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ActQuant: Sub-4-bit Action-Guided Quantization for Vision-Language-Action Models

arXiv:2605.24011v1 Announce Type: cross Abstract: Vision-Language-Action (VLA) models exhibit remarkable action generation for embodied intelligence, but their heavy compute make deployment on edge platforms impractical. Aggressive, sub-4-bit weight quantization is the natural solution, yet existing post-training quantization (PTQ) methods suffer severe performance degradation in this regime. To address this, we introduce ActQuant, an action-guided mixed-precision PTQ framework that operates in two stages: (1) an inter-tensor bit allocator that assigns each weight matrix a single bit-width based on how much it contributes to predicting the agent's actions; (2) an intra-tensor scale optimizer tunes per-block quantization scales using action-aware curvature, so that dynamic range is concentrated on the weights most influential for control. To deliver the on-device benefits of our aggressive quantization, we further introduce OmniModel.cpp, an agentic conversion pipeline that ports architectures into a native C/C++ runtime with efficient low-bit kernels. We evaluate ActQuant both in simulation and on a real-world 6-DoF UR3 arm, with all models deployed through OmniModel.cpp. On the LIBERO benchmark, ActQuant is the only method that operates at or below 3 bits-per-weight, retaining 95.0% on OpenVLA-OFT and 94.8% on $\pi_{0.5}$. Pushed further, ActQuant reaches 2.5 bpw at 90.1% on OpenVLA-OFT, compressing the backbone from 14.3 GB to 2.7 GB (5.3$\times$). On the physical UR3 arm, $\pi_{0.5}$ quantized with ActQuant retains the baseline's success rate while reducing the memory footprint by 2.5$\times$.
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When Skills Don't Help: A Negative Result on Procedural Knowledge for Tool-Grounded Agents in Offensive Cybersecurity

arXiv:2605.20023v2 Announce Type: replace Abstract: Agent Skills, structured packages of procedural knowledge loaded into an LLM agent at inference time, are widely reported to improve task pass rates by an average of 16.2~percentage points across diverse domains. Yet the same benchmarks show wide variance, with 16 of 84 tasks suffering negative deltas when Skills are introduced. The community has not yet articulated a clean mechanism for \emph{when} Skills help and when they are merely redundant overhead. We re-analyze a recently published 180-run controlled study of an MCP-grounded autonomous Capture-the-Flag (CTF) agent under four documentation conditions of increasing richness (591, 12865, 17253, and 36001 tokens) and show that these conditions correspond almost exactly to a No-Skills, Experiential-Skills, Curated-Skills, and Comprehensive-Skills ablation. In offensive cybersecurity, a domain not deeply covered by existing Skills benchmarks, the marginal benefit of Skills collapses. The spread between the no-Skills and full-Skills conditions is only 8.9~pp ($p = 0.71$, $\chi^2$; $p = 0.25$, Cochran--Armitage trend test; five of six pairwise Cohen's $h$ values fall below the $0.2$ small-effect threshold). We argue that the missing variable is \emph{environment-feedback bandwidth}. When an agent's tool layer returns strict, schema-validated, low-latency observations, the environment itself supplies the procedural correction signal that Skills are normally needed to provide. As a result, the marginal benefit of curated Skills diminishes substantially, and, in some cases (e.g., our timing side-channel setting), actively degrades performance. We articulate a falsifiable hypothesis, sketch its design implications for compound AI systems, and will release the reanalysis pipeline to support replication.
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Data-driven precision: artificial intelligence redefining immunoradiotherapy in advanced pancreatic cancer

Front Pharmacol. 2026 May 8;17:1804673. doi: 10.3389/fphar.2026.1804673. eCollection 2026.

ABSTRACT

Advanced pancreatic ductal adenocarcinoma (PDAC) remains among the most formidable challenges in oncology, driven by a profoundly immunosuppressive tumor microenvironment (TME) and pervasive resistance to systemic and local therapies. Although immune checkpoint inhibitors (ICIs) can synergize with radiotherapy (RT) in several malignancies, the clinical benefit of immunoradiotherapy (iRT) in PDAC has been modest, highlighting the limitations of population-averaged paradigms that fail to capture extensive inter- and intratumoral heterogeneity. Here, we synthesize an artificial intelligence (AI)-enabled framework to refine both the biological rationale and clinical implementation of iRT for advanced PDAC through integrative analysis of multimodal data (clinical variables, imaging, RT dose distributions, and multi-omics). We highlight advances in three domains. First, AI-based deconvolution of TME heterogeneity can delineate clinically relevant molecular subtypes and spatial immune architectures that may be therapeutically tractable. Second, AI-driven modeling can optimize spatiotemporal RT-immunotherapy interactions, informing individualized dose, fractionation, and biologically guided target definition. Third, AI-supported predictive modeling and adaptive feedback can enable response-guided treatment adjustment beyond static planning. We also discuss unresolved clinical questions and key translational barriers, including data scarcity, lack of standardization, and limited interpretability. Finally, we outline priorities for translation-prospective digital biobanks, hybrid mechanistic-data-driven modeling, and adaptive trial designs-to enable rigorous validation and clinical deployment. Collectively, these developments position AI as a catalyst to move iRT for PDAC from empiricism toward real-time, individualized precision medicine.

PMID:42181887 | PMC:PMC13194001 | DOI:10.3389/fphar.2026.1804673

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Explainable multi-omics modeling for risk stratification in pancreatic ductal adenocarcinoma

Gland Surg. 2026 Apr 30;15(4):91. doi: 10.21037/gs-2025-396. Epub 2026 Mar 27.

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies due to a lack of reliable tools for individualized risk stratification. A comprehensive understanding of the multi-omics landscape may uncover clinically applicable biomarkers and inform precision prognostic assessment. This study aims to establish a prognostic model directly from the complete omics landscape and extract biomarkers.

METHODS: We developed prognostic models using multi-omics data from a PDAC proteogenomic cohort comprising 75 deceased tumor samples. An independent cohort of 63 deceased PDAC cases from The Cancer Genome Atlas (TCGA)-pancreatic adenocarcinoma (PAAD) was used for external validation. Logistic regression models with least absolute shrinkage and selection operator (LASSO) regularization were constructed, and SHapley Additive exPlanations (SHAP) were applied to evaluate feature importance and identify signature genes. Model selection was based on the average area under the receiver operating characteristic curve (AUROC) across cross-validation folds. Functional validation was performed in PANC-1 cells by knockdown (KD) or overexpression (OE) of representative microRNA-, RNA-, and proteomics-derived signature genes, followed by Cell Counting Kit-8 (CCK-8) proliferation and Transwell migration assays.

RESULTS: Systematic evaluation of 120 multi-omics combinations identified a top-performing prognostic model integrating RNA, microRNA, proteomics, and mutation features. This model achieved a mean AUROC of 0.92Β±0.11 and accuracy of 0.87Β±0.01 on internal validation, and 0.99Β±0.00 and 0.98Β±0.01 on the TCGA test set. The sensitivity, specificity, precision, recall and F1 scores on the TCGA test set were 0.98Β±0.01, 0.97Β±0.02, 0.98Β±0.02, 0.98Β±0.01, 0.98Β±0.01, respectively. SHAP analysis revealed interpretable and clinically relevant prognostic biomarkers, many of which are implicated in immune signaling, metabolic regulation, and cell cycle control. Importantly, modulation of representative signature genes in PANC-1 cells significantly altered proliferation and migration in directions consistent with model-predicted risk associations.

CONCLUSIONS: Our findings demonstrate that explainable multi-omics machine learning frameworks can identify robust prognostic biomarkers and achieve highly accurate survival prediction in PDAC. Functional validation further supports the biological relevance of these signatures, underscoring their translational potential for personalized risk assessment.

PMID:42164702 | PMC:PMC13184197 | DOI:10.21037/gs-2025-396

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A review of organoid-immune co-culture platforms to model the immune microenvironment of hepatocellular carcinoma and guide immunotherapy

J Transl Med. 2026 May 20. doi: 10.1186/s12967-026-08278-9. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by a highly immunosuppressive and heterogeneous tumor microenvironment that limits the effectiveness of current immunotherapies. Conventional two-dimensional cultures and animal models fail to fully capture patient-specific tumor-immune interactions, creating an urgent need for more physiologically relevant platforms.

MAIN BODY: This review summarizes recent advances in co-culture systems integrating patient-derived HCC organoids with defined immune cell populations to reconstruct essential features of the tumor microenvironment. We describe strategies for organoid establishment and validation, outline immune cell integration approaches, and compare static three-dimensional cultures, microfluidic organ-on-chip systems, and bioengineered multicellular platforms. We further highlight key tumor-immune interaction mechanisms that have been functionally interrogated in these systems, including immune checkpoint-mediated T-cell dysfunction, adenosine-driven metabolic suppression, and chemokine-regulated immune recruitment. Importantly, we critically evaluate current limitations, including immune cell exhaustion artifacts, lack of stromal and vascular complexity, and variability across protocols, which may affect the reproducibility and translational interpretation of these models. While emerging studies suggest potential for predicting immunotherapy responses, robust clinical validation in HCC remains limited.

CONCLUSIONS: Organoid-immune co-culture platforms represent an emerging translational framework that bridges mechanistic tumor immunology with functional precision oncology. With improved standardization and integration of multicellular bioengineering and multi-omics technologies, these systems have strong potential to guide personalized immunotherapy strategies, although further clinical validation is required.

PMID:42163357 | DOI:10.1186/s12967-026-08278-9

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Spatial multi-omics defines cancer-associated fibroblasts subtype gradients driving metabolic support and immune remodeling in pancreatic ductal adenocarcinoma

Cancer Lett. 2026 May 16;653:218585. doi: 10.1016/j.canlet.2026.218585. Online ahead of print.

ABSTRACT

Pancreatic ductal adenocarcinoma is characterized by a fibrotic and metabolically active tumor microenvironment where cancer-associated fibroblasts (CAFs) mediate metabolic crosstalk, extracellular matrix (ECM) remodeling, and immune regulation. However, the metabolic and spatial heterogeneity of CAFs remains incompletely understood. We integrated spatial transcriptomics and spatial metabolomics data from PDAC tissues and performed SpatialGlue-based multimodal clustering to define CAF subtypes. To characterize metabolic communication, we developed an optimal transport (OT)-based metabolic inference framework to quantitatively model metabolite association between CAFs and tumor cells. Subtype-specific features were independently validated using an independent spatial metabolomics cohort and multiplex immunofluorescence (mIHC) staining. Furthermore, these features were correlated with clinical outcomes via TCGA-PAAD deconvolution. Spatial multi-omics integration identified three robust CAF subtypes with distinct signatures. OT analysis revealed differential metabolic interactions: CAF_C0 mediated amino acid/peptide transfer, CAF_C1 was the primary source of lipids, while CAF_C2 exhibited limited metabolic association but stronger immune and ECM signaling activity. Deconvolution confirmed that CAF composition was strongly associated with prognosis; CAF_C2 enrichment predicted poorer survival and gemcitabine resistance, whereas a higher CAF_C0/CAF_C1 balance correlated with improved outcomes. By combining spatial multi-omics with OT-based modeling, this study delineates metabolically and spatially distinct CAF states with clinical relevance. Our findings suggest CAFs act as both metabolic donors and immune-ECM regulators, providing new insights into stromal reprogramming and potential subtype-specific therapeutic targets in PDAC.

PMID:42144098 | DOI:10.1016/j.canlet.2026.218585

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Spatial multi-omics technologies in gastric cancer: applications and advances

Front Immunol. 2026 Apr 14;17:1767512. doi: 10.3389/fimmu.2026.1767512. eCollection 2026.

ABSTRACT

Gastric cancer (GC) is plagued by profound intratumoral heterogeneity and a complex tumor microenvironment (TME), which are the core obstacles to precise diagnosis and treatment. Conventional bulk multi-omics technologies average molecular signals across tissues, thus masking cellular heterogeneity; single-cell multi-omics resolves cellular diversity but dissociates cells from their native spatial context, leading to the loss of critical information on intercellular crosstalk and molecular spatial distribution. These limitations result in an incomplete understanding of GC pathogenesis and TME regulatory networks. Spatial multi-omics technologies, integrating genomics, transcriptomics, proteomics, and metabolomics with high-resolution spatial localization, address these key scientific problems by preserving the native tissue architecture and elucidating the spatiotemporal dynamics of molecular and cellular events in GC. This review systematically synthesizes the latest advances in the application of four major spatial multi-omics modalities in GC research over the past 15 years, with a critical evaluation of the technical performance, methodological shortcomings, and clinical translation potential of existing studies. Unlike previous reviews that only summarize research findings, this work uniquely integrates technical principles, mechanistic discoveries, and clinical translation of spatial multi-omics in GC, deeply analyzes the practical barriers to clinical application, and systematically elaborates the integration of spatial multi-omics with artificial intelligence (AI). We also identify unresolved challenges in the field and propose future development directions, providing a comprehensive and in-depth reference for the advancement of GC precision medicine based on spatial multi-omics.

PMID:42058209 | PMC:PMC13120937 | DOI:10.3389/fimmu.2026.1767512

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