In vivo-directed evolution identifies AAV-WM04 as a next-generation vector for potent and sustained hearing restoration in DFNB9

By: Yong Tao · Cenfeng Chu · Zhenzhe Cheng · Shan Yin · Yilin Sun · Ying Chen · Huifang Zhang · Shuyue Bao · Boyu Yang · Baoyi Feng · Xianyu Huang · Yao Lu · Qiuxiang Yang · Xuegao Mao · Qifang Zhou · Chenxi Jin · Zhuo Duan · Guisheng Zhong · Hao Wu

13 July 2026 at 08:00

AAV-WM04, an AAV vector identified through in-vivo-directed screening in the adult cochlea, enables highly efficient and selective inner hair cell transduction. Dual-AAV delivery of OTOF using AAV-WM04 restores hearing in a DFNA9 deafness mouse model at low doses, highlighting its translational potential for gene therapy.

Integrative Multi-Omics Analysis Identifies Thrombosis-Associated Molecular Features Linked to Germline Susceptibility and Immune Cell Communication in Gastric Cancer

Omics in Gastric

By: Xiaogang Lu · Lin Sun · Fujun Jin · Biao Cheng · Ying Huang · Yuzhu Tang · Xiaolong Nie · Feng Gao

2 September 2026 at 18:00

Chem Biol Drug Des. 2026 Sep;108(3):e70386. doi: 10.1111/cbdd.70386.

ABSTRACT

Emerging evidence indicates that coagulation-related molecular programs are associated with thrombosis, tumor progression, and molecular dysregulation in gastric cancer (GC). However, thrombosis-associated molecular features in GC and their potential links to inherited susceptibility remain insufficiently understood. Integrated analyses of transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were performed to identify thrombosis-associated genes and establish a machine learning-based prognostic signature. Genome-wide association study (GWAS), expression quantitative trait loci (eQTL), transcriptome-wide association study (TWAS), and Mendelian randomization (MR) analyses were conducted to investigate susceptibility-associated transcriptional programs in GC. Functional assays were used to evaluate candidate genes associated with malignant phenotypes. Single-cell RNA sequencing (scRNA-seq) and cell-cell communication analyses were further performed to characterize cell-type-specific expression patterns and potential intercellular interactions. A total of 22 differentially expressed thrombosis-associated genes were identified, and a prognostic signature comprising 14 genes was established. The signature stratified patients into high- and low-risk groups and showed prognostic performance in both the training and validation cohorts. Integrative GWAS, eQTL, and TWAS analyses identified susceptibility-associated transcriptional programs that were positively correlated with the thrombosis-associated risk score. Silencing ACTN2 and CRYAB significantly reduced GC cell migration and invasion. scRNA-seq analysis revealed relatively high CRYAB expression in neutrophils, and CellChat analysis suggested potential neutrophil-B cell interactions involving COLLAGEN-related signaling. This integrative multi-omics study identified a thrombosis-associated molecular signature linked to prognosis and germline susceptibility-associated transcriptional programs in GC. ACTN2 and CRYAB may represent candidate genes associated with GC cell migration and invasion, while single-cell analysis suggested potential immune-related communication features.

PMID:42681916 | PMC:PMC13534880 | DOI:10.1111/cbdd.70386

DIVER: A Multi-Stage Approach for Reasoning-intensive Information Retrieval

cs.AI, q-bio.NC updates on arXiv.org

By: Duolin Sun · Meixiu Long · Dan Yang · Junjie Wang · Yecheng Luo · Yue Shen · Jian Wang · Hualei Zhou · Chunxiao Guo · Peng Wei · Jiahai Wang · Jinjie Gu

3 April 2026 at 12:00

arXiv:2508.07995v5 Announce Type: replace-cross Abstract: Retrieval-augmented generation has achieved strong performance on knowledge-intensive tasks where query-document relevance can be identified through direct lexical or semantic matches. However, many real-world queries involve abstract reasoning, analogical thinking, or multi-step inference, which existing retrievers often struggle to capture. To address this challenge, we present DIVER, a retrieval pipeline designed for reasoning-intensive information retrieval. It consists of four components. The document preprocessing stage enhances readability and preserves content by cleaning noisy texts and segmenting long documents. The query expansion stage leverages large language models to iteratively refine user queries with explicit reasoning and evidence from retrieved documents. The retrieval stage employs a model fine-tuned on synthetic data spanning medical and mathematical domains, along with hard negatives, enabling effective handling of reasoning-intensive queries. Finally, the reranking stage combines pointwise and listwise strategies to produce both fine-grained and globally consistent rankings. On the BRIGHT benchmark, DIVER achieves state-of-the-art nDCG@10 scores of 46.8 overall and 31.9 on original queries, consistently outperforming competitive reasoning-aware models. These results demonstrate the effectiveness of reasoning-aware retrieval strategies in complex real-world tasks.

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

(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)

By: Yuping Chen · Bingtian Dong · Xinrui Jin · Chuan Liu · Ming-Hua Zheng · Xiao Liang · Yameng Sun · Hye Won Lee · Huapeng Lin · Emmanuel Tsochatzis · Salvatore Petta · Elisabetta Bugianesi · Masato Yoneda · Hannes Hagström · Jérôme Boursier · José Luis Calleja · George Boon-Bee Goh · Wah-Kheong Chan · Rocio Gallego-Durán · Arun J Sanyal · Victor de Lédinghen · Philip N Newsome · Jian-Gao Fan · Laurent Castéra · Michelle Lai · Céline Fournier-Poizat · Grace Lai-Hung Wong · Grazia Pennisi · Angelo Armandi · Atsushi Nakajima · Wen-Yue Liu · Ying Shang · Marc de Saint-Loup · Elba Llop · Kevin Kim Jun Teh · Carmen Lara-Romero · Amon Asgharpour · Sara Mahgoub · Mandy Sau-Wai Chan · Adrien Lannes · Manuel Romero-Gomez · Airong Hu · Yiling Li · Qing-Lei Zeng · Wei Gou · Hua Bian · Xiao Han · Chenlin Sun · Seung Up Kim · Terry Cheuk-Fung Yip · Gao-Jun Teng · Vincent Wai-Sun Wong · Xiaolong Qi · DiabetesLiver Integrated Management (DLIM) Consortium

30 March 2026 at 18:00

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

Generative Reasoning Re-ranker

cs.AI, q-bio.NC updates on arXiv.org

By: Mingfu Liang · Yufei Li · Jay Xu · Kavosh Asadi · Xi Liu · Shuo Gu · Kaushik Rangadurai · Frank Shyu · Shuaiwen Wang · Song Yang · Zhijing Li · Jiang Liu · Mengying Sun · Fei Tian · Xiaohan Wei · Chonglin Sun · Jacob Tao · Shike Mei · Wenlin Chen · Santanu Kolay · Sandeep Pandey · Hamed Firooz · Luke Simon

24 February 2026 at 13:00

arXiv:2602.07774v4 Announce Type: replace-cross Abstract: Recent studies increasingly explore Large Language Models (LLMs) as a new paradigm for recommendation systems due to their scalability and world knowledge. However, existing work has three key limitations: (1) most efforts focus on retrieval and ranking, while the reranking phase, critical for refining final recommendations, is largely overlooked; (2) LLMs are typically used in zero-shot or supervised fine-tuning settings, leaving their reasoning abilities, especially those enhanced through reinforcement learning (RL) and high-quality reasoning data, underexploited; (3) items are commonly represented by non-semantic IDs, creating major scalability challenges in industrial systems with billions of identifiers. To address these gaps, we propose the Generative Reasoning Reranker (GR2), an end-to-end framework with a three-stage training pipeline tailored for reranking. First, a pretrained LLM is mid-trained on semantic IDs encoded from non-semantic IDs via a tokenizer achieving $\ge$99% uniqueness. Next, a stronger larger-scale LLM generates high-quality reasoning traces through carefully designed prompting and rejection sampling, which are used for supervised fine-tuning to impart foundational reasoning skills. Finally, we apply Decoupled Clip and Dynamic sAmpling Policy Optimization (DAPO), enabling scalable RL supervision with verifiable rewards designed specifically for reranking. Experiments on two real-world datasets demonstrate GR2's effectiveness: it surpasses the state-of-the-art OneRec-Think by 2.4% in Recall@5 and 1.3% in NDCG@5. Ablations confirm that advanced reasoning traces yield substantial gains across metrics. We further find that RL reward design is crucial in reranking: LLMs tend to exploit reward hacking by preserving item order, motivating conditional verifiable rewards to mitigate this behavior and optimize reranking performance.

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