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FCGR2B (+) Macrophages as a Critical Node Linking Ferroptosis and Immunosuppression: A Multiomics Framework for Prognosis and Therapy in High-Grade Serous Ovarian Cancer

Hum Mutat. 2026 Apr 6;2026:8027584. doi: 10.1155/humu/8027584. eCollection 2026.

ABSTRACT

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is characterized by a complex tumor microenvironment and poor prognosis, yet the roles of specific tumor-associated macrophages (TAMs) subpopulations in driving disease progression remain elusive.

METHODS: This study evaluated the prognostic relevance of FCGR2B in HGSOC. Single-cell RNA sequencing identified FCGR2B + TAMs as a distinct macrophage subpopulation with unique transcriptional features. Integrative analyses combining single-cell and bulk differentially expressed genes, macrophage-associated modules, and ferroptosis-related gene sets identified 26 candidate prognostic genes, from which a four-gene signature (CRYAB, PLAUR, EREG, and C5AR1) was derived to construct the prognostic risk model. The model was validated in an independent cohort. Immune infiltration, single-cell trajectory, copy number variation, and drug-gene associations were analyzed to explore the molecular and therapeutic implications of risk stratification.

RESULTS: HGSOC patients classified as high risk exhibited poorer survival outcomes, increased infiltration of M2-like macrophages, elevated expression of immune checkpoints, and enrichment of immune- and ferroptosis-related pathways. Trajectory and copy number variation analyses revealed stage-specific gene expression patterns and amplification-associated regulation. Drug-gene association analyses further suggested that high-risk patients may be more responsive to targeted therapies and proteasome inhibitors, whereas low-risk patients may benefit from conventional chemotherapy.

CONCLUSION: FCGR2B + TAMs are closely linked to HGSOC progression, and the proposed prognostic model based on FCGR2B + TAMs provides predictive value and potential therapeutic insights for patient stratification.

PMID:41953398 | PMC:PMC13054137 | DOI:10.1155/humu/8027584

Enhancing behavioral nudges with large language model-based iterative personalization: A field experiment on electricity and hot-water conservation

arXiv:2604.03881v1 Announce Type: cross Abstract: Nudging is widely used to promote behavioral change, but its effectiveness is often limited when recipients must repeatedly translate feedback into workable next steps under changing circumstances. Large language models (LLMs) may help reduce part of this cognitive work by generating personalized guidance and updating it iteratively across intervention rounds. We developed an LLM agent for iterative personalization and tested it in a three-arm randomized experiment among 233 university residents in China, using daily electricity and shower hot-water conservation as objectively measured cases differing in friction. LLM-personalized nudges (T2) produced the largest conservation effects, while image-enhanced conventional nudges (T1) and text-based conventional nudges (C) showed similar outcomes (omnibus p = 0.009). Relative to C, T2 reduced electricity consumption by 0.56 kWh per room-day (p = 0.014), corresponding to an 18.3 percentage-point higher adjusted saving rate. This advantage emerged within the first two intervention rounds, alongside iterative updating of personalized guidance, and persisted thereafter. Hot-water outcomes followed the same direction but were smaller, less precisely estimated, and attenuated over time, consistent with stronger friction in this domain. LLM-personalized nudges emphasized prospective and context-specific guidance and were associated with higher participant engagement. This study provides field evidence that LLM-based iterative personalization can enhance behavioral nudging, with behavioral friction as a potential boundary condition. Larger trials and extension to more behaviors are warranted.

Uncertainty as a Planning Signal: Multi-Turn Decision Making for Goal-Oriented Conversation

arXiv:2604.03924v1 Announce Type: cross Abstract: Goal-oriented conversational systems require making sequential decisions under uncertainty about the user's intent, where the algorithm must balance information acquisition and target commitment over multiple turns. Existing approaches address this challenge from different perspectives: structured methods enable multi-step planning but rely on predefined schemas, while LLM-based approaches support flexible interactions but lack long-horizon decision making, resulting in poor coordination between information acquisition and target commitment. To address this limitation, we formulate goal-oriented conversation as an uncertainty-aware sequential decision problem, where uncertainty serves as a guiding signal for multi-turn decision making. We propose a Conversation Uncertainty-aware Planning framework (CUP) that integrates language models with structured planning: a language model proposes feasible actions, and a planner evaluates their long-term impact on uncertainty reduction. Experiments on multiple conversational benchmarks show that CUP consistently improves success rates while requiring fewer interaction turns. Further analysis demonstrates that uncertainty-aware planning contributes to more efficient information acquisition and earlier confident commitment.

How AI Aggregation Affects Knowledge

arXiv:2604.04906v1 Announce Type: cross Abstract: Artificial intelligence (AI) changes social learning when aggregated outputs become training data for future predictions. To study this, we extend the DeGroot model by introducing an AI aggregator that trains on population beliefs and feeds synthesized signals back to agents. We define the learning gap as the deviation of long-run beliefs from the efficient benchmark, allowing us to capture how AI aggregation affects learning. Our main result identifies a threshold in the speed of updating: when the aggregator updates too quickly, there is no positive-measure set of training weights that robustly improves learning across a broad class of environments, whereas such weights exist when updating is sufficiently slow. We then compare global and local architectures. Local aggregators trained on proximate or topic-specific data robustly improve learning in all environments. Consequently, replacing specialized local aggregators with a single global aggregator worsens learning in at least one dimension of the state.

Autonomous Agents for Scientific Discovery: Orchestrating Scientists, Language, Code, and Physics

arXiv:2510.09901v2 Announce Type: replace Abstract: Computing has long served as a cornerstone of scientific discovery. Recently, a paradigm shift has emerged with the rise of large language models (LLMs), introducing autonomous systems, referred to as agents, that accelerate discovery across varying levels of autonomy. These language agents provide a flexible and versatile framework that orchestrates interactions with human scientists, natural language, computer language and code, and physics. This paper presents our view and vision of LLM-based scientific agents and their growing role in transforming the scientific discovery lifecycle, from hypothesis discovery, experimental design and execution, to result analysis and refinement. We critically examine current methodologies, emphasizing key innovations, practical achievements, and outstanding limitations. Additionally, we identify open research challenges and outline promising directions for building more robust, generalizable, and adaptive scientific agents. Our analysis highlights the transformative potential of autonomous agents to accelerate scientific discovery across diverse domains.

From Seeing to Doing: Bridging Reasoning and Decision for Robotic Manipulation

arXiv:2505.08548v3 Announce Type: replace-cross Abstract: Achieving generalization in robotic manipulation remains a critical challenge, particularly for unseen scenarios and novel tasks. Current Vision-Language-Action (VLA) models, while building on top of general Vision-Language Models (VLMs), still fall short of achieving robust zero-shot performance due to the scarcity and heterogeneity prevalent in embodied datasets. To address these limitations, we propose FSD (From Seeing to Doing), a novel vision-language model that generates intermediate representations through spatial relationship reasoning, providing fine-grained guidance for robotic manipulation. Our approach combines a hierarchical data pipeline for training with a self-consistency mechanism that aligns spatial coordinates with visual signals. Through extensive experiments, we comprehensively validated FSD's capabilities in both "seeing" and "doing," achieving outstanding performance across 8 benchmarks for general spatial reasoning and embodied reference abilities, as well as on our proposed more challenging benchmark VABench. We also verified zero-shot capabilities in robot manipulation, demonstrating significant performance improvements over baseline methods in both SimplerEnv and real robot settings. Experimental results show that FSD achieves 40.6% success rate in SimplerEnv and 72% success rate across 8 real-world tasks, outperforming the strongest baseline by 30%.

Embodied-R1: Reinforced Embodied Reasoning for General Robotic Manipulation

arXiv:2508.13998v2 Announce Type: replace-cross Abstract: Generalization in embodied AI is hindered by the "seeing-to-doing gap," which stems from data scarcity and embodiment heterogeneity. To address this, we pioneer "pointing" as a unified, embodiment-agnostic intermediate representation, defining four core embodied pointing abilities that bridge high-level vision-language comprehension with low-level action primitives. We introduce Embodied-R1, a 3B Vision-Language Model (VLM) specifically designed for embodied reasoning and pointing. We use a wide range of embodied and general visual reasoning datasets as sources to construct a large-scale dataset, Embodied-Points-200K, which supports key embodied pointing capabilities. We then train Embodied-R1 using a two-stage Reinforced Fine-tuning (RFT) curriculum with a specialized multi-task reward design. Embodied-R1 achieves state-of-the-art performance on 11 embodied spatial and pointing benchmarks. Critically, it demonstrates robust zero-shot generalization by achieving a 56.2% success rate in the SIMPLEREnv and 87.5% across 8 real-world XArm tasks without any task-specific fine-tuning, representing a 62% improvement over strong baselines. Furthermore, the model exhibits high robustness against diverse visual disturbances. Our work shows that a pointing-centric representation, combined with an RFT training paradigm, offers an effective and generalizable pathway to closing the perception-action gap in robotics.

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.
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