❌

Normal view

Improving Safety Alignment via Balanced Direct Preference Optimization

arXiv:2603.22829v1 Announce Type: new Abstract: With the rapid development and widespread application of Large Language Models (LLMs), their potential safety risks have attracted widespread attention. Reinforcement Learning from Human Feedback (RLHF) has been adopted to enhance the safety performance of LLMs. As a simple and effective alternative to RLHF, Direct Preference Optimization (DPO) is widely used for safety alignment. However, safety alignment still suffers from severe overfitting, which limits its actual performance. This paper revisits the overfitting phenomenon from the perspective of the model's comprehension of the training data. We find that the Imbalanced Preference Comprehension phenomenon exists between responses in preference pairs, which compromises the model's safety performance. To address this, we propose Balanced Direct Preference Optimization (B-DPO), which adaptively modulates optimization strength between preferred and dispreferred responses based on mutual information. A series of experimental results show that B-DPO can enhance the safety capability while maintaining the competitive general capabilities of LLMs on various mainstream benchmarks compared to state-of-the-art methods. \color{red}{Warning: This paper contains examples of harmful texts, and reader discretion is recommended.

A multiomics Mendelian randomization study on PANoptosis-related genes and gastric cancer risk

17 March 2026 at 18:00

J Int Med Res. 2026 Mar;54(3):3000605261430163. doi: 10.1177/03000605261430163. Epub 2026 Mar 16.

ABSTRACT

ObjectiveTo explore the potential involvement of PANoptosis-related genes in gastric cancer susceptibility through multiomics analyses.MethodsSummary-data-based Mendelian randomization was performed by integrating blood-derived methylation, gene expression, and protein quantitative trait loci data with genome-wide association study results. The findings were further evaluated in The Cancer Genome Atlas cohort, followed by protein-protein interaction analysis, drug prediction, and molecular docking.ResultsSummary-data-based Mendelian randomization and colocalization analyses identified several traits suggestively associated with gastric cancer risk. Genetically predicted higher expression of apoptosis and caspase activation inhibitor (AVEN) and hepatocyte growth factor (HGF) as well as higher HGF protein levels were associated with increased risk, whereas higher levels of protein phosphatase 2 regulatory subunit B beta (PPP2R2B) appeared to be protective. Multiomics integration suggested epigenetic regulation of HGF and PPP2R2B. The Cancer Genome Atlas analysis corroborated the dysregulation of these candidates, with high AVEN expression associated with poorer survival. Protein-protein interaction and drug prediction analyses highlighted functional networks and potential therapeutics, supported by molecular docking demonstrating strong HGF-binding affinities. However, these associations did not reach statistical significance in the independent validation cohort, possibly due to limited statistical power.ConclusionsThis study identified AVEN, HGF, and PPP2R2B as potential candidate genes for gastric cancer. These findings require further validation in larger cohorts.

PMID:41840829 | DOI:10.1177/03000605261430163

❌