Search Results (1,704)

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting the central nervous system and is the most common form of dementia in the elderly. Current diagnostic methods are limited in the early and definitive diagnosis of the disease, necessitating the need for new and more reliable biomarkers. Circular RNAs (circRNAs) are non-coding, single-stranded, and highly stable RNA molecules commonly found in the eukaryotic transcriptome. Recent studies have shown that changes in the expression levels of circRNAs may play a role in AD pathogenesis. Furthermore, these molecules are considered as potential non-invasive biomarkers for early diagnosis of AD. In this study, we comprehensively assessed plasma levels of classical neurodegenerative biomarkers [amyloid-β42/amyloid-β40 (Aβ42/Aβ40) ratio, total Tau (tTau), and phosphorylated Tau (pTau)], as well as glial and inflammatory mediators, TAM receptor family members (Tyro3 and AXL), and the newly identified circular RNA molecule hsa_circ_003077. The findings revealed that the expression levels of TAM receptors were significantly increased, the Aβ42/Aβ40 ratio decreased, and both total Tau and phosphorylated Tau levels were significantly increased in AD patients. In the receiver operating characteristic (ROC) curve analysis performed to determine the diagnostic potential of hsa_circ_003077, the area under the curve (AUC) was 0.90 (95% CI: 0.82–0.97). This high AUC value suggests that hsa_circ_003077 may be a strong and novel biomarker candidate for the non-invasive diagnosis of AD. The data obtained confirmed the diagnostic efficacy of classical AD biomarkers and revealed that hsa_circ_003077 is a promising biomarker for early and accurate detection of the disease. However, in order to assess the transferability of these findings to clinical practice, confirmatory studies with larger sample groups are needed to ensure reproducibility of the results. Full article

Tumor-associated macrophages (TAMs) are pivotal in the clear cell renal cell carcinoma (ccRCC) microenvironment. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a central enzyme in one-carbon metabolism, is increasingly recognized for its oncogenic roles in both cancer cells and immune compartments. We integrated bulk and single-cell transcriptomic datasets to interrogate the expression, prognostic impact, and immunomodulatory landscape of MTHFD2 in ccRCC. Robust differential expression, meta-analysis, Cox regression, and cell type deconvolution were performed. MTHFD2 expression and its association with prognosis were validated using tissue microarrays (TMAs), multiplex IHC, and in vitro macrophage polarization assays. MTHFD2 was upregulated in ccRCC tumors and associated with poor prognosis across multiple cohorts. High MTHFD2 expression remained an independent prognostic marker after adjustment for clinical stage. Single-cell analyses identified macrophages as the principal immune subpopulation expressing MTHFD2, with MTHFD2+ macrophages displaying a transcriptional signature of immunosuppression and metabolic adaptation. In vitro, MTHFD2-induced M2 macrophage polarization was reversed by DS18561882, promoting M1 polarization. MTHFD2 is a robust biomarker for poor prognosis in ccRCC, influencing tumor–immune interactions and macrophage polarization. Targeting MTHFD2 may represent a dual-action strategy to suppress tumor growth and reprogram the tumor immune microenvironment. Full article

This study examines the effects of the e-servicescape on flow experience, positive affect, trust, website loyalty, and e-WOM in the context of online travel platforms, while investigating the moderating role of e-familiarity. Drawing on servicescape theory, the S-O-R framework, and the Technology Acceptance Model (TAM), a comprehensive research model is proposed. Data were collected from 256 consumers residing in Türkiye who had previously used online travel agencies, and the hypotheses were tested using partial least squares structural equation modeling (PLS-SEM). The findings reveal that the e-servicescape has significant positive effects on flow experience, positive affect, and trust. While flow experience was a significant predictor of positive affect, it did not have a significant direct effect on e-WOM. Furthermore, positive affect and trust, in turn, significantly predicted both website loyalty and e-WOM. Moreover, e-familiarity negatively moderated the relationship between e-servicescape and flow experience, suggesting that highly familiar users derive less immersive benefit from enhanced online environments. The study contributes to the digital tourism and consumer behavior literature by highlighting the role of user familiarity in shaping experiential outcomes. Full article

Anaplastic thyroid carcinoma (ATC) is an aggressive and lethal malignancy that carries a poor prognosis. Moreover, there are limited therapeutic options for managing ATC. There is increasing evidence that implicates the role of cancer stem cells (CSCs) in the processes of dedifferentiation in the progression, therapeutic resistance, and metastatic potential of ATC. In this review, we integrate the molecular and cellular insights into the CSCs paradigm in ATC to highlight the role of stemness-associated markers that include CD44, CD133, and ALDH1. We put special emphasis on the role of CD44 and its variant isoforms (CD44v), which play a role in the interface of cancer stemness, tumour microenvironment crosstalk, modulation of epithelial–mesenchymal transition (EMT), chemoresistance, and metastasis. The contribution of signalling pathways (PI3K/AKT/mTOR, MAPK, Notch, Wnt/β-catenin, and Hedgehog) to hypoxia, cancer-associated fibroblasts (CAFs), and tumour-associated macrophages (TAMs) in sustaining CSC niches will be discussed. The review explores advances in molecular diagnostics, imaging technologies, and targeted therapeutic strategies with the potential to disrupt CSC-driven tumour maintenance. Through integration of multigenic, epigenetic, and microenvironmental perspectives, this review highlights the potential necessity of CSC-targeted and combination therapies to improve disease outcomes in ATC. Full article

The recruitment and polarization of tumor-associated macrophages (TAMs) play a pivotal role in shaping the immunosuppressive tumor microenvironment in breast cancer. Interleukin-1 receptor accessory protein (IL1RAP), a critical co-receptor for IL-1 family cytokines, is emerging as a potential regulator of macrophage function, though its specific role in TAM biology remains to be explained. In this study, we investigated the impact of IL1RAP on macrophage recruitment and M2-like polarization. Initial bioinformatics analysis of public databases revealed a significant correlation between elevated IL1RAP expression in macrophages and signatures of immune suppression and poor prognosis in breast cancer. To functionally validate these findings, we performed IL1RAP knockdown in a murine macrophage cell line. Our results demonstrated that IL1RAP deficiency markedly impaired the migratory capacity of macrophages towards classic chemotactic stimuli. Furthermore, under M2-polarizing conditions, IL1RAP-knockdown macrophages exhibited a significantly attenuated M2 phenotype, as evidenced by the decreased expression of canonical M2 markers (e.g., Arg1, Mrc1) and reduced functional outputs. Collectively, our integrated approach combining bioinformatics and in vitro experimentation identifies IL1RAP as a novel regulator that potentiates both the recruitment and the M2 polarization of macrophages. These findings suggest that targeting the IL1RAP pathway could represent a promising therapeutic strategy for reprogramming the tumor-immune microenvironment by limiting pro-tumoral macrophage infiltration and polarization. Full article

Public digital cultural service (PDCS) platforms are central to promoting equitable access to cultural resources in the digital era; however, sustaining users’ continued engagement remains a key challenge for public-sector platforms. This study examines the psychological mechanisms underlying users’ continued use intention toward PDCS platforms within a public governance context. Building on the Technology Acceptance Model (TAM) and the Information Systems Success Model (ISSM), an integrated framework is developed that incorporates perceived government support as a moderating mechanism, thereby extending technology acceptance research to public digital cultural services. Empirical analysis, employing structural equation modeling, was conducted on survey data collected from 789 PDCS platform users in China. The results demonstrate that perceived usefulness and perceived ease of use both exert significant positive impacts on users’ continued use intention toward PDCS platforms. Perceived ease of use positively influences perceived usefulness, which further mediates the relationship between perceived ease of use and continued use intention. Additionally, information quality and system quality are confirmed to be positive antecedents of both perceived usefulness and perceived ease of use. More importantly, perceived government support significantly enhances the positive effects of both perceived usefulness and perceived ease of use on users’ continued use intention. By integrating individual technology acceptance mechanisms with institutional support factors, this study deepens understanding of user engagement in public digital cultural services and offers practical implications for enhancing platform sustainability through improvements in system design, information quality, and government support strategies. Full article

Intelligent Clinical Decision Support Systems (ICDSS) are increasingly integrated into healthcare settings to enhance clinical decision-making, efficiency, and patient safety. Despite advances in artificial intelligence-enabled decision support, ICDSS adoption remains inconsistent, particularly in complex clinical environments where professional autonomy, workflow alignment, and accountability are critical. This study examines healthcare providers’ perspectives on ICDSS through a grounded theory approach informed by established Information Systems theories, including the Unified Theory of Acceptance and Use of Technology (UTAUT), Technology Acceptance Model (TAM), Diffusion of Innovation (DOI), and the Human-Organization-Technology fit (HOT-fit) framework. Semi-structured interviews were conducted with 11 providers within a large, integrated healthcare organization, and data were analyzed using open, axial, and selective coding. The findings reveal three interrelated dimensions shaping ICDSS use: provider experience, clinical utility, and adaptation. While ICDSS were perceived as valuable for improving efficiency, supporting treatment decisions, and enhancing patient safety, their adoption was constrained by cognitive overload, workflow misalignment, data quality concerns, and perceived threats to professional autonomy. Trust, explainability, and workflow fit emerged as central mechanisms influencing selective use rather than full adoption. By grounding provider perspectives within a sociotechnical lens, this study extends existing IS theories to the context of AI-enabled clinical decision support and offers empirically grounded insights for designing ICDSS that better align with clinical practice. Full article

Accurate power-sector carbon emission data (PS-CED) are critical for ensuring sustainable practices in carbon trading and effective emission reductions. However, conventional centralized reporting systems are susceptible to data tampering, duplicate accounting, and inefficient manual verification, hindering the achievement of sustainability goals. Blockchain technology (BCT) provides transparency, immutability, and automated compliance, offering significant potential for improving the sustainability of PS-CED supervision. Despite this, its diffusion in the sector faces challenges such as data heterogeneity, security concerns, institutional differences, and resource limitations. This study integrates the Technology Acceptance Model (TAM) and the Theory of Planned Behavior (TPB) to develop a diffusion framework for BCT adoption in PS-CED supervision with a focus on sustainability. Using partial least squares structural equation modeling (PLS-SEM) and fuzzy-set qualitative comparative analysis (fsQCA), the study examines both linear effects and multiple adoption configurations. The results indicate that adoption willingness mediates the effects of perceived usefulness and ease of use, while perceived regulatory norms underscore policy pressure as a crucial external driver for fostering sustainability. Configurational analysis reveals heterogeneous diffusion patterns, with high adoption performance driven by technological capability combined with regulatory enforcement, and low performance linked to weak technological engagement and structural constraints. Based on these findings, a strategic framework is proposed to support differentiated and phased BCT adoption across organizational contexts to enhance sustainability in carbon emission supervision. This paper clarifies the diffusion mechanisms and provides practical guidance for scaling blockchain-based PS-CED supervision to promote sustainability. Full article

Mental health disorders affect nearly one billion people worldwide, yet treatment gaps exceed 75% in low- and middle-income countries. Teletherapy has emerged as a scalable solution, but its adoption differs sharply by economic context. This comparative ecological policy analysis used secondary aggregate data from WHO, World Bank, ITU, and national reports to examine teletherapy adoption in low-income (Nigeria, Kenya), middle-income (South Africa, India), and high-income countries (Norway, Canada). Descriptive statistics and simple linear regression were applied, with findings interpreted through the Consolidated Framework for Implementation Research (CFIR), Technology Acceptance Model (TAM), and Diffusion of Innovations theory. High-income countries achieved widespread adoption (>70%), enabled by universal broadband, comprehensive regulation, and strong reimbursement. Middle-income countries showed moderate uptake (15–30%), constrained by rural–urban digital divides and inconsistent policies. Low-income countries reported minimal integration (<5%), limited by unreliable internet, severe workforce shortages, high data costs, and sociocultural barriers. Digital infrastructure, regulatory maturity, and mental health workforce density explained 78% of the cross-country variance in adoption rates (R² = 0.78). Equitable scale-up of teletherapy directly supports SDGs 3, 9, 10, and 17. Targeted investment and cross-income collaboration are essential to prevent digital mental health solutions from exacerbating existing inequities. Full article

Emerging hospitality markets confront a two-speed ecosystem where operational digitalization outpaces strategic AI readiness, creating a benefit–feasibility gap. Providers recognize substantial technology value yet face implementation constraints from costs, integration complexity, and skills shortages, while guests demonstrate acceptance conditional on trust, with privacy concerns suppressing willingness to pay. Drawing on dual-perspective empirical evidence from Albania’s accommodation sector consisting of a national provider readiness assessment (N = 1821) and a guest acceptance study (N = 689) conducted in prior research, this Design Science Research study develops a segment-differentiated technological blueprint through systematic integration of Design Thinking, service blueprinting, and systems thinking methodologies. Integrated TAM-TOE-DOI framework analysis reveals three distinct provider segments requiring differentiated implementation pathways: Tech Leaders positioned for AI capabilities, Selective Adopters benefiting from smart modules, and Skeptics requiring foundational capabilities. Empirical evidence establishes that regional ecosystem characteristics outweigh organizational scale in determining adoption feasibility, trust operates as a gating condition moderating acceptance and financial commitment, and supply–demand misalignment creates bottlenecks invisible to single-perspective assessments. Theoretical contributions extend TAM-TOE-DOI frameworks from explanatory constructs to design requirements, conceptualize supply–demand alignment as an adoption mechanism, and generate two generalizable design principles: dual-constraint satisfaction requiring simultaneous provider feasibility and guest acceptance, and trust-as-architecture embedding trust mechanisms as structural properties. The proposed segment-differentiated technological blueprint offers actionable implementation pathways aligned with varying levels of provider readiness, providing transferable guidance for policymakers, technology vendors, education providers, and accommodation providers across the Western Balkans, the Mediterranean, and other post-transition economies facing similar heterogeneity in readiness and resource constraints. Full article

Breast cancer (BC) is a prevalent malignancy worldwide among women. HER2 overexpression in a subset of BC (HER2+ BC) serves as a critical oncogenic driver and contributes to immune evasion. The Raf Kinase Inhibitor Protein (RKIP), a metastasis suppressor and an immune enhancer, is underexpressed in HER2+ BC. The treatment of HER2+ BC with anti-HER2 mAbs or chemical inhibitors has resulted in significant clinical responses in a subset of patients; however, unresponsiveness in a larger subset was due to acquired and induced resistance. These findings highlight the need for the development of new effective therapies. By analyzing the signaling pathways mediated by both RKIP and HER2 in HER2+ BC, we have found that RKIP and HER2 downstream signaling and inductions showed an inverse relationship. These suggested the presence of a dysregulated RKIP-HER2 axis in HER2+ BC mediating immune evasion. These findings were corroborated by bioinformatic analyses. The immune evasion induced by the overexpression of HER2 was due, in part, to its regulation of the expression of PD-L1, the polarization of TAMs, the infiltration of suppressor cells (Tregs, MDSCs), and the inhibition of anti-tumor CD8+ T cells, resulting in an overall immunosuppressive TME. In contrast, RKIP expression inhibits critical signaling pathways that regulate HER2 expression, including the Raf-MEK-ERK, NF-kB, and PI3K/Akt pathways, thereby aborting HER2-mediated mechanisms of immune evasion. Overall, we analyzed the cross-talk signaling pathways between RKIP and HER2, established a novel dysregulated axis in HER2+ BC, and delineated the various mechanisms involved in the regulation of immune evasion by RKIP and HER2. Hence, we present various therapeutic strategies aimed at targeting the RKIP-HER2 axis in HER2+ BC to circumvent unresponsiveness to therapeutics and immune evasion. Full article

This research investigates the impact of augmented and virtual reality (AR/VR) and AI-enabled chatbots, both individually and collectively, on consumer engagement of e-commerce platforms. Moreover, this research examines the mediating effects of perceived utility, ease of use, and enjoyment and the moderating effects of product type and technology readiness, respectively. By applying the theories of Technology Acceptance Model (TAM) and Stimulus–Organism–Response (S-O-R), this research proposed this theoretical framework and adopted a mixed-method research method. This research collected its empirical findings from 486 respondents who had utilized chatbots and AR/VR technology on three of China’s most popular e-commerce platforms, including Taobao, JD.com, and Pinduoduo. Structural equation modeling was utilized for hypothesis testing, and semi-structured interviews on 30 participants were used for validation of empirical findings. Results reveal that both AI chatbot features (β = 0.35, p < 0.001) and AR/VR technologies (β = 0.42, p < 0.001) significantly enhance consumer engagement, with AR/VR demonstrating stronger effects. Perceived enjoyment emerged as the strongest mediator (AI: β = 0.14; AR/VR: β = 0.18), surpassing traditional utilitarian factors. Technology readiness significantly moderated these relationships, with high-readiness consumers showing substantially stronger responses (AI: β = 0.45; AR/VR: β = 0.52). Experience goods amplified technology effects compared to search goods. Multi-group analysis revealed platform-specific variations, while robustness checks identified diminishing returns for AI chatbots but not AR/VR technologies. This research contributes to digital marketing and information systems literature by providing empirical evidence of differential technology impacts on engagement, highlighting the dominance of hedonic over utilitarian pathways in consumer technology adoption. The findings offer practical guidance for e-commerce platforms in optimizing technology investments and designing engagement strategies. Full article

Soil nutrient analyzers are integral to precision agriculture, yet their adoption among smallholder farmers remains uneven. This study investigates the behavioral determinants of farmers’ adoption intention toward soil nutrient analyzers by extending the Technology Acceptance Model (TAM) to incorporate technology awareness as an upstream construct. Survey data were collected from smallholder farmers with prior experience using soil nutrient analyzers in Chanthaburi, Kanchanaburi, and Udon Thani provinces in Thailand. Structural equation modeling was employed to examine the direct and indirect effects of technology awareness on adoption intention through perceived usefulness and perceived ease of use. The results reveal that technology awareness exerts a significant direct influence on adoption intention and indirect effects mediated by both perceived usefulness and ease of use. In addition, perceived ease of use positively enhances perceived usefulness, reinforcing farmers’ willingness to adopt the technology. By empirically positioning technology awareness as a foundational driver within an extended TAM framework, this study advances understanding of smallholder farmers’ technology acceptance in precision agriculture. The findings offer practical insights for policymakers, extension services, and technology developers, emphasizing awareness-building initiatives and user-centered design to accelerate the diffusion of soil nutrient analyzers among smallholder farming communities. Full article