Search Results (60)

Background/Objectives: Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders driven by somatic mutations, most commonly those in JAK2, CALR, and MPL. While conventional molecular testing often focuses on these canonical mutations, emerging data suggest that additional mutations and low-variant-allele-frequency (VAF) subclones may contribute to disease progression and prognosis. Methods: We applied ultra-deep targeted sequencing with an error-correction algorithm to analyze bone marrow and peripheral blood samples from 134 patients with essential thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF), secondary myelofibrosis (MF), or post-MPN acute leukemia. Targeted sequencing panels were used to detect disease-associated and clonal driver mutations. Matched germline controls were not systematically available. Results: Low-VAF variants (<5%) were identified in 4/16 (25%) CALR, 3/7 (43%) MPL, and 9/11 (82%) TP53 mutations. In contrast, all TP53 mutations identified at leukemic transformation had VAFs > 5%, suggesting clonal expansion during progression. Paired sequencing at initial MPN diagnosis and leukemic transformation was available for three patients. JAK2 p.V617F VAFs differed according to treatment timing (Kruskal–Wallis test, p = 0.0138), with lower VAFs observed in untreated patients; however, this association may be influenced by treatment-selection confounding. Mutations in ASXL1 and SRSF2 were occasionally observed in ET and secondary MF, although their prognostic significance remains uncertain. Progression analyses were exploratory because of the limited number of events and longitudinally sampled patients, and formal survival or prognostic modeling was not performed. Conclusions: Ultra-deep error-corrected sequencing enables sensitive detection of low-VAF mutations in MPNs, including subclonal events potentially missed by less sensitive assays. These findings demonstrate the potential utility of high-sensitivity panel-based sequencing for molecular characterization of MPN, while larger longitudinal studies are required to establish the prognostic and clinical significance of these findings. Full article

The growing demand for sustainable urban infrastructure requires reliable and energy-efficient lighting solutions, particularly for urban parks characterized by dynamic energy consumption patterns. This study proposes an integrated analytical framework combining deterministic energy system modeling, a novel interaction-oriented metric, and machine learning techniques to evaluate hybrid photovoltaic (PV)–wind systems for urban park lighting applications. Multi-year hourly meteorological and lighting-demand data from millet gardens in Balıkesir and Çanakkale, Türkiye, were analyzed. A Hybrid Energy Synergy Index (HESI) was introduced to quantify the degree of concurrent contribution and coordination between PV and wind resources relative to lighting demand. The results show substantial demand variability, with an average daily demand of approximately 1609 kWh and peak values exceeding 25,600 kWh. Photovoltaic generation dominated total renewable energy production (92.95%), whereas wind energy contributed 7.05%. The average HESI value (≈0.113) indicated weak source coordination, accompanied by persistent energy deficits that occasionally exceeded −20,000 kWh. Reliability analysis revealed severe system inadequacy, with a reliability rate of only 0.000547 (0.055%). Within the evaluated design space, the highest-performing configuration consisted of 49 PV panels and 19 wind turbines; however, reliability improvements remained limited, indicating that capacity expansion alone is insufficient to ensure satisfactory performance. Machine learning models achieved high predictive accuracy for HESI forecasting (R² = 0.9902; MAE = 0.0027), while explainable artificial intelligence identified solar radiation and wind speed as the dominant environmental drivers. The results highlight the importance of integrating renewable energy capacity planning with energy storage support, improved source coordination, and adaptive energy management strategies to enhance the reliability of sustainable urban lighting systems. Full article

The ultimate goal of integrating artificial intelligence into education is to ensure the long-term stability, quality, and sustainability of the educational process, turning it into a tool that consistently improves teaching and learning. Yet its sustainable and responsible integration depends largely on a positive mindset and the pedagogical willingness of future teachers. This study examines the attitudes and readiness of pre-service teachers, specializing in preschool, primary, and subject-specific science education, toward AI integration, with a specific focus on sustainable science education and Green Lab concepts. A mixed-methods study was conducted on a sample of 251 students from the University of Split. Data were analyzed using exploratory factor analysis, standard and Welch ANOVA with Tukey’s HSD and Games–Howell post hoc tests, and multiple linear regression in IBM SPSS 20, and qualitative content analysis. The findings reveal perceived usefulness as a primary driver of AI acceptance across all groups. Science students demonstrated the highest levels of ethical and critical sensitivity but provided the lowest ratings for AI’s practical application in sustainable science education, expressing cautious attitudes and distinct concerns about system reliability. However, no significant difference was found between students with and without a science background in regard to AI’s potential to facilitate sustainable scientific concepts. Furthermore, behavioral analysis demonstrated that even initial, occasional exposure to AI tools significantly boosted students’ perceptions of its utility and sustainable application compared to non-users, whereas increasing the frequency of use resulted in no additional gains. The transition toward sustainable science education requires moving beyond technical literacy toward a comprehensive framework that integrates pedagogical usefulness with ethical responsibility and sustainable scientific application. Future studies should explore potential models that combine the methodological creativity of pre-service educators and teachers with the analytical rigor of science students. Ultimately, this research underscores that an educational policy must integrate digital advancements while strictly maintaining ethical standards and the essential role of human supervision. Full article

At the present stage, driven by China’s “Three Types of Land” reform policies, the inter-action between urban and rural construction land (URCL) has evolved from an administratively dominated allocation structure toward a market-oriented one. Under the impetus of urban–rural transition, China’s urban and rural construction land has developed a symbiotic relationship characterized by internal factor mobility and external environmental constraints. This study develops a symbiosis indicator system and applies a logistic model to quantitatively evaluate the symbiotic relationship between urban construction land and rural construction land from 2009 to 2024 and to trace its evolutionary patterns. The results reveal the following: The symbiotic relationship gradually transitions from competitive symbiosis to mutualistic symbiosis, yet it exhibits frequent fluctuations and occasional transient reversions to competition, indicating that mutualism remains unstable. Urban construction land dominates during competitive symbiosis, whereas rural construction land dominates during mutualistic symbiosis; urban dominance within mutualistic phases occurs only sporadically. The marketization of rural construction land (measured by the leased and sold area and associated income) accelerates efficient urban—rural cooperation; land expropriation and the urbanization rate are key drivers shifting the relationship from competition to mutualism. However, excessive reliance on urbanization may impede the market structure of rural construction land and disrupt the established mutualistic pattern. Full article

Background: POLE-mutated endometrial carcinomas are associated with exceptionally favorable outcomes, forming the basis for treatment de-escalation in early-stage disease. Nevertheless, rare adverse clinical courses have been reported. This study describes an unusual case of late metastatic recurrence in a POLE-mutated tumor and provides a review of similar cases in the literature. Methods: We present a detailed clinical, radiological, pathological, and molecular description of a patient who developed metastatic recurrence 16 years after initial surgery. A systematic literature search was conducted to identify reports of recurrence, progression, or cancer-related death in POLE-mutated endometrial carcinoma, with extraction of recurrence patterns, genomic features, treatment, and outcomes. Results: The patient experienced sequential pulmonary, cerebral, and leptomeningeal metastases despite harboring a canonical POLE hotspot mutation, proficient mismatch repair status, wild-type TP53, no additional known driver mutation beyond PTEN alterations. The literature review identified a small number of similarly adverse cases. Reported recurrences were heterogeneous, though distant and occasionally central nervous system involvement were noted. Conclusions: While POLE-mutated tumors overall retain an excellent prognosis, rare cases may follow an atypical and aggressive course. Improved molecular annotation and integrated risk-stratification models are needed to better identify this minority of higher-risk patients. Full article

This paper investigates a novel variant of the two-echelon vehicle routing problem (2E-VRP) within the context of modern e-commerce logistics. The model integrates time windows, occasional trucks, occasional drivers, heterogeneous regular vehicles, and two increasingly relevant types of intermediate facilities: transshipment nodes and parcel lockers. Goods are transported from a first-echelon depot to intermediate facilities via occasional trucks and heterogeneous regular trucks, then delivered to customers through occasional drivers and heterogeneous regular riders at the second echelon, or retrieved by customers from designated parcel lockers. Given significant disparities in service scope, vehicle attributes, delivery rules, and cost structures between the two echelons, the crowdsourcing model for the first echelon is redesigned, and new intermediate facilities are incorporated to expand application scenarios and further enhance the operational advantages of the crowdsourcing mode. The objective aims to minimize transportation costs and minimize customer dissatisfaction costs. This study constructed a two-echelon vehicle routing optimization model under the crowdsourcing mode with time windows and intermediate facilities and developed an improved multi-objective sparrow algorithm (IMOSSA) to solve it. Algorithm comparisons and extensive case studies validate the algorithm’s effectiveness and superiority. Scenario analysis investigates the impact of crowdsourced vehicles on routing decisions, experimentally demonstrates the crowdsourcing model’s advantages, and derives practical managerial insights. Full article

Sustainability has become a strategic priority in the hospitality sector, particularly in luxury hotels where environmental responsibility must be balanced with high service quality. This study explores hotel managers’ perceptions and experiences of implementing environmentally friendly practices in five-star hotels in Gauteng, South Africa. A qualitative research approach, guided by a constructivist paradigm, was employed using semi-structured interviews with seventeen middle-level managers from major departments in the hotels. Data were manually and software-coded, and thematic analysis produced nine interrelated themes: Adoption Culture, Collaboration Networks, Consumption Tracking, Guest Revenue Drivers, Operational Shifts, Operational Prioritisation, Staff Enablement, Structural Constraints, and Valued Pragmatism. The findings indicate that managers generally perceive sustainability as both an ethical responsibility and a business imperative, particularly in relation to brand reputation, guest expectations, and cost efficiency. However, implementation is constrained by infrastructural instability, high initial investment costs, limited supplier availability, and occasional resistance from staff and guests. The study highlights the importance of embedding sustainability within governance systems, staff practices, and organisational culture to support long-term adoption. This research offers context-specific insights into sustainability implementation in South African luxury hotels and provides practical value for hotel managers, policymakers, and sustainability stakeholders operating in resource-constrained environments. Full article

The MOPLUS project, funded by the Portuguese Recovery and Resilience Plan (PRR), aims to enhance soil organic matter, soil structure, and water retention in apple orchards located in the “Maçã de Alcobaça” Protected Geographical Indication area through organic fertilization based on locally available livestock effluents, thereby reducing reliance on synthetic fertilizers under Mediterranean climatic conditions. This study evaluated the physiological and biometric responses of apple trees subjected to four fertilization strategies (M1–M4) in three commercial ‘Gala’ orchards in central Portugal over three growing seasons (2023–2025). Measurements included leaf functional traits, gas exchange, chlorophyll fluorescence, spectral indices, vegetative growth, fruit production per tree and mean fruit weight. Interannual climatic variability and orchard-specific conditions were the dominant drivers of tree response, while fertilization effects were smaller and mainly expressed through interactions with year and orchard. When analyzed within the same orchard, fertilization strategies M2 and particularly M3 maintained physiological performance, vegetative growth, and fruit production per tree at levels comparable to full mineral fertilization. Among treatments, M3 showed the most consistent responses across sites and years, indicating that partial mineral substitution with pig slurry can sustain tree functioning while maintaining or enhancing fruit production per tree. The most restrictive strategy (M4) occasionally showed reduced photosynthetic performance under specific orchard–year combinations, suggesting a threshold effect associated with stronger mineral reduction, but without evidence of generalized physiological stress. Overall, these findings demonstrate that partial substitution of mineral fertilizers by organic amendments—especially pig slurry (M3) and, to a lesser extent, composted cattle manure (M2)—is agronomically viable, allowing apple tree performance and productivity to be maintained while enhancing system resilience under Mediterranean climatic variability. These results also provide practical decision support for site-adapted fertilization management in commercial drip-irrigated apple orchards, supporting reduced mineral fertilizer dependence without compromising productivity. Full article

In the field of logistics distribution, the two-echelon vehicle routing problem has long been a critical focus. Against the backdrop of global warming, enterprises conducting logistics operations must now prioritize not only delivery costs but also the environmental impact of carbon emissions. To address these challenges, this study integrates occasional drivers into the two-echelon vehicle routing framework, centering on carbon emission reduction. First, Affinity Propagation (AP) clustering is applied to assign customer points to transfer centers. Subsequently, an optimization model is formulated to minimize both vehicle routing costs and carbon emission costs through a collaborative delivery system involving specialized and crowdsourced vehicles. An enhanced Sparrow–Whale Optimization Algorithm (S-WOA) is proposed to solve the model. The algorithm is tested against traditional heuristic methods on three datasets of different scales. Experimental results demonstrate that the two-echelon logistics and distribution model combining specialized vehicles and occasional drivers achieves a significant reduction in total delivery costs compared to models relying solely on specialized vehicles. Further analysis reveals that, with a fixed crowdsourced compensation coefficient, increasing the crowdsourced detour coefficient leads to a decline in total delivery costs. Conversely, when the detour coefficient remains constant, raising the compensation coefficient results in an upward trend in total costs. These insights provide actionable strategies for optimizing cost-efficiency and sustainability in logistics operations. Full article

Wetlands in dryland regions are rapidly degrading under the combined effects of climate change and human regulation, yet long-term, seasonally resolved assessments of surface water extent (SWE) and its dynamics remain scarce. Here, we map and analyze seasonal surface water extent (SWE) over the period 2000–2024 in the Ile River Delta (IRD), south-eastern Kazakhstan, using Landsat TM/ETM+/OLI data within the Google Earth Engine (GEE) framework. We integrate multiple indices using the modified Normalized Difference Water Index (mNDWI), Automated Water Extraction Index (AWEI) variants, Water Index 2015 (WI2015), and Multi-Band Water Index (MBWI) with dynamic Otsu thresholding. The resulting index-wise binary water maps are merged via ensemble agreement (intersection, majority, union) to delineate three SWE regimes: stable (persists most of the time), periodic (appears regularly but not in every season), and ephemeral (appears only occasionally). Validation against Sentinel-2 imagery showed high accuracy F1-Score/Overall accuracy (F1/OA ≈ 0.85/85%), confirming our workflow to be robust. Hydroclimatic drivers were evaluated through modified Mann–Kendall (MMK) and Spearman’s (r) correlations between SWE, discharge (D), water level (WL), precipitation (P), and air temperature (AT), while a hybrid ensemble–occurrence framework was applied to identify degradation and transition patterns. Trend analysis revealed significant long–term declines, most pronounced during summer and fall. Discharge is predominantly controlled by stable spring SWE, while discharge and temperature jointly influence periodic SWE in summer–fall, with warming reducing the delta surface water. Ephemeral SWE responds episodically to flow pulses, whereas precipitation played a limited role in this semi–arid region. Spatially, area(s) of interest (AOI)-II/III (the main distributary system) support the most extensive yet dynamic wetlands. In contrast, AOI-I and AOI-IV host smaller, more constrained wetland mosaics. AOI-I shows persistence under steady low flows, while AOI-IV reflects a stressed system with sporadic high-water levels. Overall, the results highlight the dominant influence of flow regulation and distributary allocation on IRD hydrology and the need for ecologically timed releases, targeted restoration, and transboundary cooperation to sustain delta resilience. Full article

Background: Tick-borne encephalitis (TBE) virus is transmitted to humans via tick bites and occasionally via the consumption of unpasteurized milk products. According to the literature, the most important driver of TBE emergence and increase in incidence in humans is changes in human behaviour/activities. Method and principal findings: To compensate for the lack of data, expert opinions were gathered to identify the risk factors for exposure to tick bites linked to twenty-eight human activities (professional or recreational) in forests and to target prevention messages at the populations most at risk. Opinions were elicited from a total of twenty-five European experts. Seven criteria were included in the analysis for each activity: frequency, seasonality, duration of exposure, distance covered, degree of contact with vegetation, speed and average level of protection against tick bites. The activities considered to be the most at risk of exposure to tick bites are, in descending order: three occupational activities (forest monitoring activities, forestry and wood industry activities and scientific and/or analytical activities), five recreational activities and one hunting activity (mushroom picking, spending the night in the forest, hunting, naturalist activities, orienteering, and berry or fruit picking). Conclusions and significance: Prevention messages regarding tick bites could be targeted at people who engage in activities considered in this analysis to be at highest risk of exposure to tick bites. Full article

Objectives: Atypical teratoid/rhabdoid tumors (ATRTs) are rare, malignant central nervous system (CNS) neoplasms that predominantly affect infants and young children. While ATRT arises throughout the CNS, its extracranial counterpart, malignant rhabdoid tumor, occurs in other organs. A single-institutional cohort is reviewed to map anatomic distribution of pediatric ATRTs and to integrate a literature review to contextualize ATRT histogenesis from anatomical and embryological perspectives. Methods: A retrospective review was conducted on a cohort of 50 pediatric patients with ATRT treated over 20 years. Demographic, surgical, and neuroimaging data were correlated to define tumor location, extent, and compartmental involvement. A focused literature review synthesized molecular subclassifications and proposed cells of origin/cytogenesis. Results: Of the 50 ATRTs, 18 (36%) were infratentorial, 15 (30%) supratentorial, 11 (22%) in the pineal region, and 6 (12%) in the spinal compartment. Among infratentorial tumors, 10 were centered in the fourth ventricle, with or without extension into the cerebellopontine angle (CPA) cistern; the remainder arose in the CPA. Among ATRTs of the cerebral hemispheres, 3 showed bi-hemispheric involvement crossing the falx cerebri. ATRTs of the pineal region predominantly originated from the superior medullary velum. These topographic data were corelated with embryological and molecular information available in the literature. Conclusions: ATRTs arise across diverse neuroanatomical compartments—including intraparenchymal, intraventricular, extra-axial, and extradural sites—underscoring biological heterogeneity. Inactivation of SMARCB1 is the defining molecular event and principal oncogenic driver, although the upstream mechanisms precipitating these alterations remain incompletely resolved. Molecular subgroups—ATRT-TYR, ATRT-SHH, and ATRT-MYC—display distinct age distributions and anatomic predilections, implicating developmental context in tumor initiation. The characteristic cellular admixture of rhabdoid cells with mesenchymal and/or epithelial differentiation, together with intra- and extra-axial and occasional extradural presentations, supports a model in which at least a subset of ATRTs may originate from neural crest-derived lineages, despite little or no neural crest contribution to brain parenchyma development. Neural plate border progenitors with bipotent features represent a plausible intraparenchymal cell of origin. Definitive resolution of these origins and the mechanisms of SMARCB1 disruption will require integrated approaches. Further investigations are warranted to clarify these mechanisms. Full article

The sustainable development of ecologically sensitive areas, such as geoparks, requires a comprehensive understanding of the complex interactions between tourism expansion and ecosystem services (ESs). This study investigates these relationships through a case study of the Enshi Grand Canyon—Tenglongdong Cave UNESCO (United Nations Educational, Scientific, and Cultural Organization) Global Geopark, a representative karst landscape in China. We developed an integrated analytical framework that combines multi-source data with coupled modeling approaches, including the Integrated Valuation of ES and Tradeoffs (InVEST), Geographically and Temporally Weighted Regression (GTWR), Boosted Regression Tree (BRT), and structural equation modeling (SEM). This framework overcomes the limitations of single-method analyses and enables a comprehensive diagnosis of the spatiotemporal drivers and pathways influencing ES dynamics. Using this approach, we analyzed the evolution of ESs and their driving factors from 2010 to 2020. The results reveal that natural factors remained the dominant drivers of ESs (accounting for over 73% of total variation), while tourism impacts increased substantially over time and exhibited pronounced spatial heterogeneity. Specifically, (1) the tourism-driven expansion of construction land occurred largely at the expense of cultivated land and grassland, directly reducing ESs; (2) proximity to scenic areas intensified negative ecological effects, whereas proximity to roads and hotels displayed more complex, and occasionally positive, influences; and (3) tourism primarily affected ESs indirectly through land use/cover change (LUCC). This study provides a transferable framework for analyzing tourism–ecosystem service interactions and underscores the necessity of ecological zoning and adaptive management in vulnerable karst regions, offering valuable insights for the sustainable governance of other fragile ecosystems worldwide. Full article

This study examines the application of large language models (LLMs) in analyzing subjective driver perceptions during tunnel driving simulations, comparing the effectiveness of questionnaires and interviews. Building on previous research involving driver simulations, we recruited 29 new participants, collected their perceptions via questionnaires, and conducted follow-up interviews. The interview data were analyzed using three LLMs: GPT-3.5, GPT-4, and Google-Gemini. The results revealed that while GPT-4 provides more in-depth and accurate analysis, it is significantly slower than GPT-3.5. Conversely, Google-Gemini demonstrated a balance between analysis quality and speed, outperforming the other models overall. Despite the challenge of occasional misunderstandings, LLMs still have the potential to enhance the efficiency and accuracy of subjective data analysis in transportation research. Full article

Introduction: Gastrointestinal stromal tumors (GISTs) are primarily driven by mutations in KIT (KIT proto-oncogene receptor tyrosine kinase) or PDGFRA (platelet-derived growth factor receptor alpha), but resistance to tyrosine kinase inhibitors (TKIs) such as imatinib remains a major clinical challenge. Alterations in fibroblast growth factor receptor 2 (FGFR2), although rare, are emerging as important contributors to tumor progression and drug resistance. This review evaluates the molecular mechanisms, expression profiles, detection methods, and therapeutic implications of FGFR2 in GIST. Methods: We searched PubMed, Web of Science, Google Scholar, and ClinicalTrials.gov for studies published between January 2010 and June 2025, using combinations of keywords related to FGFR2, gastrointestinal stromal tumor, resistance mechanisms, gene fusion, amplification, polymorphisms, and targeted therapy. Eligible studies were critically assessed to distinguish GIST-specific data from evidence extrapolated from other cancers. Results:FGFR2 is expressed in multiple normal tissues and at variable levels in mesenchymal-derived tumors, including GIST. Its alterations occur in approximately 1–2% of GIST cases, most commonly as gene fusions (e.g., FGFR2::TACC2, <1%) or amplifications (1–2%); point mutations and clinically significant polymorphisms are extremely rare. These alterations activate the MAPK/ERK and PI3K/AKT pathways, contribute to bypass signaling, and enhance DNA damage repair, thereby promoting TKI resistance. Beyond mutations, mechanisms such as amplification, ligand overexpression, and microenvironmental interactions also play roles. FGFR2 alterations appear mutually exclusive with KIT/PDGFRA mutations but occasional co-occurrence has been reported. Current clinical evidence is largely limited to small cohorts, basket trials, or case reports. Conclusions:FGFR2 is an emerging oncogenic driver and biomarker of resistance in a rare subset of GISTs. Although direct evidence remains limited, particularly regarding DNA repair and polymorphisms, FGFR2-targeted therapies (e.g., erdafitinib, pemigatinib) show potential, especially in combination with TKIs or DNA-damaging agents. Future research should prioritize GIST-specific clinical trials, the development of FGFR2-driven models, and standardized molecular diagnostics to validate FGFR2 as a therapeutic target. Full article