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Received — 2 April 2026 ⏭

Robust transcriptomic hallmarks targeting intratumor heterogeneity in intrahepatic cholangiocarcinoma

✇(Multiomics OR Omics) AND (Pancreatic)
By: Youpei Lin · Lihua Peng · Haichao Zhao · Penghui Lin · Lv Chen · Zunyun Gong · Jian Lin · Dongbing Liu · Xupeng Yang · Xiangze Song · Mao Zhang · Shuyi Ji · Junhua Rao · Huijuan Luo · Yifei Cheng · Xiaofang Chen · Guohe Song · Hao Hou · Dongning Rao · Tiancheng Zhang · Weiren Liu · Shu Zhang · Gaoyang Xu · Juan Zhang · Liyun Xiao · Yan Liang · Yang Liu · Yuhan Chen · Zhirou Cui · Xiaoying Wang · Jian Zhou · Qiang Gao · Kui Wu · Jia Fan
31 March 2026 at 18:00

Cell Rep Med. 2026 Mar 30:102708. doi: 10.1016/j.xcrm.2026.102708. Online ahead of print.

ABSTRACT

Intratumor heterogeneity (ITH) undermines transcriptome-based stratification in intrahepatic cholangiocarcinoma (iCCA). Here, we integrate multi-omics data from multi-region, single-region, and single-cell RNA sequencing cohorts to systematically characterize gene expression ITH. We uncover that immune and stromal heterogeneity are primary drivers of ITH, leading to misclassification of a median 27.8% of tumors by existing subtyping systems. To overcome this, we identify a low-intratumor-heterogeneity/high-intertumor-variability (LIHV) gene set and develop an ITH-insensitive classification system defining five subgroups: inflammatory (SI), metabolic (SII), atypical (SIII-1), immune-silent (SIII-2), and neurodegenerative (SIII-3). These subgroups exhibit distinct clinical outcomes, molecular features, immune landscapes, and therapeutic vulnerabilities. GPRC5A and VTCN1 serve as robust immunohistochemical biomarkers for SI and SIII tumors, while serum CEA and CA19-9 identify inflammatory iCCA. Therapeutically, HSP90 inhibition synergizes with anti-PD1 in inflammatory iCCA, whereas combined anti-PD1 and anti-TIM3 suppresses neurodegenerative iCCA. Collectively, our study provides a robust molecular framework and actionable therapeutic strategies for iCCA.

PMID:41916296 | DOI:10.1016/j.xcrm.2026.102708

A monocyte-centered framework for predicting immunochemotherapy efficacy in lung squamous cell carcinoma patients

✇Omics In Lung
By: Jiangnan Zhao · Zijin Wang · Manyu Xiao · Yeyuan Zhang · Boxin Liu · Silin Chen · Yiping Tian · Dongqing Lv · Pingli Wang · Hai Song · Yuefeng Wu · Jian Liu · Kai Wang
30 March 2026 at 18:00

EMBO Mol Med. 2026 Mar 30. doi: 10.1038/s44321-026-00410-y. Online ahead of print.

ABSTRACT

Lung cancer is the leading cause of cancer-related mortality worldwide, with lung squamous cell carcinoma (LUSC) comprising 20-30% of cases. Immunochemotherapy (IC) is the standard first-line treatment for advanced LUSC, yet reliable predictors of therapeutic response remain unavailable. Using single-cell multi-omics profiling of paired pre- and post-treatment tumor and blood samples, we observed that patients responding to IC exhibited significantly higher baseline levels of peripheral blood monocytes, tumor-infiltrating classical monocytes, and APOBEC3A+ monocytes across both compartments compared with non-responders. These associations were independently validated in additional cohorts using routine complete blood count testing and multiplex immunofluorescence analysis of native tumor tissues. Our findings reveal monocyte-related parameters as clinically accessible indicators that link systemic immunity with the tumor microenvironment and hold promise for predicting IC responsiveness in patients with LUSC.

PMID:41912871 | DOI:10.1038/s44321-026-00410-y

A monocyte-centered framework for predicting immunochemotherapy efficacy in lung squamous cell carcinoma patients

✇(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Jiangnan Zhao · Zijin Wang · Manyu Xiao · Yeyuan Zhang · Boxin Liu · Silin Chen · Yiping Tian · Dongqing Lv · Pingli Wang · Hai Song · Yuefeng Wu · Jian Liu · Kai Wang
30 March 2026 at 18:00

EMBO Mol Med. 2026 Mar 30. doi: 10.1038/s44321-026-00410-y. Online ahead of print.

ABSTRACT

Lung cancer is the leading cause of cancer-related mortality worldwide, with lung squamous cell carcinoma (LUSC) comprising 20-30% of cases. Immunochemotherapy (IC) is the standard first-line treatment for advanced LUSC, yet reliable predictors of therapeutic response remain unavailable. Using single-cell multi-omics profiling of paired pre- and post-treatment tumor and blood samples, we observed that patients responding to IC exhibited significantly higher baseline levels of peripheral blood monocytes, tumor-infiltrating classical monocytes, and APOBEC3A+ monocytes across both compartments compared with non-responders. These associations were independently validated in additional cohorts using routine complete blood count testing and multiplex immunofluorescence analysis of native tumor tissues. Our findings reveal monocyte-related parameters as clinically accessible indicators that link systemic immunity with the tumor microenvironment and hold promise for predicting IC responsiveness in patients with LUSC.

PMID:41912871 | DOI:10.1038/s44321-026-00410-y

Received — 17 March 2026 ⏭

Tumor-informed liquid biopsy detection of structural variants in high grade serous ovarian cancer

✇MRD
By: Jian Li · Shiro Takamatsu · Allison L Brodsky · Thomas Welte · Katherine Calzoncinth · Veena K Vuttaradhi · Joseph Celestino · Barrett Lawson · R Tyler Hillman
16 March 2026 at 18:00

Oncoscience. 2026 Mar 5;13:44-54. doi: 10.18632/oncoscience.645. eCollection 2026.

ABSTRACT

BACKGROUND: High grade serous ovarian cancer (HGSOC) recurs frequently and commercial tests have emerged for tumor-informed, cell-free DNA (cfDNA)-based detection of minimal residual disease. These tests are based on somatic single nucleotide variants prevalent in many cancers and thus are not well matched to HGSOC, which is dominated by structural genomic rearrangements. The purpose of this study was to evaluate the feasibility of a structural-variant (SV)-informed, cfDNA-based method for detecting clonal and subclonal HGSOC disease burden.

METHODS: A method was developed for detecting patient-specific SV breakpoints using digital droplet PCR (ddPCR) with custom tumor-informed primer/probe pairs. Test parameters were first estimated using synthetic cfDNA generated by ultrasonication of genomic DNA from ovarian cancer cell lines. The optimized workflow was implemented in which whole genome sequencing of multisite pre-treatment HGSOC biopsies performed and high confidence SVs were called by multiple published SV callers. Real-time PCR and ddPCR were used for assay development.

RESULTS: Following the optimized workflow, tumor-specific SV breakpoint-spanning primers/probe sets of four HGSOC patients' multisite biopsies were designed and validated by real-time PCR and ddPCR. Together with four HGSOCs, a total of 29 SVs breakpoints-spanning tumor-informed primers/probe sets were designed and validated in multisite biopsies. 15 validated tumor-specific SVs were selected for quantification in their corresponding liquid biopsies using the validated ddPCR, and 9 had measurements in liquid biopsies.

CONCLUSIONS: Our result shows the detection of SVs from pre-treatment cfDNA using tumor-informed breakpoints-spanning ddPCR is feasible and may enable a novel and sensitive method for monitoring on-treatment disease burden.

PMID:41835357 | PMC:PMC12981705 | DOI:10.18632/oncoscience.645

SOX4 induces cisplatin resistance in cervical cancer cells by inhibiting aerobic glycolysis

✇Cell Death Discovery nature.com science feeds
By: Ruili Sun · Haofei Gong · Ran Zhao · Huiying Lv · Huijie Yang · Xiaofei Zhu · Xinlai Qian · Jian Li · Qiongzi Wang
14 March 2026 at 08:00

Cell Death Discovery, Published online: 14 March 2026; doi:10.1038/s41420-026-02954-x

SOX4 induces cisplatin resistance in cervical cancer cells by inhibiting aerobic glycolysis
Received — 11 March 2026 ⏭

Batch-of-Thought: Cross-Instance Learning for Enhanced LLM Reasoning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Xuan Yang · Furong Jia · Roy Xie · Xiong Xi · Hengwei Bian · Jian Li · Monica Agrawal
10 March 2026 at 12:00
arXiv:2601.02950v2 Announce Type: replace Abstract: Current Large Language Model reasoning systems process queries independently, discarding valuable cross-instance signals such as shared reasoning patterns and consistency constraints. We introduce Batch-of-Thought (BoT), a training-free method that processes related queries jointly to enable cross-instance learning. By performing comparative analysis across batches, BoT identifies high-quality reasoning templates, detects errors through consistency checks, and amortizes computational costs. We instantiate BoT within a multi-agent reflection architecture (BoT-R), where a Reflector performs joint evaluation to unlock mutual information gain unavailable in isolated processing. Experiments across three model families and six benchmarks demonstrate that BoT-R consistently improves accuracy and confidence calibration while reducing inference costs by up to 61%. Our theoretical and experimental analysis reveals when and why batch-aware reasoning benefits LLM systems. Our code is available at https://github.com/xuanyang19/BoT
Received — 5 March 2026 ⏭

PhyPrompt: RL-based Prompt Refinement for Physically Plausible Text-to-Video Generation

✇cs.AI, q-bio.NC updates on arXiv.org
By: Shang Wu · Chenwei Xu · Zhuofan Xia · Weijian Li · Lie Lu · Pranav Maneriker · Fan Du · Manling Li · Han Liu
5 March 2026 at 13:00
arXiv:2603.03505v1 Announce Type: cross Abstract: State-of-the-art text-to-video (T2V) generators frequently violate physical laws despite high visual quality. We show this stems from insufficient physical constraints in prompts rather than model limitations: manually adding physics details reliably produces physically plausible videos, but requires expertise and does not scale. We present PhyPrompt, a two-stage reinforcement learning framework that automatically refines prompts for physically realistic generation. First, we fine-tune a large language model on a physics-focused Chain-of-Thought dataset to integrate principles like object motion and force interactions while preserving user intent. Second, we apply Group Relative Policy Optimization with a dynamic reward curriculum that initially prioritizes semantic fidelity, then progressively shifts toward physical commonsense. This curriculum achieves synergistic optimization: PhyPrompt-7B reaches 40.8\% joint success on VideoPhy2 (8.6pp gain), improving physical commonsense by 11pp (55.8\% to 66.8\%) while simultaneously increasing semantic adherence by 4.4pp (43.4\% to 47.8\%). Remarkably, our curriculum exceeds single-objective training on both metrics, demonstrating compositional prompt discovery beyond conventional multi-objective trade-offs. PhyPrompt outperforms GPT-4o (+3.8\% joint) and DeepSeek-V3 (+2.2\%, 100$\times$ larger) using only 7B parameters. The approach transfers zero-shot across diverse T2V architectures (Lavie, VideoCrafter2, CogVideoX-5B) with up to 16.8\% improvement, establishing that domain-specialized reinforcement learning with compositional curricula surpasses general-purpose scaling for physics-aware generation.

StegaFFD: Privacy-Preserving Face Forgery Detection via Fine-Grained Steganographic Domain Lifting

✇cs.AI, q-bio.NC updates on arXiv.org
By: Guoqing Ma · Xun Lin · Hui Ma · Ajian Liu · Yizhong Liu · Wenzhong Tang · Shan Yu · Chenqi Kong · Yi Yu
4 March 2026 at 13:00
arXiv:2603.02886v1 Announce Type: cross Abstract: Most existing Face Forgery Detection (FFD) models assume access to raw face images. In practice, under a client-server framework, private facial data may be intercepted during transmission or leaked by untrusted servers. Previous privacy protection approaches, such as anonymization, encryption, or distortion, partly mitigate leakage but often introduce severe semantic distortion, making images appear obviously protected. This alerts attackers, provoking more aggressive strategies and turning the process into a cat-and-mouse game. Moreover, these methods heavily manipulate image contents, introducing degradation or artifacts that may confuse FFD models, which rely on extremely subtle forgery traces. Inspired by advances in image steganography, which enable high-fidelity hiding and recovery, we propose a Stega}nography-based Face Forgery Detection framework (StegaFFD) to protect privacy without raising suspicion. StegaFFD hides facial images within natural cover images and directly conducts forgery detection in the steganographic domain. However, the hidden forgery-specific features are extremely subtle and interfered with by cover semantics, posing significant challenges. To address this, we propose Low-Frequency-Aware Decomposition (LFAD) and Spatial-Frequency Differential Attention (SFDA), which suppress interference from low-frequency cover semantics and enhance hidden facial feature perception. Furthermore, we introduce Steganographic Domain Alignment (SDA) to align the representations of hidden faces with those of their raw counterparts, enhancing the model's ability to perceive subtle facial cues in the steganographic domain. Extensive experiments on seven FFD datasets demonstrate that StegaFFD achieves strong imperceptibility, avoids raising attackers' suspicion, and better preserves FFD accuracy compared to existing facial privacy protection methods.
Received — 25 February 2026 ⏭

CM2: Reinforcement Learning with Checklist Rewards for Multi-Turn and Multi-Step Agentic Tool Use

✇cs.AI, q-bio.NC updates on arXiv.org
By: Zhen Zhang · Kaiqiang Song · Xun Wang · Yebowen Hu · Weixiang Yan · Chenyang Zhao · Henry Peng Zou · Haoyun Deng · Sathish Reddy Indurthi · Shujian Liu · Simin Ma · Xiaoyang Wang · Xin Eric Wang · Song Wang
24 February 2026 at 13:00
arXiv:2602.12268v2 Announce Type: replace Abstract: AI agents are increasingly used to solve real-world tasks by reasoning over multi-turn user interactions and invoking external tools. However, applying reinforcement learning to such settings remains difficult: realistic objectives often lack verifiable rewards and instead emphasize open-ended behaviors; moreover, RL for multi-turn, multi-step agentic tool use is still underexplored; and building and maintaining executable tool environments is costly, limiting scale and coverage. We propose CM2, an RL framework that replaces verifiable outcome rewards with checklist rewards. CM2 decomposes each turn's intended behavior into fine-grained binary criteria with explicit evidence grounding and structured metadata, turning open-ended judging into more stable classification-style decisions. To balance stability and informativeness, our method adopts a strategy of sparse reward assignment but dense evaluation criteria. Training is performed in a scalable LLM-simulated tool environment, avoiding heavy engineering for large tool sets. Experiments show that CM2 consistently improves over supervised fine-tuning. Starting from an 8B Base model and training on an 8k-example RL dataset, CM2 improves over the SFT counterpart by 8 points on tau^-Bench, by 10 points on BFCL-V4, and by 12 points on ToolSandbox. The results match or even outperform similarly sized open-source baselines, including the judging model. CM2 thus provides a scalable recipe for optimizing multi-turn, multi-step tool-using agents without relying on verifiable rewards. Code provided by the open-source community: https://github.com/namezhenzhang/CM2-RLCR-Tool-Agent.
Received — 17 February 2026 ⏭

Mitigating the Safety-utility Trade-off in LLM Alignment via Adaptive Safe Context Learning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yanbo Wang · Minzheng Wang · Jian Liang · Lu Wang · Yongcan Yu · Ran He
17 February 2026 at 13:00
arXiv:2602.13562v1 Announce Type: cross Abstract: While reasoning models have achieved remarkable success in complex reasoning tasks, their increasing power necessitates stringent safety measures. For safety alignment, the core challenge lies in the inherent trade-off between safety and utility. However, prevailing alignment strategies typically construct CoT training data with explicit safety rules via context distillation. This approach inadvertently limits reasoning capabilities by creating a rigid association between rule memorization and refusal. To mitigate the safety-utility trade-off, we propose the Adaptive Safe Context Learning (ASCL) framework to improve the reasoning given proper context. ASCL formulates safety alignment as a multi-turn tool-use process, empowering the model to autonomously decide when to consult safety rules and how to generate the ongoing reasoning. Furthermore, to counteract the preference for rule consultation during RL, we introduce Inverse Frequency Policy Optimization (IFPO) to rebalance advantage estimates. By decoupling rule retrieval and subsequent reasoning, our method achieves higher overall performance compared to baselines.

pFedNavi: Structure-Aware Personalized Federated Vision-Language Navigation for Embodied AI

✇cs.AI, q-bio.NC updates on arXiv.org
By: Qingqian Yang · Hao Wang · Sai Qian Zhang · Jian Li · Yang Hua · Miao Pan · Tao Song · Zhengwei Qi · Haibing Guan
17 February 2026 at 13:00
arXiv:2602.14401v1 Announce Type: cross Abstract: Vision-Language Navigation VLN requires large-scale trajectory instruction data from private indoor environments, raising significant privacy concerns. Federated Learning FL mitigates this by keeping data on-device, but vanilla FL struggles under VLNs' extreme cross-client heterogeneity in environments and instruction styles, making a single global model suboptimal. This paper proposes pFedNavi, a structure-aware and dynamically adaptive personalized federated learning framework tailored for VLN. Our key idea is to personalize where it matters: pFedNavi adaptively identifies client-specific layers via layer-wise mixing coefficients, and performs fine-grained parameter fusion on the selected components (e.g., the encoder-decoder projection and environment-sensitive decoder layers) to balance global knowledge sharing with local specialization. We evaluate pFedNavi on two standard VLN benchmarks, R2R and RxR, using both ResNet and CLIP visual representations. Across all metrics, pFedNavi consistently outperforms the FedAvg-based VLN baseline, achieving up to 7.5% improvement in navigation success rate and up to 7.8% gain in trajectory fidelity, while converging 1.38x faster under non-IID conditions.
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