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Two-step clinical care pathway to predict MASLD-related advanced fibrosis and long-term outcomes in type 2 diabetes

Gut. 2026 Feb 9;75(3):576-587. doi: 10.1136/gutjnl-2025-337506.

ABSTRACT

BACKGROUND: Current guidelines recommend a two-step approach for risk stratification of metabolic dysfunction-associated steatotic liver disease (MASLD), starting with Fibrosis-4 index (FIB-4) followed by liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE).

OBJECTIVE: To evaluate this approach for predicting advanced fibrosis and liver-related events (LREs) in patients with type 2 diabetes (T2D).

DESIGN: A prospective liver biopsy cohort of T2D patients with histologically confirmed MASLD from seven centres in China was used to assess diagnostic performance for advanced fibrosis. The international VCTE-Prognosis cohort, including T2D patients with MASLD who underwent VCTE at 16 centres in the USA, Europe and Asia, with longitudinal follow-up, was used to assess LREs, defined as hepatic decompensation or hepatocellular carcinoma.

RESULTS: 4781 participants were included. In the liver biopsy cohort (n=352; 22.2% with advanced fibrosis), applying LSM thresholds of <8 kPa and >12 kPa after FIB-4 classified patients into 63.4% low-risk, 9.4% intermediate-risk and 27.3% high-risk, with a correct classification rate of 71%. In the VCTE-Prognosis cohort (n=4429; median follow-up 51.3 (IQR 27.4-70.7) months), 140 (3.2%) patients developed LREs (110 (2.5%) with hepatic decompensation and 59 (1.3%) with hepatocellular carcinoma). The two-step approach classified 72.6%, 6.8% and 20.6% of patients into low-risk, intermediate-risk and high-risk groups, with corresponding 5-year cumulative LRE incidences of 0.7%, 0.9% and 11.8%. Refining classification of intermediate FIB-4 patients using LSM <10 kPa (low-risk) and >15 kPa (high-risk) reduced the intermediate-risk group to 5.6% while preserving predictive accuracy.

CONCLUSION: The non-invasive two-step approach of FIB-4 followed by LSM effectively stratifies MASLD-related advanced fibrosis and LREs risk in T2D. Applying LSM cut-offs of 10 and 15 kPa further optimises risk stratification for future LREs.

PMID:41911049 | DOI:10.1136/gutjnl-2025-337506

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Parasites trigger epithelial cell crosstalk to drive gut–brain signalling

Nature, Published online: 25 March 2026; doi:10.1038/s41586-026-10281-5

Paracrine signalling between tuft cells and enterochromaffin cells is a key mode of immune–sensory and gut–brain communication, and accounts for the pattern of gastrointestinal symptoms that occurs during parasite infections.
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OffTopicEval: When Large Language Models Enter the Wrong Chat, Almost Always!

arXiv:2509.26495v3 Announce Type: replace Abstract: Large Language Model (LLM) safety is one of the most pressing challenges for enabling wide-scale deployment. While most studies and global discussions focus on generic harms, such as models assisting users in harming themselves or others, enterprises face a more fundamental concern: whether LLM-based agents are safe for their intended use case. To address this, we introduce operational safety, defined as an LLM's ability to appropriately accept or refuse user queries when tasked with a specific purpose. We further propose OffTopicEval, an evaluation suite and benchmark for measuring operational safety both in general and within specific agentic use cases. Our evaluations on six model families comprising 20 open-weight LLMs reveal that while performance varies across models, all of them remain highly operationally unsafe. Even the strongest models - Qwen-3 (235B) with 77.77% and Mistral (24B) with 79.96% - fall far short of reliable operational safety, while GPT models plateau in the 62-73% range, Phi achieves only mid-level scores (48-70%), and Gemma and Llama-3 collapse to 39.53% and 23.84%, respectively. While operational safety is a core model alignment issue, to suppress these failures, we propose prompt-based steering methods: query grounding (Q-ground) and system-prompt grounding (P-ground), which substantially improve OOD refusal. Q-ground provides consistent gains of up to 23%, while P-ground delivers even larger boosts, raising Llama-3.3 (70B) by 41% and Qwen-3 (30B) by 27%. These results highlight both the urgent need for operational safety interventions and the promise of prompt-based steering as a first step toward more reliable LLM-based agents.
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Lysophosphatidylcholine acyltransferase 1 promotes head and neck squamous cell carcinoma progression by enhancing COX17-dependent oxidative phosphorylation

Cell Death Discovery, Published online: 06 March 2026; doi:10.1038/s41420-026-02994-3

Lysophosphatidylcholine acyltransferase 1 promotes head and neck squamous cell carcinoma progression by enhancing COX17-dependent oxidative phosphorylation
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UniWeTok: An Unified Binary Tokenizer with Codebook Size $\mathit{2^{128}}$ for Unified Multimodal Large Language Model

arXiv:2602.14178v1 Announce Type: cross Abstract: Unified Multimodal Large Language Models (MLLMs) require a visual representation that simultaneously supports high-fidelity reconstruction, complex semantic extraction, and generative suitability. However, existing visual tokenizers typically struggle to satisfy these conflicting objectives within a single framework. In this paper, we introduce UniWeTok, a unified discrete tokenizer designed to bridge this gap using a massive binary codebook ($\mathit{2^{128}}$). For training framework, we introduce Pre-Post Distillation and a Generative-Aware Prior to enhance the semantic extraction and generative prior of the discrete tokens. In terms of model architecture, we propose a convolution-attention hybrid architecture with the SigLu activation function. SigLu activation not only bounds the encoder output and stabilizes the semantic distillation process but also effectively addresses the optimization conflict between token entropy loss and commitment loss. We further propose a three-stage training framework designed to enhance UniWeTok's adaptability cross various image resolutions and perception-sensitive scenarios, such as those involving human faces and textual content. On ImageNet, UniWeTok achieves state-of-the-art image generation performance (FID: UniWeTok 1.38 vs. REPA 1.42) while requiring a remarkably low training compute (Training Tokens: UniWeTok 33B vs. REPA 262B). On general-domain, UniWeTok demonstrates highly competitive capabilities across a broad range of tasks, including multimodal understanding, image generation (DPG Score: UniWeTok 86.63 vs. FLUX.1 [Dev] 83.84), and editing (GEdit Overall Score: UniWeTok 5.09 vs. OmniGen 5.06). We release code and models to facilitate community exploration of unified tokenizer and MLLM.
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