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Unmasking FCGR2B as a high-grade serous ovarian cancer specific marker of immune suppression and tumor progression through multi-omics mining

Transl Oncol. 2026 Apr 3;67:102748. doi: 10.1016/j.tranon.2026.102748. Online ahead of print.

ABSTRACT

BACKGROUND: Epithelial ovarian cancer (EOC) encompasses five major histological subtypes with marked genetic, immunological, and clinical heterogeneity. While genome-wide association studies (GWAS) have identified subtype-specific risk loci, a critical gap remains in understanding how plasma proteins influence immune-cell traits and contribute to EOC pathogenesis.

METHODS: We integrated subtype-stratified GWAS data from two EOC cohorts with plasma proteomics and immune-cell traits to construct protein-immune-EOC regulatory landscapes using a three-stage Mendelian randomization framework. Single-cell RNA-seq and multiplex immunofluorescence were employed to delineate the cellular distribution and spatial context of causal proteins. Subsequent analyses characterized immune infiltration, macrophage polarization, and clinicopathological associations. Drug-gene correlations were used to identify potential therapeutic targets, and transcriptomic analyses were applied to delineate the underlying transcriptional landscape.

RESULTS: We identified 20 subtype-specific protein-immune-EOC regulatory axes, with FCGR2B emerging as a causal plasma protein in immune regulation and high-grade serous ovarian cancer (HGSOC) progression. FCGR2B was highly expressed in tumor-associated macrophages and was associated with an M2-like polarization phenotype. Functional characterization revealed that FCGR2B was associated with shorter progression-free survival and an immunosuppressive tumor microenvironment. Transcriptomic analyses revealed altered NF-κB signaling upon FCGR2B knockdown, and drug-response data suggested a potential association between high FCGR2B expression and sensitivity to NF-κB inhibitors.

CONCLUSIONS: These findings delineate subtype-specific genetically informed protein-immune regulatory landscapes in EOC and identify FCGR2B as a key immunoregulatory and prognostic biomarker in HGSOC, suggesting FCGR2B as a potential therapeutic vulnerability that warrants further investigation.

PMID:41934917 | DOI:10.1016/j.tranon.2026.102748

Do Phone-Use Agents Respect Your Privacy?

arXiv:2604.00986v2 Announce Type: replace-cross Abstract: We study whether phone-use agents respect privacy while completing benign mobile tasks. This question has remained hard to answer because privacy-compliant behavior is not operationalized for phone-use agents, and ordinary apps do not reveal exactly what data agents type into which form entries during execution. To make this question measurable, we introduce MyPhoneBench, a verifiable evaluation framework for privacy behavior in mobile agents. We operationalize privacy-respecting phone use as permissioned access, minimal disclosure, and user-controlled memory through a minimal privacy contract, iMy, and pair it with instrumented mock apps plus rule-based auditing that make unnecessary permission requests, deceptive re-disclosure, and unnecessary form filling observable and reproducible. Across five frontier models on 10 mobile apps and 300 tasks, we find that task success, privacy-compliant task completion, and later-session use of saved preferences are distinct capabilities, and no single model dominates all three. Evaluating success and privacy jointly reshuffles the model ordering relative to either metric alone. The most persistent failure mode across models is simple data minimization: agents still fill optional personal entries that the task does not require. These results show that privacy failures arise from over-helpful execution of benign tasks, and that success-only evaluation overestimates the deployment readiness of current phone-use agents. All code, mock apps, and agent trajectories are publicly available at~ https://github.com/FreedomIntelligence/MyPhoneBench.

PRET is a few-shot system for pan-cancer recognition without example training

Nature Cancer, Published online: 03 April 2026; doi:10.1038/s43018-026-01141-2

Li et al. present PRET, a few-shot system for pan-cancer detection not requiring model fine-tuning, validated it in multicenter datasets and found that it outperformed existing approaches across tasks and pathologists in lymph node metastasis detection.

Metabolite-gated vascular contractility switch: OXGR1 activation mechanism enables agonist therapy for rosacea erythema

Xiao et al. identify α-KG as a rosacea-associated metabolite that activates the OXGR1-Gq-MYL9 axis in the vascular smooth muscle cells to boost contractility and suppress pathological vasodilation underlying erythema. Cryo-EM reveals a bipartite-acid pocket of OXGR1 that enables structure-guided development of A-1, a selective agonist that alleviates erythema in rosacea-like models.

Editing strigolactone hormone receptor for robust antiviral silencing in rice

Precise genome editing of the rice strigolactone receptor DWARF14 confers robust, transgene-free antiviral resistance by blocking viral suppression of endogenous RNA silencing, offering a promising strategy for durable disease protection without a yield penalty.

GISTBench: Evaluating LLM User Understanding via Evidence-Based Interest Verification

arXiv:2603.29112v1 Announce Type: new Abstract: We introduce GISTBench, a benchmark for evaluating Large Language Models' (LLMs) ability to understand users from their interaction histories in recommendation systems. Unlike traditional RecSys benchmarks that focus on item prediction accuracy, our benchmark evaluates how well LLMs can extract and verify user interests from engagement data. We propose two novel metric families: Interest Groundedness (IG), decomposed into precision and recall components to separately penalize hallucinated interest categories and reward coverage, and Interest Specificity (IS), which assesses the distinctiveness of verified LLM-predicted user profiles. We release a synthetic dataset constructed on real user interactions on a global short-form video platform. Our dataset contains both implicit and explicit engagement signals and rich textual descriptions. We validate our dataset fidelity against user surveys, and evaluate eight open-weight LLMs spanning 7B to 120B parameters. Our findings reveal performance bottlenecks in current LLMs, particularly their limited ability to accurately count and attribute engagement signals across heterogeneous interaction types.

Predicting Neuromodulation Outcome for Parkinson's Disease with Generative Virtual Brain Model

arXiv:2603.29176v1 Announce Type: new Abstract: Parkinson's disease (PD) affects over ten million people worldwide. Although temporal interference (TI) and deep brain stimulation (DBS) are promising therapies, inter-individual variability limits empirical treatment selection, increasing non-negligible surgical risk and cost. Previous explorations either resort to limited statistical biomarkers that are insufficient to characterize variability, or employ AI-driven methods which is prone to overfitting and opacity. We bridge this gap with a pretraining-finetuning framework to predict outcomes directly from resting-state fMRI. Critically, a generative virtual brain foundation model, pretrained on a collective dataset (2707 subjects, 5621 sessions) to capture universal disorder patterns, was finetuned on PD cohorts receiving TI (n=51) or DBS (n=55) to yield individualized virtual brains with high fidelity to empirical functional connectivity (r=0.935). By constructing counterfactual estimations between pathological and healthy neural states within these personalized models, we predicted clinical responses (TI: AUPR=0.853; DBS: AUPR=0.915), substantially outperforming baselines. External and prospective validations (n=14, n=11) highlight the feasibility of clinical translation. Moreover, our framework provides state-dependent regional patterns linked to response, offering hypothesis-generating mechanistic insights.

C-TRAIL: A Commonsense World Framework for Trajectory Planning in Autonomous Driving

arXiv:2603.29908v1 Announce Type: new Abstract: Trajectory planning for autonomous driving increasingly leverages large language models (LLMs) for commonsense reasoning, yet LLM outputs are inherently unreliable, posing risks in safety-critical applications. We propose C-TRAIL, a framework built on a Commonsense World that couples LLM-derived commonsense with a trust mechanism to guide trajectory planning. C-TRAIL operates through a closed-loop Recall, Plan, and Update cycle: the Recall module queries an LLM for semantic relations and quantifies their reliability via a dual-trust mechanism; the Plan module injects trust-weighted commonsense into Monte Carlo Tree Search (MCTS) through a Dirichlet trust policy; and the Update module adaptively refines trust scores and policy parameters from environmental feedback. Experiments on four simulated scenarios in Highway-env and two real-world levelXData datasets (highD, rounD) show that C-TRAIL consistently outperforms state-of-the-art baselines, reducing ADE by 40.2%, FDE by 51.7%, and improving SR by 16.9 percentage points on average. The source code is available at https://github.com/ZhihongCui/CTRAIL.

Time is Not Compute: Scaling Laws for Wall-Clock Constrained Training on Consumer GPUs

arXiv:2603.28823v1 Announce Type: cross Abstract: Scaling laws relate model quality to compute budget (FLOPs), but practitioners face wall-clock time constraints, not compute budgets. We study optimal model sizing under fixed time budgets from 5 minutes to 24 hours on consumer GPUs (RTX 4090). Across 70+ runs spanning 50M--1031M parameters, we find: (1)~at each time budget a U-shaped curve emerges where too-small models overfit and too-large models undertrain; (2)~optimal model size follows $N^* \propto t^{0.60}$, growing \emph{faster} than Chinchilla's $N^* \propto C^{0.50}$, with $\alpha = 0.60 \pm 0.07$ robustly exceeding compute-optimal across all sensitivity analyses; (3)~a \emph{dual U-shape mechanism}: short-budget U-curves arise from compute bottlenecks, while long-budget U-curves emerge from data bottlenecks (overfitting), with an intermediate regime where the U-curve temporarily disappears. These findings have immediate implications for researchers training on consumer hardware, where wall-clock time -- not FLOPs -- is the binding constraint. We release all code, logs, and 70+ experimental configurations.

Efficient and Scalable Granular-ball Graph Coarsening Method for Large-scale Graph Node Classification

arXiv:2603.29148v1 Announce Type: cross Abstract: Graph Convolutional Network (GCN) is a model that can effectively handle graph data tasks and has been successfully applied. However, for large-scale graph datasets, GCN still faces the challenge of high computational overhead, especially when the number of convolutional layers in the graph is large. Currently, there are many advanced methods that use various sampling techniques or graph coarsening techniques to alleviate the inconvenience caused during training. However, among these methods, some ignore the multi-granularity information in the graph structure, and the time complexity of some coarsening methods is still relatively high. In response to these issues, based on our previous work, in this paper, we propose a new framework called Efficient and Scalable Granular-ball Graph Coarsening Method for Large-scale Graph Node Classification. Specifically, this method first uses a multi-granularity granular-ball graph coarsening algorithm to coarsen the original graph to obtain many subgraphs. The time complexity of this stage is linear and much lower than that of the exiting graph coarsening methods. Then, subgraphs composed of these granular-balls are randomly sampled to form minibatches for training GCN. Our algorithm can adaptively and significantly reduce the scale of the original graph, thereby enhancing the training efficiency and scalability of GCN. Ultimately, the experimental results of node classification on multiple datasets demonstrate that the method proposed in this paper exhibits superior performance. The code is available at https://anonymous.4open.science/r/1-141D/.

Electric dipole moment drives the dynamics of the TNFR1 complex I signalosome

Nature, Published online: 01 April 2026; doi:10.1038/s41586-026-10304-1

Long-range interactions mediated by protein electric dipole moments have a role in driving the assembly and disassembly of super-signalling complex I for promoting NF-κB signalling.

SynLeaF: A Dual-Stage Multimodal Fusion Framework for Synthetic Lethality Prediction Across Pan- and Single-Cancer Contexts

arXiv:2603.22369v1 Announce Type: cross Abstract: Accurate prediction of synthetic lethality (SL) is important for guiding the development of cancer drugs and therapies. SL prediction faces significant challenges in the effective fusion of heterogeneous multi-source data. Existing multimodal methods often suffer from "modality laziness" due to disparate convergence speeds, which hinders the exploitation of complementary information. This is also one reason why most existing SL prediction models cannot perform well on both pan-cancer and single-cancer SL pair prediction. In this study, we propose SynLeaF, a dual-stage multimodal fusion framework for SL prediction across pan- and single-cancer contexts. The framework employs a VAE-based cross-encoder with a product of experts mechanism to fuse four omics data types (gene expression, mutation, methylation, and CNV), while simultaneously utilizing a relational graph convolutional network to capture structured gene representations from biomedical knowledge graphs. To mitigate modality laziness, SynLeaF introduces a dual-stage training mechanism employing featurelevel knowledge distillation with adaptive uni-modal teacher and ensemble strategies. In extensive experiments across eight specific cancer types and a pancancer dataset, SynLeaF achieves superior performance in 17 out of 19 scenarios. Ablation studies and gradient analyses further validate the critical contributions of the proposed fusion and distillation mechanisms to model robustness and generalization. To facilitate community use, a web server is available at https://synleaf.bioinformatics-lilab.cn.

Hypoxia-related and immune phenotype-related fusion model for non-invasive prognostication of hepatocellular carcinoma treated by TACE: a multicentre study

Gut. 2026 Mar 30:gutjnl-2025-337938. doi: 10.1136/gutjnl-2025-337938. Online ahead of print.

ABSTRACT

BACKGROUND: Survival outcomes after transarterial chemoembolisation (TACE) vary in hepatocellular carcinoma (HCC) patients, and existing prognostic scores and imaging models often lack generalisability and biological interpretability.

OBJECTIVE: To develop and validate a multimodal prognostication model for HCC that allows for a precise assessment of survival outcomes of HCC patients receiving TACE therapy.

DESIGN: This study enrolled 1448 HCC patients, including a TACE cohort (n=1349), a biomarker subset from a randomised trial (n=41), a single-cell RNA sequencing cohort and The Cancer Genome Atlas (TCGA) HCC cohort (n=50). Pre-treatment contrast-enhanced CT images were used to construct deep learning and conventional radiomic models. The early-fusion and late-fusion models (LFMs) were compared, and a clinical-radiologic model (CRM) was formed by integrating the better-performing LFM with clinical variables. Using TCGA data and single-cell transcriptomic profiles, the differences between high-score and low-score groups in tumour immune microenvironment, cellular functional states and key signalling pathways were investigated.

RESULTS: The CRM effectively stratified patients' survival across multiple independent cohorts and achieved more granular risk stratification than the existing clinical models. Multi-omic analyses revealed that in the LFM high-score group, myelocytomatosis oncogene was activated, epithelial-mesenchymal transition enhanced, glycolysis upregulated and hypoxia pathway activated. Single-cell transcriptomic data confirmed that virtually all cell types in high-risk patients scored high in hypoxia, and cytotoxic T cells had a reduced cytotoxic activity.

CONCLUSION: The CRM model can non-invasively predict the prognosis of HCC patients treated by TACE therapy.

PMID:41856522 | DOI:10.1136/gutjnl-2025-337938

SkillsBench: Benchmarking How Well Agent Skills Work Across Diverse Tasks

arXiv:2602.12670v3 Announce Type: replace Abstract: Agent Skills are structured packages of procedural knowledge that augment LLM agents at inference time. Despite rapid adoption, there is no standard way to measure whether they actually help. We present SkillsBench, a benchmark of 86 tasks across 11 domains paired with curated Skills and deterministic verifiers. Each task is evaluated under three conditions: no Skills, curated Skills, and self-generated Skills. We test 7 agent-model configurations over 7,308 trajectories. Curated Skills raise average pass rate by 16.2 percentage points(pp), but effects vary widely by domain (+4.5pp for Software Engineering to +51.9pp for Healthcare) and 16 of 84 tasks show negative deltas. Self-generated Skills provide no benefit on average, showing that models cannot reliably author the procedural knowledge they benefit from consuming. Focused Skills with 2--3 modules outperform comprehensive documentation, and smaller models with Skills can match larger models without them.

Towards AI Search Paradigm

arXiv:2506.17188v2 Announce Type: replace-cross Abstract: In this paper, we introduce the AI Search Paradigm, a comprehensive blueprint for next-generation search systems capable of emulating human information processing and decision-making. The paradigm employs a modular architecture of four LLM-powered agents (Master, Planner, Executor and Writer) that dynamically adapt to the full spectrum of information needs, from simple factual queries to complex multi-stage reasoning tasks. These agents collaborate dynamically through coordinated workflows to evaluate query complexity, decompose problems into executable plans, and orchestrate tool usage, task execution, and content synthesis. We systematically present key methodologies for realizing this paradigm, including task planning and tool integration, execution strategies, aligned and robust retrieval-augmented generation, and efficient LLM inference, spanning both algorithmic techniques and infrastructure-level optimizations. By providing an in-depth guide to these foundational components, this work aims to inform the development of trustworthy, adaptive, and scalable AI search systems.

VideoTemp-o3: Harmonizing Temporal Grounding and Video Understanding in Agentic Thinking-with-Videos

arXiv:2602.07801v3 Announce Type: replace-cross Abstract: In long-video understanding, conventional uniform frame sampling often fails to capture key visual evidence, leading to degraded performance and increased hallucinations. To address this, recent agentic thinking-with-videos paradigms have emerged, adopting a localize-clip-answer pipeline in which the model actively identifies relevant video segments, performs dense sampling within those clips, and then produces answers. However, existing methods remain inefficient, suffer from weak localization, and adhere to rigid workflows. To solve these issues, we propose VideoTemp-o3, a unified agentic thinking-with-videos framework that jointly models video grounding and question answering. VideoTemp-o3 exhibits strong localization capability, supports on-demand clipping, and can refine inaccurate localizations. Specifically, in the supervised fine-tuning stage, we design a unified masking mechanism that encourages exploration while preventing noise. For reinforcement learning, we introduce dedicated rewards to mitigate reward hacking. Besides, from the data perspective, we develop an effective pipeline to construct high-quality long video grounded QA data, along with a corresponding benchmark for systematic evaluation across various video durations. Experimental results demonstrate that our method achieves remarkable performance on both long video understanding and grounding.

Profiling of the mycobiome and metabolome: a comparative study of benign pulmonary nodules and lung adenocarcinoma

Front Cell Infect Microbiol. 2026 Feb 23;16:1732958. doi: 10.3389/fcimb.2026.1732958. eCollection 2026.

ABSTRACT

INTRODUCTION: Lung adenocarcinoma (LUAD), the most common subtype of non-small cell lung cancer, is a form of malignant pulmonary nodule that requires clinical differentiation from benign pulmonary nodules (BPN). The mechanisms underlying the development of LUAD are complex, and effective non-invasive methods for differentiating BPN from LUAD are lacking. This study aimed not only to distinguish BPN from LUAD using gut fungi and serum metabolites, but also to establish an integrated network of gut fungi-metabolite-cytokine interactions.

METHODS: Fecal and serum samples from individuals with BPN and patients with LUAD were subjected to internal transcribed spacer sequencing, ultra-performance liquid chromatography-tandem mass spectrometry, and multiplex Luminex assays to quantify gut fungi, metabolites, and cytokines, respectively.

RESULTS: A significant difference in gut fungal communities was observed between the BPN and LUAD groups. Multiple genera and species were more abundant in LUAD than in BPN. Docosapentaenoic acid n-6 (DPAn-6), indole-3-propionic acid (IPA), and interferon-γ-induced protein 10 (IP-10) were significantly elevated in the LUAD group. The integrated model established using a combination of gut fungi and metabolites demonstrated excellent performance in distinguishing BPN from LUAD. A network of interactions was established among differentially abundant gut fungi, serum metabolites, and cytokines.

CONCLUSION: Our study identifies a novel panel of fungal and metabolite biomarkers for differentiating between BPN and LUAD, and constructs a multi-omics network that provides new insights into investigating the mechanistic role of gut mycobiota dysbiosis in LUAD.

PMID:41809995 | PMC:PMC12968269 | DOI:10.3389/fcimb.2026.1732958

AutoControl Arena: Synthesizing Executable Test Environments for Frontier AI Risk Evaluation

arXiv:2603.07427v1 Announce Type: new Abstract: As Large Language Models (LLMs) evolve into autonomous agents, existing safety evaluations face a fundamental trade-off: manual benchmarks are costly, while LLM-based simulators are scalable but suffer from logic hallucination. We present AutoControl Arena, an automated framework for frontier AI risk evaluation built on the principle of logic-narrative decoupling. By grounding deterministic state in executable code while delegating generative dynamics to LLMs, we mitigate hallucination while maintaining flexibility. This principle, instantiated through a three-agent framework, achieves over 98% end-to-end success and 60% human preference over existing simulators. To elicit latent risks, we vary environmental Stress and Temptation across X-Bench (70 scenarios, 7 risk categories). Evaluating 9 frontier models reveals: (1) Alignment Illusion: risk rates surge from 21.7% to 54.5% under pressure, with capable models showing disproportionately larger increases; (2) Scenario-Specific Safety Scaling: advanced reasoning improves robustness for direct harms but worsens it for gaming scenarios; and (3) Divergent Misalignment Patterns: weaker models cause non-malicious harm while stronger models develop strategic concealment.

Large Language Model for Discrete Optimization Problems: Evaluation and Step-by-step Reasoning

arXiv:2603.07733v1 Announce Type: new Abstract: This work investigated the capabilities of different models, including the Llama-3 series of models and CHATGPT, with different forms of expression in solving discrete optimization problems by testing natural language datasets. In contrast to formal datasets with a limited scope of parameters, our dataset included a variety of problem types in discrete optimization problems and featured a wide range of parameter magnitudes, including instances with large parameter sets, integrated with augmented data. It aimed to (1) provide an overview of LLMs' ability in large-scale problems, (2) offer suggestions to those who want to solve discrete optimization problems automatically, and (3) regard the performance as a benchmark for future research. These datasets included original, expanded and augmented datasets. Among these three datasets, the original and augmented ones aimed for evaluation while the expanded one may help finetune a new model. In the experiment, comparisons were made between strong and week models, CoT methods and No-CoT methods on various datasets. The result showed that stronger model performed better reasonably. Contrary to general agreement, it also showed that CoT technique was not always effective regarding the capability of models and disordered datasets improved performance of models on easy to-understand problems, even though they were sometimes with high variance, a manifestation of instability. Therefore, for those who seek to enhance the automatic resolution of discrete optimization problems, it is recommended to consult the results, including the line charts presented in the Appendix, as well as the conclusions drawn in this study for relevant suggestions.
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