Pulmonary-Intestinal Axis: Shared Genetic Basis and Mediating Factors Identified Through Multi-Omics Analysis

By: Zhenzhu Zhang · Haoyue Liu · Yihang Su · Chengwen Wang · Wei Wang · Yinglin Li · Xiaobao Zhang · Chenguang Gao · Xue Tian · Chunqing Zhao

14 April 2026 at 18:00

Int J Chron Obstruct Pulmon Dis. 2026 Apr 7;21:561645. doi: 10.2147/COPD.S561645. eCollection 2026.

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a systemic condition with comorbidities beyond the lung (eg, cardiovascular and metabolic disorders), and gastrointestinal (GI) disorders are also common. The shared genetic basis of COPD-GI comorbidity and its mediating factors remain unclear. We hypothesized that COPD and GI diseases share pleiotropic genetic architecture implicating lipid-metabolic pathways, with smoking mediating part of the association.

METHODS: We analyzed publicly available European-ancestry GWAS summary statistics for COPD (Global Biobank Meta-analysis Initiative), 15 GI diseases (FinnGen), and smoking phenotypes (UK Biobank). Genetic correlation was estimated using linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL). Multi-trait analysis of GWAS (MTAG) boosted COPD discovery by leveraging genetically correlated GI traits. We integrated locus-to-gene mapping with multi-tissue expression quantitative trait loci (eQTL) and plasma protein quantitative trait loci (pQTL) evidence to prioritize shared loci, genes, and proteins. Bidirectional two-sample Mendelian randomization (MR) tested causal directions, and two-step mediation MR evaluated smoking.

RESULTS: COPD showed significant genetic correlation with nine GI diseases. We identified six comorbidity-associated loci (three with CADD > 12.37) and 13 unique candidate pleiotropic genes; APOE was supported by proteomic evidence. Enrichment analyses highlighted lipid-metabolism pathways. MR suggested COPD increases risk of gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), acute appendicitis, and gastric ulcer, while diverticular disease showed reverse causality toward COPD. Smoking partially mediated the COPD effect on GERD, acute appendicitis, and gastric ulcer.

CONCLUSION: COPD and multiple GI disorders share a distributed pleiotropic genetic basis within the broader systemic comorbidity spectrum of COPD. Multi-omics evidence supports a genomic pulmonary-intestinal axis in which lipid metabolism and smoking-related mechanisms contribute to COPD and GI comorbidity, providing targets for risk stratification and potential intervention.

PMID:41978582 | PMC:PMC13070119 | DOI:10.2147/COPD.S561645

ReFlow: Self-correction Motion Learning for Dynamic Scene Reconstruction

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

By: Yanzhe Liang · Ruijie Zhu · Hanzhi Chang · Zhuoyuan Li · Jiahao Lu · Tianzhu Zhang

3 April 2026 at 12:00

arXiv:2604.01561v1 Announce Type: cross Abstract: We present ReFlow, a unified framework for monocular dynamic scene reconstruction that learns 3D motion in a novel self-correction manner from raw video. Existing methods often suffer from incomplete scene initialization for dynamic regions, leading to unstable reconstruction and motion estimation, which often resorts to external dense motion guidance such as pre-computed optical flow to further stabilize and constrain the reconstruction of dynamic components. However, this introduces additional complexity and potential error propagation. To address these issues, ReFlow integrates a Complete Canonical Space Construction module for enhanced initialization of both static and dynamic regions, and a Separation-Based Dynamic Scene Modeling module that decouples static and dynamic components for targeted motion supervision. The core of ReFlow is a novel self-correction flow matching mechanism, consisting of Full Flow Matching to align 3D scene flow with time-varying 2D observations, and Camera Flow Matching to enforce multi-view consistency for static objects. Together, these modules enable robust and accurate dynamic scene reconstruction. Extensive experiments across diverse scenarios demonstrate that ReFlow achieves superior reconstruction quality and robustness, establishing a novel self-correction paradigm for monocular 4D reconstruction.

MedLA: A Logic-Driven Multi-Agent Framework for Complex Medical Reasoning with Large Language Models

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

By: Siqi Ma · Jiajie Huang · Fan Zhang · Yue Shen · Jinlin Wu · Guohui Fan · Zhu Zhang · Zelin Zang

4 March 2026 at 13:00

arXiv:2509.23725v3 Announce Type: replace Abstract: Answering complex medical questions requires not only domain expertise and patient-specific information, but also structured and multi-perspective reasoning. Existing multi-agent approaches often rely on fixed roles or shallow interaction prompts, limiting their ability to detect and resolve fine-grained logical inconsistencies. To address this, we propose \textsc{MedLA}, a logic-driven multi-agent framework built on large language models. Each agent organizes its reasoning process into an explicit logical tree based on syllogistic triads (major premise, minor premise, and conclusion), enabling transparent inference and premise-level alignment. Agents engage in a multi-round, graph-guided discussion to compare and iteratively refine their logic trees, achieving consensus through error correction and contradiction resolution. We demonstrate that \textsc{MedLA} consistently outperforms both static role-based systems and single-agent baselines on challenging benchmarks such as MedDDx and standard medical QA tasks. Furthermore, \textsc{MedLA} scales effectively across both open-source and commercial LLM backbones, achieving state-of-the-art performance and offering a generalizable paradigm for trustworthy medical reasoning.

EBPO: Empirical Bayes Shrinkage for Stabilizing Group-Relative Policy Optimization

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

By: Kevin Han · Yuhang Zhou · Mingze Gao · Gedi Zhou · Serena Li · Abhishek Kumar · Xiangjun Fan · Weiwei Li · Lizhu Zhang

24 February 2026 at 13:00

arXiv:2602.05165v3 Announce Type: replace-cross Abstract: Reinforcement Learning with Verifiable Rewards (RLVR) has proven effective for enhancing the reasoning capabilities of Large Language Models (LLMs). However, dominant approaches like Group Relative Policy Optimization (GRPO) face critical stability challenges: they suffer from high estimator variance under computational constraints (small group sizes) and vanishing gradient signals in saturated failure regimes where all responses yield identical zero rewards. To address this, we propose Empirical Bayes Policy Optimization (EBPO), a novel framework that regularizes local group-based baselines by borrowing strength from the policy's accumulated global statistics. Instead of estimating baselines in isolation, EBPO employs a shrinkage estimator that dynamically balances local group statistics with a global prior updated via Welford's online algorithm. Theoretically, we demonstrate that EBPO guarantees strictly lower Mean Squared Error (MSE), bounded entropy decay, and non-vanishing penalty signals in failure scenarios compared to GRPO. Empirically, EBPO consistently outperforms GRPO and other established baselines across diverse benchmarks, including AIME and OlympiadBench. Notably, EBPO exhibits superior training stability, achieving high-performance gains even with small group sizes, and benefits significantly from difficulty-stratified curriculum learning.

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