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S1P-TREM2 axis protects immunosuppressive neutrophils from ferroptosis to promote tumour progression in hepatocellular carcinoma

✇Omics in Hepatocellular
By: Jun Ma · Tong Wu · Diyu Chen · Can Zhu · Shanhe Huang · Keyi Du · Chuanhui Peng · Junru Chen · Yunhao Chen · Haiyang Xie · Feng Zhang · Jianzhong Chen · Shusen Zheng · Jian Wu

Gut. 2026 Sep 7:gutjnl-2025-337414. doi: 10.1136/gutjnl-2025-337414. Online ahead of print.

ABSTRACT

BACKGROUND: Neutrophils are increasingly recognised as immunosuppressive drivers of hepatocellular carcinoma (HCC), yet their persistence in the oxidative, lipid-rich tumour microenvironment remains poorly understood.

OBJECTIVE: To elucidate the metabolic and molecular programmes that enable tumour-associated neutrophils (TANs) to resist ferroptosis and sustain immunosuppression in HCC.

DESIGN: We employed human HCC samples, multiple murine HCC models, transcriptomic and lipidomic profiling, genetic loss-of-function systems and therapeutic interventions. Ferroptosis sensitivity, lipid metabolic rewiring and immunological consequences of TANs were systematically evaluated across models and validated in patient datasets and biospecimens.

RESULTS: TANs in human HCC and mouse models exhibit pronounced lipid accumulation and oxidative stress compared with peripheral neutrophils. Multi-omic profiling revealed that TANs are enriched for lipid-binding gene programmes and undergo rewiring towards sphingolipid and unsaturated fatty acid metabolism. We identified triggering receptor expressed on myeloid cells 2 (TREM2) as a key lipid-sensing receptor selectively expressed in TANs. Functional deletion of TREM2 reprogrammed the tumour immune microenvironment, restoring CD8+ T cell activity and suppressing HCC progression. Mechanistically, tumour-derived sphingosine-1-phosphate (S1P) activates TREM2, triggering nuclear factor erythroid 2-related factor 2 (NRF2)-mediated transcription of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), thereby promoting ferroptosis resistance. TREM2 expression is transcriptionally induced by granulocyte-macrophage colony-stimulating factor-signal transducer and activator of transcription 3 (GM-CSF-STAT3) signalling. Genetic deletion of TREM2, clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated knockout of sphingosine kinase 1/2 (SPHK1/2) in tumour cells, or pharmacological inhibition of S1P synthesis disrupts this protective lipid-immune circuit, sensitises TANs to ferroptosis and restricts tumour growth. Therapeutically, a peptide-based TREM2 inhibitor reprogrammes TANs, restores CD8+ T cell function and enhances anti-programmed cell death protein 1 (PD-1) immunotherapy efficacy. Clinically, TREM2+ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are enriched in HCC tumours, correlate with SPHK1/2 expression and T cell dysfunction and associate with poor patient prognosis.

CONCLUSION: Our study uncovers the S1P-TREM2-NRF2 axis as a critical metabolic-immune circuit that preserves neutrophil survival and immunosuppressive function in HCC. Targeting this lipid-dependent ferroptosis resistance pathway offers a promising therapeutic strategy to overcome immunotherapy resistance in liver cancer.

PMID:42705697 | DOI:10.1136/gutjnl-2025-337414

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S1P-TREM2 axis protects immunosuppressive neutrophils from ferroptosis to promote tumour progression in hepatocellular carcinoma

✇(Multiomics OR Omics) AND (Pancreatic)
By: Jun Ma · Tong Wu · Diyu Chen · Can Zhu · Shanhe Huang · Keyi Du · Chuanhui Peng · Junru Chen · Yunhao Chen · Haiyang Xie · Feng Zhang · Jianzhong Chen · Shusen Zheng · Jian Wu

Gut. 2026 Sep 7:gutjnl-2025-337414. doi: 10.1136/gutjnl-2025-337414. Online ahead of print.

ABSTRACT

BACKGROUND: Neutrophils are increasingly recognised as immunosuppressive drivers of hepatocellular carcinoma (HCC), yet their persistence in the oxidative, lipid-rich tumour microenvironment remains poorly understood.

OBJECTIVE: To elucidate the metabolic and molecular programmes that enable tumour-associated neutrophils (TANs) to resist ferroptosis and sustain immunosuppression in HCC.

DESIGN: We employed human HCC samples, multiple murine HCC models, transcriptomic and lipidomic profiling, genetic loss-of-function systems and therapeutic interventions. Ferroptosis sensitivity, lipid metabolic rewiring and immunological consequences of TANs were systematically evaluated across models and validated in patient datasets and biospecimens.

RESULTS: TANs in human HCC and mouse models exhibit pronounced lipid accumulation and oxidative stress compared with peripheral neutrophils. Multi-omic profiling revealed that TANs are enriched for lipid-binding gene programmes and undergo rewiring towards sphingolipid and unsaturated fatty acid metabolism. We identified triggering receptor expressed on myeloid cells 2 (TREM2) as a key lipid-sensing receptor selectively expressed in TANs. Functional deletion of TREM2 reprogrammed the tumour immune microenvironment, restoring CD8+ T cell activity and suppressing HCC progression. Mechanistically, tumour-derived sphingosine-1-phosphate (S1P) activates TREM2, triggering nuclear factor erythroid 2-related factor 2 (NRF2)-mediated transcription of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), thereby promoting ferroptosis resistance. TREM2 expression is transcriptionally induced by granulocyte-macrophage colony-stimulating factor-signal transducer and activator of transcription 3 (GM-CSF-STAT3) signalling. Genetic deletion of TREM2, clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated knockout of sphingosine kinase 1/2 (SPHK1/2) in tumour cells, or pharmacological inhibition of S1P synthesis disrupts this protective lipid-immune circuit, sensitises TANs to ferroptosis and restricts tumour growth. Therapeutically, a peptide-based TREM2 inhibitor reprogrammes TANs, restores CD8+ T cell function and enhances anti-programmed cell death protein 1 (PD-1) immunotherapy efficacy. Clinically, TREM2+ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are enriched in HCC tumours, correlate with SPHK1/2 expression and T cell dysfunction and associate with poor patient prognosis.

CONCLUSION: Our study uncovers the S1P-TREM2-NRF2 axis as a critical metabolic-immune circuit that preserves neutrophil survival and immunosuppressive function in HCC. Targeting this lipid-dependent ferroptosis resistance pathway offers a promising therapeutic strategy to overcome immunotherapy resistance in liver cancer.

PMID:42705697 | DOI:10.1136/gutjnl-2025-337414

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From the invasive front to organotropic pre-metastatic niches: spatial immune regulatory networks governing cholangiocarcinoma dissemination and metastasis-intercepting immunotherapy

✇Omics In Lung
By: Longhao Zhang · Kai Zhang · Zhihong Chen · Xin Lu

Front Immunol. 2026 Aug 20;17:1919864. doi: 10.3389/fimmu.2026.1919864. eCollection 2026.

ABSTRACT

Cholangiocarcinoma is an aggressive biliary tract malignancy in which metastatic relapse and primary or acquired resistance to immunotherapy remain major causes of mortality. Although immune checkpoint inhibitors have improved first-line treatment for advanced biliary tract cancer, most patients do not achieve durable benefit, indicating that immune failure is not explained by a single checkpoint pathway. In this Review, we propose a spatial immune-regulatory continuum for cholangiocarcinoma dissemination. Most direct single-cell and spatial evidence currently derives from intrahepatic cholangiocarcinoma, and its applicability to perihilar and distal disease remains to be established. This continuum begins in the tumor core and invasive front, where malignant cells, cancer-associated fibroblasts, tumor-associated macrophages, endothelial and lymphatic cells, regulatory T cells, immature neutrophils and excluded or dysfunctional cytotoxic T cells form a pro-invasive ecosystem. It then extends through extracellular vesicles, soluble mediators and lymphovascular routes that may educate organotropic pre-metastatic niches. Finally, lymph node, lung, liver, peritoneal and bone microenvironments provide organ-specific extracellular matrix, myeloid and stromal programs that enable immune evasion and metastatic colonization. By integrating clinical evidence, multi-omics studies, single-cell and spatial transcriptomics, extracellular vesicle biology, pre-metastatic niche concepts and emerging therapeutic strategies, we argue that cholangiocarcinoma metastasis should be targeted before overt dissemination whenever possible. In this Review, "metastasis-intercepting immunotherapy" is used as an author-defined conceptual framework for strategies intended to prevent or disrupt the immune-stromal conditions that enable dissemination and colonization, rather than merely shrink established metastatic lesions. Metastasis-intercepting immunotherapy will likely require rational combinations that reprogram the invasive front, restore dendritic-cell-mediated antigen presentation, block tumor-stroma-myeloid circuits, disrupt EV-mediated communication that may contribute to niche formation and select patients using spatial biomarkers rather than bulk immune markers alone.

PMID:42694469 | PMC:PMC13539491 | DOI:10.3389/fimmu.2026.1919864

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EvoCode-Bench: Evaluating Coding Agents in Multi-Turn Iterative Interactions

✇cs.AI, q-bio.NC updates on arXiv.org
By: Haiyang Shen · Xuanzhong Chen · Wendong Xu · Yun Ma · Liang Chen · Kuan Li
arXiv:2605.24110v1 Announce Type: new Abstract: Coding agents are increasingly used as iterative development partners, but most benchmarks still evaluate one specification followed by one final assessment. This leaves out a basic question: can an agent keep its own codebase working as requirements change? We introduce EvoCode-Bench, a benchmark of 26 stateful coding tasks and 227 evaluated rounds. Each task preserves the agent's workspace for 5-15 rounds, states requirements through observable behavior, and uses cumulative executable tests to check new requirements and still-active prior ones. We evaluate 13 coding agents with two metrics: MT@4, a four-attempt fail-stop multi-round score, and SR, a single-round score from a reference-completed prior state. For most agents, SR exceeds MT@4 by 22-40 points. The gap also changes rankings: the highest-SR agent (78.9) ranks only third in persistent execution (44.0 MT@4). Even the strongest agents achieve only about 50% success on multi-turn metrics, and aggregate pass rate drops below half of round-1 performance by round 5. Failure analysis shows tier-dependent behavior: weaker agents fail early, while stronger agents survive long enough to expose specification-tracking and regression failures. We release the benchmark data and Harbor multi-turn infrastructure.
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Mode-as-Sequence: Translating Multimodal Motion Prediction into Unified Sequential Mode Modeling

✇cs.AI, q-bio.NC updates on arXiv.org
By: Zikang Zhou · Haibo Hu · Xinhong Chen · Yifan Zhang · Nan Guan · Yung-Hui Li · Chun Jason Xue · Jianping Wang
arXiv:2605.24037v1 Announce Type: cross Abstract: Multimodal motion forecasting is inherently under-supervised: each training scene provides only one realized future, yet multiple plausible futures exist. This sparse supervision often leads to mode collapse (redundant hypotheses and insufficient mode coverage) and unreliable confidence ranking when predicting a small set of trajectories. We propose Mode-as-Sequence, a unified decoding framework that translates an unordered mode set into an ordered mode sequence and explicitly models mode-to-mode dependency. Under this framework, we develop two complementary instantiations. ModeSeq performs recurrent mode decoding, where each mode is generated conditioned on the previously generated modes, encouraging diverse, non-redundant hypotheses with calibrated confidence ordering. To remove the mode-by-mode autoregressive bottleneck, we further propose Parallel ModeSeq, which preserves the same causal dependency using masked mode-to-mode self-attention while decoding all modes in a single forward pass, enabling efficient large-$K$ inference and scalable joint-scene prediction. To learn representative modes and calibrated confidence under sparse labels, we introduce Early-Match-Take-All (EMTA) and its joint-scene extension MA-EMTA, together with a lightweight ranking regularizer that reduces confidence inversions. Extensive experiments on large-scale benchmarks demonstrate consistent improvements in both ranking-oriented metrics and best-of-K accuracy across datasets, horizons, and object types. In the Waymo Open Dataset challenges, ModeSeq achieves 1st place in the 2024 LiDAR-free motion prediction track, and Parallel ModeSeq achieves 1st place in the 2025 Interaction Prediction Challenge, validating the effectiveness of Mode-as-Sequence for both accuracy and efficiency.
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PiXTime: A Model for Federated Time Series Forecasting with Heterogeneous Data across Nodes

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yiming Zhou · Jiahao Wang · Mingyue Cheng · Hao Wang · Defu Lian · Enhong Chen
arXiv:2601.05613v2 Announce Type: replace-cross Abstract: While collaborative forecasting on distributed time series is highly desirable, directly pooling localized datasets is often impractical due to data sharing constraints. Federated learning offers a promising alternative, yet conventional federated learning algorithms require homogeneous model architectures, which are incompatible with the structural discrepancies, such as unaligned temporal resolutions and mismatched variable channels, commonly observed across decentralized nodes. To bridge this gap, we introduce PiXTime, a novel Transformer-based framework designed to natively accommodate and leverage structurally heterogeneous temporal data. At its core, PiXTime adopts a parameter-decoupling architecture, strategically partitioning the model into localized personalized modules and a globally aggregated shared backbone. Specifically, node-specific local modules act as dimensional adapters, projecting raw sequences of diverse lengths into a unified representation space. Concurrently, a globally synchronized VE Table injects consistent categorical identities into the feature space, allowing the shared backbone to collaboratively learn and generalize representations across inconsistent variable distributions. Comprehensive evaluations on multiple benchmarks demonstrate that PiXTime achieves state-of-the-art performance in heterogeneous federated environments, while maintaining robust superiority in standard homogeneous and centralized forecasting settings.
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Data Difficulty and the Generalization--Extrapolation Tradeoff in LLM Fine-Tuning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Siyuan Liu · Tinghong Chen · Xinghan Li · Yifei Wang · Jingzhao Zhang
arXiv:2605.12906v2 Announce Type: replace-cross Abstract: Data selection during supervised fine-tuning (SFT) can critically change the behavior of large language models (LLMs). Although existing work has studied the effect of selecting data based on heuristics such as perplexity, difficulty, or length, the reported findings are often inconsistent or context-dependent. In this work, we systematically study the role of data difficulty in fine-tuning from both empirical and theoretical perspectives, and find that there is no universally optimal difficulty level; rather, its effectiveness depends on the dataset size. We show that for a fixed data budget, there exists an optimal data difficulty for SFT, and that this optimal difficulty shifts toward harder data as the data budget increases. To explain this phenomenon, we conduct controlled synthetic experiments that reveal a simple underlying mechanism: the interplay between the (in-distribution) generalization gap and the extrapolation gap. We further support this mechanism through a theoretical analysis using PAC-Bayesian generalization bounds. Overall, our results clarify how data size and difficulty jointly affect the trade-off between generalization and extrapolation in SFT, providing guidance for difficulty-based data selection under certain model and data conditions.
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EBV strain interacts with host HLA to drive nasopharyngeal carcinoma risk

✇Nature - Issue - nature.com science feeds
By: Yanhong Chen · Jingtong Liang · Wanlin Zhang · Xinyu Zhang · Xinyi Zhang · Ching-Yuan Wang · Fei Yao · Shanshan Zhang · Xiang Zhou · Weimin Ye · Ruimei Feng · Yonglin Cai · Zhe Zhang · Mingfang Ji · Qian Cui · Xihong Lin · Jiesen Li · Jialei Xu · Qiuting Zhang · Qinyao Huang · Yingying Cheng · Yanran Luo · Xiaoping Ye · Qisheng Feng · Minzhong Tang · Mu-Sheng Zeng · Yi-Xin Zeng · Zhonghua Liu · Weiwei Zhai · Jianjun Liu · Miao Xu

Nature, Published online: 15 April 2026; doi:10.1038/s41586-026-10416-8

A genome-to-genome association study identifies host and viral risk factors that interact to drive nasopharyngeal carcinoma endemicity in southern China.
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Safety-Aligned 3D Object Detection: Single-Vehicle, Cooperative, and End-to-End Perspectives

✇cs.AI, q-bio.NC updates on arXiv.org
By: Brian Hsuan-Cheng Liao · Chih-Hong Cheng · Hasan Esen · Alois Knoll
arXiv:2604.03325v1 Announce Type: cross Abstract: Perception plays a central role in connected and autonomous vehicles (CAVs), underpinning not only conventional modular driving stacks, but also cooperative perception systems and recent end-to-end driving models. While deep learning has greatly improved perception performance, its statistical nature makes perfect predictions difficult to attain. Meanwhile, standard training objectives and evaluation benchmarks treat all perception errors equally, even though only a subset is safety-critical. In this paper, we investigate safety-aligned evaluation and optimization for 3D object detection that explicitly characterize high-impact errors. Building on our previously proposed safety-oriented metric, NDS-USC, and safety-aware loss function, EC-IoU, we make three contributions. First, we present an expanded study of single-vehicle 3D object detection models across diverse neural network architectures and sensing modalities, showing that gains under standard metrics such as mAP and NDS may not translate to safety-oriented criteria represented by NDS-USC. With EC-IoU, we reaffirm the benefit of safety-aware fine-tuning for improving safety-critical detection performance. Second, we conduct an ego-centric, safety-oriented evaluation of AV-infrastructure cooperative object detection models, underscoring its superiority over vehicle-only models and demonstrating a safety impact analysis that illustrates the potential contribution of cooperative models to "Vision Zero." Third, we integrate EC-IoU into SparseDrive and show that safety-aware perception hardening can reduce collision rate by nearly 30% and improve system-level safety directly in an end-to-end perception-to-planning framework. Overall, our results indicate that safety-aligned perception evaluation and optimization offer a practical path toward enhancing CAV safety across single-vehicle, cooperative, and end-to-end autonomy settings.
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Stabilizing Unsupervised Self-Evolution of MLLMs via Continuous Softened Retracing reSampling

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yunyao Yu · Zhengxian Wu · Zhuohong Chen · Hangrui Xu · Zirui Liao · Xiangwen Deng · Zhifang Liu · Senyuan Shi · Haoqian Wang
arXiv:2604.03647v1 Announce Type: cross Abstract: In the unsupervised self-evolution of Multimodal Large Language Models, the quality of feedback signals during post-training is pivotal for stable and effective learning. However, existing self-evolution methods predominantly rely on majority voting to select the most frequent output as the pseudo-golden answer, which may stem from the model's intrinsic biases rather than guaranteeing the objective correctness of the reasoning paths. To counteract the degradation, we propose \textbf{C}ontinuous \textbf{S}oftened \textbf{R}etracing re\textbf{S}ampling (\textbf{CSRS}) in MLLM self-evolution. Specifically, we introduce a Retracing Re-inference Mechanism (\textbf{RRM}) that the model re-inferences from anchor points to expand the exploration of long-tail reasoning paths. Simultaneously, we propose Softened Frequency Reward (\textbf{SFR}), which replaces binary rewards with continuous signals, calibrating reward based on the answers' frequency across sampled reasoning sets. Furthermore, incorporated with Visual Semantic Perturbation (\textbf{VSP}), CSRS ensures the model prioritizes mathematical logic over visual superficiality. Experimental results demonstrate that CSRS significantly enhances the reasoning performance of Qwen2.5-VL-7B on benchmarks such as MathVision. We achieve state-of-the-art (SOTA) results in unsupervised self-evolution on geometric tasks. Our code is avaible at https://github.com/yyy195/CSRS.
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Fine-grained Analysis of Stability and Generalization for Stochastic Bilevel Optimization

✇cs.AI, q-bio.NC updates on arXiv.org
By: Xuelin Zhang · Hong Chen · Bin Gu · Tieliang Gong · Feng Zheng
arXiv:2604.04090v1 Announce Type: cross Abstract: Stochastic bilevel optimization (SBO) has been integrated into many machine learning paradigms recently, including hyperparameter optimization, meta learning, and reinforcement learning. Along with the wide range of applications, there have been numerous studies on the computational behavior of SBO. However, the generalization guarantees of SBO methods are far less understood from the lens of statistical learning theory. In this paper, we provide a systematic generalization analysis of the first-order gradient-based bilevel optimization methods. Firstly, we establish the quantitative connections between the on-average argument stability and the generalization gap of SBO methods. Then, we derive the upper bounds of on-average argument stability for single-timescale stochastic gradient descent (SGD) and two-timescale SGD, where three settings (nonconvex-nonconvex (NC-NC), convex-convex (C-C), and strongly-convex-strongly-convex (SC-SC)) are considered respectively. Experimental analysis validates our theoretical findings. Compared with the previous algorithmic stability analysis, our results do not require reinitializing the inner-level parameters at each iteration and are applicable to more general objective functions.
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FlowPIE: Test-Time Scientific Idea Evolution with Flow-Guided Literature Exploration

✇cs.AI, q-bio.NC updates on arXiv.org
By: Qiyao Wang · Hongbo Wang · Longze Chen · Zhihao Yang · Guhong Chen · Hamid Alinejad-Rokny · Hui Li · Yuan Lin · Min Yang
arXiv:2603.29557v1 Announce Type: new Abstract: Scientific idea generation (SIG) is critical to AI-driven autonomous research, yet existing approaches are often constrained by a static retrieval-then-generation paradigm, leading to homogeneous and insufficiently divergent ideas. In this work, we propose FlowPIE, a tightly coupled retrieval-generation framework that treats literature exploration and idea generation as a co-evolving process. FlowPIE expands literature trajectories via a flow-guided Monte Carlo Tree Search (MCTS) inspired by GFlowNets, using the quality of current ideas assessed by an LLM-based generative reward model (GRM) as a supervised signal to guide adaptive retrieval and construct a diverse, high-quality initial population. Based on this population, FlowPIE models idea generation as a test-time idea evolution process, applying selection, crossover, and mutation with the isolation island paradigm and GRM-based fitness computation to incorporate cross-domain knowledge. It effectively mitigates the information cocoons arising from over-reliance on parametric knowledge and static literature. Extensive evaluations demonstrate that FlowPIE consistently produces ideas with higher novelty, feasibility and diversity compared to strong LLM-based and agent-based frameworks, while enabling reward scaling during test time.
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Generative Data Transformation: From Mixed to Unified Data

✇cs.AI, q-bio.NC updates on arXiv.org
By: Jiaqing Zhang · Mingjia Yin · Hao Wang · Yuxin Tian · Yuyang Ye · Yawen Li · Wei Guo · Yong Liu · Enhong Chen
arXiv:2602.22743v2 Announce Type: replace Abstract: Recommendation model performance is intrinsically tied to the quality, volume, and relevance of their training data. To address common challenges like data sparsity and cold start, recent researchs have leveraged data from multiple auxiliary domains to enrich information within the target domain. However, inherent domain gaps can degrade the quality of mixed-domain data, leading to negative transfer and diminished model performance. Existing prevailing \emph{model-centric} paradigm -- which relies on complex, customized architectures -- struggles to capture the subtle, non-structural sequence dependencies across domains, leading to poor generalization and high demands on computational resources. To address these shortcomings, we propose \textsc{Taesar}, a \emph{data-centric} framework for \textbf{t}arget-\textbf{a}lign\textbf{e}d \textbf{s}equenti\textbf{a}l \textbf{r}egeneration, which employs a contrastive decoding mechanism to adaptively encode cross-domain context into target-domain sequences. It employs contrastive decoding to encode cross-domain context into target sequences, enabling standard models to learn intricate dependencies without complex fusion architectures. Experiments show \textsc{Taesar} outperforms model-centric solutions and generalizes to various sequential models. By generating enriched datasets, \textsc{Taesar} effectively combines the strengths of data- and model-centric paradigms. The code accompanying this paper is available at~ \textcolor{blue}{https://github.com/USTC-StarTeam/Taesar}.
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ProGRank: Probe-Gradient Reranking to Defend Dense-Retriever RAG from Corpus Poisoning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Xiangyu Yin · Yi Qi · Chih-hong Cheng
arXiv:2603.22934v1 Announce Type: new Abstract: Retrieval-Augmented Generation (RAG) improves the reliability of large language model applications by grounding generation in retrieved evidence, but it also introduces a new attack surface: corpus poisoning. In this setting, an adversary injects or edits passages so that they are ranked into the Top-$K$ results for target queries and then affect downstream generation. Existing defences against corpus poisoning often rely on content filtering, auxiliary models, or generator-side reasoning, which can make deployment more difficult. We propose ProGRank, a post hoc, training-free retriever-side defence for dense-retriever RAG. ProGRank stress-tests each query--passage pair under mild randomized perturbations and extracts probe gradients from a small fixed parameter subset of the retriever. From these signals, it derives two instability signals, representational consistency and dispersion risk, and combines them with a score gate in a reranking step. ProGRank preserves the original passage content, requires no retraining, and also supports a surrogate-based variant when the deployed retriever is unavailable. Extensive experiments across three datasets, three dense retriever backbones, representative corpus poisoning attacks, and both retrieval-stage and end-to-end settings show that ProGRank provides stronger defence performance and a favorable robustness--utility trade-off. It also remains competitive under adaptive evasive attacks.
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PERMA: Benchmarking Personalized Memory Agents via Event-Driven Preference and Realistic Task Environments

✇cs.AI, q-bio.NC updates on arXiv.org
By: Shuochen Liu · Junyi Zhu · Long Shu · Junda Lin · Yuhao Chen · Haotian Zhang · Chao Zhang · Derong Xu · Jia Li · Bo Tang · Zhiyu Li · Feiyu Xiong · Enhong Chen · Tong Xu
arXiv:2603.23231v1 Announce Type: new Abstract: Empowering large language models with long-term memory is crucial for building agents that adapt to users' evolving needs. However, prior evaluations typically interleave preference-related dialogues with irrelevant conversations, reducing the task to needle-in-a-haystack retrieval while ignoring relationships between events that drive the evolution of user preferences. Such settings overlook a fundamental characteristic of real-world personalization: preferences emerge gradually and accumulate across interactions within noisy contexts. To bridge this gap, we introduce PERMA, a benchmark designed to evaluate persona consistency over time beyond static preference recall. Additionally, we incorporate (1) text variability and (2) linguistic alignment to simulate erratic user inputs and individual idiolects in real-world data. PERMA consists of temporally ordered interaction events spanning multiple sessions and domains, with preference-related queries inserted over time. We design both multiple-choice and interactive tasks to probe the model's understanding of persona along the interaction timeline. Experiments demonstrate that by linking related interactions, advanced memory systems can extract more precise preferences and reduce token consumption, outperforming traditional semantic retrieval of raw dialogues. Nevertheless, they still struggle to maintain a coherent persona across temporal depth and cross-domain interference, highlighting the need for more robust personalized memory management in agents. Our code and data are open-sourced at https://github.com/PolarisLiu1/PERMA.
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Efficient Personalized Reranking with Semi-Autoregressive Generation and Online Knowledge Distillation

✇cs.AI, q-bio.NC updates on arXiv.org
By: Kai Cheng · Hao Wang · Wei Guo · Weiwen Liu · Yong Liu · Yawen Li · Enhong Chen
arXiv:2603.07107v1 Announce Type: cross Abstract: Generative models offer a promising paradigm for the final stage reranking in multi-stage recommender systems, with the ability to capture inter-item dependencies within reranked lists. However, their practical deployment still faces two key challenges: (1) an inherent conflict between achieving high generation quality and ensuring low-latency inference, making it difficult to balance the two, and (2) insufficient interaction between user and item features in existing methods. To address these challenges, we propose a novel Personalized Semi-Autoregressive with online knowledge Distillation (PSAD) framework for reranking. In this framework, the teacher model adopts a semi-autoregressive generator to balance generation quality and efficiency, while its ranking knowledge is distilled online into a lightweight scoring network during joint training, enabling real-time and efficient inference. Furthermore, we propose a User Profile Network (UPN) that injects user intent and models interest dynamics, enabling deeper interactions between users and items. Extensive experiments conducted on three large-scale public datasets demonstrate that PSAD significantly outperforms state-of-the-art baselines in both ranking performance and inference efficiency.
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Survey of Computerized Adaptive Testing: A Machine Learning Perspective

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yan Zhuang · Qi Liu · Haoyang Bi · Zhenya Huang · Weizhe Huang · Jiatong Li · Junhao Yu · Zirui Liu · Zirui Hu · Yuting Hong · Zachary A. Pardos · Haiping Ma · Mengxiao Zhu · Shijin Wang · Enhong Chen
arXiv:2404.00712v3 Announce Type: replace-cross Abstract: Computerized Adaptive Testing (CAT) offers an efficient and personalized method for assessing examinee proficiency by dynamically adjusting test questions based on individual performance. Compared to traditional, non-personalized testing methods, CAT requires fewer questions and provides more accurate assessments. As a result, CAT has been widely adopted across various fields, including education, healthcare, sports, sociology, and the evaluation of AI models. While traditional methods rely on psychometrics and statistics, the increasing complexity of large-scale testing has spurred the integration of machine learning techniques. This paper aims to provide a machine learning-focused survey on CAT, presenting a fresh perspective on this adaptive testing paradigm. We delve into measurement models, question selection algorithm, bank construction, and test control within CAT, exploring how machine learning can optimize these components. Through an analysis of current methods, strengths, limitations, and challenges, we strive to develop robust, fair, and efficient CAT systems. By bridging psychometric-driven CAT research with machine learning, this survey advocates for a more inclusive and interdisciplinary approach to the future of adaptive testing.
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More Bang for the Buck: Process Reward Modeling with Entropy-Driven Uncertainty

✇cs.AI, q-bio.NC updates on arXiv.org
By: Lang Cao · Renhong Chen · Yingtian Zou · Chao Peng · Huacong Xu · Yuxian Wang · Wu Ning · Qian Chen · Mofan Peng · Zijie Chen · Peishuo Su · Yitong Li
arXiv:2503.22233v4 Announce Type: replace-cross Abstract: We introduce the Entropy-Driven Uncertainty Process Reward Model (EDU-PRM), a novel entropy-driven training framework for process reward modeling that enables dynamic, uncertainty-aligned segmentation of complex reasoning steps, eliminating the need for costly manual step annotations. Unlike previous Process Reward Models (PRMs) that rely on static partitioning and human labeling, EDU-PRM automatically anchors step boundaries at tokens with high predictive entropy, effectively capturing intrinsic logical transitions and facilitating efficient exploration of diverse reasoning paths. On the ProcessBench benchmark, EDU-PRM outperforms strong public PRM baselines, such as Math-Shepherd PRM and Omega PRM, and EDU-PRM achieves comparable results with SOTA models while only using 1.5% training data. Furthermore, by leveraging our proposed EDU sampling strategy, we observe accuracy boosts from 64.7% to 67.3% for generative reasoning tasks, accompanied by a reduction of 32% in token usage. These findings underscore the potential of EDU-PRM as a scalable and annotation-efficient paradigm for process supervision in mathematical reasoning, paving the way for more efficient and robust approaches to complex mathematical problem solving.
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Merlin: A Computed Tomography Vision-Language Foundation Model and Dataset

✇cs.AI, q-bio.NC updates on arXiv.org
By: Louis Blankemeier · Ashwin Kumar · Joseph Paul Cohen · Jiaming Liu · Longchao Liu · Dave Van Veen · Syed Jamal Safdar Gardezi · Hongkun Yu · Magdalini Paschali · Zhihong Chen · Jean-Benoit Delbrouck · Eduardo Reis · Robbie Holland · Cesar Truyts · Christian Bluethgen · Yufu Wu · Long Lian · Malte Engmann Kjeldskov Jensen · Sophie Ostmeier · Maya Varma · Jeya Maria Jose Valanarasu · Zhongnan Fang · Zepeng Huo · Zaid Nabulsi · Diego Ardila · Wei-Hung Weng · Edson Amaro Junior · Neera Ahuja · Jason Fries · Nigam H. Shah · Greg Zaharchuk · Marc Willis · Adam Yala · Andrew Johnston · Robert D. Boutin · Andrew Wentland · Curtis P. Langlotz · Jason Hom · Sergios Gatidis · Akshay S. Chaudhari
arXiv:2406.06512v2 Announce Type: replace-cross Abstract: The large volume of abdominal computed tomography (CT) scans coupled with the shortage of radiologists have intensified the need for automated medical image analysis tools. Previous state-of-the-art approaches for automated analysis leverage vision-language models (VLMs) that jointly model images and radiology reports. However, current medical VLMs are generally limited to 2D images and short reports. Here to overcome these shortcomings for abdominal CT interpretation, we introduce Merlin, a 3D VLM that learns from volumetric CT scans, electronic health record data and radiology reports. This approach is enabled by a multistage pretraining framework that does not require additional manual annotations. We trained Merlin using a high-quality clinical dataset of paired CT scans (>6 million images from 15,331 CT scans), diagnosis codes (>1.8 million codes) and radiology reports (>6 million tokens). We comprehensively evaluated Merlin on 6 task types and 752 individual tasks that covered diagnostic, prognostic and quality-related tasks. The non-adapted (off-the-shelf) tasks included zero-shot classification of findings (30 findings), phenotype classification (692 phenotypes) and zero-shot cross-modal retrieval (image-to-findings and image-to-impression). The model-adapted tasks included 5-year chronic disease prediction (6 diseases), radiology report generation and 3D semantic segmentation (20 organs). We validated Merlin at scale, with internal testing on 5,137 CT scans and external testing on 44,098 CT scans from 3 independent sites and 2 public datasets. The results demonstrated high generalization across institutions and anatomies. Merlin outperformed 2D VLMs, CT foundation models and off-the-shelf radiology models. We also release our trained models, code, and dataset, available at: https://github.com/StanfordMIMI/Merlin.
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Perception-R1: Advancing Multimodal Reasoning Capabilities of MLLMs via Visual Perception Reward

✇cs.AI, q-bio.NC updates on arXiv.org
By: Tong Xiao · Xin Xu · Zhenya Huang · Hongyu Gao · Quan Liu · Qi Liu · Enhong Chen
arXiv:2506.07218v3 Announce Type: replace-cross Abstract: Enhancing the multimodal reasoning capabilities of Multimodal Large Language Models (MLLMs) is a challenging task that has attracted increasing attention in the community. Recently, several studies have applied Reinforcement Learning with Verifiable Rewards (RLVR) to the multimodal domain in order to enhance the reasoning abilities of MLLMs. However, these works largely overlook the enhancement of multimodal perception capabilities in MLLMs, which serve as a core prerequisite and foundational component of complex multimodal reasoning. Through McNemar's test, we find that existing RLVR method fails to effectively enhance the multimodal perception capabilities of MLLMs, thereby limiting their further improvement in multimodal reasoning. To address this limitation, we propose Perception-R1, which introduces a novel visual perception reward that explicitly encourages MLLMs to perceive the visual content accurately, thereby can effectively incentivizing both their multimodal perception and reasoning capabilities. Specifically, we first collect textual visual annotations from the CoT trajectories of multimodal problems, which will serve as visual references for reward assignment. During RLVR training, we employ a judging LLM to assess the consistency between the visual annotations and the responses generated by MLLM, and assign the visual perception reward based on these consistency judgments. Extensive experiments on several multimodal reasoning benchmarks demonstrate the effectiveness of our Perception-R1, which achieves state-of-the-art performance on most benchmarks using only 1,442 training data. Our code and dataset will be available at https://github.com/tongxiao2002/Perception-R1.
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