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Journal of Medical Internet Research
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Evaluating Large Language Models in Clinical Audiology (AUDIOLOGYBENCH): Benchmark Development and Validation Study
Background: Large language models (LLMs) are increasingly being explored for clinical decision support, but their performance in audiology has not been systematically benchmarked using clinically grounded case materials and rubric-based safety evaluations. Objective: This study aimed to develop and evaluate AUDIOLOGYBENCH, a 3-tier benchmark for characterizing frontier LLM capability in clinical audiology along (1) curated domain knowledge, (2) literature-derived evidence, and (3) clinical reaso
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(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
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A Non-Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development
Adv Sci (Weinh). 2026 May 26:e75839. doi: 10.1002/advs.75839. Online ahead of print.ABSTRACTLung 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 datas
A Non-Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development
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
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Omics In Lung
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A Non-Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development
Adv Sci (Weinh). 2026 May 26:e75839. doi: 10.1002/advs.75839. Online ahead of print.ABSTRACTLung 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 datas
A Non-Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development
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
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cs.AI, q-bio.NC updates on arXiv.org
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Test-Time Deep Thinking to Explore Implicit Rules
arXiv:2605.24828v1 Announce Type: new Abstract: With the continuous advancement of Large Language Models (LLMs), intelligent agents are becoming increasingly vital. However, these agents often fail in environments governed by implicit rules--hidden constraints that cannot be observed directly and must be inferred through interaction. This causes agents to fall into repetitive trial-and-error loops, ultimately leading to task failure. To address this challenge, we propose Test-Time Exploration (
Test-Time Deep Thinking to Explore Implicit Rules
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cs.AI, q-bio.NC updates on arXiv.org
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EchoDistill:Alignment Noisy-to-Clean Self-Distillation for Robust Audio LLMs
arXiv:2605.23954v1 Announce Type: cross Abstract: Audio Large Language Models (ALLMs) are highly vulnerable to real-world noise, which often induces severe semantic drift and hallucinations. Existing robustness methods primarily rely on waveform-level acoustic enhancement, answer-level supervision, or the internal suppression of noise representations. To address these issues, we propose echodistill, an alignment-based noisy-to-clean self-distillation framework. Echodistill leverages a frozen cl
EchoDistill:Alignment Noisy-to-Clean Self-Distillation for Robust Audio LLMs
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cs.AI, q-bio.NC updates on arXiv.org
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$M^3-Verse$: A "Spot the Difference" Challenge for Large Multimodal Models
arXiv:2512.18735v2 Announce Type: replace-cross Abstract: Modern Large Multimodal Models (LMMs) have demonstrated extraordinary ability in static image and single-state spatial-temporal understanding. However, their capacity to comprehend the dynamic changes of objects within a shared spatial context between two distinct video observations, remains largely unexplored. This ability to reason about transformations within a consistent environment is particularly crucial for advancements in the fie
$M^3-Verse$: A "Spot the Difference" Challenge for Large Multimodal Models
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cs.AI, q-bio.NC updates on arXiv.org
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Large Language Models for Combinatorial Optimization of Design Structure Matrix
arXiv:2506.09749v3 Announce Type: replace-cross Abstract: In complex engineering systems, the dependencies among components or development activities are often modeled and analyzed using Design Structure Matrix (DSM). Reorganizing elements within a DSM to minimize feedback loops and enhance modularity or process efficiency constitutes a challenging combinatorial optimization (CO) problem in engineering design and operations. As problem sizes increase and dependency networks become more intricat
Large Language Models for Combinatorial Optimization of Design Structure Matrix
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Journal of Medical Internet Research
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Investigating the Effect of Hospital Infection Control Informatization on Optimizing Microbiological Specimen Submission Before Antibiotic Therapy: Failure Mode and Effects Analysis
Background: Antimicrobial resistance (AMR) poses a critical global health threat, with inappropriate antibiotic use being a major driver. Timely microbiological specimen submission before initiating antibiotic therapy is a cornerstone of antimicrobial stewardship (AMS), enabling pathogen-directed therapy and reducing unnecessary broad-spectrum exposure. However, suboptimal compliance remains common due to workflow interruptions, technological barriers, and behavioral factors. Failure Mode and Ef