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Exploration of multi-omics liquid biopsy approaches for multi-cancer early detection: The PROMISE study

Innovation (Camb). 2025 Aug 6;7(1):101076. doi: 10.1016/j.xinn.2025.101076. eCollection 2026 Jan 5.

ABSTRACT

Although circulating cell-free DNA (cfDNA) methylation has emerged as the mainstream approach in multi-cancer detection blood tests (MCDBTs), the potential of integrating proteins and mutations, to enhance its performance remains unclear. The PROMISE study (NCT04972201) was conducted to investigate the feasibility of a multi-omics integration strategy in MCDBTs across nine types of cancers in head and neck (excluding nasopharynx), esophagus, lung, stomach, liver, biliary tract, pancreas, colorectum, and ovary. Blood samples were prospectively collected from 1,706 participants (840 non-cancer; 866 cancer) and then randomly divided into training and validation sets. The complementarity between various omics were investigated, and specific omics features were carefully selected for further multimodal model construction. The methylation-based classifier outperformed both the mutation-based and protein-based classifiers. As 95.0% of cancer cases detected by the mutation-based classifier were simultaneously identified by the methylation-based classifier, while 14.0% of the protein-positive samples were missed, protein markers may provide complementary value to the methylation-based classifier. Compared with the methylation-based classifier, the multimodal classifier combining methylation and protein features exhibited an improved sensitivity of 75.1% (95% confidence interval [CI], 69.3%-80.3%) at the same specificity of 98.8% with the accuracy of top predicted origin (TPO1) of 73.1% (95% CI, 66.2%-79.2%). Notably, the TPO1 accuracy reached 100% in liver and ovarian cancers with negative results of the methylation-based classifier. Collectively, these data suggest that the integration of protein markers in the multimodal classifier can offer additional benefits to the methylation-based classifier, particularly in identifying liver and ovarian cancers.

PMID:41737326 | PMC:PMC12925926 | DOI:10.1016/j.xinn.2025.101076

Combined Immersive and Nonimmersive Virtual Reality With Mirror Therapy for Patients With Stroke: Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Stroke frequently leads to various functional impairments. Both virtual reality (VR) and mirror therapy (MT) have shown efficacy in stroke rehabilitation. In recent years, the combination of these two approaches has emerged as a potential treatment for stroke patients. Objective: This systematic review and meta-analysis aim to evaluate the efficacy of combined immersive and non-immersive VR with MT in stroke rehabilitation. Methods: Five electronic databases were systematically searched for relevant articles published up to Jan. 2025. Randomized controlled trials (RCTs) that investigated combination treatment of VR and MT for participants with stroke were included. A grey literature search was also conducted. The risk of bias and the certainty of the evidence were assessed using the Cochrane collaboration’s tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline, respectively. Results: A total of 475 participants from 14 RCTs were included, of which 7 were eligible for meta-analysis. Meta-analysis revealed significant improvements in upper extremity (UE) motor function and hand dexterity, as evidenced by Fugl-Meyer assessment of upper extremity (FMA-UE) (MD 3.50, 95% CI 1.47 to 5.53; P=0.0007), manual function test (MFT) (MD 2.15, 95% CI 1.22 to 3.09; P6 months or not) revealed significant differences in the FMA-UE outcome. However, the pooled FMA-UE improvement did not consistently exceed the established minimal clinically important difference (MCID; 4.25–7.25), indicating that while statistically significant, the clinical meaningfulness of the observed effect remains uncertain. Narrative evidence also suggested potential benefits for lower extremity function, dynamic balance, and quality of life, though these findings were not meta-analyzed and should be interpreted with caution. Conclusions: Moderate-quality evidence supports VR-MT as a promising nonpharmacological intervention to improve upper extremity function and hand dexterity in stroke rehabilitation. While the intervention demonstrates statistically significant effects, it does not reach the minimum clinically important difference for the FMA-UE outcome. Preliminary descriptive evidence indicates possible advantages for lower extremity function, balance, and quality of life. Clinical Trial: PROSPERO CRD42024572150

Deep whole-genome analysis of 494 hepatocellular carcinomas

Nature, Published online: 14 February 2024; doi:10.1038/s41586-024-07054-3

The Chinese Liver Cancer Atlas project depicts a panoramic genomic landscape of hepatocellular carcinoma, covering candidate coding and non-coding drivers, mutational signatures, extrachromosomal circular DNA, subclonal catastrophic events and detailed evolutionary history.
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