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Scaling DPPs for RAG: Density Meets Diversity

arXiv:2604.03240v1 Announce Type: cross Abstract: Retrieval-Augmented Generation (RAG) enhances Large Language Models (LLMs) by grounding generation in external knowledge, yielding relevance responses that are aligned with factual evidence and evolving corpora. Standard RAG pipelines construct context through relevance ranking, performing point-wise scoring between the user query and each corpora chunk. This formulation, however, ignores interactions among retrieved candidates, leading to redundant contexts that dilute density and fail to surface complementary evidence. We argue that effective retrieval should optimize jointly for both density and diversity, ensuring the grounding evidence that is dense in information yet diverse in coverage. In this study, we propose ScalDPP, a diversity-aware retrieval mechanism for RAG that incorporates Determinantal Point Processes (DPPs) through a lightweight P-Adapter, enabling scalable modeling of inter-chunk dependencies and complementary context selection. In addition, we develop a novel set-level objective, Diverse Margin Loss (DML), that enforces ground-truth complementary evidence chains to dominate any equally sized redundant alternatives under DPP geometry. Experimental results demonstrate the superiority of ScalDPP, substantiating our core statement in practice.

Robust transcriptomic hallmarks targeting intratumor heterogeneity in intrahepatic cholangiocarcinoma

Cell Rep Med. 2026 Mar 30:102708. doi: 10.1016/j.xcrm.2026.102708. Online ahead of print.

ABSTRACT

Intratumor heterogeneity (ITH) undermines transcriptome-based stratification in intrahepatic cholangiocarcinoma (iCCA). Here, we integrate multi-omics data from multi-region, single-region, and single-cell RNA sequencing cohorts to systematically characterize gene expression ITH. We uncover that immune and stromal heterogeneity are primary drivers of ITH, leading to misclassification of a median 27.8% of tumors by existing subtyping systems. To overcome this, we identify a low-intratumor-heterogeneity/high-intertumor-variability (LIHV) gene set and develop an ITH-insensitive classification system defining five subgroups: inflammatory (SI), metabolic (SII), atypical (SIII-1), immune-silent (SIII-2), and neurodegenerative (SIII-3). These subgroups exhibit distinct clinical outcomes, molecular features, immune landscapes, and therapeutic vulnerabilities. GPRC5A and VTCN1 serve as robust immunohistochemical biomarkers for SI and SIII tumors, while serum CEA and CA19-9 identify inflammatory iCCA. Therapeutically, HSP90 inhibition synergizes with anti-PD1 in inflammatory iCCA, whereas combined anti-PD1 and anti-TIM3 suppresses neurodegenerative iCCA. Collectively, our study provides a robust molecular framework and actionable therapeutic strategies for iCCA.

PMID:41916296 | DOI:10.1016/j.xcrm.2026.102708

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