Search Results (131,385)

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense desmoplastic stroma that actively drives malignant progression. However, the specific contributions of E3 ubiquitin ligases within the cancer-associated fibroblast (CAFs) compartment to the PDAC landscape remain largely elusive. Methods: Pancreatic tissue samples were collected from the First Affiliated Hospital of Harbin Medical University. Gene expression was analyzed by RT-PCR, and single-cell RNA sequencing (scRNA-seq) data were integrated for cell subtype identification. Kaplan-Meier survival analysis assessed gene expression and survival. Pseudotime analysis and CellChat evaluated fibroblast transitions and intercellular communication. Cell lines were transfected with RBX1 siRNAs, and protein levels were measured by Western blotting. Proliferation was assessed using colony formation and EdU staining. Statistical analyses were performed using R (v4.4) and GraphPad Prism 8.0. Results: Thirteen E3 ubiquitin ligases were significantly upregulated in PDAC and correlated with unfavorable clinical outcomes. Among these, RBX1 was identified as a candidate preferentially expressed in CAF populations and strongly associated with poor prognosis. Single-cell transcriptomic profiling and pseudotime analysis further revealed that RBX1-positive CAFs were predominantly involved in extracellular matrix remodeling and pro-tumorigenic pathways. Functional assays demonstrated that silencing RBX1 markedly inhibited PAAD cell proliferation and tumor growth both in vitro and in xenograft models. Mechanistically, RBX1 was found to upregulate Tenascin C (TNC) expression, while ectopic overexpression of TNC partially rescued the growth suppression induced by RBX1 knockdown. Conclusions: Our findings suggest that RBX1 facilitates PDAC progression through a CAF-related mechanism and TNC regulation, positioning RBX1 as a potential therapeutic target for PDAC intervention. Full article

This study describes participants’ views and insights into crafting effective communication aimed at smokeless tobacco and nicotine pouch prevention among fire academy trainees and new recruits. Firefighters have elevated rates of smokeless tobacco use compared with the general population. Nicotine pouches have also gained popularity among this occupational group. We launched a pilot project centered in rural Northern California counties to uncover factors that can be used to communicate smokeless tobacco and nicotine pouch prevention messages within the firefighter workplace. As a first step, we conducted semi-structured interviews with firefighter subject matter experts, including fire chiefs, fire academy instructors, wildlands firefighters, and recent fire academy graduates. This purposive sample (n = 13) was obtained through referrals from the project’s Community Advisory Board, composed of fire service professionals. Interviews were audio recorded and transcribed. Next, the qualitative interviews were thematically analyzed. The results focus on two aspects of effective workplace communication in the service to delivery of smokeless tobacco and nicotine pouch prevention messages: content (core information conveyed in a message), and format (how the message is transmitted or displayed). Examples of the former are the importance of keeping oneself healthy so that one can do one’s job; do not risk a future compensation claim due to smokeless tobacco or nicotine pouch use. Examples of the latter are the use of brevity; humor. Because firefighters often initiate use of these products after they join the fire service, communicating prevention messages in the workplace during the firefighter training and recruitment stage may help disrupt the uptake of nicotine products. Full article

Background: Medication use in paediatric populations is inherently complex and carries a heightened risk of prescribing errors, particularly within primary health-care settings. Despite this concern, evidence describing paediatric prescribing errors in Saudi Arabia remains scarce. Hence, the present study aimed to evaluate the prevalence and patterns of prescribing errors in paediatric primary care and to characterize the pharmacist-led interventions undertaken to resolve these errors. Methods: A prospective, mixed-methods cross-sectional study was conducted over three months at a primary health-care centre. Paediatric outpatient prescriptions were systematically reviewed during routine practice by trained clinical pharmacists. All suspected errors were independently validated and classified for severity by a multidisciplinary expert panel. Descriptive statistics were used to summarise prescribing errors, and associations with patient and prescription characteristics were assessed using chi-square tests. Qualitative data were analysed using a descriptive thematic approach to explore mechanisms of error identification and the nature of corrective pharmacist interventions. Results: A total of 545 paediatric outpatient prescriptions were reviewed, of which 142 prescriptions (26.1%) contained at least one prescribing error. Across these prescriptions, a total of 145 individual prescribing errors were identified. Dose-related errors were the most common (68.3%), followed by inaccuracies in dosing frequency (11.0%) and inappropriate drug selection (9.0%). The occurrence of prescribing errors was significantly associated with patient weight (p = 0.016), the number of medications per prescription (p < 0.001), and the recorded diagnosis (p = 0.018). The majority of errors were intercepted prior to medication dispensing (93.0%), and no cases of patient harm were identified. Qualitative analysis revealed that errors were predominantly detected through cross-checking with authoritative drug references, recalculation of weight-based doses, and application of clinical judgement, and were most often resolved through direct communication with the prescribing clinician. Conclusions: Prescribing errors occur frequently in paediatric outpatient settings; however, most are preventable with appropriate safeguards. Pharmacists play a critical role in identifying and resolving these errors before they result in patient harm. Enhancing paediatric prescribing support systems and strengthening interprofessional collaboration may further advance medication safety within primary health-care services. Full article

Background: Diabetes mellitus is a global health challenge, especially among homeless people. Early prediction of diabetes can reduce treatment costs and improve interventions. This study aimed to identify predictors of diabetes among homeless adults by utilizing artificial intelligence and providing recommendations for diabetes prevention. Methods: A case-control study of 150 homeless adults in Giza, Egypt (99 diabetes cases and 51 controls), analyzed 43 variables collected through interviews and physiological measures, with missing data imputed. Feature selection using recursive feature elimination and univariate and correlation analyses reduced the predictors to 13 variables. The class imbalance was addressed using synthetic minority over-sampling on the training set. Six models and a stacking ensemble with XGBoost as a meta-learner were evaluated using 5-fold cross-validation and performance metrics, including the accuracy, precision, recall, F1-score, and AUC-ROC. Results: The key predictors included BMI, systolic blood pressure, triceps skinfold thickness, waist circumference, lifestyle factors, comorbidities, diastolic blood pressure, age, medication adherence, educational level, marital status, duration of residence, and diabetes knowledge. Individual classifiers achieved a moderate performance (accuracy: 56.7–70.0%, F1-score: 0.686–0.781). The stacking ensemble substantially outperformed individual models, achieving a 95.45% accuracy, a 100% precision, a 93.75% recall, a 0.968 F1-score, and a 0.979 AUC-ROC on the test set. Conclusions: Machine learning models can reliably predict diabetes. The proposed hybrid stacking model outperformed conventional classifiers in terms of the prediction performance, highlighting the benefits of ensemble learning and sophisticated resampling strategies in dealing with imbalanced medical data. It is recommended that healthcare institutions integrate AI-powered diagnostic assistance technology into clinical processes to aid in the early detection and treatment of diabetes. Full article

Recent breakthroughs in large language models have made it feasible to effectively summarize cross-lingual dialogue information, proving essential for the global communication context. However, existing methodologies encounter difficulties in maintaining factual consistency across multiple dialogue exchanges and lack clear explanations of the summarization process. This paper presents a novel factually consistent prompting technology with large language models to address these challenges in cross-lingual dialogue summarization. First, we propose a factual replacement mechanism to enhance information analysis by incorporating noise information into summarization candidates. We adopt a self-guidance framework to enforce factual consistency, enhancing information flow tracking in cross-lingual hybrid dialogue scenarios with the assistance of GPT-based models. Furthermore, we introduce a view-aware chain-of-thought-driven architecture to improve the interpretability and transparency of the cross-lingual dialogue summarization process. Comprehensive experimental evaluations on cross-lingual summarization tasks, spanning English, French, Spanish, Russian, Chinese, and Arabic, and hybrid cross-lingual tasks substantiate that the proposed model achieves superior performance relative to state-of-the-art baselines. Full article

The rapid evolution of artificial intelligence technologies toward the agentic AI paradigm enables the emergence of the Agentic Web in the future Internet. Agent communication plays a critical role in constructing the Agentic Web but faces unique challenges posed by the edge–network–cloud continuum in the future Internet. This paper provides a comprehensive overview of state-of-the-art agent communication protocols and technologies, evaluating their readiness to support the construction of the Agentic Web. We first survey representative communication protocols and analyze the key technologies they employ, assessing their effectiveness in addressing the challenges for agent communications in the future Internet. We then identify critical gaps between existing approaches and the requirements of the Agentic Web, and propose a unified architectural framework grounded in virtualization and service-oriented principles to address these gaps. Such a framework may greatly facilitate the development of a pluralistic ecosystem in which various agent communication technologies and protocols can be freely developed and fully utilized. We also discuss open topics and possible directions for future research toward a fully realized Agentic Web. Full article

Gallbladder diseases spanning cholelithiasis, cholecystitis, and gallbladder cancer represent a clinically heterogeneous continuum in which type 2 diabetes mellitus (T2DM) acts as a key metabolic modifier. Conventional models centered on bile supersaturation alone do not sufficiently account for the persistent inflammation and inter-individual variability frequently observed in practice. Here, we synthesize emerging evidence implicating the gut microbiota–bile acid (BA) axis as an integrative mechanism linking metabolic dysregulation, barrier dysfunction, and biliary pathobiology in the diabetic host. Hyperglycemia and insulin resistance, together with impaired mucosal resilience, are associated with shifts in microbial community structure and BA-transforming functions (e.g., bile salt hydrolase and 7α-dehydroxylation), favoring a more hydrophobic BA pool. These changes may disrupt BA receptor signaling, including FXR–FGF15/19 and TGR5-related pathways, thereby amplifying metabolic inflammation, promoting lithogenic bile formation, and impairing gallbladder motility. In parallel, barrier vulnerability may facilitate microbial translocation and LPS-driven immune activation, reinforcing a feed-forward loop that supports the gallstone–inflammation–carcinogenesis trajectory. Translationally, microbiome- and BA-oriented strategies (dietary patterns, bile acid therapeutics, and targeted microbiome modulation) are promising adjuncts, yet precision management should explicitly consider medication- and weight loss–related confounding—particularly with incretin-based therapies—to optimize biliary outcomes across disease stages. Full article

Mobile Edge Computing (MEC) is a key enabler of 5G/6G services, but multi-base-station deployment enlarges the attack surface and motivates edge-native intrusion detection systems (IDSs). Existing MEC-based IDSs are mainly single-node or centralized, which struggle with heterogeneous traffic across next-generation Node Bs (gNBs) and incur latency and network load due to data aggregation. To address these limitations, this paper proposes a Column-Wise Autoencoder Ensemble (CW-AE) distributed learning framework for multi-MEC environments. Each MEC node trains column-wise autoencoder encoders locally to extract compact latent features, and a master MEC trains a stacking-based meta-classifier using concatenated latent features, avoiding raw traffic transfer and parameter averaging. By preserving node-specific behavior while integrating heterogeneous features, CW-AE improves detection performance and reduces communication overhead. Using the real-world 5G-NIDD dataset collected from two physical 5G base stations, we compare local single-node, centralized, and CW-AE-based distributed learning. The results show that CW-AE achieves superior detection capability and network efficiency, making it suitable for scalable edge IDS deployments. Full article

The intestinal microbiome plays a fundamental role in canine health and well-being, regulating functions, including digestion, immunity, metabolism, and behavior. Dysbiosis refers to the disruption of the balanced composition of resident commensal communities, and gut bacteria can influence behavior via neurological, metabolic, endocrine, and immune-mediated pathways. Growing evidence supports the existence of a bidirectional communication between the gut and the central nervous system, known as the gut–brain axis, through which intestinal microorganisms may influence behavior via neurological, metabolic, endocrine, and immune-mediated pathways. Despite the expanding interest in this field, the contribution of intestinal dysbiosis to the development and severity of behavioral and neurological disorders in companion dogs remains poorly understood. This review aims to critically analyze the literature from 2011 to 18 September 2025 concerning the association between dysbiosis, the gut–brain axis, and both gastrointestinal and non-gastrointestinal illnesses in dogs. To our knowledge, this review represents the first application of Text Mining (TM) in this domain: TM facilitates the identification and analysis of valuable information from extensive datasets, converting unstructured content into structured data, thereby enabling quantitative analysis. We used the following search terms on three bibliographic databases (PubMed, Scopus, and Web of Science): “dysbiosis” AND “canine” OR “dog” AND “gut–brain axis” AND “behavior”. Of the 1176 records retrieved, 35 studies were checked following the PRISMA guidelines, and they met the predefined inclusion criteria in the final analysis. Full article

The introduction of significantly shorter, all-oral regimens has significantly shifted the management of drug-resistant tuberculosis (DR-TB) towards a more tolerable and patient-centred therapeutic approach that aims to enhance treatment adherence, clinical outcomes, and quality of life among patients. Nigeria has gradually adopted this all-oral, shorter regimen, but the impact of this regimen in programmatic settings has not yet been studied. In 2022, a longitudinal, two-armed cohort study was conducted to explore the effectiveness, safety, and feasibility of the all-oral shorter regimen in the programmatic management of RR/MDR-TB in Nigeria. Consenting and eligible RR/MDR-TB patients receiving the all-oral regimen (intervention group) in four states were consecutively enrolled and compared to those receiving the standard of care (SOC). Treatment effectiveness, proportion, and 95% confidence intervals of favourable and unfavourable outcomes were measured at the end of treatment and during follow-up (six and 12 months post-treatment). In total 383 Participants were followed monthly throughout the 9–12-month treatment phase and then reassessed at 6 and 12 months after treatment completion, giving a total possible observation period of up to 24 months (185 received the intervention and 198 the standard of care). At the end of follow-up, there was a higher but non-significant proportion of favourable outcomes among the intervention vs. SOC group (80% vs. 69.7%); a higher proportion of favourable outcomes was also noted at the end of treatment among intervention participants (81.1 vs. 76.8%). Around one third of patients reported at least one serious adverse event (SAE), with no significant differences between arms, and none were deemed related to the use of medication. Intervention participants reported greater improvements in health-related quality of life between baseline and four months compared to those receiving the SOC. These findings support the programmatic use of all-oral shorter treatment for RR/MDR-TB as a regimen that is effective, tolerable, safe, and associated with enhanced health-related quality of life for patients in Nigeria. Full article

Background: Responders to the September 11, 2001, WTC attacks experience high rates of PTSD, and existing treatments often lead to high dropout and low care use. Objectives: This randomized, double-blind, sham-controlled trial assesses the feasibility and acceptability of transcutaneous auricular vagus nerve stimulation (taVNS) as a potential PTSD treatment for 9/11 responders. Methods: A total of 32 WTC responders aged 18+ with PTSD, recruited via the World Trade Center Health Program, participated; those with current psychosis, unstable medical conditions, or recent trial involvement were excluded. Participants were randomly assigned to taVNS or sham groups and asked to use the device for 15 min daily for 8 weeks, with staff and participants blinded. Primary outcomes included recruitment, adherence, retention, and feedback. Secondary outcomes examined changes in depression (PHQ-9), anxiety (GAD-7), and sleep (PSQI). Data were analyzed with mixed-effects models focusing on PTSD and mental health symptoms. Results: The taVNS group showed modest PTSD improvement, with a 10-point CAPS-5 reduction in 40% of stimulation participants versus 28.5% sham; no significant differences in self-reported symptoms were found. Discussion: Daily taVNS over eight weeks is feasible and acceptable, warranting larger studies to detect differences and identify subgroups with greater benefit. Trial registration: “taVNS to Reduce PTSD Symptoms in WTC Responders” (NCT05212714); registered 9 September 2021. Full article

Osteoarthritis (OA) represents a degenerative joint disease which advances through cartilage breakdown, synovial inflammation, and subchondral bone transformation until it causes persistent pain and mobility loss. The scientific community lacks complete knowledge about OA disease mechanisms and post-operative healing processes despite arthroplasty surgery providing effective symptom relief. This study investigated plasma proteomic changes in OA patients before and after arthroplasty. The cohort included eight OA patients undergoing knee or hip arthroplasty and ten age-, sex-, and body mass index-matched healthy controls. Plasma proteins were analyzed using liquid chromatography–tandem mass spectrometry following enzymatic digestion and depletion of high-abundance components. The bioinformatic analysis together with quantitative methods showed that OA patients experienced changes in inflammatory pathways, extracellular matrix remodeling, immune system regulation and coagulation processes. A total of 93 proteins were differentially abundant in the pre-operative comparison. Among these, 63 proteins were consistently up-regulated and 23 were consistently down-regulated across both pre- and post-operative time points. In addition, 20 proteins exhibited post-operative-specific changes. These findings highlight both persistent disease-associated alterations and transient proteomic shifts linked to post-operative recovery. Overall, this study identifies candidate plasma proteomic signatures associated with OA and surgical intervention, providing exploratory insights into disease monitoring and potential personalized therapeutic strategies. Full article

Respiratory syncytial virus (RSV), a member of the genus Orthopneumovirus, is an etiological agent in infant lower respiratory tract infections (LRTIs) producing substantial global morbidity. Here, secretoglobin (Scgb1a1)-derived progenitors play a primary role in triggering innate, inflammatory, and cell state transitions in response to RSV LRTIs. Whether RSV activation of innate signaling in this epithelial sentinel population leads to chronic airway disease is unknown. To understand the role of innate signaling in Scgb1a1-derived progenitors, a model of RSV post-viral disease (PVLD) was developed and studied in the presence or absence of RelA conditional knockout (CKO). Single-cell RNA sequencing (scRNA-seq) studies showed that RSV-PVLD induced a transition of atypical, differentiation-intermediate, alveolar type 2 (aAT2) cells characterized by tumor protein 63 (TRP63), aquaporin 3 (AQP3), and Itgβ4 expression, as well as changes in PDGFRβ mesenchyme. A single-cell trajectory analysis and lineage-tracing experiments using Scgb1a1 CreER^TM X mTmG mice demonstrated that the Scgb1a1+ populations were precursors to the aAT2 population. Mechanistically, we found that the formation of the aAT2 population was prevented by RelA CKO. A differential gene expression analysis revealed that RSV-PVLD coordinately upregulates nuclear receptor subfamily 1 group D (Nr1d1/2), clock and basic helix-loop-helix ARNT-like 1 (Bmal) genes both in the aAT2 cell and in its Pdgfrα+ mesenchymal niche in a RelA-dependent manner. A systematic analysis of intercellular epithelial–mesenchymal communication in the scRNA-seq data showed that the clock-dysregulated epithelial–mesenchymal niche produces aberrant ANGPTL4 expression. ANGPTL4 upregulation was confirmed by the measurement of both its mRNA and protein. Moreover, ANGPTL4 is biologically active in the BALF of RSV-PVLD mice, inhibiting lipoprotein lipase activity. We conclude that RSV-PVLD is mediated, at least in part, by RelA signaling in Scgb1a1-derived epithelial progenitors, dysregulating ANGPTL4 signaling in an epithelial–mesenchymal niche, resulting in persistence of atypical alveolar epithelial cells with dysregulated of clock gene expression. Full article

Digital platforms became central to institutional participation during the COVID-19 pandemic, yet little is known about how participants experience digitally mediated decision-making processes and which conditions foster high-quality deliberation. Guided by an ecological perspective from community psychology, this study examined university staff’s experiences with platform-based participation, focusing on the relationship between online participation practices, digital empowerment, and perceived deliberative quality. In November 2021, faculty and technical/administrative staff at an Italian university (N = 673) completed an online questionnaire assessing platform use (Microsoft Teams), participation practices, perceived benefits and limitations of digital platforms, digital empowerment, and deliberative quality (critical awareness and engagement). Exploratory factor analyses supported multidimensional measures of platform perceptions and deliberative quality. Hierarchical regression analyses showed that interaction rules and perceived improvements in participation processes were the strongest predictors of deliberative quality. Platform benefits related to participatory quality were positively associated with both outcomes, while efficiency-related benefits showed a small negative association with critical awareness. Digital empowerment uniquely predicted deliberative engagement above and beyond participation practices. Overall, results suggest that deliberative quality in digital institutional settings depends more on structured interaction and empowerment-supportive conditions than on platform use frequency, with implications for designing sustainable online and hybrid participatory processes. Full article

Rapid, state-led urbanization in China often generates socio-spatial vulnerabilities, leaving interstitial “waiting lands” in a state of regulatory and ecological limbo. This paper investigates “nomadic gardens”—spontaneous, resident-led cultivation in Jinan—as a bottom-up strategy for adaptive capacity. Using a mixed-methods approach involving site typologies and community surveys (n = 100), we identify eight distinct garden forms that function as socio-ecological buffers, mitigating the risks of social isolation and psychological distress among elderly residents. Findings reveal a significant resilience gap caused by rigid land-use policies that prioritize ornamental aesthetics over functional productivity. We propose an Adaptive Urbanism framework that utilizes modular design and transitional governance to transform these precarious spaces into managed resilience assets. By shifting the planning focus from enforcement to risk-responsive design, this research provides a scalable model for sustainable urban risk management in rapidly transforming global cities. Full article