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Screening of Hepatocellular Carcinoma in Hepatic Cirrhosis Patients by a Novel Blood-Based Multi-Omics Test

Technol Cancer Res Treat. 2026 Jan-Dec;25:15330338261435022. doi: 10.1177/15330338261435022. Epub 2026 Mar 23.

ABSTRACT

IntroductionHepatocellular carcinoma (HCC) screening in patients with hepatic cirrhosis (HC) relies on ultrasound and alpha-fetoprotein (US + AFP), which has limitations in sensitivity, particularly for early-stage HCC detection. This study aims to evaluate the performance of a novel multi-omics blood test, HCCscreen, with its individual components (methylation, AFP, Des-γ-Carboxy Prothrombin (DCP), mutations) and the standard US + AFP for HCC screening in a hepatic cirrhotic population.MethodsA total of 5078 patients with known high-risk for HCC were recruited. A prospective screening study was conducted on 650 patients with hepatic cirrhosis identified by ultrasound. Blood samples were collected from all patients before the confirmation of diagnosis by imaging and/or pathological examinations. The performance of HCCscreen, individual markers and US + AFP were calculated and compared. Statistics was performed with Graphpad Prism 5.0.ResultsHCCscreen exhibited a sensitivity of 86.3% at a specificity of 81.3%, with a positive predictive value (PPV) of 28.2% and a negative predictive value (NPV) of 98.6%. The positive likelihood ratio (LR+) was 4.61 and the negative LR (LR-) was 0.17. The positive detection rate (PDR) for all markers increased with more advanced HCC stages, whether Barcelona Clinic Liver Cancer (BCLC) or clinical staging. Among the single-omics, methylation showed the highest PDR, followed by AFP, DCP and mutations. HCCscreen demonstrated superior overall performance with an AUC of 0.87, outperforming individual markers like methylation (AUC = 0.76), AFP (AUC = 0.83), and DCP (AUC = 0.77). Crucially, HCCscreen's PDR was significantly higher than US + AFP in early-stage HCC (BCLC-0 and clinical stage I). Furthermore, while AFP's PDR varied significantly by sex, HCCscreen's performance remained consistent across all demographics. Correlation analysis revealed a significant association only between the HCCscreen score and the methylation score.ConclusionsThe multi-omics approach of HCCscreen significantly enhances early HCC detection in patients with hepatic cirrhosis compared to both its individual components and the current standard of US + AFP. Its robust and consistent performance across patient demographics underscores its potential as a superior tool for population-wide early HCC screening.

PMID:41869803 | PMC:PMC13009828 | DOI:10.1177/15330338261435022

Screening of Hepatocellular Carcinoma in Hepatic Cirrhosis Patients by a Novel Blood-Based Multi-Omics Test

Technol Cancer Res Treat. 2026 Jan-Dec;25:15330338261435022. doi: 10.1177/15330338261435022. Epub 2026 Mar 23.

ABSTRACT

IntroductionHepatocellular carcinoma (HCC) screening in patients with hepatic cirrhosis (HC) relies on ultrasound and alpha-fetoprotein (US + AFP), which has limitations in sensitivity, particularly for early-stage HCC detection. This study aims to evaluate the performance of a novel multi-omics blood test, HCCscreen, with its individual components (methylation, AFP, Des-γ-Carboxy Prothrombin (DCP), mutations) and the standard US + AFP for HCC screening in a hepatic cirrhotic population.MethodsA total of 5078 patients with known high-risk for HCC were recruited. A prospective screening study was conducted on 650 patients with hepatic cirrhosis identified by ultrasound. Blood samples were collected from all patients before the confirmation of diagnosis by imaging and/or pathological examinations. The performance of HCCscreen, individual markers and US + AFP were calculated and compared. Statistics was performed with Graphpad Prism 5.0.ResultsHCCscreen exhibited a sensitivity of 86.3% at a specificity of 81.3%, with a positive predictive value (PPV) of 28.2% and a negative predictive value (NPV) of 98.6%. The positive likelihood ratio (LR+) was 4.61 and the negative LR (LR-) was 0.17. The positive detection rate (PDR) for all markers increased with more advanced HCC stages, whether Barcelona Clinic Liver Cancer (BCLC) or clinical staging. Among the single-omics, methylation showed the highest PDR, followed by AFP, DCP and mutations. HCCscreen demonstrated superior overall performance with an AUC of 0.87, outperforming individual markers like methylation (AUC = 0.76), AFP (AUC = 0.83), and DCP (AUC = 0.77). Crucially, HCCscreen's PDR was significantly higher than US + AFP in early-stage HCC (BCLC-0 and clinical stage I). Furthermore, while AFP's PDR varied significantly by sex, HCCscreen's performance remained consistent across all demographics. Correlation analysis revealed a significant association only between the HCCscreen score and the methylation score.ConclusionsThe multi-omics approach of HCCscreen significantly enhances early HCC detection in patients with hepatic cirrhosis compared to both its individual components and the current standard of US + AFP. Its robust and consistent performance across patient demographics underscores its potential as a superior tool for population-wide early HCC screening.

PMID:41869803 | PMC:PMC13009828 | DOI:10.1177/15330338261435022

Effect of a Digital-Driven Physician-Pharmacist Collaborative Model for Diabetes in Primary Health Care: Cluster Randomized Trial

Background: Evidence-based physician-pharmacist collaborative clinics have demonstrated significant short-term benefits for patients with type 2 diabetes (T2D), but their long-term effectiveness remains unclear, especially in primary health care settings. Objective: This study aimed to explore the long-term effectiveness and cost-effectiveness of a novel, digital-driven, multifaceted physician-pharmacist collaborative model for managing patients with T2D in underresourced settings. Methods: We conducted a 12-month cluster randomized controlled trial from May 2021 to December 2022 across 6 primary health care settings in China. Guided by the theory of planned behavior, the intervention involved routine therapy from physicians along with pharmaceutical interventions from pharmacists. These were delivered through a combination of face-to-face visits and mobile health care. The intervention group received 4 face-to-face visits and biweekly remote education sessions over the 12 months. We conducted intention-to-treat analyses to estimate differences in clinical and behavior indicators between the intervention and control groups. Primary outcomes included glycosylated hemoglobin and 10-year atherosclerotic cardiovascular risk. Data were analyzed using adjusted generalized estimation equations. Results: This study included 574 patients (291 in the intervention group and 283 in the control group). Over 12 months, patients in the intervention group had significant reductions in hemoglobin A1c (–2.57 vs –1.96, respectively; P<.001; 95% CI –1.027 to –0.238) and 10-year atherosclerotic cardiovascular risk (–1.35 vs 0.01, respectively; P<.001; 95% CI –1.690 to –0.630) compared with the control group. Substantial improvements were also observed in several secondary outcomes, including fasting blood glucose, 2-hour postprandial blood glucose, waist circumference, waist-to-hip ratio, blood pressure, triglyceride, and total cholesterol. Total diabetes-related costs decreased, and patient satisfaction improved significantly in the intervention group. There were no significant differences in BMI, high-density lipoprotein, or low-density lipoprotein. Conclusions: These findings suggest that the physician-pharmacist collaborative model could improve the long-term quality and efficiency of T2D management and reduce medical costs in underresourced areas globally. Patients with T2D, especially those with central obesity or high cardiovascular risk, may benefit more from collaborative clinics. Trial Registration: Chinese Clinical Trial Registry ChiCTR2000031839; https://www.chictr.org.cn/showproj.html?proj=51910

Risk-adaptive therapy guided by dynamic ctDNA in nasopharyngeal carcinoma

Nature, Published online: 11 March 2026; doi:10.1038/s41586-026-10244-w

A clinical trial testing whether monitoring ctDNA clearance during treatment for nasopharyngeal cancer could be used to inform decisions about an individual’s subsequent therapeutic programme shows promising results.

RxnNano:Training Compact LLMs for Chemical Reaction and Retrosynthesis Prediction via Hierarchical Curriculum Learning

arXiv:2603.02215v1 Announce Type: cross Abstract: Chemical reaction prediction is pivotal for accelerating drug discovery and synthesis planning. Despite advances in data-driven models, current approaches are hindered by an overemphasis on parameter and dataset scaling. Some methods coupled with evaluation techniques that bypass fundamental challenges in reaction representation and fail to capture deep chemical intuition like reaction common sense and {topological atom mapping logic}. We argue that the core challenge lies in instilling these knowledge into the models. To this end, we propose a unified framework that prioritizes chemical understanding over scale through three key innovations: (1) a {Latent Chemical Consistency} objective that models reactions as movements on a continuous chemical manifold, ensuring reversible and physically plausible transformations; (2) a {Hierarchical Cognitive Curriculum} that trains the model through progressive stages, from syntax mastery to semantic reasoning, building robust chemical intuition; (3) {Atom-Map Permutation Invariance (AMPI)}, which force the model to learn invariant relational topology and balance multi-task learning. (4)and structured plan-based reasoning to improve the performance of the LLMs. Our compact {0.5B-parameter model}, \textbf{RxnNano} significantly outperforms fine-tuned LLMs ten times larger (>7B) and all the domain baselines, achieving a 23.5\% Top-1 accuracy improvement on rigorous benchmarks without test-time augmentation. https://github.com/rlisml/RxnNano.

Pailitao-VL: Unified Embedding and Reranker for Real-Time Multi-Modal Industrial Search

arXiv:2602.13704v1 Announce Type: cross Abstract: In this work, we presented Pailitao-VL, a comprehensive multi-modal retrieval system engineered for high-precision, real-time industrial search. We here address three critical challenges in the current SOTA solution: insufficient retrieval granularity, vulnerability to environmental noise, and prohibitive efficiency-performance gap. Our primary contribution lies in two fundamental paradigm shifts. First, we transitioned the embedding paradigm from traditional contrastive learning to an absolute ID-recognition task. Through anchoring instances to a globally consistent latent space defined by billions of semantic prototypes, we successfully overcome the stochasticity and granularity bottlenecks inherent in existing embedding solutions. Second, we evolved the generative reranker from isolated pointwise evaluation to the compare-and-calibrate listwise policy. By synergizing chunk-based comparative reasoning with calibrated absolute relevance scoring, the system achieves nuanced discriminative resolution while circumventing the prohibitive latency typically associated with conventional reranking methods. Extensive offline benchmarks and online A/B tests on Alibaba e-commerce platform confirm that Pailitao-VL achieves state-of-the-art performance and delivers substantial business impact. This work demonstrates a robust and scalable path for deploying advanced MLLM-based retrieval architectures in demanding, large-scale production environments.

WiSparse: Boosting LLM Inference Efficiency with Weight-Aware Mixed Activation Sparsity

arXiv:2602.14452v1 Announce Type: cross Abstract: Large Language Models (LLMs) offer strong capabilities but incur high inference costs due to dense computation and memory access. Training-free activation sparsity is a promising approach for efficient LLM inference, yet existing methods often rely solely on activation information and uniform sparsity ratios. This overlooks the critical interplay with weights and inter-block sensitivity variation, leading to suboptimal performance. We identify two key phenomena in modern LLMs: 1) less significant activations may align with highly important weights, and 2) sparsity sensitivity varies non-monotonically across model blocks. We propose Weight-aware Mixed-Granularity Training-free Activation Sparsity (WiSparse), which leverages both activation and weight information for adaptive sparsity allocation. Specifically, we introduce a weight-aware mechanism integrating activation magnitudes with precomputed weight norms to accurately identify salient channels. This is combined with a mixed-granularity allocation scheme: a global budget is distributed across blocks via evolutionary search to protect sensitive regions, then refined within blocks to minimize reconstruction error. We improve sparse kernels and demonstrate effectiveness on three representative models. Notably, at 50% sparsity, WiSparse preserves 97% of Llama3.1's dense performance, surpassing the strongest baseline by 2.23 percentage points while achieving a 21.4% acceleration in end-to-end inference speed. Our research advances the limits of training-free approaches for efficient LLM inference, pushing the boundaries of achievable speedup without training.
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