Search Results (37,152)

Toll-like receptors (TLRs) are essential components of the innate immune system that enable host cells to sense microbial and endogenous danger signals and to initiate inflammatory and antimicrobial responses. Activation of TLRs triggers complex intracellular signaling networks that culminate in the induction of pro-inflammatory cytokines, type I interferons, and co-stimulatory molecules. In addition to the well-characterized nuclear factor κB (NF-κB) and interferon regulatory factor (IRF) pathways, mitogen-activated protein kinases (MAPKs) play a critical modulatory role in TLR signaling. MAPK/ERK kinase (MEK) inhibitors were originally developed for the treatment of cancer and are widely used in clinical oncology. Accumulating evidence indicates that pharmacological inhibition of MEK/extracellular signal regulated kinase (ERK) signaling profoundly affects immune cell function and TLR-driven responses. Depending on timing, dose, and disease context, MEK inhibition can attenuate excessive inflammation but may also interfere with protective host defense mechanisms. This duality highlights the context-dependent role of MEK/ERK signaling in infection and inflammation. In this review, I summarize current knowledge on the integration of MEK/ERK signaling into TLR-mediated innate immune responses and discuss the immunological consequences of MEK inhibition in infectious and inflammatory settings. By synthesizing mechanistic and translational studies, I aim to provide a framework for understanding MEK inhibitors as immune modulators rather than as broadly acting anti-inflammatory agents. Full article

Background/Objectives: Artificial intelligence (AI) is increasingly transforming cardiology through advanced analytical tools capable of identifying complex patterns across cardiovascular imaging, electrophysiology, and clinical datasets. Machine learning (ML) and deep learning (DL) algorithms are being integrated into echocardiography, cardiac computed tomography (CT), cardiac magnetic resonance imaging (MRI), and electrocardiography (ECG), enabling earlier diagnosis and more personalized cardiovascular care. This narrative review summarizes current clinical and organizational applications of AI in cardiology and discusses emerging concepts related to explainable and trustworthy AI. Methods: A narrative review was conducted according to SANRA recommendations using the PubMed, MEDLINE, Web of Science, and Scopus databases, including peer-reviewed publications from 2015 to 2026 addressing clinical, organizational, and ethical applications of AI in cardiology, with particular emphasis on cardiovascular imaging, electrocardiography, heart failure, digital health, and explainable AI frameworks. Results: Substantial evidence demonstrates that AI-based tools can achieve expert-level performance in cardiovascular imaging interpretation, automated electrocardiographic analysis, and clinical risk prediction. Across multiple cardiovascular settings, AI has been associated with improved diagnostic accuracy, enhanced workflow efficiency, and earlier detection of cardiovascular disease. Predictive models support risk stratification in heart failure and ischemic heart disease, while chatbots and digital health platforms may facilitate patient engagement, remote monitoring, and continuity of care. Despite these advances, important challenges remain, including algorithmic bias, limited transparency, insufficient external validation, data heterogeneity, and barriers to routine clinical implementation. Emerging explainable AI approaches may improve model interpretability, clinician confidence, and the safe adoption of AI-driven decision support systems. Conclusions: Artificial intelligence is rapidly evolving from a research-oriented technology into a clinically relevant component of cardiovascular care. Current evidence indicates that AI can enhance diagnostic performance, improve risk prediction, streamline clinical workflows, and facilitate more personalized management across multiple cardiovascular domains. However, the successful translation of AI into routine practice will depend on robust external validation, transparent decision-making mechanisms, regulatory oversight, and clinician acceptance. The development of explainable and trustworthy AI frameworks represents a critical step toward the safe, ethical, and sustainable integration of AI into modern cardiology. Full article

Acute myeloid leukemia (AML) is a biologically heterogeneous malignancy in which therapeutic decision-making is increasingly guided by molecular and immunophenotypic diagnostics. Advances in genomic profiling and risk stratification have enabled the integration of targeted agents into frontline and relapsed/refractory treatment strategies. Among these, midostaurin, venetoclax, and gemtuzumab ozogamicin represent paradigm-shifting therapies whose clinical benefit depends on accurate and timely diagnosis. This review examines the diagnostic frameworks that inform the use of these agents and discusses their incorporation into contemporary AML management. Midostaurin has demonstrated improved outcomes in patients with FLT3-mutated AML when combined with intensive chemotherapy, underscoring the importance of early molecular testing. Venetoclax, a BCL-2 inhibitor, has expanded therapeutic options for older or unfit patients when used with hypomethylating agents or low-dose cytarabine, with emerging evidence linking response to cytogenetic and molecular features. Gemtuzumab ozogamicin, an anti-CD33 antibody–drug conjugate, illustrates the clinical relevance of immunophenotypic assessment and risk-adapted dosing strategies. We highlight current evidence supporting diagnosis-driven therapy selection, practical considerations for clinical implementation, and ongoing challenges, including resistance mechanisms and optimal sequencing. Integrating precise diagnostic tools with targeted therapies represents a critical step toward personalized AML care and improved patient outcomes. Full article

Cellulose is the most promising abundant renewable polymer material with the highest potential for the future low-carbon biorefineries. However, its utilization in industry is limited by the structural recalcitrance as a result of organization of crystalline domains, fibrillar architecture hierarchy and intramolecular and intermolecular hydrogen bonding which is responsible for access restriction for the catalysts and consequent cleavage of the glycosidic bonds. Therefore, efficient depolymerization of cellulose is of paramount importance as a step in biomass conversion into the low molecular products. In this review, the recent advances in cellulose depolymerization are discussed. The chemical, enzymatic, thermal, thermochemical, mechanochemical, oxidative and hybrid catalytic method is thoroughly discussed. Attention is paid to the mechanism of the depolymerization reaction steps as glycosidic bond activation as hydrolytic, radical mediated, and energy assisted pathways. Selectivity and conversion efficiency based on substrate morphology, solvent system and catalyst design are also discussed. Further, there is a comparison of key performance metrics which are relevant for the industrial process as product yield, carbon efficiency, energy demand, stability of the catalyst, solvent recyclability and impact to the environmental lifecycle. The pros and cons of the various methods are also represented. Processes based on mineral acids enable rapid conversion. However, they suffer from corrosion, waste handling issues and degradation by-products. On the other hand, enzymatic depolymerization processes offer relatively high selectivity but they are limited in terms of feedstock sensitivity and slow reaction kinetics. The downstream valorization mechanisms are also described with the result being that no single available technology is capable of satisfying all industrial requirements. Thus, future progress expects integrated circular processes where advanced catalysis, process intensification and digital optimization strategies take place. Full article

Background: The convergence of machine learning (ML), gamification, and critical thinking assessment within adaptive educational platforms has accelerated since 2020, driven by large language models (LLMs) and graph neural networks (GNNs). No prior systematic review has jointly addressed all three dimensions, and Central Asian educational contexts remain underrepresented. Methods: Following PRISMA 2020 guidelines, we searched Scopus (n  =  4396) and OpenAlex (n  =  4152) for publications from 2016 to 2026. Quality assessment used the Mixed Methods Appraisal Tool (MMAT 2018; threshold ≥  2), yielding 82 papers. Five research questions addressed ML personalization (RQ1), gamification and engagement (RQ2), critical thinking assessment tools (RQ3), recommendation algorithms (RQ4), and regional applicability in Kazakhstan and Central Asia (RQ5). Results: Transformer-based and GNN models dominate the recent literature (52% of corpus from 2025), with an accuracy of 91–97% for dropout prediction and learning path recommendation under single-institution conditions. Gamification studies report up to 90% student satisfaction; LLM-based critical thinking assessment shows promise but faces validity concerns. Thirteen papers address Central Asian contexts. Conclusions: Significant gaps persist: no integrated gamification–critical thinking framework exists, recommendation systems lack explainability, and Kazakh-language datasets are severely underrepresented. Future research should prioritize multilingual adaptive systems, explainable algorithms, and privacy-preserving federated learning for low-resource contexts. Full article

Single-cell omics technologies have transformed the study of cellular heterogeneity, enabling high-resolution analysis of tissue development and complex traits. In sheep and goats, these approaches have been applied to skin, hair follicles, reproductive organs, metabolic tissues, and adipose tissue, revealing cell type-specific regulatory programs underlying traits such as wool quality, fertility, growth, and fat deposition. However, most studies rely on single-cell RNA sequencing (scRNA-seq) and are limited by incomplete genome annotation, insufficient coverage of production traits, and weak integration with population genetics, restricting their application in molecular breeding. This review summarizes advances in single-cell omics in sheep and goats, focusing on tissue development and trait formation. We further discuss emerging strategies that integrate single-cell multi-omics, spatial transcriptomics, and population genetics to resolve regulatory mechanisms in a cell type-specific and spatially informed context. Finally, we discuss CRISPR/Cas9-based validation to link genotype and phenotype, accelerating gene discovery and precision breeding in small ruminants. Full article

Background: Precise intraoperative localisation of small colorectal tumours during laparoscopic surgery remains challenging due to absent tactile feedback and subserosal tumour location. Current standard methods, particularly India ink tattooing, demonstrate 15–30% failure rates for lesions less than 10 mm, leading to prolonged operative times, incomplete resections, and re-operations. Multiple emerging technologies promise improved localisation, yet comparative evidence remains fragmented. Objective: To map and characterise the current landscape of intraoperative marking and identification technologies for small colorectal tumour localisation during laparoscopic surgery, with emphasis on radiofrequency-based methods and alternative approaches, and to identify evidence gaps guiding future research. Methods: Following PRISMA-ScR guidelines, we systematically searched PubMed, Web of Science, and Scopus databases from January 2000 through December 2025 for studies evaluating tumour localisation technologies in colorectal cancer surgery, including primary tumour localisation during laparoscopic colectomy and localisation of colorectal liver metastases during hepatic surgery, or transferable anatomical applications with documented translational potential to colorectal surgery. Two independent reviewers screened all records, with discrepancies resolved through discussion and a third senior reviewer consulted for unresolved disagreements; data were extracted on technical performance, safety, feasibility, cost-effectiveness, usability, innovation potential, and evidence quality. Results: We included 89 studies comprising 18 colorectal-specific articles and 71 transferable/GI-adjacent studies. Detection success rates ranged from 71% to 100% across modalities. Near-infrared fluorescence with indocyanine green demonstrated the strongest clinical evidence with 75–100% detection across eight colorectal studies encompassing 2134 procedures and seamless workflow integration. Radiofrequency identification systems achieved 91.9–99% detection in feasibility studies with promising tissue penetration of 15–35 mm but limited colorectal validation. Electromagnetic navigation excelled in rigid organs with 85–98% success but showed degraded performance in mobile bowel at 71–75%. Critical evidence gaps included absent head-to-head comparative trials, non-standardised outcome metrics limiting cross-study comparability, and limited long-term safety data with only 14 studies providing follow-up exceeding six months. Conclusions: ICG fluorescence represents the most clinically mature technology identified, representing a priority candidate for colorectal-specific validation in challenging localisation scenarios. RFID systems demonstrate promising characteristics justifying prioritised research investment through adequately powered comparative trials. Future research must emphasise consortium-based comparative effectiveness studies, standardised outcome metrics, and integration with robotic and AI-assisted surgical platforms to accelerate clinical translation. Full article

Theranostics is a novel approach that integrates diagnostic and therapeutic efficacy on a single platform, holding great promise for precision medicine by enabling real-time monitoring of disease progression and therapeutic response. Despite significant advances, the successful development and delivery of theranostic systems are critically limited by multiple biological barriers present at systemic, tissue, cellular, anatomical, and immunological levels. These barriers restrict bioavailability, target accessibility, and therapeutic efficacy, while often increasing off-target accumulation and adverse effects. This review provides a comprehensive overview of the major biological barriers encountered in theranostic development, including physiological barriers such as plasma protein binding, renal clearance, and hepatic metabolism; anatomical barriers like endothelial linings, the blood–brain barrier (BBB), and the tumor microenvironment; cellular barriers involving membrane permeability, intracellular trafficking, and endo-lysosomal entrapment; and immunological barriers such as immune recognition, inflammatory responses, and complement activation. Special emphasis is placed on the BBB, highlighting its structural complexity, transport mechanisms, and strategies such as molecular Trojan-horse technology, receptor-mediated and adsorptive-mediated transcytosis, and nanocarrier-based approaches to enhance central nervous system delivery. The review further discusses targeted delivery challenges, including receptor heterogeneity and multidrug resistance, and critically evaluates current strategies to overcome these barriers through surface functionalization, stimuli-responsive systems, biomimetic carriers, and controlled-release mechanisms. Finally, recent advances, clinical challenges, and future perspectives—including personalized theranostics, artificial intelligence—assisted design, and next-generation barrier-penetrating systems—are explored. Overall, this review aims to provide a structured understanding of biological barriers in theranostics and highlight innovative approaches to improve their translational potential. Full article

Wind turbines are increasingly deployed at larger scales and in harsher operating environments, leading to greater structural complexity, stronger load variability, and higher maintenance demands across both drivetrain and structural components. Reported field data indicate that gearboxes and bearings account for approximately 30–40% of total turbine downtime, while blade-related failures contribute roughly 20–25% of reported failure events, primarily through fatigue, delamination, leading-edge erosion, and lightning-induced defects. In parallel, large-scale and offshore turbines show increasing susceptibility to tower fatigue cracking, corrosion-assisted degradation, and flange joint bolt-preload loss under cyclic and environmental loading. This review provides a comprehensive applied-engineering synthesis of failure mechanisms, reliability challenges, and monitoring strategies for major wind turbine components, including gearboxes, bearings, blades, towers, and flange joints. A wide range of condition monitoring, structural health monitoring (SHM), and prognostics and health management (PHM) approaches is critically examined, including vibration analysis, acoustic emission, ultrasonic inspection, infrared thermography, impedance-based sensing, electromagnetic methods, machine vision, SCADA-based diagnostics, and artificial-intelligence-assisted fault classification. The review compares these techniques in terms of detectable damage types, spatial coverage, sensitivity, deployment practicality, and limitations under real operating conditions. In addition, statistical reliability methods and data-driven models are discussed to interpret failure trends and uncertainty. Recent AI-based studies have reported fault classification accuracies exceeding 90% under controlled or semi-controlled conditions; however, their field reliability remains constrained by data imbalance, domain shift, limited labeled failure datasets, model interpretability, and insufficient validation under realistic turbine operating environments. The main contribution of this review is an integrated applied synthesis that connects drivetrain and structural failure mechanisms with measurable monitoring indicators, diagnostic technologies, AI-enabled PHM limitations, and predictive-maintenance decision needs. The paper provides practical guidance for monitoring design, early fault detection, predictive maintenance, and long-term reliability improvement in next-generation wind turbine systems. Full article

Background: Artificial intelligence (AI) is increasingly being integrated into implant dentistry, where clinical decision-making depends on the interpretation of complex radiographic and patient-specific data. Although multiple applications have been proposed across diagnostic imaging, treatment planning, intraoperative support and outcome prediction, their clinical validity and real-world applicability remain incompletely defined and their use raises relevant medico-legal considerations. Methods: A narrative review was conducted through a structured search of PubMed/MEDLINE, Scopus, and Web of Science, including English-language studies published between 2010 and February 2026. Clinical and experimental studies, as well as relevant reviews addressing AI applications in implant dentistry, were included. A qualitative thematic synthesis was performed due to methodological heterogeneity. Results: AI applications are mainly concentrated in diagnostic imaging, particularly CBCT analysis, where high levels of performance are consistently reported. In treatment planning, systems support specific decision-making tasks rather than comprehensive strategies, while intraoperative applications are integrated into navigation and robotic systems to improve procedural accuracy. Predictive models for implant outcomes have been developed, although their reliability remains influenced by dataset variability and study design. Conclusions: AI currently represents a supportive tool in implant dentistry, with greater applicability in standardized tasks. Its integration into complex clinical decision-making remains limited, highlighting the need for clinically oriented validation and cautious implementation in practice. Full article

The integration of collaborative robots into industrial environments requires rigorous safety validation under the Power and Force Limiting (PFL) regime. This review article systematically maps the technological and normative development of certified Pressure and Force Measurement Devices (PFMDs) and experimental biofidelic instruments for Physical Human–Robot Interaction (pHRI) between the years 2011 and 2026. A quantitative screening of 68 studies revealed a publication peak in impact metrology in 2021. This peak occurred with a five-year latency after the release of the ISO/TS 15066 technical specification. Although global interest in collaborative robotics steadily grows, the publication trend indicates a gradual shift in scientific focus from reactive testing toward proactive prevention. A methodological deconstruction of four Research Questions (RQs) identifies persistent limitations in safety evaluation. The findings demonstrate that the internal structure of conventional sensors induces nonlinear shock filtering and parasitic oscillations (RQ1). Furthermore, the rigid fixation of test stands generates unrealistic pressure spikes. This physical limitation forces a transition to flexible and pendulum-based configurations (RQ2). Commercial flat films physically fail due to sensor saturation and introduced stiffness. Such failures accelerate the development of conformable electronic skins (e-skins) and multimodal test manikins (RQ3). To ensure interlaboratory reproducibility within the current ISO 10218-2:2025 standard, the text defines imperative metrological parameters. These parameters strictly include frequency response, calibration protocols, and volumetric mapping of inertial masses (RQ4). Furthermore, the analysed publications were systematically stratified into distinct technological categories, strictly reflecting their primary engineering domains, ranging from empirical metrological evaluation and sensor hardware design to advanced numerical modeling. Finally, the vision for future research anticipates a definitive shift toward proactive anti-collision technologies, encompassing Artificial Intelligence (AI), machine vision, and Augmented Reality/Virtual Reality/Mixed reality (AR/VR/MR). Future methodologies must also consider demographic anisotropies and the cognitive fatigue of the human operator. Full article

The Internet of Vehicles (IoV) is reshaping intelligent transportation through pervasive connectivity, real-time data exchange, cooperative perception, and vehicle–edge–cloud services, while also expanding cybersecurity and privacy risks across heterogeneous cyber–physical environments. This paper presents a PRISMA 2020-informed systematic review of IoV security and privacy protection research. A cross-layer and lifecycle-oriented analytical framework is developed by integrating a four-layer IoV architecture—sensing layer, network access layer, coordinative computing layer, and application layer—with a five-stage data lifecycle covering data collection, transmission, storage, usage, and disposal. Based on this framework, the paper examines representative threat surfaces, vehicle-to-everything (V2X) communication security, public key infrastructure (PKI) based authentication, trust management, privacy-preserving data sharing, intrusion detection, active defense, and AI-assisted security analytics. Privacy-preserving mechanisms, including differential privacy, federated learning, blockchain, homomorphic encryption, and secure multi-party computation, are further compared in terms of deployment layer, lifecycle stage, real-time suitability, and representative performance evidence. In addition, the review discusses the engineering relevance of UNECE WP.29 R155/R156, ISO/SAE 21434, and related national standards, with emphasis on compliance evidence, over-the-air (OTA) governance, supply-chain coordination, and lifecycle cybersecurity management. The review shows that no single protection mechanism can simultaneously satisfy the requirements of real-time performance, scalability, privacy preservation, trustworthiness, and regulatory compliance in dynamic IoV environments. Future research should emphasize lightweight and adaptive protection, cross-layer trust coordination, privacy–utility co-optimization, trustworthy AI-assisted security operations, and evidence-based lifecycle governance. This review provides a structured reference for researchers and a practical basis for secure and privacy-aware IoV system design. Full article

Background/Objectives: This review explores the role of artificial intelligence (AI), particularly with deep learning and machine learning, in the detection and classification of papilledema using retinal fundus imaging. Methods: The study synthesizes historical, technical, and clinical insights, comparing AI-based diagnostic accuracy with conventional methods. Results: Our findings demonstrate that AI systems, especially convolutional neural networks (CNNs), offer sensitivity and specificity comparable to, or even surpassing, expert-level fundoscopy. Conclusions: These results suggest significant implications for early diagnosis, triage, and telemedicine integration in ophthalmic care. Full article

Virtual reality can support the preparation and rehearsal of assembly tasks by providing a safe and repeatable digital representation of workstations. This study presents the development and laboratory feasibility validation of a geometry- and procedure-oriented VR simulation model for the assembly and disassembly of end-effectors on an industrial robot. The workflow was implemented using the Almega AX-V6 robotic workstation as a case study and included geometric acquisition of the real robot, CAD modelling in SolidWorks, redesign of the original end-effector connection using a quick-change flange concept, creation of two alternative end-effector models, modelling of the laboratory workspace in SketchUp, and scene enhancement in Twinmotion. The resulting robot and environment models were integrated in Pixyz Review and deployed through an Oculus Rift-based VR setup. Compared with the original flange concept, which required twelve screws, the redesigned training concept used two screws and two nuts, reducing the number of fastening elements by 66.7% and the number of screw positions by 83.3%. The VR implementation supported visual inspection, controller-based placement and alignment, and symbolic confirmation of fastening steps; it did not include force feedback, threaded fastening physics, automatic error scoring, or quantified transfer-of-training evaluation. Laboratory feasibility validation confirmed correct asset integration, spatial correspondence with the physical workplace, and functional executability of the target exchange sequence. The results show that the workflow is useful as a case-study pipeline for CAD-to-VR modelling and assembly rehearsal, while controlled user studies are still required before claims about training effectiveness can be made. Full article

The integration of biochar into asphalt binders represents a significant advancement toward global sustainability in pavement engineering. Produced through biomass pyrolysis, biochar enables the valorization of agricultural and industrial waste while reducing dependence on petroleum-derived binder constituents. This review critically synthesizes current research regarding the impact of biochar on the physical, rheological, and aging performance of bitumen. The evidence consistently shows that biochar improves binder stiffness, raises softening points, and strengthens rutting resistance at elevated temperatures, largely due to its porous microstructure and high carbon content. Biochar-modified binders also exhibit enhanced aging resistance through the adsorption of volatile light fractions. These improvements are primarily ascribed to the carbonaceous composition and high porosity of the biochar particles. However, systemic challenges, including phase stability at high concentrations, long-term oxidative aging, and a lack of standardized characterization protocols, hinder widespread implementation. By identifying consistent findings, contradictions, and critical research gaps across the literature, this review provides a consolidated foundation to guide the transition of biochar-modified bitumen from laboratory investigation to large-scale pavement infrastructure applications. Full article