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HyperGuide: Hyperbolic Guidance for Efficient Multi-Step Reasoning in Large Language Models

arXiv:2605.24140v1 Announce Type: new Abstract: Multi-step reasoning remains a central challenge for large language models: single-pass generation is efficient but lacks accuracy; tree-search methods explore multiple paths but are computation-heavy. We address this gap by distilling reasoning progress into a hyperbolic geometric signal that guides step-by-step generation. Our approach is motivated by a structural observation: in combinatorial reasoning trees, solution-bearing states are few while dead ends are exponentially numerous. The hyperbolic space matches this asymmetry, with compact volume near the origin and exponentially expanding capacity toward the boundary, so that distance-to-origin naturally encodes solution proximity while angular separation distinguishes branches requiring different next operations. We train a lightweight head to project LLM hidden states into this space, then fine-tune a low-rank adapter interactively on its own reasoning attempts to act on the injected signal. Across multiple benchmarks, the geometric signal yields consistent gains, with larger improvements on deeper reasoning chains. Our code is publicly available at https://github.com/yuyuliu11037/HyperGuide.

Uni-DPO: A Unified Paradigm for Dynamic Preference Optimization of LLMs

arXiv:2506.10054v4 Announce Type: replace-cross Abstract: Direct Preference Optimization (DPO) has emerged as a cornerstone of reinforcement learning from human feedback (RLHF) due to its simplicity and efficiency. However, existing DPO-based methods typically treat all preference pairs equally, overlooking substantial variations in data quality and learning difficulty, which leads to inefficient data utilization and suboptimal performance. To address this limitation, we propose Uni-DPO, a unified dynamic preference optimization framework that jointly considers (a) the inherent quality of preference pairs and (b) the model's evolving performance during training. By adaptively reweighting samples based on both factors, Uni-DPO enables more effective use of preference data and achieves superior performance. Extensive experiments across models and benchmarks demonstrate the effectiveness and generalization of Uni-DPO. On textual tasks, Gemma-2-9B-IT fine-tuned with Uni-DPO surpasses the leading LLM, Claude 3 Opus, by 6.7 points on Arena-Hard. On mathematical and multimodal tasks, Uni-DPO consistently outperforms baseline methods across all benchmarks, providing strong empirical evidence of its effectiveness and robustness.

Integrated spatial transcriptomics and pan-cancer XGBoost modeling uncover spatial drivers of immune exclusion and predict immunotherapy response

Cancer Immunol Immunother. 2026 Apr 2;75(4):131. doi: 10.1007/s00262-026-04374-3.

ABSTRACT

Immunotherapy has revolutionized cancer treatment, yet characterizing the spatial complexity of the tumor immune microenvironment remains a challenge. In this study, we established a comprehensive computational framework integrating multi-omics profiling across 27 cancer types to decode immune-related non-coding RNA regulatory networks. Moving beyond traditional bulk analysis, we utilized spatial transcriptomics to dissect the spatial localization of these regulators. We identified the SNHG6-BIRC5 axis as a critical driver of the "immune-cold" phenotype in lung adenocarcinoma. We provide visual evidence that this axis localizes to tumor nests and negatively correlates with T- cell infiltration, elucidating a mechanism of spatial immune exclusion. Validating the clinical relevance of these findings, genome-scale CRISPR-Cas9 screening data confirmed the functional essentiality of these targets for cancer cell survival. Furthermore, pharmacogenomic analysis revealed that high expression of this axis correlates with sensitivity to chemotherapy agents like Vinblastine, suggesting a potential stratification strategy for patients with immune-excluded tumors. To expand the clinical utility to immunotherapy prediction, we developed a pan-cancer XGBoost machine learning model incorporating 14 high-performance regulatory features. This model achieved robust performance in distinguishing immunotherapy responders from non-responders with an AUC of 0.771, outperforming traditional markers such as PD-L1. Collectively, this study highlights spatial determinants of immune exclusion and chemotherapy sensitivity- and presents a generalized machine- learning tool for precision immunotherapy stratification. The developed online resource is freely available to facilitate community-wide biomarker discovery.

PMID:41925746 | DOI:10.1007/s00262-026-04374-3

Integrated spatial transcriptomics and pan-cancer XGBoost modeling uncover spatial drivers of immune exclusion and predict immunotherapy response

2 April 2026 at 18:00

Cancer Immunol Immunother. 2026 Apr 2;75(4):131. doi: 10.1007/s00262-026-04374-3.

ABSTRACT

Immunotherapy has revolutionized cancer treatment, yet characterizing the spatial complexity of the tumor immune microenvironment remains a challenge. In this study, we established a comprehensive computational framework integrating multi-omics profiling across 27 cancer types to decode immune-related non-coding RNA regulatory networks. Moving beyond traditional bulk analysis, we utilized spatial transcriptomics to dissect the spatial localization of these regulators. We identified the SNHG6-BIRC5 axis as a critical driver of the "immune-cold" phenotype in lung adenocarcinoma. We provide visual evidence that this axis localizes to tumor nests and negatively correlates with T- cell infiltration, elucidating a mechanism of spatial immune exclusion. Validating the clinical relevance of these findings, genome-scale CRISPR-Cas9 screening data confirmed the functional essentiality of these targets for cancer cell survival. Furthermore, pharmacogenomic analysis revealed that high expression of this axis correlates with sensitivity to chemotherapy agents like Vinblastine, suggesting a potential stratification strategy for patients with immune-excluded tumors. To expand the clinical utility to immunotherapy prediction, we developed a pan-cancer XGBoost machine learning model incorporating 14 high-performance regulatory features. This model achieved robust performance in distinguishing immunotherapy responders from non-responders with an AUC of 0.771, outperforming traditional markers such as PD-L1. Collectively, this study highlights spatial determinants of immune exclusion and chemotherapy sensitivity- and presents a generalized machine- learning tool for precision immunotherapy stratification. The developed online resource is freely available to facilitate community-wide biomarker discovery.

PMID:41925746 | PMC:PMC13046951 | DOI:10.1007/s00262-026-04374-3

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