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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

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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

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Targeting the MNK1-MYH9 axis blocks YAP1 recruitment to prevent thrombosis and platelet activation-induced NETosis

MNK1 acts as a structural shield on MYH9, preventing YAP1-mediated platelet activation. Developing MD2 to lock this MNK1-MYH9 complex introduces a safe antithrombotic strategy, shifting the therapeutic paradigm from kinase inhibition to stabilizing protein-protein interactions against immunothrombosis.
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Looped GPT-BERT: Trading Parameters for Computation in Small Language Modeling

arXiv:2609.09691v1 Announce Type: cross Abstract: When training data are limited, increasing parameter count is not the only way to improve language-model performance. A small parameter set, when repeatedly applied, can also deliver comparable performance. We study Looped GPT-BERT in the BabyLM 2026 Strict-small setting, combining GPT-BERT's masked next-token and causal language-modeling objectives with depth-wise parameter sharing. We train on a preprocessed 7.48M-word English corpus and compare objective ratios, non-looped and looped architectures, and loop counts. Our final $4\times12$ model uses four physical layers for twelve recurrent traversals and contains 12.18M parameters. The BabyLM 2026 leaderboard reports an Overall Average of 35.42 and an NLP Average of 48.48. Compared with public BabyLM 10M Strict-small GPT-2 and GPT-BERT baselines, it achieves comparable performance on selected linguistic and downstream metrics, including BLiMP and GLUE, with fewer parameters. The loop ablations show that additional recurrent computation can improve training and preserve strong performance on selected linguistic tasks, whereas poorer performance on other tasks may reveal an inherent limitation of the looped design: using only a few physical layers restricts the model's representational space.
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The Latent Space: Foundation, Evolution, Mechanism, Ability, and Outlook

arXiv:2604.02029v1 Announce Type: new Abstract: Latent space is rapidly emerging as a native substrate for language-based models. While modern systems are still commonly understood through explicit token-level generation, an increasing body of work shows that many critical internal processes are more naturally carried out in continuous latent space than in human-readable verbal traces. This shift is driven by the structural limitations of explicit-space computation, including linguistic redundancy, discretization bottlenecks, sequential inefficiency, and semantic loss. This survey aims to provide a unified and up-to-date landscape of latent space in language-based models. We organize the survey into five sequential perspectives: Foundation, Evolution, Mechanism, Ability, and Outlook. We begin by delineating the scope of latent space, distinguishing it from explicit or verbal space and from the latent spaces commonly studied in generative visual models. We then trace the field's evolution from early exploratory efforts to the current large-scale expansion. To organize the technical landscape, we examine existing work through the complementary lenses of mechanism and ability. From the perspective of Mechanism, we identify four major lines of development: Architecture, Representation, Computation, and Optimization. From the perspective of Ability, we show how latent space supports a broad capability spectrum spanning Reasoning, Planning, Modeling, Perception, Memory, Collaboration, and Embodiment. Beyond consolidation, we discuss the key open challenges, and outline promising directions for future research. We hope this survey serves not only as a reference for existing work, but also as a foundation for understanding latent space as a general computational and systems paradigm for next-generation intelligence.
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Goose: Anisotropic Speculation Trees for Training-Free Speculative Decoding

arXiv:2604.02047v1 Announce Type: cross Abstract: Speculative decoding accelerates large language model inference by drafting multiple candidate tokens and verifying them in a single forward pass. Candidates are organized as a tree: deeper trees accept more tokens per step, but adding depth requires sacrificing breadth (fallback options) under a fixed verification budget. Existing training-free methods draft from a single token source and shape their trees without distinguishing candidate quality across origins. We observe that two common training-free token sources - n-gram matches copied from the input context, and statistical predictions from prior forward passes - differ dramatically in acceptance rate (~6x median gap, range 2-18x across five models and five benchmarks). We prove that when such a quality gap exists, the optimal tree is anisotropic (asymmetric): reliable tokens should form a deep chain while unreliable tokens spread as wide branches, breaking through the depth limit of balanced trees. We realize this structure in GOOSE, a training-free framework that builds an adaptive spine tree - a deep chain of high-acceptance context-matched tokens with wide branches of low-acceptance alternatives at each node. We prove that the number of tokens accepted per step is at least as large as that of either source used alone. On five LLMs (7B-33B) and five benchmarks, GOOSE achieves 1.9-4.3x lossless speedup, outperforming balanced-tree baselines by 12-33% under the same budget.
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Mimosa Framework: Toward Evolving Multi-Agent Systems for Scientific Research

arXiv:2603.28986v1 Announce Type: new Abstract: Current Autonomous Scientific Research (ASR) systems, despite leveraging large language models (LLMs) and agentic architectures, remain constrained by fixed workflows and toolsets that prevent adaptation to evolving tasks and environments. We introduce Mimosa, an evolving multi-agent framework that automatically synthesizes task-specific multi-agent workflows and iteratively refines them through experimental feedback. Mimosa leverages the Model Context Protocol (MCP) for dynamic tool discovery, generates workflow topologies via a meta-orchestrator, executes subtasks through code-generating agents that invoke available tools and scientific software libraries, and scores executions with an LLM-based judge whose feedback drives workflow refinement. On ScienceAgentBench, Mimosa achieves a success rate of 43.1% with DeepSeek-V3.2, surpassing both single-agent baselines and static multi-agent configurations. Our results further reveal that models respond heterogeneously to multi-agent decomposition and iterative learning, indicating that the benefits of workflow evolution depend on the capabilities of the underlying execution model. Beyond these benchmarks, Mimosa modular architecture and tool-agnostic design make it readily extensible, and its fully logged execution traces and archived workflows support auditability by preserving every analytical step for inspection and potential replication. Combined with domain-expert guidance, the framework has the potential to automate a broad range of computationally accessible scientific tasks across disciplines. Released as a fully open-source platform, Mimosa aims to provide an open foundation for community-driven ASR.
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ResAdapt: Adaptive Resolution for Efficient Multimodal Reasoning

arXiv:2603.28610v2 Announce Type: replace-cross Abstract: Multimodal Large Language Models (MLLMs) achieve stronger visual understanding by scaling input fidelity, yet the resulting visual token growth makes jointly sustaining high spatial resolution and long temporal context prohibitive. We argue that the bottleneck lies not in how post-encoding representations are compressed but in the volume of pixels the encoder receives, and address it with ResAdapt, an Input-side adaptation framework that learns how much visual budget each frame should receive before encoding. ResAdapt couples a lightweight Allocator with an unchanged MLLM backbone, so the backbone retains its native visual-token interface while receiving an operator-transformed input. We formulate allocation as a contextual bandit and train the Allocator with Cost-Aware Policy Optimization (CAPO), which converts sparse rollout feedback into a stable accuracy-cost learning signal. Across budget-controlled video QA, temporal grounding, and image reasoning tasks, ResAdapt improves low-budget operating points and often lies on or near the efficiency-accuracy frontier, with the clearest gains on reasoning-intensive benchmarks under aggressive compression. Notably, ResAdapt supports up to 16x more frames at the same visual budget while delivering over 15% performance gain. Code is available at https://github.com/Xnhyacinth/ResAdapt.
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CRAFT-GUI: Curriculum-Reinforced Agent For GUI Tasks

arXiv:2508.11360v2 Announce Type: replace Abstract: As autonomous agents become adept at understanding and interacting with graphical user interface (GUI) environments, a new era of automated task execution is emerging. Recent studies have demonstrated that Reinforcement Learning (RL) can effectively enhance agents' performance in dynamic interactive GUI environments. However, these methods face two key limitations: (1) they overlook the significant variation in difficulty across different GUI tasks by treating the entire training data as a uniform set, which hampers the agent's ability to adapt its learning process; and (2) most approaches collapse task-specific nuances into a single, coarse reward, leaving the agent with a uniform signal that yields inefficient policy updates. To address these limitations, we propose CRAFT-GUI, a curriculum learning framework based on Group Relative Policy Optimization (GRPO) that explicitly accounts for the varying difficulty across trajectories. To enable more fine-grained policy optimization, we design a reward function that combines simple rule-based signals with model-judged evaluation, providing richer and more nuanced feedback during training. Experimental results demonstrate that our method achieves significant improvements over previous state-of-the-art approaches, outperforming them by 5.6% on public benchmarks Android Control and 10.3% on our internal online benchmarks, respectively. These findings empirically validate the effectiveness of integrating reinforcement learning with curriculum learning in GUI interaction tasks.
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FNDC1 Competitively Binds Gbeta2 to Suppress the beta-Catenin-Destruction Complex and Promote Gastric Cancer Malignancy

FASEB J. 2026 Mar 31;40(6):e71634. doi: 10.1096/fj.202503587R.

ABSTRACT

Gastric cancer (GC) is a leading cause of cancer-related deaths and has high recurrence rate. Although fibronectin domain-containing protein 1 (FNDC1) is implicated in GC progression, its molecular mechanisms remain unclear. Multi-omics analyses (TCGA, GEO datasets) were used to assess FNDC1 expression and clinical correlation. In vitro (cell proliferation, invasion, EMT markers) and in vivo (xenograft) experiments, combined with molecular assays (Co-IP, WB, ChIP), explored FNDC1's function and mechanism. FNDC1 was significantly upregulated in GC, correlating with advanced clinicopathological features and poor prognosis. Knockdown of FNDC1 suppressed GC cell proliferation, invasion, and metastasis by inhibiting EMT and Wnt/β-catenin signaling. Mechanistically, FNDC1 competitively bound the WD5 domain (residues 224-254) of Gβ2, disrupting Gβγ-Dvl1 interaction. This prevented Dvl1 degradation, promoted Axin1 ubiquitination, and destabilized the β-catenin-destruction complex (GSK3 β-APC-Axin1), leading to β-catenin accumulation and Wnt pathway activation. FNDC1 drives GC malignancy by targeting the Gβ2-Dvl1 axis to activate Wnt/β-catenin signaling, suggesting FNDC1 as a novel prognostic biomarker and therapeutic target.

PMID:41808415 | PMC:PMC12976582 | DOI:10.1096/fj.202503587R

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Prompt-SID: Learning Structural Representation Prompt via Latent Diffusion for Single-Image Denoising

arXiv:2502.06432v3 Announce Type: replace-cross Abstract: Many studies have concentrated on constructing supervised models utilizing paired datasets for image denoising, which proves to be expensive and time-consuming. Current self-supervised and unsupervised approaches typically rely on blind-spot networks or sub-image pairs sampling, resulting in pixel information loss and destruction of detailed structural information, thereby significantly constraining the efficacy of such methods. In this paper, we introduce Prompt-SID, a prompt-learning-based single image denoising framework that emphasizes preserving of structural details. This approach is trained in a self-supervised manner using downsampled image pairs. It captures original-scale image information through structural encoding and integrates this prompt into the denoiser. To achieve this, we propose a structural representation generation model based on the latent diffusion process and design a structural attention module within the transformer-based denoiser architecture to decode the prompt. Additionally, we introduce a scale replay training mechanism, which effectively mitigates the scale gap from images of different resolutions. We conduct comprehensive experiments on synthetic, real-world, and fluorescence imaging datasets, showcasing the remarkable effectiveness of Prompt-SID. Our code will be released at https://github.com/huaqlili/Prompt-SID.
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From Narrow to Panoramic Vision: Attention-Guided Cold-Start Reshapes Multimodal Reasoning

arXiv:2603.03825v1 Announce Type: cross Abstract: The cold-start initialization stage plays a pivotal role in training Multimodal Large Reasoning Models (MLRMs), yet its mechanisms remain insufficiently understood. To analyze this stage, we introduce the Visual Attention Score (VAS), an attention-based metric that quantifies how much a model attends to visual tokens. We find that reasoning performance is strongly correlated with VAS (r=0.9616): models with higher VAS achieve substantially stronger multimodal reasoning. Surprisingly, multimodal cold-start fails to elevate VAS, resulting in attention distributions close to the base model, whereas text-only cold-start leads to a clear increase. We term this counter-intuitive phenomenon Lazy Attention Localization. To validate its causal role, we design training-free interventions that directly modulate attention allocation during inference, performance gains of 1$-$2% without any retraining. Building on these insights, we further propose Attention-Guided Visual Anchoring and Reflection (AVAR), a comprehensive cold-start framework that integrates visual-anchored data synthesis, attention-guided objectives, and visual-anchored reward shaping. Applied to Qwen2.5-VL-7B, AVAR achieves an average gain of 7.0% across 7 multimodal reasoning benchmarks. Ablation studies further confirm that each component of AVAR contributes step-wise to the overall gains. The code, data, and models are available at https://github.com/lrlbbzl/Qwen-AVAR.
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