Search Results (8,071)

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer defined by the absence of estrogen and progesterone receptors, as well as the lack of human epidermal growth factor 2 receptor overexpression. TNBC is associated with early onset, high metastatic potential, therapeutic resistance, and poor clinical outcomes exacerbated by the limited availability of effective targeted therapies. Advances in multi-omics profiling have further stratified TNBC into distinct molecular subtypes, each exhibiting unique genomic, epigenomic, and immune-related features that influence therapeutic responsiveness. This review explores the interplay between TNBC molecular heterogeneity, immune evasion mechanisms, and epigenetic regulation. TNBC demonstrates variable immunogenicity, with tumor-infiltrating lymphocytes serving as important prognostic and predictive biomarkers. However, immune escape commonly occurs through tumor microenvironment remodeling, T-cell exhaustion, cancer stem cell enrichment, and immune checkpoint pathways activation. Although immune checkpoint inhibitors have improved outcomes in selected patients, particularly in combination with chemotherapy, primary and acquired therapeutic resistance remain a significant challenge. Emerging evidence highlights the central role of epigenetic mechanisms in regulating immune-related gene expression and shaping the tumor immune microenvironment. Epigenetic silencing of antigen presentation machinery, interferon signaling pathways, and chemokine expression contributes to immune evasion and immunotherapy resistance. Importantly, pharmacological modulation of epigenetic regulators can restore immune recognition and induce “viral mimicry” through reactivation of endogenous retroelements, thereby enhancing antitumor immunity. Collectively, this review underscores the therapeutic potential of integrating epigenetic therapies with immunotherapy and chemotherapy to overcome immune resistance in TNBC. A deeper understanding of epigenetic-immune interactions may facilitate the development of more precise and effective treatment strategies tailored to TNBC molecular subtypes. Full article

Guaranteeing equitable access to computational thinking (CT) remains a persistent challenge in computing education, particularly across socioeconomically diverse school contexts. Although prior research has demonstrated the effectiveness of block-based and physical computing environments, limited empirical evidence has examined whether structured instructional mediation can compensate for contextual disparities. This quasi-experimental pre–post study addresses this gap by analyzing CT development in three socioeconomically diverse primary schools in Chile ($N=88$, third grade), including private urban, public urban, and rural public institutions. Students engaged in scaffolded Scratch programming and Arduino simulation activities designed to explicitly support abstraction, sequencing, and debugging processes. These activities were framed within a broader STEAM learning approach, integrating computational thinking with problem-solving, experimentation, and interdisciplinary reasoning. Statistical analysis revealed significant differences in instructional time across contexts ($F(2,85)=14.62$, $p<0.001$, ${\eta }^2=0.26$), indicating structural disparities in pacing. However, no statistically significant differences were observed in CT gains ($F(2,85)=0.31$, $p=0.74$), suggesting that structured pedagogical scaffolding buffered contextual inequalities. These findings provide empirical evidence from a Latin American non-WEIRD context and advance the conceptualization of instructional mediation as a compensatory mechanism for equity in early computing education. This study contributes to digital equity research by demonstrating that instructional design quality may play a more decisive role than infrastructural availability in enabling computational thinking development for all learners. Full article

Background and Objectives: Outcomes after trauma are traditionally attributed to injury severity and acute physiologic derangement. However, host vulnerability at presentation—reflecting underlying physiologic and nutritional status—may also be associated with bleeding severity and transfusion requirements following acute injury. Whether such vulnerability contributes additional risk information beyond established factors remains incompletely understood. Materials and Methods: We conducted a retrospective cohort study of adult trauma patients using a single-center trauma registry. Host vulnerability was assessed using a composite score (CE; range 0–3) based on admission hypoalbuminemia (<3.5 g/dL), anemia (hemoglobin < 11 g/dL), and reduced renal function (estimated glomerular filtration rate < 60 mL/min/1.73 m²). Primary outcomes were any blood transfusion and massive transfusion, defined as transfusion of ≥10 units of packed red blood cells within 24 h of admission. Associations between CE score and transfusion outcomes were evaluated using univariable and multivariable logistic regression models adjusted for age, Injury Severity Score (ISS), admission lactate level, and systolic blood pressure (SBP). Results: Among 4105 trauma patients, transfusion requirements increased progressively with higher CE scores. Rates of any transfusion rose from 21.7% in patients with CE 0 to 78.6% in those with CE 3, while massive transfusion increased from 1.9% to 23.1% across the same categories. In multivariable analyses, each 1-point increase in CE score was independently associated with higher odds of any transfusion (adjusted odds ratio [aOR] 3.21, 95% confidence interval [CI] 2.80–3.68) and massive transfusion (aOR 1.73, 95% CI 1.45–2.07). Conclusions: A composite score reflecting host vulnerability at presentation was associated with bleeding severity and transfusion requirements after trauma, beyond injury severity and acute physiologic factors. These findings suggest that simple laboratory-based markers may provide additional information for early risk stratification of hemorrhagic outcomes after trauma. Full article

Background: Benign paroxysmal positional vertigo (BPPV) is the most common cause of peripheral vertigo and is diagnosed clinically, yet many patients initially present in primary care. Early identification may optimize referral and management. Objective: To perform a pilot Phase 1 validation of the Benign Paroxysmal Positional Vertigo Screening Questionnaire (BPPV-SQ), a brief screening questionnaire designed for future use in general practice (primary care settings where patients are initially evaluated by general practitioners), assessing its ability to identify BPPV, suggest canal involvement, and support progression to Phase 2 validation. Methods: In this prospective observational study, 108 patients with positional vertigo and no neurological signs were evaluated in a specialist setting. The 7-item dichotomous questionnaire (score 0–3 for diagnostic core) was administered prior to bedside examination, which served as the reference standard. Results: Higher questionnaire scores were associated with an increased probability of confirmed BPPV. Among patients with the maximum score of 3, BPPV was confirmed in 73.5% of cases, with a lateralization concordance of 69.4% between questionnaire responses and specialist diagnosis. In contrast, lower scores (0–1) were associated with a markedly lower rate of confirmed BPPV (14.3%). Conclusions: In this pilot Phase 1 validation, the BPPV-SQ demonstrated score-dependent diagnostic reliability and acceptable lateralization agreement in high-score patients, supporting progression to Phase 2 validation in primary care. Full article

Background/Objectives: Light-chain cast nephropathy remains a major cause of morbidity in newly diagnosed multiple myeloma (MM), and rapidly reducing circulating free light chains (FLCs) is considered essential for renal recovery and survival. Methods: We conducted a single-center retrospective study evaluating high- and medium-cut-off hemodialysis (HCO/MCO HD) in newly diagnosed MM patients presenting with acute kidney injury (AKI). Consecutive patients treated at the University Medical Center Ljubljana between 1 January 2020 and 31 December 2023 were included. As per institutional protocols, HCO/MCO HD- and myeloma-directed therapy were initiated on the day of diagnosis. Primary endpoints were the magnitude of FLC reduction, renal and hematologic responses at three months, and overall survival. Results: The median FLC concentration at presentation was 9630 mg/L. FLC levels declined rapidly after HCO/MCO HD initiation, reaching 2400 mg/L by day 7, 1083 mg/L by day 14, and 370 mg/L by day 30. MCO HD achieved kapa FLC clearance comparable to HCO HD for the lambda isotype. Despite a median of only four HCO/MCO-HD sessions, the reduction in FLC was rapid, with an additional decline observed over time, while the median FLC concentration fell below 500 mg/L. At three months, the overall hematologic response was 87%, including very good partial response or better in 35% of patients, and renal response in 79% of patients. Achieving a ≥70% FLC reduction by day 7 was associated with superior outcomes, including markedly longer median overall survival (82.5 vs. 23.2 months). Conclusions: Our data show that HCO/MCO-HD treatment alongside anti-myeloma therapy achieves sustained FLC reduction in newly diagnosed MM with AKI and early FLC reduction is highlighted as a key determinant of survival. Full article

Background: Childhood obesity is a major public health concern associated with adverse metabolic outcomes later in life. Despite increased awareness, unhealthy lifestyle behaviors—including suboptimal diet quality, physical inactivity, insufficient sleep, and unfavorable body composition—remain prevalent in pediatric populations. Effective, child-centered educational tools for early prevention are still limited. Methods: We developed the Lifestyle Tridimensional Pyramid, an educational model integrating nutrition, physical activity, and sleep within a single, three-dimensional framework. The model also addresses body composition by emphasizing the balance between skeletal muscle and adipose tissue and the interdependence of lifestyle behaviors. This narrative review is supported by an umbrella review of 17 systematic reviews and meta-analyses published between 2010 and 2025, synthesizing evidence on lifestyle behaviors of pediatric obesity. Results: High- to moderate-quality evidence indicates that adherence to Mediterranean-style dietary patterns, regular moderate-to-vigorous physical activity, adequate sleep duration, and a healthier body composition might prevent the development of obesity and improved cardiometabolic profiles in children and adolescents. The pyramid provides a structured, visually accessible tool to support lifestyle counseling in pediatric outpatient settings and is adaptable to school- and community-based health promotion. Conclusions: Although prospective validation studies are warranted, the Lifestyle Tridimensional Pyramid represents a practical, evidence-informed framework to support integrated lifestyle education and improve primary and secondary prevention of pediatric obesity. Full article

Background: Schizophrenia in adolescence disrupts neurodevelopment and long-term functioning. While symptom reduction remains a primary treatment goal, quality of life (QoL) represents a critical, patient-centered outcome. Pharmacogenetic variability, particularly in CYP2D6 metabolism of second-generation antipsychotics, may influence tolerability and subjective well-being beyond symptom control. Materials and Methods: Forty-seven adolescents (aged 14–18 years) diagnosed with schizophrenia (DSM-5) were followed in routine clinical care. CYP2D6 genotyping classified patients as normal metabolizers (NM, n = 27) or reduced-function metabolizers (RFM, including intermediate/poor, n = 20). Symptom severity was assessed with PANSS, QoL was assessed with the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q), and adverse effects (hyperprolactinemia, extrapyramidal symptoms, sedation, metabolic changes) were monitored. Non-parametric tests and multiple linear regression were applied. Results: At 12 months, RFM patients showed significantly higher PANSS scores, markedly more adverse reactions (95% vs. 48.1%), and lower PQ-LES-Q total and domain scores (all p < 0.0001) compared to NM patients. A regression analysis identified the metabolizer status (β = −0.410, p = 0.001), extrapyramidal symptoms (β = −0.248, p = 0.003), sedation (β = −0.193, p = 0.029), and hyperprolactinemia (β = −0.190, p = 0.012) as independent predictors of a reduced QoL, explaining 84% of the variance. The residual symptom severity was not independently associated. Conclusions: In adolescent schizophrenia, the CYP2D6-reduced metabolizer status is the strongest independent predictor of long-term QoL impairment, associated primarily through a substantially higher burden of treatment-related adverse effects (metabolic, endocrine, neurological, and sedative) rather than through persistence of psychotic symptoms alone. These findings support early pharmacogenetic testing to guide individualized dosing and improve tolerability and patient-reported outcomes. Full article

The Basel Accords refer to a series of international banking regulatory frameworks developed by the Basel Committee on Banking Supervision to strengthen the stability and resilience of the global banking system. Introduced as Basel I, Basel II, and Basel III, these accords establish minimum capital requirements, risk management standards, and supervisory principles for internationally active banks. Their primary purpose is to reduce the risk of bank failure, promote financial stability, and enhance consistency in banking regulation across jurisdictions. The Basel III framework and its 2017 Final Reforms represent the most advanced stage of this regulatory evolution, addressing weaknesses revealed by the global financial crisis and subsequent regulatory experience. Banking institutions play a central role in economic development, making their stability essential. The global financial crisis that began in 2007 exposed significant weaknesses in existing regulatory frameworks and led to the failure of several major banks, despite the earlier establishment of Basel I and Basel II by the Basel Committee on Banking Supervision. These shortcomings prompted the development of the Basel III framework as a direct response to the crisis. However, early criticisms of the initial Basel III Accord, particularly regarding variability in risk-weighted assets, reliance on internal models, and opportunities for regulatory arbitrage, led the Basel Committee to issue the Basel III Final Reforms in 2017, which represented a substantial upgrade to the post-crisis regulatory architecture. This study reviews the evolution of the Basel Accords; examines the key components of Basel I, Basel II, and Basel III; and analyses the enhancements introduced through the Basel III Final Reforms. It also considers the major arguments and criticisms surrounding these accords, highlighting the persistent challenges of achieving global regulatory consistency. Given the inability of earlier Basel frameworks to prevent bank failures and the fact that many jurisdictions have yet to fully implement the 2017 reforms, the paper underscores the need for ongoing evaluation of international banking regulation as national authorities adapt and refine their supervisory approaches to strengthen financial stability. Full article

Background: Postoperative hemorrhage is a severe complication after pancreatic surgery. While bleeding related to pancreatic fistula is well characterized, hemorrhage secondary to biliary leakage remains poorly understood. This study investigates the incidence, associated factors, clinical course, and outcomes of hepaticojejunostomy insufficiency-associated arterial hemorrhage (HIAA). Methods: This retrospective single-center study included 1413 patients who underwent pancreatic surgery with hepaticojejunostomy between 2004 and 2014. Demographics, underlying disease, surgical procedures, postoperative complications, management strategies, and outcomes were analyzed. Results: HIAA occurred in 13 patients (0.9%), accounting for one third of all erosion-related hemorrhages. The median onset was 16 days postoperatively, and 77% were preceded by sentinel bleeding. Completion pancreatectomy and sepsis were significantly associated with HIAA. The right hepatic artery was the most frequent bleeding source. Primary interventional angiography achieved hemostasis in 62.5% of patients, while 61.5% required surgical revision. Thirty- and ninety-day mortality rates were 15.4% and 30.8%, respectively, compared with 2.1% and 3.7% in the overall cohort. Conclusions: HIAA is a rare but highly lethal complication after pancreatic surgery. It represents a distinct clinical entity characterized by delayed onset, frequent sentinel bleeding, an association with sepsis and completion pancreatectomy, and markedly increased mortality. Early recognition, prompt imaging, and an interventional-first strategy are essential to improve outcomes. Full article

Background/Objectives: Breast MRI surveillance for women with a personal history of breast cancer (PHBC) is often limited by costs and acquisition times. This study aims to identify the optimal abbreviated breast MR (ABMR) protocol for this population by assessing the diagnostic performance of different sequence additions. Methods: This retrospective study included 1002 women with PHBC who underwent postoperative breast MRI with ultrafast sequences. Propensity score matching using 12 variables yielded recurrence (n = 21) and nonrecurrence (n = 42) groups with balanced characteristics. Four ABMR protocols were simulated by sequentially combining sequences: Step 1 (FAST protocol) included precontrast T1-weighted imaging (T1WI), early-phase T1WI, and subtracted maximal intensity projection (MIP). Step 2 added ultrafast MIP; Step 3 incorporated delayed-phase T1WI; and Step 4 included T2WI and diffusion weighted imaging (DWI). Three expert breast radiologists independently reviewed MRIs. Sensitivity, specificity, accuracy, and area under the curve (AUC) were assessed. Results: Sensitivity, specificity, and accuracy for ABMR protocols ranged from 76.2% to 90.5%, 88.1% to 92.9%, and 85.7% to 90.5%, respectively. The FAST protocol alone provided reliable performance (sensitivity: 81%; specificity: 88.1–90.5%; accuracy: 85.7–87.3%). Additional sequences yielded modest improvements, but no statistically significant differences were observed across all 3 readers (p > 0.05). ABMR protocols demonstrated equivalent diagnostic performance for PHBC surveillance. Conclusions: The FAST protocol alone provided reliable results, indicating its potential as a primary ABMR protocol. While additional sequences slightly improved specificity, they did not significantly enhance diagnostic accuracy. Full article

Computational thinking (CT) is increasingly recognized as a foundational skill in primary education, yet its developmental progression in the early school years remains underexplored. This study examined CT as a competence comprising three core concepts—sequences, loops, and conditionals—through a cognitive developmental lens. A total of 517 students in Grades 1 to 3 in Greece were assessed using the Greek adaptation of the Beginners Computational Thinking Test (BCTt), a validated tool for young learners. To examine performance trends, conceptual interrelations, and learner profiles, we employed repeated-measures ANOVAs, correlation analysis, and cluster analysis. The results showed that students performed highest in sequences, followed by loops and conditionals, with statistically significant differences across concepts. This pattern was also reflected in the cluster analysis, which identified three distinct student profiles differing in both overall performance and conceptual emphasis. Overall, the findings underscore the progressive nature of CT development and highlight the need for instruction aligned with students’ cognitive readiness and conceptual growth. Full article

Background: Ventricular septal rupture (VSR) following acute myocardial infarction (AMI) creates an abrupt left-to-right shunt that can progress to cardiogenic shock (CS). Once CS develops, mortality increases dramatically and delayed repair becomes less feasible. Intra-aortic balloon pumps (IABPs) are widely used to facilitate delayed repair; however, whether initiating IABP before CS onset improves survival remains unclear. Methods: We retrospectively analyzed 124 patients with AMI-related VSR (2009–2024), categorized by IABP timing relative to CS onset (defined as first catecholamine administration) into pre-CS, post-CS, and no-IABP groups. The primary outcome was all-cause mortality within 90 days after AMI onset. Kaplan–Meier curves and Cox proportional hazards models were applied, with subgroup analyses by CS status. Results: The 90-day survival rate was 68.2% in the pre-CS IABP group, 14.3% in the post-CS group, and 35.1% in the no-IABP group. Pre-CS IABP was associated with significantly lower mortality compared with no-IABP (adjusted HR = 0.401, 95% CI 0.174–0.925, p = 0.032) and post-CS IABP (adjusted HR = 0.369, 95% CI 0.149–0.910, p = 0.030). In the CS subgroup, IABP use did not improve survival (19.4% vs. 17.6%, p = 0.365). Among non-CS patients, IABP use was independently associated with lower mortality (85.7% vs. 50.0%, p = 0.027; adjusted HR = 0.178, 95% CI 0.040–0.801, p = 0.025). Conclusions: Given the retrospective design and limited sample size, these findings are hypothesis-generating. Early IABP use was associated with improved short-term survival, an effect not observed once CS had developed. These findings support early risk stratification to identify high-risk patients who may benefit from timely hemodynamic support. Full article

Varroa destructor (Bee mite) and Deformed Wing Virus are primary causes of honeybee colony collapse. This study developed an automated AI-based vision inspection system for detecting bee mites and deformed bees using the YOLO algorithm. The system integrates an RGB camera, a beecomb rotation motor, and an image transmission module to enable automated dual-sided image acquisition of the beecomb. The image characteristics of normal bees, bee mites, and deformed bees were analyzed, and YOLO-based object detection models were developed to classify them. Six YOLO models—based on YOLOv8 and YOLOv11 architectures across three model sizes (nano, small, and large)—were evaluated on 405 test images (6441 objects). The proposed system reduced the inspection time from 240 s required for manual method to 20 s per beecomb, achieving 12-fold efficiency improvement. Comparative analysis showed model-task specialization: YOLOv8l excelled in detecting small bee mites (F1: 92.5%, mAP[0.5]: 92.1%), while YOLOv11s achieved the highest performance for morphologically diverse deformed bees (F1: 95.1%). Error analysis indicated that detection performance was influenced by morphological characteristics. Deformed bee detection errors correlated with overlap in wing-to-body ratio: DB Type II exhibited 18.6% miss rate, while DB Type III achieved perfect detection. In bee mite detection, a sensitivity–specificity trade-off was observed: YOLOv11l had the lowest false negatives (2.5%) but highest false positives, while YOLOv8l demonstrated superior discrimination. These results demonstrate the practical potential of the proposed system for field deployment in apiaries, supporting early pest diagnosis and improved colony health management. The model-task specialization framework provides guidance for architecture selection based on object characteristics. Future work will focus on multi-location validation and real-time monitoring integration. Full article

Neoproterozoic iron formations (NIFs), deposited during Cryogenian glaciation events, are critical for understanding early Earth oxidation events and the evolution of glacial–interglacial environments. Apatite, a common accessory mineral in iron formations, holds significant implications for sedimentary environments and diagenetic processes, but these aspects remain underexplored. This study focuses on the Hengyang NIF in the Nanhua Basin, South China. Using whole-rock geochemistry and major and trace element analysis of apatite, we investigate the environmental significance of apatite and associated diagenetic processes. Our results show that the Hengyang NIF are formed through the mixing of low-temperature hydrothermal fluids, seawater, and terrigenous detrital materials, with hydrothermal contributions increasing progressively from the bottom to the top of the iron formation layers. Whole-rock geochemical proxies indicate that the depositional water column evolved from relatively oxidizing to weakly oxidizing conditions. The study further demonstrates that the rare earth element patterns in apatite, characterized by middle rare earth element enrichment, are primarily controlled by porewater chemistry during diagenesis. In contrast, Ce anomalies and the V/Cr and V/(V + Ni) ratios in apatite, which are strongly influenced by fluid–rock interactions and magnetite recrystallization, no longer reliably reflect the primary depositional environment. The Th/U ratio in apatite, due to its geochemical stability, aligns with whole-rock trends and serves as a more reliable redox proxy. Based on these findings, we propose a three-stage depositional-diagenetic model: the early and late stages are characterized by high-energy, rapid sedimentation with minimal diagenetic modification, while the middle stage is dominated by low-energy, stagnant conditions with slow sedimentation rates, leading to prolonged diagenesis and significant decoupling of mineral geochemical signatures. This study emphasizes the need to distinguish between sedimentary and diagenetic signals when using mineral geochemical proxies to reconstruct paleoenvironments and provides new insights into the genesis of Neoproterozoic iron formations. Full article

Rolling bearing simulations are often too computationally expensive for early design decisions, because many simulations are required in a large design of experiments. Therefore, the aim of this systematic literature review is to provide an overview of how machine learning (ML) is used to integrate engineering knowledge in advance when simulations are the primary data source for supervised learning. In the 11 included studies, ML is mainly applied as regression models trained on simulation data to replace repeated solver calls. The applications can be classified into three domains—contact mechanics, lubrication, and dynamics—mostly linked to their domain specific outputs. In most cases, ML models replace the simulation once the model is trained and validated, followed by optimization, which is often performed on the surrogate using evolutionary algorithms. Surrogates have the potential to enable design-space exploration, sensitivity analysis, and uncertainty propagation, but this capability is not yet fully exploited in current practice. The purpose of this review article is to provide a summary of methodological building blocks and practical guidelines to assist researchers and engineers in selecting appropriate ML workflows for simulation-based analysis of rolling bearings in the areas of tribology, dynamics, service life, load capacity, and system-level investigations. Full article