Search Results (7,131)

In this study, we investigate the learning opportunities offered in the enactment of a finger pattern activity with numbers exceeding 10 that shows how smaller units can be composed into larger units. Research on early arithmetic learning shows the importance of students understanding numbers as composed units and making use of arithmetic strategies that are based on unitizing rather than single-unit counting. The Many Hands activity was enacted in an intervention program focusing on 6-year-olds’ learning of structuring numbers and number relations during one school year, conducted in collaboration with teachers. The activity, with numbers exceeding 10, was enacted at the end of the program. Video observations of 19 teaching episodes in which the activity was used were analyzed using the variation theory of learning. The analysis focused on identifying which aspects of numbers were made visible for students to discern and how finger patterns became a tool for structuring numbers and number relations. Five aspects were made visible in the enactments of the Many Hands activity: (i) small numbers as composed units; (ii) units within units; (iii) units within units and new, larger units; (iv) relationships between units in the number system; and (v) place value. In 12 of the 19 episodes, the teacher or the students used their fingers to show and see the structure of numbers in relation to the identified aspects. Full article

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

Rationale: The ProMisE molecular classification improves risk assessment in endometrial cancer (EC), but 3–11% of cases exhibit overlapping molecular features, complicating clinical decisions. We analyzed the prevalence and clinicopathological profiles of multiple-classifier ECs in a large Polish cohort. Methods: In this retrospective study (2022–2025), 1075 ECs from four institutions were classified by MMR and p53 immunohistochemistry and POLE exon sequencing. Tumors showing ≥2 molecular features (e.g., MMRd–p53abn, POLEmut–p53abn) were categorized as multiple-classifier ECs. Results: Multiple-classifier ECs comprised 6.9% (74/1075), with MMRd–p53abn (3.9%) being most common. These tumors exhibited more aggressive features vs. MMRd-only: G3 (28.57% vs. 11.79%, p = 0.002), non-endometrioid histology (11.9% vs. 2.85%, p = 0.018), and high–intermediate/high-risk (HIR/HR) groups (59.52% vs. 37.80%, p = 0.001). POLEmut–p53abn (N = 4) and POLEmut–MMRd–p53abn (N = 10) tumors showed advanced stages (75% and 40% FIGO III–IV, respectively), in contrast to classical POLEmut tumors (6.7% FIGO III–IV), and higher rates of nodal metastases. Conclusions: Co-occurrence of molecular classifiers, including triple-classifier tumors, correlates with more adverse profiles and may undermine current stratification paradigms. This study emphasizes the need to further investigate and refine molecular risk models to account for overlapping profiles. Full article

Laizhou Bay, a semi-enclosed bay, is prone to storm surges from cold waves due to its geographic and environmental characteristics. This study uses satellite data, in situ measurements, and the MIKE numerical model to analyze storm surges along Laizhou Bay’s coast under no-dike conditions. It examines the surges caused by cold waves with different intensities and directions. This study provides the storm surge disaster risk levels along Laizhou Bay’s coast. The results show that the maximum sustained wind speed during cold waves is distributed between the NW and NE. The NE wind direction causes the most severe storm surge along Laizhou Bay. Under NE-directed cold waves with level 12 wind, the maximum risk areas for Level III and IV are approximately 1341 km² and 1294 km², respectively. Dongying, Shouguang, and Hanting exhibit large Level I and II risk zones. The maximum seawater intrusion distance along the Kenli coast is about 41 km. The coastal segment from Kenli to Changyi is most severely affected by storm surges. It is recommended to effectively maintain and heighten seawalls along this segment to mitigate storm surge disasters caused by strong NE winds. Full article

Background/Objectives: Mutations in the BRCA1 and BRCA2 genes are well-known risk factors for ovarian cancer. They are also associated with response to platinum-based chemotherapy; however, their definitive impact on patient prognosis remains not fully understood. This study aimed to investigate the influence of BRCA mutation status on the age of ovarian cancer onset and on treatment outcomes in patients with high-grade serous ovarian cancer. Methods: This single-center retrospective analysis included newly diagnosed FIGO stage III and IV HGSOC patients treated between June 2018 and April 2023. Patients’ age, tumor histology, CA125 levels, BRCA mutation status, type of treatment (neoadjuvant or adjuvant chemotherapy), and surgical outcomes were collected and analyzed. Survival analyses were performed using the Kaplan–Meier method and log-rank test. Results: Pathogenic mutations were identified in 25 patients (15 in BRCA1, 10 in BRCA2). Patients with a BRCA mutation were diagnosed at a significantly younger age (median 58.78 years) compared to non-carriers (66.81 years; p < 0.001), with BRCA1 carriers being diagnosed the youngest (median 46.52 years). The study found no statistically significant difference in progression-free survival (PFS) between BRCA carriers and non-carriers. However, a significant improvement in overall survival (OS) was observed for patients with a BRCA1 mutation (p = 0.036). No significant OS difference was found for BRCA2 carriers. Conclusions: BRCA mutations, particularly in the BRCA1 gene, are associated with an earlier onset ovarian cancer. BRCA1 mutation appears to be a favorable prognostic factor for overall survival in patients with HGSOC. Our findings demonstrate the clinical implications of different BRCA mutations and support the need for further research in larger cohorts to confirm their influence on prognostic effects. Full article

Transcranial direct current stimulation (tDCS) can modulate cortical excitability in a polarity-specific manner, yet identical protocols often produce inconsistent outcomes across sessions or individuals. This narrative review proposes that much of this variability arises from the brain’s intrinsic temporal landscape. Integrating evidence from chronobiology, sleep research, and non-invasive brain stimulation, we argue that tDCS produces reliable, polarity-specific after-effects only within a circadian–homeostatic “window of efficacy”. On the circadian (Process C) axis, intrinsic alertness, membrane depolarisation, and glutamatergic gain rise in the late biological morning and early evening, whereas pre-dawn phases are marked by reduced excitability and heightened inhibition. On the homeostatic (Process S) axis, consolidated sleep renormalises synaptic weights, widening the capacity for further potentiation, whereas prolonged wakefulness saturates plasticity and can even reverse the usual anodal/cathodal polarity rules. Human stimulation studies mirror this two-process fingerprint: sleep deprivation abolishes anodal long-term-potentiation-like effects and converts cathodal inhibition into facilitation, while stimulating at each participant’s chronotype-aligned (phase-aligned) peak time amplifies and prolongs after-effects even under equal sleep pressure. From these observations we derive practical recommendations: (i) schedule excitatory tDCS after restorative sleep and near the individual wake-maintenance zone; (ii) avoid sessions at high sleep pressure or circadian troughs; (iii) log melatonin phase, chronotype, recent sleep and, where feasible, core temperature; and (iv) consider mild pre-heating or time-restricted feeding as physiological primers. By viewing Borbély’s two-process model and allied metabolic clocks as adjustable knobs for plasticity engineering, this review provides a conceptual scaffold for personalised, time-sensitive tDCS protocols that could improve reproducibility in research and therapeutic gain in the clinic. Full article

Van der Waals (vdW) heterostructures, typically composed of two-dimensional (2D) atomic layers, have attracted significant attention over the past few decades. Their performance is closely dependent on their composition and interlayer interactions. In this study, we constructed four types of 2D hexagonal BP monolayer (h-BP)/borophosphene vdW heterostructures with different stacking orders: (i) B-B stacking, (ii) P-P stacking, (iii) moire-I, and (iv) moire-II. Their structural stability and their electronic and optical properties were explored by using first-principles calculations. The results show that h-BP/borophosphene heterostructures can maintain their configurations with good structural stability and minimal lattice mismatch. All vdW heterostructures exhibit semiconducting characteristics, and their band gaps are highly dependent on interlayer stacking orders. Due to the regular atomic arrangement and enhanced interlayer dipole interactions, the B-B stacking bilayer opens a relatively large band gap of 0.157 eV, while the moire-II bilayer exhibits a very small band gap of 0.045 eV because of its irregular atom arrangements. By calculating the complex dielectric function, optical absorption spectra of B-B and P-P stacking bilayers were discussed. This study suggests that h-BP/borophosphene heterostructures have desirable optical properties, broadening the potential applications of the constituent monolayers. Full article

Untreated sewage sludge (SS) and misused stabilization technologies have contributed to great contamination and the accumulation of various pollutants in agricultural soils. Regarding micro-pollutants’ degradation, scalable and effective technologies are still scarce. Although many attempts at composting adaptations have been discussed, only a few have been tested individually under outdoor conditions. To investigate different composting methods (bioaugmentation and semipermeable cover) for the removal of micro-pollutants frequently found in SS, we performed a set of on-site experiments. Windrows of SS and olive pruning were used as the compostable material and were subjected to (i) bioaugmentation with the fungus Penicillium oxalicum, (ii) covered composting, (iii) covered and bioaugmented composting, and (iv) a conventional composting pile, which was included as a control. The entire experiment lasted 99 days. Bioaugmentation without cover increased the phosphorus content, favored a reduction in heavy metal content, and was the only treatment that reduced carbamazepine at the end of the process. Moreover, the inoculation of P. oxalicum under semipermeable cover increased the richness, diversity, and dominance of specific microbial taxa and total bacterial abundance. The four mature composts obtained met the standards required to be classified in the B fertilizer category, showing that we reduced most of the micro-pollutants, and passed the germination test. Full article

PD-L1, PD-1, FOXP3, and miR-155 are emerging as key modulators of immune evasion and progression of oral squamous cell carcinoma (OSCC). This study investigated the clinical relevance of their gene expression and variants in HPV-negative OSCC. Bulk-tissue mRNA expression was evaluated in 70 patients, while variants in PD-1 (rs36084323), PD-L1 (rs822336, rs4143815, copy number variation), FOXP3 (rs3761548, rs2232365), and miR-155 (rs767649) were assessed in 134 patients. Expression data were validated using the TCGA cohort of 222 HPV-negative OSCC cases. Low FOXP3 expression was significantly associated with tumor stage (MMA: p = 0.028, TCGA: p = 0.025) and poor overall survival (MMA: p = 0.0004, TCGA: p = 0.019) in both cohorts. Declining FOXP3 expression correlated with advancing tumor stages, and low FOXP3 expression was significantly associated with poor survival in advanced stage III–IV tumors (MMA: p = 0.001, TCGA: p = 0.015), but not early-stage tumors. High miR-155 expression was associated with recurrence (p = 0.002) and poor survival in the MMA (p = 0.007), but not TCGA cohort. MiR-155 rs767649 was associated with alcohol consumption (p = 0.018). These findings point to FOXP3 and miR-155 as potential prognostic biomarkers for HPV-negative OSCC. Stage-specific FOXP3 expression suggests a dynamic immunoregulatory role, with implications for optimizing immunotherapy timing. Further studies are warranted to resolve cellular context and stage-adapted immune interventions in HPV-negative OSCC. Full article

The deformation characteristics of the surrounding rock in tunnel groups are considered critical for the design of support structures and the assurance of the long-term safety of deep-buried diversion tunnels. The deformation behavior of surrounding rock in tunnel groups was investigated to guide structural support design. Field tests and numerical simulations were performed to analyze the distribution of ground stress and the ground reaction curve under varying conditions, including rock type, tunnel spacing, and burial depth. A solid unit–structural unit coupled simulation approach was adopted to derive the two-liner support characteristic curve and to examine the propagation behavior of concrete cracks. The influences of surrounding rock strength, reinforcement ratio, and secondary lining thickness on the bearing capacity of the secondary lining were systematically evaluated. The following findings were obtained: (1) The tunnel group effect was found to be negligible when the spacing (D) was ≥65 m and the burial depth was 1600 m. (2) Both P₀.₃ and P_max of the secondary lining increased linearly with reinforcement ratio and thickness. (3) For surrounding rock of grade III (IV), 95% u_lim and 90% u_lim were found to be optimal support timings, with secondary lining forces remaining well below the cracking stress during construction. (4) For surrounding rock of grade V in tunnels with a burial depth of 200 m, 90% u_lim is recommended as the initial support timing. Support timings for tunnels with burial depths between 400 m and 800 m are 40 cm, 50 cm, and 60 cm, respectively. Design parameters should be adjusted based on grouting effects and monitoring data. Additional reinforcement is recommended for tunnels with burial depths between 1000 m and 2000 m to improve bearing capacity, with measures to enhance impermeability and reduce external water pressure. These findings contribute to the safe and reliable design of support structures for deep-buried diversion tunnels, providing technical support for design optimization and long-term operation. Full article

Objective: Uncovering the renoprotective and anti-inflammatory effects of atorvastatin treatment in diabetic-and-obese rats by employing traditional renal function indicators (urea and creatinine) and four prototypical cytokines (IL-1β, il-6, IL-17α, TNFα). Method: Twenty-eight male Wistar rats, aged 6 months, 350–400 g, were randomized into four groups. The first group, G-I, the denominated control, were fed standard chow over the whole course of the experiments. The rodents in G-II were exposed to a High-Fat Diet. The last two groups were exposed to Streptozotocin peritoneal injection (35 mg/kg of body weight). A short biochemical assessment was performed before diabetes model induction to ensure appropriate glucose metabolism before experiments. Following model induction, only rodents in group G-IV were gradually introduced to the same High-Fat Diet as received by G-II. Model confirmation 10 days after injections marked the start of statin treatment in group G-IV, by daily gavage of atorvastatin 20 mg/kg of body weight/day for 21 days. At the end of the experiments, the biochemical profile of interest comprised typical renal retention byproducts (urea and creatinine) and the inflammatory profile described using plasma levels of TNFα, IL-17α, IL-6, and IL-1β. Results: Treatment with Atorvastatin was associated with a statistically significant improvement in renal function in G-IV compared to untreated diabetic rodents in G-III. Changes in inflammatory activity showed partial association with statin therapy, TNFα and IL-17α mirroring the trend in urea and creatinine values. Conclusions: Our results indicate that atorvastatin treatment yields a myriad of pleiotropic activities, among which renal protection was clearly demonstrated in this model of diabetic-and-obese rodents. The statin impact on inflammation regulation may not be as clear-cut, but the potential synergy of renal function preservation and partial tapering of inflammatory activity requires further research in severely metabolically challenged models. Full article

Proto-oncogenes in the RAS superfamily play dual roles in maintaining cellular homeostasis, such as regulating growth signals and contributing to cancer development through proliferation and deregulation. Activating proto-oncogenes in vitro transforms cells, underscoring their centrality in gene regulation and cellular networks. Despite decades of research, poor outcomes in advanced cancers reveal gaps in understanding Ras-driven mechanisms or therapeutic strategies. This narrative review examines RAS genes and Ras proteins in both housekeeping functions, such as cell growth, apoptosis, and protein trafficking, as well as in tumorigenesis, integrating insights from human (HRAS, KRAS, NRAS), mouse (Hras, Kras, Nras), and Drosophila melanogaster (ras) models. While RAS mutations are tightly linked to human tumors, the interplay between their standard and oncogenic functions remains complex. Even within the same tissue, distinct cancer pathways—such as the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways—can drive varied disease courses, complicating treatment. Advanced-stage cancers add further challenges, including heterogeneity, protective microenvironments, drug resistance, and adaptive progression. This synthesis organizes current knowledge of RAS gene regulation and Ras protein function from genomic alterations and intracellular signaling to membrane dynamics and extracellular interactions, offering a layered perspective on the Ras pathway’s role in both housekeeping and tumorigenic contexts. Full article

West Africa faces persistent food and nutrition insecurity despite agricultural efforts, exacerbated by population growth, climate change, and socio-economic vulnerabilities. This study argues that integrating food processing principles with nutrition-sensitive agriculture (NSA) and nutrition-smart agriculture (NSmartAg) offers a transformative solution for human health. Therefore, we delineate these interconnected concepts and highlight their synergistic potential for a nutrition-focused food system. Likewise, critical analysis of key regional challenges, including infrastructural weaknesses, policy gaps, and gender inequities, was made prior to identifying significant opportunities for leveraging food processing as a strategic entry point to accelerate the implementation of NSA and NSmartAg. Based on these insights, six strategic pathways are proposed to achieve this objective: (i) integrating food processing into policies; (ii) investing in interdisciplinary R&D that puts nutrition and health benefits at the forefront of desired outcomes along with others; (iii) strengthening farmer and food processor capacities; (iv) improving agri-food infrastructure; (v) fostering multi-sectoral collaboration; and (vi) prioritizing youth engagement and market development. By adopting these integrated strategies, West African countries can build more resilient, equitable, and nutrition-centered food systems, ultimately improving public health outcomes and fostering sustainable regional development. Full article

Hepatitis E virus (HEV) poses a significant public health concern, particularly among immunocompromised populations. This study aimed to investigate HEV seroprevalence, clinical characteristics, and associated risk factors in people living with HIV (PLWH) in Shanghai, China. A retrospective analysis was conducted on serum IgG and IgM antibodies specific to HEV in 670 PLWH and 464 HIV-negative health-check attendees. The overall anti-HEV seropositivity rate among PLWH was 30.15% (202/670, 95% CI 26.68–33.62), with an IgG positivity rate of 30.00% (201/670, 95% CI 26.53–33.47). IgM positivity was observed in 1.19% (8/670, 95% CI 0.59–2.39) of PLWH, and dual IgM/IgG positivity was observed in 1.04% (7/670, 95% CI 0.50–2.16) of PLWH. The seropositivity rate of anti-HEV IgG in the HIV-negative health-check attendees was 17.67% (82/464, 95% confidence interval: 14.20–21.14), with no IgM positivity, which was significantly lower than that in PLWH (χ² = 22.84, p < 0.001). Univariate and multivariate analyses identified advanced World Health Organization (WHO) HIV stage (III/IV) as an independent risk factor for HEV co-infection (p < 0.05). Notably, no significant associations were observed with age, gender, CD4 count, or liver function parameters. These findings underscore the importance of implementing HEV screening protocols and developing targeted preventive strategies for PLWH. Full article

Hydrogen produced from renewable sources has the potential to tackle various energy challenges, from allowing cost-effective transportation of renewable energy from production to consumption regions to decarbonizing intensive energy consumption industries. Due to its application versatility and non-greenhouse gaseous emissions characteristics, it is expected that hydrogen will play an important role in the decarbonization strategies set out for 2050. Currently, there are some barriers and challenges that need to be addressed to fully take advantage of the opportunities associated with hydrogen. The present work aims to characterize the state of the art of different hydrogen production, storage, transport, and distribution technologies, which compose the hydrogen value chain. Based on the information collected it was possible to conclude the following: (i) Electrolysis is the frontrunner to produce green hydrogen at a large scale (efficiency up to 80%) since some of the production technologies under this category have already achieved a commercially available state; (ii) in the storage phase, various technologies may be suitable based on specific conditions and purposes. Technologies of the physical-based type are the ones mostly used in real applications; (iii) transportation and distribution options should be viewed as complementary rather than competitive, as the most suitable option varies based on transportation distance and hydrogen quantity; and (iv) a single value chain configuration cannot be universally applied. Therefore, each case requires a comprehensive analysis of the entire value chain. Methodologies, like life cycle assessment, should be utilized to support the decision-making process. Full article