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Correction: Integrative multi-omics and machine learning reveals the spatial niche distribution and role of CYP27A1+TAMs in immunotherapy response in non-small cell lung cancer

Front Immunol. 2026 Mar 16;17:1822612. doi: 10.3389/fimmu.2026.1822612. eCollection 2026.

ABSTRACT

[This corrects the article DOI: 10.3389/fimmu.2026.1782545.].

PMID:41918731 | PMC:PMC13033988 | DOI:10.3389/fimmu.2026.1822612

RFC4 drives temozolomide resistance in glioblastoma by activating STK38-BECN1-dependent autophagy

Nat Commun. 2026 Mar 23. doi: 10.1038/s41467-026-70798-1. Online ahead of print.

ABSTRACT

Glioblastoma (GBM) remains a lethal brain tumor due to therapy resistance. While autophagy contributes to temozolomide (TMZ) resistance, its regulation is incompletely understood. This study investigates the role of replication factor RFC4, which is associated with poor prognosis and TMZ resistance in GBM. Multi-omics analyses and molecular experiments reveal that TMZ-induced chromatin accessibility enables transcription factor YY1 to bind the RFC4 promoter and upregulate its expression. RFC4, in turn, stabilizes the kinase STK38, which is essential for autophagosome formation. The RFC4-STK38 interaction facilitates BECN1 recruitment, thereby activating autophagy. Phosphorylation of STK38 at T444 stabilizes this complex, whereas a phospho-deficient mutant impairs autophagy. In vivo, RFC4 overexpression confers TMZ resistance, reversible by autophagy inhibition. Thus, our findings identify the RFC4-STK38-BECN1 axis as a mechanism underlying TMZ resistance and a potential target for precision therapy in GBM.

PMID:41872171 | DOI:10.1038/s41467-026-70798-1

When Silence Is Golden: Can LLMs Learn to Abstain in Temporal QA and Beyond?

arXiv:2602.04755v2 Announce Type: replace-cross Abstract: Large language models (LLMs) rarely admit uncertainty, often producing fluent but misleading answers, rather than abstaining (i.e., refusing to answer). This weakness is even evident in temporal question answering, where models frequently ignore time-sensitive evidence and conflate facts across different time-periods. In this paper, we present the first empirical study of training LLMs with an abstention ability while reasoning about temporal QA. Existing approaches such as calibration might be unreliable in capturing uncertainty in complex reasoning. We instead frame abstention as a teachable skill and introduce a pipeline that couples Chain-of-Thought (CoT) supervision with Reinforcement Learning (RL) guided by abstention-aware rewards. Our goal is to systematically analyze how different information types and training techniques affect temporal reasoning with abstention behavior in LLMs. Through extensive experiments studying various methods, we find that RL yields strong empirical gains on reasoning: a model initialized by Qwen2.5-1.5B-Instruct surpasses GPT-4o by $3.46\%$ and $5.80\%$ in Exact Match on TimeQA-Easy and Hard, respectively. Moreover, it improves the True Positive rate on unanswerable questions by $20\%$ over a pure supervised fine-tuned (SFT) variant. Beyond performance, our analysis shows that SFT induces overconfidence and harms reliability, while RL improves prediction accuracy but exhibits similar risks. Finally, by comparing implicit reasoning cues (e.g., original context, temporal sub-context, knowledge graphs) with explicit CoT supervision, we find that implicit information provides limited benefit for reasoning with abstention. Our study provides new insights into how abstention and reasoning can be jointly optimized, providing a foundation for building more reliable LLMs.
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