Search Results (736)

Background/Objectives: The RTK-RAS signaling cascade is a central axis in colorectal cancer (CRC) pathogenesis, governing cellular proliferation, survival, and therapeutic resistance. Somatic alterations in key pathway genes—including KRAS, NRAS, BRAF, and EGFR—are pivotal to clinical decision-making in precision oncology. However, the integration of these genomic events with clinical and demographic data remains hindered by fragmented resources and a lack of accessible analytical frameworks. To address this challenge, we developed AI-HOPE-RTK-RAS, a domain-specialized conversational artificial intelligence (AI) system designed to enable natural language-based, integrative analysis of RTK-RAS pathway alterations in CRC. Methods: AI-HOPE-RTK-RAS employs a modular architecture combining large language models (LLMs), a natural language-to-code translation engine, and a backend analytics pipeline operating on harmonized multi-dimensional datasets from cBioPortal. Unlike general-purpose AI platforms, this system is purpose-built for real-time exploration of RTK-RAS biology within CRC cohorts. The platform supports mutation frequency profiling, odds ratio testing, survival modeling, and stratified analyses across clinical, genomic, and demographic parameters. Validation included reproduction of known mutation trends and exploratory evaluation of co-alterations, therapy response, and ancestry-specific mutation patterns. Results: AI-HOPE-RTK-RAS enabled rapid, dialogue-driven interrogation of CRC datasets, confirming established patterns and revealing novel associations with translational relevance. Among early-onset CRC (EOCRC) patients, the prevalence of RTK-RAS alterations was significantly lower compared to late-onset disease (67.97% vs. 79.9%; OR = 0.534, p = 0.014), suggesting the involvement of alternative oncogenic drivers. In KRAS-mutant patients receiving Bevacizumab, early-stage disease (Stages I–III) was associated with superior overall survival relative to Stage IV (p = 0.0004). In contrast, BRAF-mutant tumors with microsatellite-stable (MSS) status displayed poorer prognosis despite higher chemotherapy exposure (OR = 7.226, p < 0.001; p = 0.0000). Among EOCRC patients treated with FOLFOX, RTK-RAS alterations were linked to worse outcomes (p = 0.0262). The system also identified ancestry-enriched noncanonical mutations—including CBL, MAPK3, and NF1—with NF1 mutations significantly associated with improved prognosis (p = 1 × 10⁻⁵). Conclusions: AI-HOPE-RTK-RAS exemplifies a new class of conversational AI platforms tailored to precision oncology, enabling integrative, real-time analysis of clinically and biologically complex questions. Its ability to uncover both canonical and ancestry-specific patterns in RTK-RAS dysregulation—especially in EOCRC and populations with disproportionate health burdens—underscores its utility in advancing equitable, personalized cancer care. This work demonstrates the translational potential of domain-optimized AI tools to accelerate biomarker discovery, support therapeutic stratification, and democratize access to multi-omic analysis. Full article

Seed germination and early seedling growth are pivotal stages that define crop establishment and yield potential. Conventional agrochemicals used to improve these processes often raise environmental concerns, highlighting the need for sustainable alternatives. In this study, we demonstrated that water treated with cylindrical dielectric barrier discharge (c-DBD) plasma, enriched with nitric oxide (NO) and reactive nitrogen species (RNS), markedly enhanced onion (Allium cepa) seed germination and seedling vigor. The plasma-treated water (PTW) promoted rapid imbibition, broke dormancy, and accelerated germination rates beyond 98%. Seedlings irrigated with PTW exhibited significantly increased biomass, root and shoot length, chlorophyll content, and antioxidant enzyme activities, accompanied by reduced lipid peroxidation. Transcriptomic profiling revealed that PTW orchestrated a multifaceted regulatory network by upregulating gibberellin biosynthesis genes (GA3OX1/2), suppressing abscisic acid signaling components (ABI5), and activating phenylpropanoid metabolic pathways (PAL, 4CL) and antioxidant defense genes (RBOH1, SOD). These molecular changes coincided with elevated NO₂⁻ and NO₃⁻ levels and finely tuned hydrogen peroxide dynamics, underpinning redox signaling crucial for seed activation and stress resilience. Our findings establish plasma-generated NO-enriched water as an innovative, eco-friendly technology that leverages redox and hormone crosstalk to stimulate germination and early growth, offering promising applications in sustainable agriculture. Full article

In alignment with global educational trends, Australia has adopted a pluralistic approach to initial teacher education (ITE), encompassing traditional university-based programs, employment-integrated models and vocational training routes. This diversification of pathways has emerged as a strategic response to persistent workforce challenges, including chronic shortages, uneven distribution of qualified educators, and limited demographic diversity within the profession. Rather than supplanting conventional ITE models, these alternative pathways serve as complementary options, broadening access and enhancing system responsiveness to evolving societal and educational needs. The rise in non-traditional routes represents a deliberate response to the well-documented global teacher shortage, frequently examined in comparative educational research. Central to their design is a restructuring of traditional program elements, particularly duration and delivery methods, to facilitate more flexible and context-sensitive forms of teacher preparation. Such approaches often create opportunities for individuals who may be excluded from conventional pathways due to socioeconomic constraints, geographic isolation, or non-linear career trajectories. Significantly, the diversity introduced by alternative entry candidates has the potential to enrich school learning environments. These educators often bring a wide range of prior experiences, disciplinary knowledge, and cultural perspectives, contributing to more inclusive and representative teaching practices. The implications for student learning are substantial, particularly in disadvantaged communities where culturally and professionally diverse teachers may enhance engagement and academic outcomes. From a policy perspective, the development of flexible, multifaceted teacher education pathways constitutes a critical component of a sustainable workforce strategy. As demand for qualified teachers intensifies, especially in STEM disciplines and in rural, regional and remote areas, the role of alternative pathways is likely to become increasingly pivotal in achieving broader goals of equity, quality and innovation in teacher preparation. Full article

Gastric cancer remains the fourth leading cause of cancer-related mortality worldwide. Advanced disease is associated with a poor prognosis, emphasizing the critical importance of early diagnosis through endoscopy. In addition to prognosis, disease extent also plays a pivotal role in guiding management strategies. Therefore, accurate locoregional staging (T and N staging) is vital for optimal prognostic and therapeutic planning. Endoscopic ultrasound (EUS) has long been an essential tool in this regard, with computed tomography (CT) and, more recently, positron emission tomography–computed tomography (PET–CT) serving as alternative imaging modalities. EUS is particularly valuable in the assessment of early gastric cancer, defined as tumor invasion confined to the mucosa or submucosa. These tumors are increasingly managed by endoscopic resection techniques offering improved post-treatment quality of life. EUS has also recently been utilized in the restaging process after neoadjuvant chemotherapy, aiding in the evaluation of tumor resectability and prognosis. Its performance may be further enhanced through the application of emerging techniques such as contrast-enhanced endosonography, EUS elastography, and artificial intelligence systems. In advanced, unresectable disease, complications such as gastric outlet obstruction (GOO) severely impact patient quality of life. In this setting, EUS-guided gastroenterostomy (EUS-GE) offers a less invasive alternative to surgical gastrojejunostomy. This review summarizes and critically analyzes the role of EUS in the context of gastric cancer, highlighting its applications across different stages of the disease and evaluating its performance relative to other diagnostic modalities. Full article

The rapid recombination of photoinduced charge carriers in semiconductors remains a significant challenge for their practical application in photocatalysis. This study presents the design of a step-scheme (S-scheme) heterojunction composed of carbon nitride (g-C₃N₄) and nickel-based metal–organic framework (Ni-MOF) to achieve enhanced charge separation. The establishment of an S-scheme charge transfer configuration at the interface of the Ni-MOF/g-C₃N₄ heterostructure plays a pivotal role in enabling efficient charge carrier separation, and hence, high CO₂ photoreduction efficiency with a CO evolution rate of 1014.6 µmol g⁻¹ h⁻¹ and selectivity of 95% under simulated solar illumination. CO evolution represents an approximately 3.7-fold enhancement compared to pristine Ni-MOF. Density functional theory (DFT) calculations, supported by in situ irradiated X-ray photoelectron spectroscopy (XPS) and electron paramagnetic resonance (EPR) experimental results, confirmed the establishment of a well-defined and strongly bonded interface, which improves the charge transfer and separation following the S-scheme mechanism. This study sheds light on MOF-based S-scheme heterojunctions as fruitful and selective alternatives for practical CO₂ photoreduction. Full article

As a pivotal economic province in China, Jiangsu’s efforts in civil building energy conservation are critical to achieving the national “dual carbon” goals. This paper proposes a hybrid model that integrates wavelet transform, support vector regression (SVR), and extreme learning machine (ELM) to predict the civil building energy consumption of Jiangsu Province. Based on data from statistical yearbooks, the historical energy consumption of civil buildings is calculated. Through a grey relational analysis (GRA), the key factors influencing the civil building energy consumption are identified. The wavelet transform technique is then applied to decompose the energy consumption data into a trend component and a fluctuation component. The SVR model predicts the trend component, while the ELM model captures the fluctuation patterns. The final prediction results are generated by combining these two predictions. The results demonstrate that the hybrid model achieves superior performance with a Mean Absolute Percentage Error (MAPE) of merely 1.37%, outperforming both individual prediction methods and alternative hybrid approaches. Furthermore, we develop three prospective scenarios to analyze civil building energy consumption trends from 2023 to 2030. The analysis reveals that the observed patterns align with the Environmental Kuznets Curve (EKC). These findings provide valuable insights for provincial governments in future policy-making and energy planning. Full article

Introduction: Liver transplantation remains the definitive treatment for end-stage liver disease but faces critical challenges including organ shortages and preservation difficulties, particularly with extended criteria donor (ECD) grafts. Hypothermic machine perfusion (HMP) represents a promising alternative to traditional static cold storage (SCS). Methods: This retrospective study analyzed outcomes from 62 liver transplant recipients between 2016 and 2025, comparing 8 grafts preserved by HMP using the Liver Assist^® system and 54 grafts preserved by SCS. Parameters assessed included postoperative complications, hemodynamic stability, ischemia times, and survival outcomes. Results: HMP significantly reduced surgical (0% vs. 75.9%, p = 0.01) and biliary complications (0% vs. 34.4%, p = 0.004), improved hemodynamic stability post-reperfusion (∆MAP%: 1 vs. 21, p = 0.006), and achieved superior one-year survival rates (100% vs. 84.4%). Despite longer ischemia periods, grafts treated with HMP exhibited fewer adverse effects from ischemia-reperfusion injury. Discussion: These findings highlight the substantial benefits of HMP, particularly in improving graft quality from marginal donors and reducing postoperative morbidity. Further adoption of this technology could significantly impact liver transplantation outcomes by expanding the viable donor pool. Conclusions: The study underscores the effectiveness of hypothermic machine perfusion (HMP) as a superior preservation method compared to traditional static cold storage (SCS), HMP appears to be associated with improved short-term outcomes in liver transplantation. By substantially reducing postoperative complications and enhancing graft viability, HMP emerges as a pivotal strategy for maximizing the use of marginal donor organs. Further research and broader clinical implementation are recommended to validate these promising results and to fully harness the potential of HMP in liver transplantation. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that significantly affects patients’ quality of life. Dupilumab, a monoclonal antibody targeting interleukin (IL)-4 receptor alpha (IL-4Rα), has been the standard biologic therapy for moderate-to-severe AD. This review compares dupilumab with tralokinumab—a promising alternative that selectively neutralizes IL-13—by examining their distinct mechanisms, clinical efficacy, safety profiles, and practical considerations. While both biologics are highly effective, pivotal monotherapy trials indicate numerically higher efficacy rates for dupilumab. Regarding safety, while long-term data show comparable rates of serious adverse events, dupilumab is associated with a higher incidence of both conjunctivitis and injection-site reactions. Key practical differences include dupilumab’s broader indications and approval for infants (≥6 months), versus tralokinumab’s flexible maintenance dosing and notable efficacy in head and neck AD. By highlighting these key distinctions, this review aims to support personalized treatment selection in AD. However, no direct head-to-head clinical trials have yet compared dupilumab and tralokinumab, and the available evidence is based on indirect comparisons from separate pivotal studies. Full article

Compared to road trucks, the use of trains to move goods along railway lines is a more sustainable freight transport system. In Norway, where several main lines are single tracks, the insufficient length of many of the existing passing loops considerably restricts the operational and economic benefits of long trains. This brief technical note revolves around the possible upgrade of the Røros line connecting Oslo and Trondheim to accommodate 650 m-long freight trains as an alternative to the heavily trafficked Dovre line. Pivoting on regulatory standards, this exploratory work identifies the minimum set of infrastructure modifications required to achieve the necessary increase in capacity by extending the existing passing loops and creating a branch line. The results indicate that 8 freight train routes can be efficiently implemented, in addition to the 12 existing passenger train routes. This brief technical note employs building information modeling software Trimble Novapoint edition 2024 to position the existing railway infrastructure on topographic data and visualize the suggested upgrade. Notwithstanding the limitations of this exploratory work, dwelling on capacity calculation and the design of infrastructure upgrades, the results demonstrate that modest and well-placed interventions can significantly enhance the strategic value of a single-track rail corridor. This brief technical note sheds light on the main areas to be addressed by future studies to achieve a comprehensive evaluation of the infrastructure upgrade, also covering technical construction and economic aspects. Full article

Glutamate, the primary excitatory neurotransmitter in the central nervous system, plays a pivotal role in synaptic signaling, learning, and memory. Abnormal glutamate levels are implicated in various neurological disorders, including epilepsy, Alzheimer’s disease, and ischemic stroke. Despite the utility of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) in diagnosing such conditions, the development of effective glutamate-sensitive contrast agents remains a challenge. In this study, we present ultrasmall, citric acid-coated superparamagnetic iron oxide nanoparticles (CA-SPIONs) as highly selective and sensitive MRS probes for glutamate detection. These 5 nm magnetite CA-SPIONs exhibit a stable dispersion in physiological buffers and undergo aggregation in the presence of glutamate, significantly enhancing the T₂ MRS contrast power. At physiological glutamate levels, the CA-SPIONs yielded a pronounced signal change ratio of nearly 60%, while showing a negligible response to other neurotransmitters such as GABA and dopamine. Computational simulations confirmed the mechanism of glutamate-mediated aggregation and its impact on transversal relaxation rates and relaxivities. The sensitivity and selectivity of CA-SPIONs underscore their potential as eco-friendly, iron-based alternatives for future neurological sensing applications targeting glutamatergic dysfunction. Full article

The composition design of asphalt mixtures plays a pivotal role in determining pavement performance and durability. To improve skeleton stability, paving uniformity, and mechanical strength, this research proposes a three-dimensional optimization framework for asphalt mixture design, focusing on aggregate gradation and optimum asphalt content. A skeleton-dense and anti-segregation gradation optimization method was developed by integrating a previously established skeleton-dense model with a segregation tendency prediction approach. In parallel, a mechanically driven method for determining optimum asphalt content was proposed by introducing the maximum migration shear stress as a performance-based alternative to the conventional Marshall stability parameter. Research results show that asphalt mixtures designed and compacted with the optimized gradation exhibit significantly enhanced high-temperature stability, while maintaining satisfactory low-temperature cracking resistance and moisture susceptibility. Field validation was conducted through the construction of a trial pavement section using the optimized gradation under recommended mixing and compaction temperatures. The resulting pavement demonstrated excellent compaction, strong resistance to segregation, and a highly stable spatial structure. These findings confirm the effectiveness of the proposed methodology in enhancing the high-temperature deformation resistance and overall structural integrity of asphalt mixtures. Full article

Accurate permeability predictions remain pivotal for understanding fluid flow in porous media, influencing crucial operations across petroleum engineering, hydrogeology, and related fields. Traditional approaches, while robust, often grapple with the inherent heterogeneity of reservoir rocks. With the advent of deep learning, convolutional neural networks (CNNs) have emerged as potent tools in image-based permeability estimation, capitalizing on micro-CT scans and digital rock imagery. This paper introduces a novel paradigm, employing vision transformers (ViTs)—a recent advancement in computer vision—for this crucial task. ViTs, which segment images into fixed-sized patches and process them through transformer architectures, present a promising alternative to CNNs. We present a methodology for implementing ViTs for permeability prediction, its results on diverse rock samples, and a comparison against conventional CNNs. The prediction results suggest that, with adequate training data, ViTs can match or surpass the predictive accuracy of CNNs, especially in rocks exhibiting significant heterogeneity. This study underscores the potential of ViTs as an innovative tool in permeability prediction, paving the way for further research and integration into mainstream reservoir characterization workflows. Full article

Varicella-zoster virus (VZV) poses significant public health challenges as the etiological agent of varicella (chickenpox) and herpes zoster (HZ), given its high transmissibility and potential for severe complications. The introduction of VZV vaccines—particularly the vOka-based live attenuated and glycoprotein gE-based recombinant subunit vaccines—has substantially reduced the global incidence of these diseases. However, live attenuated vaccines raise concerns regarding safety and immunogenicity, especially in immunocompromised populations, while recombinant subunit vaccines, such as Shingrix, exhibit high efficacy but are associated with side effects and adjuvant limitations. Recent advancements in vaccine technology, including mRNA vaccines, viral vector vaccines, and virus-like particle (VLP) vaccines, offer promising alternatives with improved safety profiles and durable immunity. This review synthesizes current knowledge on VZV vaccine mechanisms, clinical applications, and immunization strategies, while also examining future directions in vaccine development. The findings underscore the pivotal role of VZV vaccines in disease prevention and highlight the need for continued research to enhance their public health impact. Full article

Suzetrigine represents a groundbreaking advancement in acute pain management as the first FDA-approved selective Na_v1.8 inhibitor. This comprehensive review synthesizes data from clinical trials, pharmacological studies, and prescribing information to evaluate its mechanism, efficacy, safety, and clinical implications. With demonstrated superiority over placebo in pivotal trials (SPID48: 29.3–48.4; p < 0.0001) and a favorable safety profile devoid of opioid-like addiction risks, suzetrigine offers a much-needed alternative in the opioid crisis era. However, its modest effect size compared to full-dose opioids, CYP3A-mediated drug interactions, and limited long-term data warrant judicious use. This article provides a balanced perspective on suzetrigine’s role in modern pain management protocols. Full article

The contemporary food environment is experiencing substantial transformations, and sustainability and the pursuit of novel ingredients have become pivotal factors in consumer decision-making and business strategy formulation. The emergence of alternative proteins has significant implications for sustainability, climate change mitigation and animal welfare, and can potentially promote the achievement of different United Nations Sustainable Development Goals. The spread of these novel foods requires significant attention, particularly concerning younger demographics, which are often considered to be more environmentally and ethically aware when making dietary choices. This study investigates the psychological and attitudinal factors that shape young consumers’ intention to consume plant-based, insect-based, and cultured meat alternative proteins, and verifies the existence of heterogeneous segments of consumers. To this purpose principal component analysis and k-means cluster analysis are employed using data from an online survey conducted in Italy, with a sample of 350 young consumers. The findings reveal that the intention to consume alternative protein sources is not particularly pronounced among the young consumers and differs according to the type of alternative protein. Three different profiles of young consumers were found: traditionalist (39% of the sample); enthusiastic (17%) and open-minded (44%). These segments differ significantly with respect to consumption intention, socio-demographic, lifestyle and psychological variables. The results provide useful insights for policymakers to design targeted interventions to encourage young consumers’ sustainable food choices. The findings could also be useful for marketers interested in investing in such innovations as they can benefit from an in-depth knowledge of this market segment. Full article