In this work, we study how the relevance/quality and quantity of past data influence performance by analyzing a contextual Newsvendor problem, in which a decision-maker trades off between underage and overage costs under uncertain demand. We consider a setting in which past demands observed under “close by” contexts come from close by distributions and analyze the performance of data-driven algorithms through a notion of context-dependent worst-case expected regret. We analyze the broad class of Weighted Empirical Risk Minimization (WERM) policies which weigh past data according to their similarity in the contextual space. This class includes classical policies such as ERM, k-Nearest Neighbors and kernel-based policies. Our main methodological contribution is to characterize exactly the worst-case regret of any WERM policy on any given configuration of contexts. To the best of our knowledge, this provides the first understanding of tight performance guarantees in any contextual decision-making problem, with past literature focusing on upper bounds via concentration inequalities. We instead take an optimization approach, and isolate a structure in the Newsvendor loss function that allows to reduce the infinite-dimensional optimization problem over worst-case distributions to a simple line search. This in turn allows us to unveil fundamental insights that were obfuscated by previous general-purpose bounds. We characterize actual guaranteed performance as a function of the contexts, as well as granular insights on the learning curve of algorithms.
Objective: Emerging evidence substantiates the cardiometabolic index (CMI) as a pivotal indicator demonstrating robust associations with an array of cardiovascular pathologies. However, its specific link to coronary heart disease (CHD) remains insufficiently explored. This study aimed to investigate both the association and the predictive value of CMI for CHD in a clinical cohort. Methods: This retrospective study included patients with suspected CHD who underwent coronary angiography at the Cardiology Department of Chengde Central Hospital between October 2023 and December 2024. Participants were stratified into CHD and non-CHD groups based on angiographic results. A LASSO regression and a logistic regression framework was implemented to examine the influence of age, sex, hypertension, diabetes, smoking, WBC, CK, CMI, and LDL-C on CHD. The association between CMI and CHD was explored using restricted cubic spline (RCS) methodology. The diagnostic efficacy of the model was scrutinized through the utilization of the area under the curve (AUC). Results: CMI exhibits an independent predictor for CHD, particularly in individuals with high CMI values (Q4 group), where the risk of CHD is markedly elevated. Furthermore, a linear relationship exists between CMI and CHD. Calibration curves demonstrate a strong alignment correlation linking predicted to observed probabilities. Decision curve analysis (DCA) reveals that the model provides substantial clinical benefit within a threshold probability range of 0.13 to 0.72. Receiver operating characteristic (ROC) curve analysis indicates that CMI possesses certain predictive merit for the occurrence of CHD. Conclusion: A positive association exists between CMI and incidence of CHD. Additionally, CMI serves as an independent risk factor, demonstrating certain predictive power in clinical settings, thereby effectively forecasting the risk of CHD occurrence.
Chronic refractory wounds exhibit a complex etiology characterized by prolonged healing and pathological chronic inflammation, which pose significant challenges to wound recovery and may increase the risk of cancer over time. In recent years, the autophagy mechanism has emerged as a focal point of research. This process is regulated by nutritional status, growth factors, and cellular stress. Autophagy facilitates the removal of damaged organelles and misfolded proteins, recycles nutrients, contributes to immune defense, and aids in the elimination of pathogens. Endothelial autophagy is particularly crucial in the healing of chronic refractory wounds. It may be activated under conditions of ischemia, hypoxia, inflammation, and infection, thereby inhibiting cell proliferation and tissue repair while assisting cells in maintaining homeostasis and managing various stressors. Consequently, investigating the autophagic mechanisms in vascular endothelial cells during chronic refractory wound healing is essential for the development of novel wound treatment strategies.
Purpose:Dry eye disease (DED) is a multifactorial chronic disorder of the ocular surface, characterized by reduced tear secretion, tear film instability, and inflammation. Oxidative stress is pivotal in DED pathogenesis. Qingxuan Runmu Yin (QRY) has shown substantial clinical efficacy in managing DED. This study aims to elucidate the molecular mechanisms underlying the antioxidant and anti-inflammatory effects of QRY in DED. Methods:A benzalkonium chloride (BAC)-induced DED mouse model was established to evaluate QRY's protective effects on the ocular surface. RNA sequencing identified differentially expressed genes (DEGs, fold change >1.5, P < 0.05) among control, untreated DED, and QRY-treated DED mice. Transcriptomic analysis of DEGs was conducted. The active ingredients and targets of the ten Chinese herbal medicines in QRY were obtained from the TCMSP and TCMIP databases, whereas DED and oxidative stress-related genes were identified from the DisGeNET, OMIM, and GeneCards databases. A Chinese herbal medicine-active ingredient-target-disease network was constructed. The key pathways and targets of QRY against DED were investigated through transcriptomics and network pharmacology, and experimental validation was performed. Results:QRY alleviated ocular surface damage in DED mice by repairing goblet cells, improving corneal damage, enhancing tear secretion, and reducing inflammatory factors and reactive oxygen species (ROS). Combined transcriptomic and network pharmacology analyses indicated that QRY reduced oxidative stress in DED by inhibiting pathways such as NF-κB and TNF. In vitro, QRY improved the survival of human corneal epithelial (HCE) cells damaged by oxidative stress. It inhibited the NF-κB signaling pathway and reduced levels of the pro‑inflammatory cytokines IL‑1β, IL‑6, and TNF‑α. In addition, QRY lowered ROS levels and enhanced superoxide dismutase (SOD) activity. Conclusion:This study is the first to demonstrate that QRY mitigates ocular surface inflammation and oxidative stress in DED, providing a scientific foundation for its clinical application.
Microwave ablation (MWA) is a minimally invasive thermal ablation technique that eradicates thyroid tumors by rapidly increasing tissue temperature to 60-100 degrees Celsius (°C) through dielectric hysteresis. This focused electromagnetic heating leads to irreversible protein denaturation, cell membrane disruption, and coagulative necrosis. Within the ablation zone, mitochondria and the endoplasmic reticulum sustain severe thermal injury accompanied by DNA double-strand breaks. The resulting cell death occurs via apoptosis, pyroptosis, and ferroptosis, while necrotic tissue triggers a robust inflammatory response that facilitates debris clearance and tissue remodeling. Damage-associated molecular patterns (DAMPs) and heat shock proteins (HSPs), released from dying cells, mediate immunogenic cell death (ICD) and promote dendritic cell activation and cytotoxic T lymphocyte (CTL) responses, leading to systemic antitumor immunity. Moreover, thermal injury disrupts the local vasculature, resulting in transient ischemia and hypoxia that activate the hypoxia-inducible factor-1 alpha (HIF-1α) pathway and stimulate vascular repair and fibrosis through transforming growth factor-beta (TGF-β) and vascular endothelial growth factor (VEGF) signaling. In addition, peripheral immune alterations and immune-related gene activation suggest potential synergy between MWA and immune checkpoint blockade. Collectively, MWA not only provides effective local tumor destruction but also reshapes the tumor immune microenvironment, offering a rationale for combined thermal and immunotherapeutic strategies in thyroid oncology.
