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Development and Preliminary Evaluation of a Conversational Agent Delivering Problem-Solving Therapy for Family Caregivers of Children With a Chronic Health Condition: Multiphase Mixed Methods Study

✇Journal of Medical Internet Research
By: Weichao Yuwen · Liying Wang · Serena Jinchen Xie · Myra Divina · Xuehong Fan · William Kearns · Teresa M Ward
Background: Family caregivers of children with chronic health conditions experience substantial physical and mental health burdens, including burnout, anxiety, depression, fatigue, and sleep disturbances. Despite this need, validated digital mental health tools tailored to family caregivers remain limited. AI-powered conversational agents offer a promising approach for delivering on-demand, personalized mental health support, yet development and evaluation frameworks for this population are lacking. Objective: This paper describes the iterative development and formative evaluation of COCO (Caring of Caregivers Online), a conversational agent designed for family caregivers of children with chronic health conditions. COCO integrates problem-solving therapy (PST) and motivational interviewing (MI) within a human-in-the-loop development framework that progressed from rule-based interactions to a large language model (LLM)–powered conversational agent. Methods: COCO was developed across four phases: (1) caregiver persona and dialogue development based on PST and MI; (2) usability testing of a low-fidelity prototype with standardized patients in a single session of PST; (3) usability testing of a high-fidelity prototype with caregivers in a single session of PST (n=38); (4) integration of an LLM into COCO. The Wizard-of-Oz method was used across phases 2 and 3 to collect naturalistic dialogues and refine COCO’s conversational design. In phase 3, usability of COCO was assessed using the System Usability Scale (SUS). Caregiver emotions were measured before and after the session using 6 subscales of the PANAS-X. In phase 4, GPT-4 was integrated into COCO with few-shot learning and evaluated by research team members using the caregiver personas. Descriptive statistics were used to summarize quantitative measures. The MI principles and techniques used by COCO across the 4 phases were coded using the . Results: In phase 1, 4 gold-standard dialogues were developed using caregiver personas. In phase 2, standardized patients described COCO as validating and identified its problem-solving and on-demand support as helpful for caregivers. In phase 3, COCO-Wizard-of-Oz achieved a mean SUS score of 75.6% (SD 12.9%), reflecting acceptable usability. Participants demonstrated significant improvement in negative affect, sadness, guilt, and fatigue following PST sessions (
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Hybrid Physics-AI Framework of Body Center of Mass Dynamics from Wrist-Worn Sensors

✇cs.AI, q-bio.NC updates on arXiv.org
By: Shuhao Que · Valentina Breschi · Ying Wang
arXiv:2609.12304v1 Announce Type: new Abstract: Wrist-worn IMU has been widely used for daily-life health monitoring. Yet, it does not fully represent whole-body dynamics, for which the body center of mass (COM) is considered the physiological reference standard. Therefore, this work proposes a simplified kinematic model (KM), which is designed to map the wrist IMU to the COM acceleration. It is built upon several reductive assumptions that enable the solvability of the dynamic equations based on wrist IMU measurements alone. This work further proposes three types of hybrid AI modeling methods, namely human kinematic model-based neural network (HKM-NN) models, to leverage the power of both grey-box and black-box modeling. The HKM-NN methods include serial learning (ser-) and two approaches of simultaneous learning (sim1- and sim2-). The proposed models are trained and tested using our dataset, which includes wrist IMU measurements and ground-truth COM measurements from 10 healthy volunteers during six gait activities and sit-to-stand (SS) transitional movement. The results demonstrate the feasibility of estimating COM acceleration from wrist IMU measurements. Our KM model yields satisfactory results, with an error ranging from 6.7% to 12.5% for gait activities and 5.6% for the SS. In comparison with the KM model, our HKM-NN models significantly enhance the performance, achieving 5.3% to 9.3% errors for gait activities, and the best error of 3.9% for the SS. In addition, the HKM-NN models demonstrate distinct robustness characteristics under noisy test conditions, with sim1-/sim2- generally maintaining greater robustness under Gaussian perturbations, while the KM model exhibits comparatively strong robustness under salt-and-pepper noise. These findings highlight the importance of combining biomechanical structure with data-driven learning for wearable sensing applications operating under imperfect and noisy measurement conditions.
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Multi-Omics and Molecular Simulation Identify KIF11 as a Candidate Direct Target of Resveratrol in Hepatocellular Carcinoma

✇Omics in Hepatocellular
By: Yeying Wang · Shun Wan · Wanjia Qiao · Renpeng Li · Jinyu Zhao · Wenbo Meng

J Hepatocell Carcinoma. 2026 Aug 26;13:615781. doi: 10.2147/JHC.S615781. eCollection 2026.

ABSTRACT

OBJECTIVE: Hepatocellular carcinoma (HCC) has poor prognosis and variable immunotherapy response. Resveratrol exhibits anti-HCC activity, but its direct targets and association with immunotherapy response are unclear. This study identifies core resveratrol targets in HCC and evaluates their prognostic and predictive value.

METHODS: Resveratrol targets were intersected with TCGA-LIHC differentially expressed genes. A prognostic risk model was built using LASSO-Cox regression. Drug-target binding was assessed by molecular dynamics simulations and qRT-PCR. Single-cell and spatial transcriptomics, cell-cell communication, and a pan-immunotherapy cohort were used to investigate KIF11. An HCC mouse model validated immunomodulatory effects via flow cytometry.

RESULTS: Thirty-four resveratrol-associated targets were identified, enriched in metabolism pathways. A nine-gene risk model showed robust prognostic performance. Resveratrol stably binds to KIF11's ATP-binding pocket. KIF11 is overexpressed in malignant hepatocytes and proliferating T cells; KIF11⁺ cells orchestrate VEGF-mediated microenvironment remodeling. High KIF11 expression correlated with poor prognosis but predicted superior survival in the immunotherapy cohort, a phenomenon attributed to the observation that KIF11-high tumors exhibit both enhanced immunogenicity and active immunosuppression. In vivo, resveratrol enhanced CD8⁺ T cell infiltration, proliferation, effector function, and central memory T cells, while reducing Tregs.

CONCLUSION: KIF11 drives HCC progression and predicts immunotherapy response. It is a candidate direct resveratrol target and a potential biomarker for patient stratification in immune checkpoint therapy, although further experimental validation is warranted.

PMID:42670538 | PMC:PMC13526380 | DOI:10.2147/JHC.S615781

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Disruption of the AR/ZNF217/PROM2 axis sensitizes prostate cancer to ferroptosis and enzalutamide therapy

✇Oncogenesis - nature.com science feeds
By: Wenjun Hao · Peng Liang · Wanglong Zheng · Minglu Sheng · Yulin Peng · Xiang Gao · Haolin Zhao · Yuyan Zhu · Yanlong Wang · Bo Fan · Zhihong Dai · Xu Sun · Liang Wang · Huan Qi · Ying Wang · Yan Wang · Zhenlong Yu · Zhiyu Liu

Oncogenesis, Published online: 11 August 2026; doi:10.1038/s41389-026-00649-7

Disruption of the AR/ZNF217/PROM2 axis sensitizes prostate cancer to ferroptosis and enzalutamide therapy
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Captioning Daily Activity Images in Early Childhood Education: Benchmark and Algorithm

✇cs.AI, q-bio.NC updates on arXiv.org
By: Sixing Li · Zhibin Gu · Ziqi Zhang · Weiguo Pan · Bing Li · Ying Wang · Hongzhe Liu
arXiv:2604.01941v1 Announce Type: cross Abstract: Image captioning for Early Childhood Education (ECE) is essential for automated activity understanding and educational assessment. However, existing methods face two key challenges. First, the lack of large-scale, domain-specific datasets limits the model's ability to capture fine-grained semantic concepts unique to ECE scenarios, resulting in generic and imprecise descriptions. Second, conventional training paradigms exhibit limitations in enhancing professional object description capability, as supervised learning tends to favor high-frequency expressions, while reinforcement learning may suffer from unstable optimization on difficult samples. To address these limitations, we introduce ECAC, a large-scale benchmark for ECE daily activity image captioning, comprising 256,121 real-world images annotated with expert-level captions and fine-grained labels. ECAC is further equipped with a domain-oriented evaluation protocol, the Teaching Toy Recognition Score (TTS), to explicitly measure professional object naming accuracy. Furthermore, we propose RSRS (Reward-Conditional Switch of Reinforcement Learning and Supervised Fine-Tuning), a hybrid training framework that dynamically alternates between RL and supervised optimization. By rerouting hard samples with zero rewards to supervised fine-tuning, RSRS effectively mitigates advantage collapse and enables stable optimization for fine-grained recognition. Leveraging ECAC and RSRS, we develop KinderMM-Cap-3B, a domain-adapted multimodal large language model. Extensive experiments demonstrate that our model achieves a TTS of 51.06, substantially outperforming state-of-the-art baselines while maintaining superior caption quality, highlighting its potential for specialized educational applications.
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PAR$^2$-RAG: Planned Active Retrieval and Reasoning for Multi-Hop Question Answering

✇cs.AI, q-bio.NC updates on arXiv.org
By: Xingyu Li · Rongguang Wang · Yuying Wang · Mengqing Guo · Chenyang Li · Tao Sheng · Sujith Ravi · Dan Roth
arXiv:2603.29085v1 Announce Type: new Abstract: Large language models (LLMs) remain brittle on multi-hop question answering (MHQA), where answering requires combining evidence across documents through retrieval and reasoning. Iterative retrieval systems can fail by locking onto an early low-recall trajectory and amplifying downstream errors, while planning-only approaches may produce static query sets that cannot adapt when intermediate evidence changes. We propose \textbf{Planned Active Retrieval and Reasoning RAG (PAR$^2$-RAG)}, a two-stage framework that separates \emph{coverage} from \emph{commitment}. PAR$^2$-RAG first performs breadth-first anchoring to build a high-recall evidence frontier, then applies depth-first refinement with evidence sufficiency control in an iterative loop. Across four MHQA benchmarks, PAR$^2$-RAG consistently outperforms existing state-of-the-art baselines, compared with IRCoT, PAR$^2$-RAG achieves up to \textbf{23.5\%} higher accuracy, with retrieval gains of up to \textbf{10.5\%} in NDCG.
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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

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

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Targeting sialic acid metabolism: a therapeutic strategy against gastric cancer driven by WZ35

✇Omics in Gastric
By: Boxiang Hong · Ying Wang · Xinran Feng · Lihan Wei · Yichen Huang · Xiawei Zhang · Longyuchen Xu · Pinyan Jin · Liyuan Huang · Rui Li · Xinyu Wu · Zhi Li · Hangyu Ye · Tongke Chen · Xiaoyan Wang · Hao Zhang

Cell Oncol (Dordr). 2026 Mar 23;49(2):60. doi: 10.1007/s13402-026-01194-6.

ABSTRACT

Glycolytic reprogramming is closely associated with the occurrence and progression of gastric cancer. Specifically, the energy derived from glucose metabolism and the cellular proteins by its intermediate products influence gastric cancer development. However, as an important branch of glucose metabolism, sialic acid metabolism and its mediated sialylation modifications remain insufficiently studied in gastric cancer, and their specific relationship with malignant tumor progression requires further exploration. This study employed a multi‑omics approach, integrating metabolomics, single‑cell RNA sequencing, and bulk RNA sequencing analyses, to investigate the metabolic landscape of gastric cancer and its associated alterations. The results indicated that sialic acid is a characteristic metabolite in malignant gastric cancer tissues. It modulates biological functions such as immune response, proliferative activity, and metabolic remodeling within gastric cancer tissues by influencing sialylation modifications. Furthermore, we identified the drug WZ35, which can inhibit the malignant proliferation of gastric cancer by targeting both sialic acid metabolism and sialylated protein modifications. We put forward a conjecture that the metabolism and modification of sialic acid promote the malignant development of gastric cancer, and we discovered that the drug WZ35 has an inhibitory effect on the sialic acid metabolism of gastric cancer.

GRAPHICAL ABSTRACT:

PMID:41870836 | PMC:PMC13009457 | DOI:10.1007/s13402-026-01194-6

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ARL-Tangram: Unleash the Resource Efficiency in Agentic Reinforcement Learning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Bangjun Xiao · Yihao Zhao · Xiangwei Deng · Shihua Yu · Yuxing Xiang · Huaqiu Liu · Qiying Wang · Liang Zhao · Hailin Zhang · Xuanzhe Liu · Xin Jin · Fuli Luo
arXiv:2603.13019v1 Announce Type: cross Abstract: Agentic reinforcement learning (RL) has emerged as a transformative workload in cloud clusters, enabling large language models (LLMs) to solve complex problems through interactions with real world. However, unlike traditional RL, agentic RL demands substantial external cloud resources, e.g., CPUs for code execution and GPUs for reward models, that exist outside the primary training cluster. Existing agentic RL framework typically rely on static over-provisioning, i.e., resources are often tied to long-lived trajectories or isolated by tasks, which leads to severe resource inefficiency. We propose the action-level orchestration, and incorporate it into ARL-Tangram, a unified resource management system that enables fine-grained external resource sharing and elasticity. ARL-Tangram utilizes a unified action-level formulation and an elastic scheduling algorithm to minimize action completion time (ACT) while satisfying heterogeneous resource constraints. Further, heterogeneous resource managers are tailored to efficiently support the action-level execution on resources with heterogeneous characteristics and topologies. Evaluation on real-world agentic RL tasks demonstrates that ARL-Tangram improves average ACT by up to 4.3$\times$, speeds up the step duration of RL training by up to 1.5$\times$, and saves the external resources by up to 71.2$\%$. This system has been deployed to support the training of the MiMo series models.
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IntPro: A Proxy Agent for Context-Aware Intent Understanding via Retrieval-conditioned Inference

✇cs.AI, q-bio.NC updates on arXiv.org
By: Guanming Liu · Meng Wu · Peng Zhang · Yu Zhang · Yubo Shu · Xianliang Huang · Kainan Tu · Ning Gu · Liuxin Zhang · Qianying Wang · Tun Lu
arXiv:2603.03325v1 Announce Type: cross Abstract: Large language models (LLMs) have become integral to modern Human-AI collaboration workflows, where accurately understanding user intent serves as a crucial step for generating satisfactory responses. Context-aware intent understanding, which involves inferring user intentions from situational environments, is inherently challenging because it requires reasoning over both the immediate context and the user's underlying motivations that drive their behavior. Moreover, existing approaches often treat intent understanding as a static recognition task, overlooking users' accumulated intent patterns that could provide valuable references for more accurate and generalizable understanding. To address this gap, we propose IntPro, a proxy agent that learns to adapt to individual users via retrieval-conditioned intent inference. We design intent explanations that abstract how contextual signals connect to expressed intents, and store them in an individual intent history library for retrieval. We train IntPro through supervised fine-tuning on retrieval-conditioned trajectories and multi-turn Group Relative Policy Optimization (GRPO) with tool-aware reward functions, enabling the agent to learn when to leverage historical intent patterns and when to infer directly. Experiments across three diverse scenarios (Highlight-Intent, MIntRec2.0, and Weibo Post-Sync) demonstrate that IntPro achieves strong intent understanding performance with effective context-aware reasoning capabilities across different scenarios and model types.
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