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Multi-omics-driven personalized management of advanced HCC

Cell Rep Med. 2026 Oct 2:103085. doi: 10.1016/j.xcrm.2026.103085. Online ahead of print.

ABSTRACT

Hepatocellular carcinoma (HCC) management is challenging due to its complex tumor microenvironment and poor treatment responses. Here, using tumor specimens from a prospective clinical trial of combined transarterial chemoembolization (TACE) with immune checkpoint blockade (ICB), we perform exhaustive multi-omics analysis including spatial proteomics and transcriptomics, single-cell RNA sequencing, and bulk transcriptomics. These analyses reveal that treatment response is associated with enrichment of anti-tumor T cell regions that are regulated by cGAS-STING activation within immune-suppressive epithelial cells. Conversely, fibrotic processes impede these pro-response processes. Based on these insights, we test triple combination therapy consisting of cGAS activation, immune checkpoint blockade, and anti-fibrosis strategies, which shows improved efficacy over dual therapy. To identify patients who would benefit, we construct a predictive model using a group sparse learning algorithm. Our findings provide a blueprint for crafting personalized HCC therapies using next-generation biomarkers.

PMID:42826719 | DOI:10.1016/j.xcrm.2026.103085

Multi-omics-driven personalized management of advanced HCC

Cell Rep Med. 2026 Oct 2:103085. doi: 10.1016/j.xcrm.2026.103085. Online ahead of print.

ABSTRACT

Hepatocellular carcinoma (HCC) management is challenging due to its complex tumor microenvironment and poor treatment responses. Here, using tumor specimens from a prospective clinical trial of combined transarterial chemoembolization (TACE) with immune checkpoint blockade (ICB), we perform exhaustive multi-omics analysis including spatial proteomics and transcriptomics, single-cell RNA sequencing, and bulk transcriptomics. These analyses reveal that treatment response is associated with enrichment of anti-tumor T cell regions that are regulated by cGAS-STING activation within immune-suppressive epithelial cells. Conversely, fibrotic processes impede these pro-response processes. Based on these insights, we test triple combination therapy consisting of cGAS activation, immune checkpoint blockade, and anti-fibrosis strategies, which shows improved efficacy over dual therapy. To identify patients who would benefit, we construct a predictive model using a group sparse learning algorithm. Our findings provide a blueprint for crafting personalized HCC therapies using next-generation biomarkers.

PMID:42826719 | DOI:10.1016/j.xcrm.2026.103085

SPTLC2-driven sphingolipid reprogramming of neutrophils impairs anti-tumour immunity and drives liver cancer progression

Oncogene, Published online: 28 September 2026; doi:10.1038/s41388-026-03996-2

SPTLC2-driven sphingolipid reprogramming of neutrophils impairs anti-tumour immunity and drives liver cancer progression

Occamy-1.0: Open Pareto-frontier 35B Intelligence for Co-work

arXiv:2609.11977v1 Announce Type: new Abstract: Co-work agents execute complex workflows that combine information gathering, tool use, coding, and file manipulation across many model invocations. Because cost and latency accumulate over the full episode, their practical value depends not only on peak capability but also on how efficiently that capability is delivered. Yet many steps in everyday work emphasize state tracking, coordination, recovery, and follow-through rather than frontier-scale reasoning. We present Occamy-1.0, a cost-efficient co-work model obtained by further training the post-trained Qwen3.6-35B-A3B checkpoint. We construct execution-grounded data and environments, capture replayable long-horizon trajectories across multiple harnesses, and use staged post-training to develop and consolidate complementary execution capabilities. Across a broad suite of co-work benchmarks, Occamy-1.0 is consistently among the strongest comparably sized models and remains competitive with substantially larger frontier systems on several tasks. Under our stated evaluation and pricing protocol, its aggregate performance across four representative benchmarks places it at the low-cost knee of the observed cost--performance Pareto frontier. Supporting evaluations in tool calling, coding, and instruction following further show that this specialization preserves broad agentic capability. We release the model weights and a subset of the training data to support research on practical co-work agents and agentic post-training.

VBVR-Pro: A Scalable and Verifiable Suite for Native Visual Reasoning

arXiv:2608.26105v2 Announce Type: replace-cross Abstract: Native visual reasoning treats visual generation as the medium of reasoning itself: visual states (i.e. images and videos) are not merely inputs to be understood or outputs to be rendered, but first-class substrates for problem solving beyond language. Yet progress remains bottlenecked by the lack of scalable training tasks, reliable feedback, and controlled comparisons across generative substrates. In this work, we introduce VBVR-Pro, a closed-loop testbed that makes native visual reasoning through generation trainable, verifiable, optimizable, and experimentally controllable. 1) Task scaling. VBVR-Pro turns visual reasoning into a controlled task space of 300 procedurally generated tasks. Models trained on VBVR-Pro show strong transfer beyond the proposed suite across seven external visual reasoning benchmarks such as RISE-Video, MME-CoF-Pro, and BabyVision. 2) Verifiable rewards. VBVR-Pro provides verifiable reward scorers for task-grounded evaluation. Through a systematic study of leading MLLMs as judges, we identify recurring failure modes of the prevalent VLM-as-a-judge paradigm. In contrast, the proposed scorers are grounded in deterministic, task-specific rules, achieve fine-grained alignment with human judgments. Importantly, they serve as reliable reward signals for large-scale multi-task reinforcement learning and demonstrate stronger post-RL performance across visual reasoning tasks. 3) Mechanism study. VBVR-Pro enables controlled modality studies across more than 30 image, video, and interleaved generators. Our analysis shows that video generation remains strongest for tasks requiring persistent spatiotemporal state tracking, while interleaved generation provides a compute-efficient alternative. Critically, ablations and probing suggest the presence of vision-native trajectories that are crucial to visual reasoning. We release all data, models, scorers, and code.

Circular RNA MCM3 recruits USP49 to stabilize PTBP1 and promote cisplatin resistance in cervical squamous cell carcinoma

Oncogene, Published online: 12 September 2026; doi:10.1038/s41388-026-03988-2

Circular RNA MCM3 recruits USP49 to stabilize PTBP1 and promote cisplatin resistance in cervical squamous cell carcinoma

Author Correction: Radiotherapy-triggered reduction of platinum-based chemotherapeutic prodrugs in tumours

Nature Biomedical Engineering, Published online: 10 September 2026; doi:10.1038/s41551-026-01810-8

Author Correction: Radiotherapy-triggered reduction of platinum-based chemotherapeutic prodrugs in tumours

Antisense oligonucleotides against Il6ra ameliorate cancer cachexia in mice

Cancer cachexia is a devastating metabolic syndrome for which there are no approved treatments. Li and colleagues developed an RNA-targeted therapy, which ameliorates cachectic symptoms, reduces inflammation, and extends survival in mouse cancer models. The study provides an approach for treating cancer cachexia and paves the road for clinical studies.

A Trust-Network-Based Federated Learning Framework for Multi-Center Aging Clock Prediction

arXiv:2609.10108v1 Announce Type: cross Abstract: Aging clocks quantify biological aging and help characterize individual health status. What protein interactions are important for accurate aging clocks, and are they zeroth-order or higher-order? Addressing these questions requires learning from large molecular datasets distributed across medical centers, where privacy constraints prevent centralized data sharing. Federated learning offers a natural solution but faces four challenges in this setting: limited local sample sizes, sparse and directional inter-center trust, the need to retain discriminative age prediction while supporting interpretation, and model drift and forgetting under heterogeneous cross-center data. We propose TNFL, a trust-network-based federated learning framework that progressively propagates models along directed pairwise trust relations without centralized aggregation. TNFL combines an age-aware mixture-of-experts model with generative replay to preserve previously learned information and reduce forgetting and drift. Experiments across multiple molecular datasets show that TNFL enables effective aging-clock prediction with limited local data, provides interpretable age-dependent prediction patterns, and maintains stable performance across interaction orders. To investigate the biological questions, we analyze TNFL-identified pairwise protein interactions and their higher-order organization through functional and network analyses. The identified interactions repeatedly form coordinated higher-order subnetworks spanning multiple aging-related biological systems, with several proteins recurring across subnetworks. These findings suggest that TNFL captures molecular relationships beyond isolated pairwise associations and reveals coherent higher-order biological organization associated with aging.

Denisovans from southwestern China and their subsistence strategies

Nature, Published online: 09 September 2026; doi:10.1038/s41586-026-10997-4

Evidence from Bianfu Cave shows specialized hunting, expedient stone-tool production and extensive bone use of Denisovans, providing new insights into their ecology, behaviour and cultural legacy in eastern Asia.

PANDO: Efficient Multimodal AI Agents via Online Skill Distillation

arXiv:2605.24785v2 Announce Type: new Abstract: Recent advances in multimodal web agents often rely on increased inference-time computation, including rollout search, verifier passes, offline skill discovery, and specialist model stacks. This raises a central question: can a web agent become more efficient as it accumulates experience, rather than more expensive? We first analyze trajectories from VisualWebArena and identify three recurring sources of inefficiency: repeat-action loops, hidden discovery costs, and low prompt-cache reuse. We then introduce PANDO, a single-rollout online skill-distillation framework that maintains a structured Skill Library and combines progress reflection, confidence-based skill demotion, hierarchical routing, visual compression, and cache-aware prompting. On the full set of 910 VisualWebArena tasks, PANDO achieves a 58.3% success rate, outperforming SGV (54.0%) and our WALT reproduction (45.2%), while using 58% fewer tokens than SGV and 61% fewer tokens than WALT, without any pre-evaluation discovery budget. A 300-task ablation further shows that rules and routines provide most of the success gains, while routing, compression, and cache-aware prompting convert the larger skill library into lower marginal token cost. Finally, we introduce three trajectory-level efficiency metrics -- Action Repetition Rate, Step Overhead Ratio, and Prompt Cache Utilization -- to make efficiency visible beyond terminal success.

L2IR: Revealing Latent Intent in Graph Fraud Detection

arXiv:2605.26040v1 Announce Type: new Abstract: Graph fraud detection has long depended on Graph Neural Networks (GNNs) to propagate and aggregate information across relational data. A critical obstacle in practice, however, is that fraudsters frequently disguise themselves by forging numerous connections with benign users, causing fraud signals to be progressively diluted during neighborhood aggregation and undermining detection reliability. While recent efforts have used Large Language Models (LLMs) to provide rich semantic cues for fraud detection, the underlying intent behind suspicious connections remains insufficiently explored. Compounding this issue, the scarcity of annotated fraud samples makes it difficult to train detectors that remain robust under heavy camouflage. To address these gaps, we propose L2IR, an LLM-driven Latent Intent Revealing framework for graph fraud detection. By uncovering latent intent from both user behaviors and suspicious connections, L2IR extracts intent-aware representations from raw behavioral traces and reasons about the true purpose behind individual connections, effectively distinguishing supportive links from misleading ones. It further incorporates adaptive self-training to enhance robustness under limited supervision. Evaluations on two real-world datasets characterized by pervasive camouflage demonstrate that L2IR surpasses strong baselines and can function as a plug-in enhancement for a range of GNN-based detectors, improving AUPRC by up to 8.27%.

VaaWIT: Visual-Aware Adaptation of Large Language Models for Multilingual Web Image Translation

arXiv:2605.24675v1 Announce Type: cross Abstract: Translating text embedded in Web images is crucial for improving content accessibility and cross-lingual information retrieval, particularly within social media and e-commerce domains. Although Large Vision-Language Models (LVLMs) have advanced multimodal understanding, applying them to Web image translation remains challenging due to the visual representation gap: standard encoders often prioritize high-level semantics over the fine-grained visual details required for recognizing diverse character morphologies. To address this challenge, we propose VaaWIT, an end-to-end framework that adapts Large Language Models for multilingual Web image translation. The framework introduces two key technical contributions: (1) a Dual-Stream Attention Module (DSAM), which facilitates bidirectional interaction between multilingual semantic features and detailed visual representations, thereby synthesizing unified features robust to textual variations; and (2) a Visual-Aware Adapter (VAA), a parameter-efficient fine-tuning strategy that dynamically injects these fused visual cues into the frozen LLM backbone. This design enables the model to align the visual context with linguistic reasoning effectively while minimizing computational costs. Extensive experiments on eight tasks on three public benchmarks demonstrate that VaaWIT significantly outperforms state-of-the-art (SOTA) open-source baselines and achieves competitive performance against proprietary models. These results validate the efficacy of integrating fine-grained visual perception into LLMs for complex Web content analysis.

Mix-MoE: Improving Multilingual Machine Translation of Large Language Models through Mixed MoEs

arXiv:2605.24681v1 Announce Type: cross Abstract: Large Language Models (LLMs) have shown great promise in multilingual machine translation (MT), even with limited bilingual supervision. However, fine-tuning LLMs with parallel corpora presents major challenges, namely parameter interference. To address these issues, we propose Mix-MoE, a mixed Mixture-of-Experts framework designed to train LLMs for multilingual MT. Our framework operates in two distinct stages: (1) post-pretraining with MoE on monolingual corpora, and (2) post-pretraining with MoE on parallel corpora. Crucially, we divide the MoE layers into two specialized groups: Language Model Experts (LM Experts) and Machine Translation Experts (MT Experts). LM Experts are designed to capture and retain the monolingual knowledge learned by the pre-trained LLM. MT Experts, on the other hand, are specifically trained to acquire and store bilingual translation knowledge. Furthermore, to facilitate effective interaction between these specialized experts and leverage potential underlying structural patterns in text, we introduce a routing mechanism enhanced by Fourier Transform features derived from model representations. The experimental results demonstrate that Mix-MoE excels in multilingual MT, significantly outperforming existing baselines and showing notable progress in mitigating parameter interference.

CONF-KV: Confidence-Aware KV Cache Eviction with Mixed-Precision Storage for Long-Horizon LLM

arXiv:2605.24786v1 Announce Type: cross Abstract: Long-horizon LLM inference turns the key--value (KV) cache into the dominant GPU memory consumer and makes per-token attention increasingly expensive. Many common eviction policies use static recency windows or historical attention, leaving unused a signal computed on every decoding step: the model's current uncertainty. We introduce CONF-KV, a KV-cache manager that converts the next-token distribution into a scalar confidence score and uses it to choose the per-step cache budget, retaining more context when the model is uncertain and pruning aggressively when it is confident. Within each budget, tokens are ranked by a composite of accumulated attention mass and recency, while a protected recent window preserves local coherence. We combine the policy with blockwise online-softmax attention, mixed FP16/INT8 storage, and a pyramidal per-layer budget variant. Across four model families and generated lengths up to 4K, CONF-KV stays near the footprint of a fixed 512-token sliding window while remaining within 1.5--2.1 perplexity points of full KV. On Needle-in-a-Haystack up to 32K tokens, CONF-KV reaches 91.4% retrieval accuracy versus 53.8% for sliding windows and 80.6% for H2O; on 75 VisualWebArena tasks it retains 95.3% of full-KV success at 2.8 times lower peak memory.

Agent Learning via Early Experience

arXiv:2510.08558v3 Announce Type: replace Abstract: A long-term goal of language agents is to learn and improve through their own experience, ultimately outperforming humans in complex, real-world tasks. However, training agents from experience data with reinforcement learning remains difficult in many environments, which either lack verifiable rewards (e.g., websites) or require inefficient long-horizon rollouts (e.g., multi-turn tool use). As a result, most current agents rely on supervised fine-tuning on expert data, which is challenging to scale and generalizes poorly. This limitation stems from the nature of expert demonstrations: they capture only a narrow range of scenarios, and expose the agent to limited environment diversity. We address this limitation with a middle-ground paradigm we call early experience: interaction data generated by the agent's own actions, where the resulting future states serve as supervision without reward signals. Within this paradigm, we study two strategies of using such data: (1) implicit world modeling, which uses collected states to ground the policy in environment dynamics; and (2) self-reflection, where the agent learns from its suboptimal actions to improve reasoning and decision-making. Evaluation across eight diverse environments and multiple model families shows that our approaches consistently improve effectiveness and out-of-domain generalization, highlighting the value of early experience. Moreover, in environments with verifiable rewards, our results provide promising signals that early experience offers a strong foundation for subsequent reinforcement learning, making it a practical bridge between imitation learning and fully experience-driven agents.

Safety in Embodied AI: A Survey of Risks, Attacks, and Defenses

arXiv:2605.02900v2 Announce Type: replace-cross Abstract: Embodied Artificial Intelligence (Embodied AI) integrates perception, cognition, planning, and interaction into agents that operate in open-world, safety-critical environments. As these systems gain autonomy and enter domains such as transportation, healthcare, and industrial or assistive robotics, ensuring their safety becomes both technically challenging and socially indispensable. Unlike digital AI systems, embodied agents must act under uncertain sensing, incomplete knowledge, and dynamic human-robot interactions, where failures can directly lead to physical harm. This survey provides a comprehensive and structured review of safety research in embodied AI, examining attacks and defenses across the full embodied pipeline, from perception and cognition to planning, action and interaction, and agentic system. We introduce a multi-level taxonomy that unifies fragmented lines of work and connects embodied-specific safety findings with broader advances in vision, language, and multimodal foundation models. Our review synthesizes insights from over 500 papers spanning adversarial, backdoor, jailbreak, and hardware-level attacks; attack detection, safe training and robust inference; and risk-aware human-agent interaction. This analysis reveals several overlooked challenges, including the fragility of multimodal perception fusion, the instability of planning under jailbreak attacks, and the trustworthiness of human-agent interaction in open-ended scenarios. By organizing the field into a coherent framework and identifying critical research gaps, this survey provides a roadmap for building embodied agents that are not only capable and autonomous but also safe, robust, and reliable in real-world deployment.

ProcCtrlBench: Evaluating Process-Level Defects and Control Preservation in LLM Coding Agents

arXiv:2605.20251v4 Announce Type: replace-cross Abstract: Existing benchmarks for LLM coding agents primarily evaluate final outcomes. While useful for measuring overall capability, these metrics provide limited visibility and often miss defects that arise during execution. We present ProcCtrlBench, a benchmark for execution-process evaluation in LLM coding agents. ProcCtrlBench organizes recurrent execution defects into a reusable ontology covering 11 defect types in 4 categories, and evaluates agent trajectories through standardized process evidence rather than final outcomes alone. To support comparison across heterogeneous agents, ProcCtrlBench standardizes raw logs into a unified trajectory representation and reports calibrated scorecards over process-level findings. In addition, ProcCtrlBench uses control preservation as a way to quantify execution-process quality, capturing whether execution remains interpretable, interruptible, correctable, reversible, and able to hand back authority when needed. We evaluate ProcCtrlBench on 200 cases sampled from three benchmarks: AndroidBench, TerminalBench, and SWE-bench-Verified. Results show that ProcCtrlBench can be instantiated with useful reliability, provides more stable semantics than direct thresholding, and reveals meaningful differences in execution quality that are often overlooked by conventional outcome-based evaluation.

A framework for building a synthetic cell from the SynCell Asia Initiative

Nature Biotechnology, Published online: 26 May 2026; doi:10.1038/s41587-026-03153-w

Building a living cell from scratch requires overcoming a bottleneck that has remained unresolved despite decades of progress: orchestrating the spatiotemporal integration of core functional modules. To tackle this barrier, the SynCell Asia Initiative outlines a strategy for developing core functional modules followed by their systems-level integration through the establishment of a centralized, artificial intelligence (AI)-driven biofoundry.

Integrative multi-omics analysis identifies stromal-immune crosstalk as a determinant of immunotherapy efficacy and establishes a prognostic signature in gastric cancer

Comput Biol Chem. 2026 Apr 23;124(Pt 1):109095. doi: 10.1016/j.compbiolchem.2026.109095. Online ahead of print.

ABSTRACT

Immune checkpoint inhibitors like pembrolizumab exhibit variable efficacy in metastatic gastric cancer (GC). This study aimed to identify molecular drivers of pembrolizumab response, explore mechanisms of immune checkpoint inhibitors (ICIs) efficacy, and develop a prognostic signature. Transcriptomic analysis of pembrolizumab-treated GC (TIGER database) identified 165 response-associated differentially expressed genes (DEGs). Functional annotation and single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) revealed that responder-upregulated genes (R-DEGs) were enriched in immune activation pathways and mainly localized to CD8 + T/NK cells. In contrast, non-responder-upregulated genes (D-DEGs) were linked to extracellular matrix (ECM) remodeling and mainly expressed in fibroblasts/endothelial cells. CellChat analysis demonstrated that key DEGs mediate immune-stromal crosstalk via MHC-I and collagen/laminin signaling. A prognostic signature (Lasso-StepCox[forward] Riskscore; LSR: APOD, APOH, BATF2, GJA1, MAGED1, SLC5A1, SLCO2A1, VWF, VCAN) was derived and validated in four independent GC cohorts from the GEO and Cancer Genome Atlas (TCGA) database. Multi-omics analyses showed that LSR-high tumors exhibited aggressive clinicopathological features, increased stromal components, reduced cytotoxic immune infiltration, diminished tumor mutational burden (TMB), and poorer prognosis. Immunohistochemistry (IHC) and spatial transcriptomics in GC showed that stromal VWF/VCAN expression correlates with reduced CD8⁺ T cell granzyme B expression, suggesting T cell dysfunction. High VWF expression in GC predicted poor survival, and a combined VWF/VCAN score showed enhanced prognostic stratification. This study highlights stromal-immune crosstalk as a driver of pembrolizumab resistance and provides a signature as a clinical tool for prognosis and personalized therapy in metastatic GC.

PMID:42068630 | DOI:10.1016/j.compbiolchem.2026.109095

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