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Wearable-informed generative digital avatars predict task-conditioned post-stroke locomotion

arXiv:2512.14329v2 Announce Type: replace-cross Abstract: Dynamic prediction of locomotor capacity after stroke could enable more individualized rehabilitation, yet current assessments largely provide static impairment scores and do not indicate whether patients can perform specific tasks such as slope walking or stair climbing. Here, we present a wearable-informed data-physics hybrid generative framework that reconstructs a stroke survivor's locomotor control from wearable inertial sensing and predicts task-conditioned post-stroke locomotion in new environments. From a single 20 m level-ground walking trial recorded by five IMUs, the framework personalizes a physics-based digital avatar using a healthy-motion prior and hybrid imitation learning, generating dynamically feasible, patient-specific movements for inclined walking and stair negotiation. Across 11 stroke inpatients, predicted postures reached 82.2% similarity for slopes and 69.9% for stairs, substantially exceeding a physics-only baseline. In a multicentre pilot randomized study (n = 21; 28 days), access to scenario-specific locomotion predictions to support task selection and difficulty titration was associated with larger gains in Fugl-Meyer lower-extremity scores than standard care (mean change 6.0 vs 3.7 points; $p
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A data-physics hybrid generative model for patient-specific post-stroke motor rehabilitation using wearable sensor data

arXiv:2512.14329v1 Announce Type: cross Abstract: Dynamic prediction of locomotor capacity after stroke is crucial for tailoring rehabilitation, yet current assessments provide only static impairment scores and do not indicate whether patients can safely perform specific tasks such as slope walking or stair climbing. Here, we develop a data-physics hybrid generative framework that reconstructs an individual stroke survivor's neuromuscular control from a single 20 m level-ground walking trial and predicts task-conditioned locomotion across rehabilitation scenarios. The system combines wearable-sensor kinematics, a proportional-derivative physics controller, a population Healthy Motion Atlas, and goal-conditioned deep reinforcement learning with behaviour cloning and generative adversarial imitation learning to generate physically plausible, patient-specific gait simulations for slopes and stairs. In 11 stroke survivors, the personalized controllers preserved idiosyncratic gait patterns while improving joint-angle and endpoint fidelity by 4.73% and 12.10%, respectively, and reducing training time to 25.56% relative to a physics-only baseline. In a multicentre pilot involving 21 inpatients, clinicians who used our locomotion predictions to guide task selection and difficulty obtained larger gains in Fugl-Meyer lower-extremity scores over 28 days of standard rehabilitation than control clinicians (mean change 6.0 versus 3.7 points). These findings indicate that our generative, task-predictive framework can augment clinical decision-making in post-stroke gait rehabilitation and provide a template for dynamically personalized motor recovery strategies.
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Single-cell and multi-omics analysis identifies TRIM9 as a key ubiquitination regulator in pancreatic cancer

Front Immunol. 2025 Sep 19;16:1631708. doi: 10.3389/fimmu.2025.1631708. eCollection 2025.

ABSTRACT

This study investigates the role of ubiquitination-related genes in pancreatic cancer (PC) using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and multi-omics approaches. scRNA-seq data (GSE155698) from PC samples identified 12 cell types, with endothelial cells exhibiting high ubiquitination scores (High_ubiquitin-Endo) and enriched interactions with fibroblasts/macrophages via WNT, NOTCH, and integrin pathways. Spatial transcriptomics (GSE235315) validated cell-type localization. Mendelian randomization (SMR) analysis prioritized TRIM9 as a PC-protective gene, downregulated in tumors and correlated with better survival. WGCNA revealed TRIM9-co-expressed modules linked to prognosis. A machine learning-based prognostic model (CoxBoost+RSF) integrating seven genes (TSPAN6, TSC1, RNF167, PBXIP1, LRRC49, KATNAL2, IGF2BP2) stratified patients into high/low-risk groups with distinct survival, mutation burdens, and immune infiltration. TRIM9 overexpression suppressed PC cell proliferation/migration in vitro, while knockdown enhanced malignancy. Mechanistically, TRIM9 promoted K11-linked ubiquitination and proteasomal degradation of HNRNPU, dependent on its RING domain. In vivo, TRIM9 overexpression reduced tumor growth, rescued by HNRNPU co-expression. Integrated analyses highlight TRIM9 as a tumor suppressor and prognostic biomarker, mediated via ubiquitination-dependent regulation of HNRNPU stability. This work provides insights into ubiquitination-driven PC pathogenesis and therapeutic targeting.

PMID:41050689 | PMC:PMC12491318 | DOI:10.3389/fimmu.2025.1631708

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Urinary Tumor DNA-based Liquid Biopsy in Bladder Cancer Management: A Systematic Review

Eur Urol Focus. 2025 Aug 1:S2405-4569(25)00178-6. doi: 10.1016/j.euf.2025.06.009. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Urinary tumor DNA (utDNA) has emerged as a promising biomarker in the care, diagnosis, early detection, recurrence monitoring, and prognosis of bladder cancer (BCa). Its noninvasive nature, ease of access, and cost effectiveness make it an attractive option for both patients and health care providers. This review describes the current state of utDNA as a marker of BCa.

METHODS: Articles published between 2015 and 2025 on current utDNA-based techniques in BCa were identified and analyzed for relevance and insight into utDNA research and usage.

KEY FINDINGS AND LIMITATIONS: Recent investigations underscore the noninvasiveness and superior tumor detection capabilities of utDNA, particularly in the detection of minimal residual disease. Moreover, utDNA provides actionable information, such as tumor grade and staging information, to support precise treatment decisions, including targeted immunotherapy regimens and bladder preservation strategies. Although utDNA has shown promising results in small studies, larger studies must be performed before it can be considered as a standard procedure in clinical practice.

CONCLUSIONS AND CLINICAL IMPLICATIONS: Urinary tumor DNA has demonstrated great potential to improve on most, if not all, stages of detection, treatment, and monitoring of BCa. By preserving the low cost and noninvasiveness of urine cytology, and by replacing its suboptimal accuracy with a precision rivaling and often exceeding cystoscopy and circulating tumor DNA-based methods, utDNA offers patients a more comfortable, repeatable, and accurate way of detecting BCa. With increased sensitivity and accuracy, everything from low-grade tumors to the earliest signs of recurrence can be detected more effectively, optimizing patient treatment courses and improving outcomes.

PMID:40753029 | DOI:10.1016/j.euf.2025.06.009

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Worldwide Innovative Network (WIN) Consortium in Personalized Cancer Medicine: Bringing next-generation precision oncology to patients

Oncotarget. 2025 Mar 12;16:140-162. doi: 10.18632/oncotarget.28703.

ABSTRACT

The human genome project ushered in a genomic medicine era that was largely unimaginable three decades ago. Discoveries of druggable cancer drivers enabled biomarker-driven gene- and immune-targeted therapy and transformed cancer treatment. Minimizing treatment not expected to benefit, and toxicity-including financial and time-are important goals of modern oncology. The Worldwide Innovative Network (WIN) Consortium in Personalized Cancer Medicine founded by Drs. John Mendelsohn and Thomas Tursz provided a vision for innovation, collaboration and global impact in precision oncology. Through pursuit of transcriptomic signatures, artificial intelligence (AI) algorithms, global precision cancer medicine clinical trials and input from an international Molecular Tumor Board (MTB), WIN has led the way in demonstrating patient benefit from precision-therapeutics through N-of-1 molecularly-driven studies. WIN Next-Generation Precision Oncology (WINGPO) trials are being developed in the neoadjuvant, adjuvant or metastatic settings, incorporate real-world data, digital pathology, and advanced algorithms to guide MTB prioritization of therapy combinations for a diverse global population. WIN has pursued combinations that target multiple drivers/hallmarks of cancer in individual patients. WIN continues to be impactful through collaboration with industry, government, sponsors, funders, academic and community centers, patient advocates, and other stakeholders to tackle challenges including drug access, costs, regulatory barriers, and patient support. WIN's collaborative next generation of precision oncology trials will guide treatment selection for patients with advanced cancers through MTB and AI algorithms based on serial liquid and tissue biopsies and exploratory omics including transcriptomics, proteomics, metabolomics and functional precision medicine. Our vision is to accelerate the future of precision oncology care.

PMID:40073368 | PMC:PMC11907938 | DOI:10.18632/oncotarget.28703

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Hepatocellular carcinoma detection via targeted enzymatic methyl sequencing of plasma cell-free DNA

Epigenetic variants carried by circulating tumor DNA can be used as biomarkers for early detection of hepatocellular carcinoma (HCC) by noninvasive liquid biopsy. However, traditional methylation analysis meth...
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