Transformer-Based Multitask Framework Integrating Habitat and Deep Learning for Predicting Early Disease Control and Survival in Immunotherapy-Treated Hepatocellular Carcinoma

By: Xiaona Fu · Yusheng Guo · Bingxin Gong · Jie Lou · Ning Wang · Xuejun Chen · Hongtao Hu · Rundong Wang · Xiaofang Guo · Shanmei Li · Yangyang Xie · Shichao Long · Mengsi Li · Shubo Pan · Wen Shen · Zhaogang Zhang · Zifang Song · Pengchen Liang · Xiaoyun Liang · Peng Sun · Guilin Zhang · Shanshan Jiang · Jinxiang Zhang · Lian Yang

27 September 2026 at 18:00

Adv Sci (Weinh). 2026 Sep 27:e78005. doi: 10.1002/advs.78005. Online ahead of print.

ABSTRACT

Hepatocellular carcinoma (HCC) patients show heterogeneous responses to immune checkpoint inhibitors (ICIs). This study developed ECOS-Net, a transformer-based multitask network integrating CT-derived habitat and 2.5-dimensional (2.5D) deep learning features for simultaneously predicting early disease control (DC) and overall survival (OS). Of 1,234 patients with HCC enrolled from eight institutions and public databases, 832 ICI-treated patients were used for model development. ECOS-Net fused features using multi-head attention and generated early DC probabilities and OS risk scores. ECOS-DC achieved AUCs of 0.836, 0.822, and 0.817 in training, internal validation, and external test sets, outperforming clinical models (all p values < 0.05). ECOS-OS yielded C-indices of 0.730, 0.722, and 0.720, respectively. Integrated models also showed favorable external performance (early DC AUC: 0.825; OS C-index: 0.741). Patients with higher ECOS-DC probabilities had a higher likelihood of early DC, whereas those with higher ECOS-OS risk had shorter OS, with directionally consistent associations across most subgroups. Exploratory biological analyses suggested that the higher ECOS-DC probability and lower ECOS-OS risk groups were associated with immune-active tumor microenvironment features. Therefore, ECOS-Net shows potential as a non-invasive imaging-based risk stratification framework for simultaneously predicting early DC and OS in ICI-treated HCC patients.

PMID:42801546 | PMC:PMC13616327 | DOI:10.1002/advs.78005

A Non-Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development

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

By: Qian Tang · Chen Lian · Xinyan Han · Xuhan Zhang · Zihan Wang · Boyu Wang · Taoyu Zhu · Xinrui Lin · Xiaolei Wang · Yaping Xu · Manyu Xiao · Zijin Wang · Junming Li · Silin Chen · Yunze Wang · Yufei Liu · Songsong Li · Zuolin Shen · Xi Lu · Xueqi Han · Yilu Zhou · Mingyang Xiao · Jiayi Ran · Xiaoran Cao · Xinyi Xu · Hugo Sámano-Sánchez · Alfredo Rodríguez · Lian Wang · Shuifang Chen · Zhanyu Xu · Shirong Zhang · Nuo Yang · Yong Tang · Jian Liu

26 May 2026 at 18:00

Adv Sci (Weinh). 2026 May 26:e75839. doi: 10.1002/advs.75839. Online ahead of print.

ABSTRACT

Lung squamous cell carcinoma (LUSC) lacks clearly defined key drivers and effective targeted therapies, reflecting an incomplete understanding of its molecular pathogenesis. Here, we identify SMAD4 as a critical regulator of three-dimensional (3D) genome organization in LUSC and uncover a mechanistic link between tumor suppressor loss and oncogenic transcriptional activation. By integrating clinical datasets, genetically engineered mouse models, human and murine LUSC cell lines, and multi-omics analyses, we demonstrate that SMAD4 deficiency promotes LUSC progression by unleashing EP300-mediated enhancer-promoter looping at the SOX2 locus. Mechanistically, SMAD4 does not directly bind SOX2 regulatory elements but instead constrains chromatin looping by sequestering EP300 away from loop anchor regions. Loss of SMAD4 leads to enhanced H3K27ac deposition, aberrant SOX2 activation, and increased LUSC tumor cell proliferation. Together, these findings reveal a non-canonical role for a transcription factor (e.g., SMAD4) in regulating dysregulated 3D genome architecture to inhibit tumor development.

PMID:42189071 | DOI:10.1002/advs.75839

A Non-Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development

Omics In Lung

By: Qian Tang · Chen Lian · Xinyan Han · Xuhan Zhang · Zihan Wang · Boyu Wang · Taoyu Zhu · Xinrui Lin · Xiaolei Wang · Yaping Xu · Manyu Xiao · Zijin Wang · Junming Li · Silin Chen · Yunze Wang · Yufei Liu · Songsong Li · Zuolin Shen · Xi Lu · Xueqi Han · Yilu Zhou · Mingyang Xiao · Jiayi Ran · Xiaoran Cao · Xinyi Xu · Hugo Sámano-Sánchez · Alfredo Rodríguez · Lian Wang · Shuifang Chen · Zhanyu Xu · Shirong Zhang · Nuo Yang · Yong Tang · Jian Liu

26 May 2026 at 18:00

Adv Sci (Weinh). 2026 May 26:e75839. doi: 10.1002/advs.75839. Online ahead of print.

ABSTRACT

Lung squamous cell carcinoma (LUSC) lacks clearly defined key drivers and effective targeted therapies, reflecting an incomplete understanding of its molecular pathogenesis. Here, we identify SMAD4 as a critical regulator of three-dimensional (3D) genome organization in LUSC and uncover a mechanistic link between tumor suppressor loss and oncogenic transcriptional activation. By integrating clinical datasets, genetically engineered mouse models, human and murine LUSC cell lines, and multi-omics analyses, we demonstrate that SMAD4 deficiency promotes LUSC progression by unleashing EP300-mediated enhancer-promoter looping at the SOX2 locus. Mechanistically, SMAD4 does not directly bind SOX2 regulatory elements but instead constrains chromatin looping by sequestering EP300 away from loop anchor regions. Loss of SMAD4 leads to enhanced H3K27ac deposition, aberrant SOX2 activation, and increased LUSC tumor cell proliferation. Together, these findings reveal a non-canonical role for a transcription factor (e.g., SMAD4) in regulating dysregulated 3D genome architecture to inhibit tumor development.

PMID:42189071 | DOI:10.1002/advs.75839

Turning Stale Gradients into Stable Gradients: Coherent Coordinate Descent with Implicit Landscape Smoothing for Lightweight Zeroth-Order Optimization

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

By: Chen Liang · Xiatao Sun · Qian Wang · Daniel Rakita

26 May 2026 at 12:00

arXiv:2605.14373v2 Announce Type: replace-cross Abstract: Zeroth-Order (ZO) optimization is pivotal for scenarios where backpropagation is unavailable, such as memory-constrained on-device learning and black-box optimization. However, existing methods face a stark trade-off: they are either sample-inefficient (e.g., standard finite differences) or suffer from high variance due to randomized estimation (e.g., random subspace methods). In this work, we propose Coherent Coordinate Descent (CoCD), a deterministic, sample-efficient, and budget-aware ZO optimizer. Theoretically, we formalize the notion of gradient coherence and demonstrate that CoCD is equivalent to Block Cyclic Coordinate Descent (BCCD) with ``warm starts,'' effectively converting historical (stale) gradients from a liability into a computational asset. This mechanism enables $O(1)$ query complexity per step while maintaining global descent directions. Furthermore, we derive error bounds revealing a counter-intuitive insight: larger finite-difference step sizes can induce an implicit smoothing effect on the optimization landscape by reducing the effective smoothness constant, thereby improving convergence stability. Experiments on MLP, CNN, and ResNet architectures (up to 270k parameters) demonstrate that CoCD significantly outperforms BCCD in terms of sample efficiency and convergence loss/accuracy, and exhibits superior stability over randomized ZO methods. Our results suggest that deterministic, structure-aware updates offer a superior alternative to randomization for lightweight ZO optimization.

Reinforcing Numerical Reasoning in LLMs for Tabular Prediction via Structural Priors

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

By: Pengxiang Cai · Zihao Gao · Wanchen Lian · Jintai Chen

10 March 2026 at 12:00

arXiv:2510.17385v3 Announce Type: replace-cross Abstract: Tabular prediction traditionally relies on gradient-boosted decision trees and deep learning models, which excel in specific tasks but lack interpretability and transferability. Reasoning large language models (LLMs) promise cross-task adaptability with transparent reasoning traces, yet their potential for tabular data remains unrealized. To bridge this gap, we propose a reasoning framework centered on Permutation Relative Policy Optimization (PRPO), a reinforcement learning method that encodes column-permutation invariance as a structural prior. By estimating advantages across label-preserving permutations, PRPO transforms sparse rewards into dense signals, activating latent numerical reasoning capabilities of LLMs with limited supervision. Extensive experiments show that our method matches fully supervised baselines and dominates in zero-shot settings, performing on par with 32-shot strong baselines. Remarkably, our 8B model significantly outperforms much larger LLMs, achieving up to a 53.17% improvement over DeepSeek-R1 (685B).

AECBench: A Hierarchical Benchmark for Knowledge Evaluation of Large Language Models in the AEC Field

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

By: Chen Liang · Zhaoqi Huang · Haofen Wang · Fu Chai · Chunying Yu · Huanhuan Wei · Zhengjie Liu · Yanpeng Li · Hongjun Wang · Ruifeng Luo · Xianzhong Zhao

17 February 2026 at 13:00

arXiv:2509.18776v3 Announce Type: replace-cross Abstract: Large language models (LLMs), as a novel information technology, are seeing increasing adoption in the Architecture, Engineering, and Construction (AEC) field. They have shown their potential to streamline processes throughout the building lifecycle. However, the robustness and reliability of LLMs in such a specialized and safety-critical domain remain to be evaluated. To address this challenge, this paper establishes AECBench, a comprehensive benchmark designed to quantify the strengths and limitations of current LLMs in the AEC domain. The benchmark features a five-level, cognition-oriented evaluation framework (i.e., Knowledge Memorization, Understanding, Reasoning, Calculation, and Application). Based on the framework, 23 representative evaluation tasks were defined. These tasks were derived from authentic AEC practice, with scope ranging from codes retrieval to specialized documents generation. Subsequently, a 4,800-question dataset encompassing diverse formats, including open-ended questions, was crafted primarily by engineers and validated through a two-round expert review. Furthermore, an "LLM-as-a-Judge" approach was introduced to provide a scalable and consistent methodology for evaluating complex, long-form responses leveraging expert-derived rubrics. Through the evaluation of nine LLMs, a clear performance decline across five cognitive levels was revealed. Despite demonstrating proficiency in foundational tasks at the Knowledge Memorization and Understanding levels, the models showed significant performance deficits, particularly in interpreting knowledge from tables in building codes, executing complex reasoning and calculation, and generating domain-specific documents. Consequently, this study lays the groundwork for future research and development aimed at the robust and reliable integration of LLMs into safety-critical engineering practices.

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