Search Results (18,297)

Background: Hormone-receptor-positive (HR+)/HER2-negative (HER2−breast cancer (BC) is characterized by low immunogenicity and an immunosuppressive microenvironment. These features likely contribute to the inconsistent clinical activity of immune checkpoint inhibitors (ICIs) in this BC subtype. We conducted a systematic review of clinical trials evaluating ICIs in HR+/HER2− BC patients, focusing on potential biomarkers of response and resistance to these drugs. Methods: We systematically searched in Medline via PubMed, EMBASE, and CENTRAL for phase II/III clinical trials published between 2013 and 2023, testing ICIs alone or in combination with other agents in HR+/HER2− BC patients at any stage. All the searches were performed up to 27 January 2024. Data on study characteristics, clinical outcomes, and biomarker profiles were extracted, and due to study heterogeneity, a narrative synthesis was performed, without risk-of-bias assessment or meta-analysis. Results: Twenty-five studies were included, with 3298 patients enrolled overall. Eighteen of these trials enrolled patients with advanced disease. All trials investigated ICI combination regimens, more frequently with chemotherapy, CDK4/6 inhibitors, or other immunotherapeutic agents. Most of the studies enrolling patients with advanced disease failed to show a significant clinical activity of ICIs. In the early setting, neoadjuvant chemo-immunotherapy with nivolumab or pembrolizumab increased the rate of complete responses compared to chemotherapy alone. Moreover, high programmed death-ligand 1 (PD-L1) expression, low ER (estrogen receptor), and high tumor-infiltrating lymphocyte (TIL) levels correlated with improved outcomes. Consistently, markers indicating enhanced immune activation, such as the MammaPrint High 2 (MP2) genomic signature, were associated with increased ICI sensitivity. Discussion: Despite the limited overall efficacy, ICIs may represent a viable therapeutic option for a selected subset of HR+/HER2− BC patients. However, this systematic review is limited by study heterogeneity and the inclusion of ongoing or immature trials, which prevents quantitative analysis and may affect future conclusions on ICIs in HR+/HER2− breast cancer. Finally, optimized combination strategies could enhance tumor immunogenicity, while predictive biomarkers such as PD-L1, TILs, or specific genomic signatures could identify responsive patients. Full article

Verticillium wilt, caused by Verticillium dahliae, severely threatens various crops and trees worldwide. This study aimed to characterize the function of a CUE (coupling of ubiquitin conjugation to endoplasmic reticulum (ER) degradation)-domain-containing protein, VdCUE, in V. dahliae, which exhibits sequence divergence between the defoliating strain XJ592 and the non-defoliating strain XJ511. We generated ∆VdCUE-knockout mutants and evaluated their phenotypes in growth and virulence. Functional analyses included verifying the signal peptide activity of VdCUE, testing its ability to induce cell death or inhibit BAX-induced cell death in Nicotiana benthamiana leaves, and identifying host targets via yeast two-hybrid screening. The ∆VdCUE mutants showed reduced formation of melanized microsclerotia but no other obvious growth defects. Cotton plants infected with the ∆VdCUE mutants exhibited a significantly lower disease index and defoliation rate. VdCUE was confirmed to be secreted via a functional signal peptide, but it neither triggered cell death nor inhibited BAX-induced cell death. Three putative host targets were identified and supported by AI-based three-dimensional structural modeling, including tRNA-specific 2-thiouridylase, peptidyl-prolyl cis-trans isomerase, and 40S ribosomal protein, which may mediate VdCUE-dependent virulence regulation. These findings reveal VdCUE as a key virulence factor in V. dahliae, contributing to our understanding of its pathogenic mechanism. Full article

Chronic kidney disease of unknown origin (CKDu) is a public health concern, particularly in agricultural communities, with multiple environmental exposures hypothesized as potential contributors. This study employed a targeted exposure assessment using personal silicone wristbands to characterize chemical exposures among women living and working in CKDu-affected regions of Guatemala. Participants wore wristbands for seven days, passively sampling air and dermal exposures. Overall, 45 wristbands were collected from 37 female participants (19 sugarcane workers and 18 community members). Of the 1530 chemicals measured using a single semi-quantitative method, 103 were detected, with an average of 27 chemicals per wristband (range: 16–40). Polycyclic aromatic hydrocarbon (PAH) levels were higher in community members’ wristbands, whereas workers exhibited higher exposure to pesticides (i.e., pendimethalin and fipronil). Workers had worse kidney function compared to community members, with almost half of the workers having an estimated glomerular filtration rate, eGFR, <90 mL/min/1.73 m². Correlations were observed between kidney function markers and specific chemicals, with the strongest correlation between albumin-to-creatinine ratio and pyrene levels (ρ = 0.57, p < 0.01) among workers. Women in agricultural regions of Guatemala experience widespread exposure to diverse environmental chemicals, some of which may contribute to kidney function decline. Full article

This article presents a comprehensive bibliometric analysis of scientific production in Central America between 1996 and 2023, based on data indexed in the Scopus database. The study frames the investigation within the broader context of scientific visibility and regional development, aiming to evaluate trends in research productivity, thematic specialization, and patterns of scientific collaboration across Belize, Guatemala, Honduras, El Salvador, Nicaragua, Costa Rica, and Panama. A total of 35,146 articles authored by researchers affiliated with institutions in Central America were analyzed using indicators such as publication volume, subject areas, journal impact and co-authorship data provided by Scopus. The findings reveal a consistent annual growth rate of 7%, yet with marked disparities among countries. Costa Rica, Panama, and Guatemala account for 82% of the total scientific output, while the remaining countries contribute only 18%. Research activity is primarily concentrated in the medical, agricultural, biological, and environmental sciences. Over 80% of publications involve international collaboration, predominantly with the United States, Spain, and Mexico, whereas intraregional cooperation remains limited. The analysis underscores the region’s reliance on global research networks and reveals persistent internal asymmetries in scientific development. The results suggest the need for increased investment in national research systems, stronger regional collaboration, and targeted strategies to balance scientific production across countries. Full article

Investigating rainfall infiltration mechanisms and slope stability dynamics under varying vegetation cover conditions is essential for advancing ecological slope protection methodologies. This research focuses on large-scale outdoor slope models, with the objective of monitoring soil moisture variations in real-time during rainfall events on four types of slopes: bare, herbaceous, shrub, and mixed herb–shrub planting. Combining direct shear tests for unsaturated soil with numerical simulations, and considering the weakening effect of water on shear strength, this study analyzes slope stability. The findings reveal significant spatial variations in rainfall infiltration rates, with maximum values recorded at a burial depth of 0.2 m, declining as the burial depth increases. Different types of vegetation have distinct impacts on slope infiltration patterns: herbaceous increases cumulative infiltration by 21.32%, while shrub reduces it by 61.06%. The numerically simulated moisture content values demonstrate strong congruence with field-measured data. Compared with monoculture herbaceous or shrub root systems, the mixed herb–shrub root system exhibits the most significant enhancement effects on shear strength parameters. Under high water content conditions, root systems demonstrate substantially greater improvement in cohesion than in internal friction angle. Before rainfall, shrub vegetation contributed the most significant improvement to the safety factor, increasing it from 2.766 to 3.046, followed by herbaceous and mixed herb–shrub vegetation, which raised it to 2.81 and 2.948. After rainfall, mixed herb–shrub vegetation demonstrated the greatest enhancement of the safety factor, elevating it from 1.139 to 1.361, followed by herbaceous and shrub vegetation, which increased it to 1.192 and 1.275. The study offers preliminary insights and a scientific basis for the specific conditions tested for selecting and optimizing eco-friendly slope protection measures. Full article

Implicit learning describes learning from experience that is not available to conscious awareness. The question of whether some individuals are better implicit learners than others has suggested and may contribute to difference in performance among experts. Across four experiments, adult participants completed the Serial Interception Sequence Learning (SISL) task across multiple parallel learning assessment forms. Previously, SISL sequence-specific performance has been shown to resist explicit knowledge influence, allowing for repeated reassessments of implicit learning with novel statistical structure. Our findings indicate that group-level sequence-specific performance occurred robustly in each reassessment; however, participants who exhibited more sequence-specific performance on one assessment did not exhibit better performance on parallel assessments, indicating no rank-order stability in learning. In all four experiments, with two to twelve reassessments of learning, no participants exhibited consistently better sequence learning rates than the other participants, indicating no evidence for a better ability in implicit learning. Measurements of other cognitive constructs, such as processing speed collected in parallel, exhibited robust individual differences. In Experiment 4, a general battery of cognitive measurements showed typical individual differences in measures of working memory, processing speed, and personality, but none correlated with implicit learning ability. We hypothesize that implicit learning arises from a general process of neuroplasticity reorganizing functions during practice and that our findings suggest that this process occurs at a basically similar rate across all people. Everybody learns from practice implicitly, but results suggest that the learning rate does not vary substantially across this sample. Full article

Probiotics are microorganisms with recognized beneficial properties that are used to improve host health. In particular, probiotics administered as spores, such as those belonging to the genera Bacillus and Alkalihalobacillus, are attracting great interest due to their high tolerance to gastrointestinal conditions. This in vitro study aimed to assess the probiotic attributes potentially contributing to the in vivo beneficial effects of a commercial spore-based probiotic formulation composed of four Alkalihalobacillus clausii strains. The tolerance and survival of the spores from the formulation in simulated gastrointestinal fluids, as well as their germination rate and adhesion to mucins, were analyzed. Furthermore, metabolic properties of spore-derived vegetative cells were assessed, including lactose degradation and biosynthesis of antioxidant enzymes (catalase and superoxide dismutase), group B vitamins (B₂, B₈, B₉, and B₁₂), short-chain fatty acids (acetate, propionate, and butyrate), and D-lactate. A. clausii spores were shown to survive in artificial gastric juice, adhere to mucins and germinate in vitro, and replicate in simulated intestinal fluid, suggesting their potential resilience in the gastrointestinal tract, where they can exert beneficial effects after germination. A. clausii was also able to produce beneficial enzymes and metabolites, including β-galactosidase, catalase, superoxide dismutase, group B vitamins, and short-chain fatty acids, but it was unable to produce D-lactic acid. Our findings highlight the probiotic properties and potential of such A. clausii strains in both their spore and vegetative forms, reinforcing the clinical relevance of this multi-strain spore-based formulation for enhancing intestinal health. Full article

Porcine enteric coronaviruses (CoVs), including swine acute diarrhea syndrome coronavirus (SADS-CoV), porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and porcine transmissible gastroenteritis virus (TGEV), are major pathogens causing porcine viral diarrhea syndrome (VDS), which brings significant economic losses to the swine industry; distinguishing between these clinically similar viruses has become a serious challenge. We developed a highly specific and interference-resistant porcine CoV multiplex digital PCR (dPCR) assay. The assay exhibited robust anti-interference capabilities, as the concentrations of the four viruses did not affect their accurate quantification. The coefficients of variation (CV%) of intra-batch and inter-batch repeatability for all target viruses were less than 11%. The limit of quantification (LoQ) of this dPCR assay reached 7.5 copies/reaction for each target, and it was one order of magnitude more sensitive than qPCR. The limits of detection (LoD) for SADS-CoV, PEDV, PDCoV, and TGEV were 2.72, 3.00, 3.56, and 3.19 copies/reaction, respectively. A total of 408 known samples were used for validation tests, and the results were highly consistent with the known conditions, showing a compliance rate of 97–100%. The diagnostic specificity (Dsp) of the method was 99–100%. In conclusion, the developed multiplex dPCR assay is highly suitable for early detection and quarantine in four porcine CoVs. The results indicate that this dPCR method is characterized by high specificity, anti-interference capabilities, repeatability, and high sensitivity. It also demonstrates a high compliance rate and diagnostic specificity in sample detection. This multiplex dPCR will contribute to the control of porcine enteric CoV-caused VDS and provide clues for subsequent research. Full article

Introduction. Pediatric polytrauma (PPT) and major trauma in pediatric patients (PMT) present unique challenges compared to adult trauma care due to distinct anatomical and physiological differences. PPT/PMT remains the leading cause of death in children, responsible for over 50% of pediatric deaths and 15% of pediatric hospital admissions due to its long-term effects. This single-institution study focuses on the initial management of PPT/PMT from an orthopedics and traumatology point of view. Material and Methods. In the present study, data of PPT/PMT managed in one single institution, an academic level I pediatric trauma center, in patients <18 years of age, were analyzed over different periods. Over a 10-year period, diaphyseal femur fractures were analyzed as indicators of damage control (DCO) versus definitive treatment. Over a 4-year period (2021–2024), the associated lesions of PPT (head injuries, thoracic and abdominal lesions, spine lesions, major blood vessel lesions, and major musculoskeletal injury) were analyzed. Over a 1-year period (2019), the overall in-hospital mortality and admission rates in the pediatric intensive care unit were analyzed. Results. In the 10-year period, among 298 diaphyseal femur fractures, 46/298 (15%) were classified as PPT in which DCO was performed according to age as follows: in the age-group 15–17 years 23/23 (100%) with temporary external fixation (ExFix); in the age group 12–14 years, 9/14 (64%) with ExFix and 5/14 (26%) and elastic stable intramedullary nails (ESINs); in the age group 5–11 years, 1/5 (20%) with ExFix and 4 with ESIN; in the age group 0–4 years, 2/4 (50%) with ESIN and 2/4 (50%) with a cast. In the 4-year period, PPT/PMTs were associated with 60% head injury, 25% thoracic lesion(s), 18% abdominal lesion(s), 16% spine injury, 5% lesion of a major blood vessel, and 30% major musculoskeletal injuries. In 2019, there were 193 patients admitted to the emergency room as PPT/PMT: 115 were ≤12 years old and 78 were >12 years old. On admission, 46% were admitted to the pediatric intensive care unit, and 65% were admitted to the department of traumatology as inpatients. The in-hospital mortality rate was 7%. Discussion and Conclusions. In our institution, pediatric trauma is assessed using the Pediatric Trauma Score (PTS), and the workup follows the ATLS guidelines with a dedicated trauma team. The role of the orthopedic surgeon during the primary evaluation of PPT/PMT is to contribute to stopping bleeding and hemorrhagic shock. In PPT/PMT, DCO in adolescents is superimposable to adults, whilst in babies and children, DCO is still performed, but it is not a form of temporary external fixation. Full article

Background/Objectives: Obesity is increasing worldwide, driven by unhealthy dietary habits and sedentary lifestyles. Genetic variations in taste receptor genes, particularly TAS1R2 and TAS2R38, may influence taste preferences, dietary intake, and obesity risk. This study examined associations between TAS1R2 and TAS2R38 polymorphisms, sugar-sweetened beverage (SSB) intake, and obesity risk in Kuwaiti adolescents. Methods: A cross-sectional study was conducted among 260 adolescents aged 11–14 years recruited from public schools in Kuwait. Genotyping of five single-nucleotide polymorphisms (SNPs) was performed using TaqMan assays. Associations between SNPs, SSB intake, and obesity parameters were evaluated using multinomial logistic regression and non-parametric tests, adjusted for age, sex, nationality, BMI z-scores, basal metabolic rate, and physical activity. p-values were corrected using the Benjamini–Hochberg method. Results: The rs713598 SNP in TAS2R38 showed a marginal association with BMI percentiles and z-scores. Adolescents carrying the CC genotype of rs10246939 SNP in TAS2R38 had significantly lower odds of high SSB consumption (>3 servings/week) compared with T-allele carriers (p = 0.018, OR= 0.24, 95% CI = 0.08–0.79). No significant associations were detected for TAS1R2 SNPs. Conclusions: Variations in TAS2R38 were linked to obesity measures and beverage intake in Kuwaiti adolescents, supporting a potential genetic contribution to dietary behaviors. These findings highlight the importance of taste receptor genetics in obesity research, though replication in larger and more diverse populations is required. Full article

Background: Shift work, especially during nighttime hours, disrupts the circadian system and is linked to higher rates of metabolic, gastrointestinal, cardiovascular, and neurocognitive disorders. Emerging evidence suggests that gut microbiota may mediate these associations. This systematic review assessed whether shift work alters gut microbiota composition and explored potential health consequences. Methods: A systematic search was conducted in PubMed, Scopus, and ScienceDirect from inception to March 2025. Studies reporting gut microbiota alterations in adult shift workers were included. Two reviewers independently screened articles and extracted data. Risk of bias was assessed using the NIH Quality Assessment Tool and the ROBINS-E framework. Five studies met the eligibility criteria and were included in the final synthesis. Results: The selected studies comprised four observational investigations with small sample sizes and one Mendelian randomization study leveraging large-scale genetic datasets. Observational studies reported reduced α-diversity and increased relative abundance of pro-inflammatory genera—including Escherichia/Shigella, Blautia, and Dialister—in night shift workers. These microbiota alterations were associated with gastrointestinal complaints and indicators of cardiometabolic dysfunction. The Mendelian randomization study provided preliminary evidence supporting a causal relationship between circadian misalignment, gut dysbiosis, and increased cardiovascular risk. Conclusions: Shift work is associated with significant alterations in gut microbiota composition that may contribute to adverse health outcomes. However, current evidence is limited and heterogeneous, preventing firm causal conclusions. Further high-quality longitudinal and interventional research is needed to clarify underlying mechanisms and inform preventive strategies. Full article

With the increasing penetration of renewable energy, the stochastic and intermittent nature of its generation increases operational uncertainty and vulnerability, posing significant challenges for grid stability. However, traditional algorithms typically identify critical nodes by focusing solely on the network topology or power flow, or by combining the two, which leads to the inaccurate and incomplete identification of essential nodes. To address this, we propose the Three-Dimensional Value-Based Gravity Model (3V-GM), which integrates structural and electrical–physical attributes across three layers. In the plane layer, we combine each node’s global topological position with its real-time supply–demand voltage state. In the line layer, we introduce an electrical coupling distance to quantify the strength of electromagnetic interactions between nodes. In the point layer, we apply eigenvector centrality to detect latent hub nodes whose influence is not immediately apparent. The performance of our proposed method was evaluated by examining the change in the load loss rate as nodes were sequentially removed. To assess the effectiveness of the 3V-GM approach, simulations were conducted on the IEEE 39 system, as well as six other benchmark networks. The simulations were performed using Python scripts, with operational parameters such as bus voltages, active and reactive power flows, and branch impedances obtained from standard test cases provided by MATPOWER v7.1. The results consistently show that removing the same number of nodes identified by 3V-GM leads to a greater load loss compared to the six baseline methods. This demonstrates the superior accuracy and stability of our approach. Additionally, an ablation experiment, which decomposed and recombined the three layers, further highlights the unique contribution of each component to the overall performance. Full article

Both climate change and human activities have had a significant impact on hydrological processes. Quantification of affecting factors on river regime changes is scientifically essential for understanding hydrological processes and sustainable water resources management in the basins. This study investigates the features of variations in meteorological and hydrological variables in the Liuhe River Basin (LRB) from 1956 to 2020 based on various observed records and statistical methods. It then quantitatively identifies the possible impacts of climate variability and human activities on runoff in the LRB using the empirical methods and the Budyko framework. The results show that (1) the runoff demonstrates a significantly decreasing trend over the past 65 years, but the rainfall has no obvious trend with significant interannual fluctuations, and potential evapotranspiration exhibits a weekly decreasing trend, particularly in summer. (2) The runoff series can be divided into two periods, i.e., the baseline (1956–1969) and change (1970–2020) periods, and the change period can also be divided into two stages, i.e., stage I (1970–1999) and stage II (2000–2020). (3) Human activities are the dominant factors in the runoff decline in the LRB, with the contribution rates being greater than 80% in the change period, particularly for stage II. The analysis of this study can provide a reference for the rational utilization of water resources in the LRB. Full article

To explore a direct predictive model for the tensile strength of ultra-high-performance concrete (UHPC), machine learning (ML) algorithms are presented. Initially, a database comprising 178 samples of UHPC tensile strength with varying parameters is established. Then, feature engineering strategies are proposed to optimize the robustness of ML models under a small-sample condition. Further, the performance and efficiency of algorithms are compared under default hyperparameters and hyperparameter tuning, respectively. Moreover, the utilization of SHapley Additive exPlanations (SHAP) enables the analysis of the relationships between UHPC tensile strength and its influencing factors. The quantitative analysis results indicate that ensemble algorithms exhibit superior performance, indicated by R² values of above 0.92, under default hyperparameters. After hyperparameter tuning, both conventional and ensemble models achieve R² values exceeding 0.94. However, Bayesian ridge regression (BRR) consistently demonstrates a suboptimal performance, irrespective of hyperparameter tuning. Notably, Categorical Boosting (CatBoost) requires a substantial duration of 1208 s, which is notably more time-consuming than that of other algorithms. The most influential feature identified is fiber reinforcement index with a contribution of 37.5%, followed by the water-to-cement ratio, strain rate, and cross-sectional size. The nonlinear relationship between UHPC tensile strength and the top four factors is visualized, and the critical thresholds are identified. Full article

Qilian Mountain National Park, an important forest ecosystem in northwest China, plays a crucial role in achieving the national “dual carbon” goals and advancing sustainable forest management. This study focuses on the systematic assessment of forest carbon storage and its market economic value, employing multi-source data fusion and the GARCH-M(1,1) model to integrate forest carbon storage data from 2000 to 2020 with historical trading records from the EU and Chinese carbon markets (2017–2025). The study utilizes three dynamic carbon pricing scenarios—low, medium, and high—to assess the carbon storage capacity and economic value of the park’s forest ecosystems. Results show that forest carbon storage increased by approximately 4.0 × 10⁷ tons, with an average annual growth rate of 0.27%. Under the high carbon pricing scenario in 2025, the forest carbon sink value in the EU market reaches CNY 518.2 billion, approximately 12.5 times that of the Chinese market, highlighting the differences in market maturity and volatility persistence. Through Monte Carlo simulations and dynamic pricing analysis, this research reveals the substantial market potential of Qilian Mountain’s forest carbon sinks, providing data-driven support for regional carbon trading optimization, ecological compensation mechanisms, and sustainable forest management, while contributing to the global carbon trading system and international cooperation in forest-based climate mitigation. Full article