂ emissions decreased by 3–22.7%. However, it was found that the addition of hydrogen usually increased NOx emissions; in some modes, it increased particulate and hydrocarbon emissions and extended the total combustion duration due to the reduced oxygen concentration and the formation of a richer mixture. The results showed that the effect of hydrogen on the operation of a diesel engine is strongly dependent on the load and speed; therefore, the benefits of its application can be achieved only under carefully coordinated operating conditions that ensure a favorable compromise between combustion intensification, fuel economy and emission control. Full article

Moderate wine consumption has historically been associated with a J-shaped relationship between dose and total mortality, driven primarily by cardiovascular protection, enhanced endothelial function, improved glucose metabolism, and anti-inflammatory and antioxidant effects attributable to both ethanol and grape-derived phenolic constituents. Yet in recent years, international alcohol guidelines have shifted markedly towards the assertion that ‘no safe level’ of alcohol exists. This transition has occurred despite the continued consistency of mechanistic, clinical, and epidemiological evidence demonstrating hormetic (biphasic) responses to wine and its constituents and despite methodological controversies over the mathematical models used in several recent national guideline revisions. This narrative review synthesises mechanistic evidence on hormesis and wine-specific biological effects—including polyphenols, resveratrol, nitric oxide signalling, platelet modulation, and endothelial benefits—with epidemiological data on J-shaped associations with cardiovascular disease, diabetes, and total mortality. It further examines key methodological changes in recent guidelines, particularly the adoption of the ‘Sheffield model’ and the exclusion of or reduced emphasis on cardioprotective outcomes. The review argues that these methodological decisions, rather than new scientific evidence, largely explain the departure from earlier guideline thresholds that allowed moderate wine consumption. Understanding wine’s biological specificity, the differential health implications of drinking patterns and contexts, and the limitations of model-driven policy changes is essential to develop coherent, evidence-informed public health recommendations. Full article

Carboplatin/paclitaxel (CP) chemotherapy is the cornerstone of therapy for advanced stage ovarian cancer (OC). However, despite initial sensitivity, this regimen cannot avoid the emergence of resistance. Ixabepilone ± bevacizumab (IB) is a combination recently added to NCCN guidelines for the treatment of platinum-resistant OC. It would be desirable to identify biomarkers able to differentiate patients who are resistant to CP and IB, and biomarkers that identify which patients may benefit from IB treatment. We analyzed whole-exome-sequencing (WES) data from 49 OC patients exposed to CP, including 28 platinum-sensitive vs. 21 platinum-resistant, and 31 additional platinum-resistant patients, including 16 responders (i.e., CR/PR) vs. 15 non-responders (SD/PD) to ixabepilone ± bevacizumab. Comprehensive genetic analyses were performed to identify alterations correlated with resistance to CP and IB. WES analysis of CP responders vs. non-responders revealed differences in HRD-signatures (p < 0.05), OS (p < 0.005) and gain/loss-of-function in multiple genes associated with tumor growth/progression including but not limited to ACVR2A, INHBA, MAP3K7, ATG5, SGK1, FYN, RSPO3, NOD1 and LRRK2. WES analysis of platinum-resistant IB-treated patients revealed additional nominally significant genes and deranged pathways including gains in the DROSHA and SDHA genes in responders vs. non-responders (p < 0.05). Patients harboring HRD-signatures showed significantly higher sensitivity to CP and prolonged survival compared to HRD-negative patients. Alterations in genes associated with tumor growth/progression correlated with resistance to CP regimen and may represent novel “druggable” candidate biomarkers for the targeted treatment of CP/IB-resistant patients. Further validation in independent cohorts and preclinical experiments in CP/IB-resistant models are warranted to establish the clinical utility of these findings. Full article

Quantitative EEG features such as frontal alpha asymmetry, spectral ratios and signal-complexity measures are often presented as interpretable biomarkers of emotion. Such claims require the markers to generalize across individuals, yet common evaluation protocols allow overlapping epochs and recordings from the same participants to appear in both training and test sets. We re-evaluated qEEG-based valence and arousal recognition on DEAP and DREAMER under trial-grouped, participant-independent, within-participant and cross-dataset protocols. Epoch-pooled evaluation on DEAP gave ROC-AUC values of 0.689 for valence and 0.711 for arousal, whereas participant-independent evaluation of the same features and model returned 0.493 and 0.447. Grouping epochs by trial accounted for about 0.06 of that difference and separating participants for a further 0.13 to 0.17. The same features identified participants with accuracy of 0.998 on DEAP and 0.891 on DREAMER, and a predictor that used no EEG, assigning each trial its participant’s training-set positive rate, accounted for 42 to 84 percent of the above-chance discrimination of the epoch-pooled model. Emotion-related effects were reproducible within participants on DEAP but close to zero on DREAMER, and their direction reversed for about 40 percent of features across participants. In a matched participant-level comparison using a single fixed estimator in both arms, training on a participant’s own data improved DEAP valence by 0.092 AUC (95% CI 0.029 to 0.157, Holm-adjusted $p=0.042$) and gave no reliable benefit for DEAP arousal or for either DREAMER target. Across the channels shared by the two datasets, per-feature arousal effect sizes correlated moderately, although no individual feature reached false-discovery-rate significance in both datasets. Pooled qEEG emotion-recognition scores can therefore reflect participant-specific recording structure rather than transferable affective information. Population-level claims require participant-independent evaluation, while personalization should be considered only where stable within-person effects are demonstrated. Full article

Shale gas reservoirs are characterized by low permeability, nanoscale pore structures, and complex fracture networks. Multistage fractured horizontal wells are an important technology for commercial shale gas development. However, many shale gas productivity models primarily emphasize gas transport within the reservoir and fracture system, while pressure variations caused by frictional losses along the horizontal wellbore are often simplified or treated separately. To address this issue, this study develops a fully coupled multiscale dual-porosity numerical model that integrates the shale matrix, hydraulic fractures, and horizontal wellbore within a unified simulation framework. The model incorporates key physical mechanisms governing shale gas transport, including Knudsen diffusion, Langmuir adsorption–desorption, stress sensitivity, and non-Darcy flow in fractures. Meanwhile, the Darcy–Weisbach equation is introduced to describe wellbore frictional pressure losses. The reliability of the proposed model is validated through history matching with field production data from the Changning shale gas reservoir. The results demonstrate that neglecting wellbore friction losses leads to a 30–50% overestimation of horizontal well productivity, indicating that wellbore friction has a significant impact on fracture flow distribution and productivity prediction. Furthermore, an exponent factor r is introduced to characterize and evaluate non-uniform fracture placement patterns. The results show that toe-dense fracture placement can increase cumulative gas production by approximately 37.8% compared with uniform fracture placement when r = 1.10, which yields the highest cumulative gas production among the tested cases. However, the additional production benefit becomes substantially smaller after the initial increase and remains relatively stable as r further increases. This study improves the understanding of friction-induced heel-to-toe effects and provides an effective numerical approach for productivity prediction and fracture placement design in shale gas horizontal wells. Full article

Background: Lung cancer remains the leading cause of cancer-related mortality worldwide, with five-year survival below 5% for metastatic small cell lung cancer (SCLC) and below 10% for metastatic non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors have improved outcomes, but primary and acquired resistance, driven by tumor microenvironment immunosuppression, antigen heterogeneity, and T-cell exhaustion, leaves a substantial unmet need. T-cell engagers (TCEs), bispecific antibodies that redirect cytotoxic T-cells to tumor cells independent of MHC-I-restricted antigen presentation, offer a mechanistically distinct approach. Methods: We conducted a structured narrative review, without formal PRISMA methodology or meta-analytic pooling, of PubMed, Embase, and ClinicalTrials.gov through June 2026, supplemented by conference abstracts from ASCO, ESMO, AACR, and ATS, covering clinical, translational, and preclinical evidence for TCEs across established and emerging targets in thoracic malignancy. Results: Tarlatamab, a DLL3/CD3 bispecific TCE, received full FDA approval in November 2025 based on DeLLphi-304 data showing a median overall survival benefit of 13.6 versus 8.3 months over chemotherapy (HR 0.60; p < 0.001), establishing proof-of-concept for the TCE platform in lung cancer and NCCN Category 1 status in ES-SCLC. Beyond DLL3, an expanding pipeline of targets, including Claudin-18.2, TROP-2, FOLR1, CD70, and HER2, is under active TCE development; several of these antigens have independently validated tumor-selective expression through approved or late-stage antibody-drug conjugates (ADCs), providing target-level clinical de-risking for TCE development, though the two modalities have distinct requirements for antigen density and internalization that must be independently validated. Novel tri-specific constructs incorporating costimulatory domains and combination strategies with checkpoint inhibitors are in early clinical development. Conclusions: Tarlatamab approval validates the TCE platform in lung cancer, but overcoming TME-mediated resistance, antigen heterogeneity, and class-specific toxicities including cytokine release syndrome remains the central challenge. Rational TCE design, incorporating costimulatory signaling, antigen selection informed by parallel ADC validation data, and evidence-based combination strategies, offers the most credible path toward expanding this platform’s impact in metastatic lung cancer. Full article

Earth Observation (EO) analysis increasingly relies on large and heterogeneous satellite datasets, yet developing EO workflows often requires specialized expertise in data selection, geospatial programming, and cloud-based processing. Recent advances in Large Language Models (LLMs) offer new opportunities for natural-language interaction with EO systems, although challenges related to transparency, reproducibility, and domain-specific reasoning remain. This study presents SeaScope, an explainable AI framework that integrates LLMs, Retrieval-Augmented Generation (RAG), scientific knowledge retrieval, and Google Earth Engine (GEE) to transform natural-language requests into transparent and executable EO workflows. The framework combines knowledge retrieval, code generation, cloud execution, provenance tracking, and interactive visualization within a unified environment. A pilot implementation is demonstrated through maritime and coastal monitoring applications, including oil spill detection, vessel monitoring, water quality assessment, floating debris detection, and air quality analysis. Multiple state-of-the-art LLMs are evaluated under both RAG and non-RAG configurations using representative EO case studies. The results indicate substantial differences among model families and show that retrieval augmentation can significantly improve workflow generation quality and reliability for capable models, while providing more limited benefits for smaller models. The proposed framework demonstrates the potential of explainable AI agents to support transparent, reproducible, and scalable EO analysis. Full article

Aging is the strongest risk factor for chronic diseases such as cardiovascular diseases, cancer, diabetes, and neurodegenerative disorders. Advances in geroscience indicate that pharmacological modulation of conserved molecular pathways may extend healthspan and delay multimorbidity. A structured narrative review of the PubMed, Scopus, and Web of Science literature published between January 2010 and May 2026 was conducted, with seminal earlier studies retained where relevant. The review focused on molecular pathways implicated in aging, pharmacological interventions targeting these pathways, and their preclinical and clinical evaluation. Particular emphasis was placed on translational evidence, including human biomarker studies and randomized clinical trials, and on the distinction between biomarker modulation and clinically meaningful outcomes. Repurposed drugs such as metformin and rapamycin have among the most extensive preclinical and translational evidence, although clinical evidence for broadly applicable geroprotection remains limited. Statins, SGLT2 inhibitors, GLP-1 receptor agonists, and menopausal hormone therapy have established disease-specific or cardiometabolic benefits that may have indirect relevance to geroprotection, but direct effects on biological aging and healthspan remain unproven. Other candidates, including senolytics, NAD⁺ precursors, taurine, and epigenetic reprogramming approaches, are at different stages of translational development, with evidence ranging from promising preclinical findings to early human studies. Across interventions, a substantial gap remains between mechanistic plausibility and clinically validated geroprotection. Geroprotective pharmacology represents a promising but incompletely validated approach to extending healthspan. Major uncertainties include the absence of universally accepted biomarkers and clinical endpoints of biological aging, heterogeneity in treatment response, optimal timing and duration of interventions, and long-term safety. Future research should prioritize adequately powered randomized clinical trials integrating standardized measures of biological aging with clinically meaningful outcomes, alongside biomarker-guided patient selection, appropriate treatment timing, and careful assessment of long-term safety. The future of geroprotective medicine will depend not only on identifying additional pharmacological targets, but on demonstrating that their modulation produces durable and clinically meaningful benefits in humans. Full article