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ART: Action-based Reasoning Task Benchmarking for Medical AI Agents

arXiv:2601.08988v1 Announce Type: new Abstract: Reliable clinical decision support requires medical AI agents capable of safe, multi-step reasoning over structured electronic health records (EHRs). While large language models (LLMs) show promise in healthcare, existing benchmarks inadequately assess performance on action-based tasks involving threshold evaluation, temporal aggregation, and conditional logic. We introduce ART, an Action-based Reasoning clinical Task benchmark for medical AI agents, which mines real-world EHR data to create challenging tasks targeting known reasoning weaknesses. Through analysis of existing benchmarks, we identify three dominant error categories: retrieval failures, aggregation errors, and conditional logic misjudgments. Our four-stage pipeline -- scenario identification, task generation, quality audit, and evaluation -- produces diverse, clinically validated tasks grounded in real patient data. Evaluating GPT-4o-mini and Claude 3.5 Sonnet on 600 tasks shows near-perfect retrieval after prompt refinement, but substantial gaps in aggregation (28--64%) and threshold reasoning (32--38%). By exposing failure modes in action-oriented EHR reasoning, ART advances toward more reliable clinical agents, an essential step for AI systems that reduce cognitive load and administrative burden, supporting workforce capacity in high-demand care settings
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A Marketplace for AI-Generated Adult Content and Deepfakes

arXiv:2601.09117v1 Announce Type: cross Abstract: Generative AI systems increasingly enable the production of highly realistic synthetic media. Civitai, a popular community-driven platform for AI-generated content, operates a monetized feature called Bounties, which allows users to commission the generation of content in exchange for payment. To examine how this mechanism is used and what content it incentivizes, we conduct a longitudinal analysis of all publicly available bounty requests collected over a 14-month period following the platform's launch. We find that the bounty marketplace is dominated by tools that let users steer AI models toward content they were not trained to generate. At the same time, requests for content that is "Not Safe For Work" are widespread and have increased steadily over time, now comprising a majority of all bounties. Participation in bounty creation is uneven, with 20% of requesters accounting for roughly half of requests. Requests for "deepfake" - media depicting identifiable real individuals - exhibit a higher concentration than other types of bounties. A nontrivial subset of these requests involves explicit deepfakes despite platform policies prohibiting such content. These bounties disproportionately target female celebrities, revealing a pronounced gender asymmetry in social harm. Together, these findings show how monetized, community-driven generative AI platforms can produce gendered harms, raising questions about consent, governance, and enforcement.
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GI-Bench: A Panoramic Benchmark Revealing the Knowledge-Experience Dissociation of Multimodal Large Language Models in Gastrointestinal Endoscopy Against Clinical Standards

arXiv:2601.08183v2 Announce Type: replace-cross Abstract: Multimodal Large Language Models (MLLMs) show promise in gastroenterology, yet their performance against comprehensive clinical workflows and human benchmarks remains unverified. To systematically evaluate state-of-the-art MLLMs across a panoramic gastrointestinal endoscopy workflow and determine their clinical utility compared with human endoscopists. We constructed GI-Bench, a benchmark encompassing 20 fine-grained lesion categories. Twelve MLLMs were evaluated across a five-stage clinical workflow: anatomical localization, lesion identification, diagnosis, findings description, and management. Model performance was benchmarked against three junior endoscopists and three residency trainees using Macro-F1, mean Intersection-over-Union (mIoU), and multi-dimensional Likert scale. Gemini-3-Pro achieved state-of-the-art performance. In diagnostic reasoning, top-tier models (Macro-F1 0.641) outperformed trainees (0.492) and rivaled junior endoscopists (0.727; p>0.05). However, a critical "spatial grounding bottleneck" persisted; human lesion localization (mIoU >0.506) significantly outperformed the best model (0.345; p
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Circulating metabolites, genetics and lifestyle factors in relation to future risk of type 2 diabetes

Nat Med. 2026 Jan 14. doi: 10.1038/s41591-025-04105-8. Online ahead of print.

ABSTRACT

The human metabolome reflects complex metabolic states affected by genetic and environmental factors. However, metabolites associated with type 2 diabetes (T2D) risk and their determinants remain insufficiently characterized. Here we integrated blood metabolomic, genomic and lifestyle data from up to 23,634 initially T2D-free participants from ten cohorts. Of 469 metabolites examined, 235 were associated with incident T2D during up to 26 years of follow-up, including 67 associations not previously reported across bile acid, lipid, carnitine, urea cycle and arginine/proline, glycine and histidine pathways. Further genetic analyses linked these metabolites to signaling pathways and clinical traits central to T2D pathophysiology, including insulin resistance, glucose/insulin response, ectopic fat deposition, energy/lipid regulation and liver function. Lifestyle factors-particularly physical activity, obesity and diet-explained greater variations in T2D-associated versus non-associated metabolites, with specific metabolites revealed as potential mediators. Finally, a 44-metabolite signature improved T2D risk prediction beyond conventional factors. These findings provide a foundation for understanding T2D mechanisms and may inform precision prevention targeting specific metabolic pathways.

PMID:41535386 | DOI:10.1038/s41591-025-04105-8

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Multi-omics to study chronic respiratory diseases and viral infections

Eur Respir Rev. 2026 Jan 14;35(179):240286. doi: 10.1183/16000617.0286-2024. Print 2026 Jan.

ABSTRACT

Despite recent advances, the underlying mechanisms of the development and progression of many chronic respiratory diseases remain to be elucidated. Factors such as heterogeneity and complexity of human diseases and difficulty interpreting large datasets hinder research into chronic respiratory diseases. Omics assesses the changes in specific biological entities, such as mRNA expression, epigenetics/epigenomics, genomics, proteomics, metagenomics and metabolomics, and provides valuable insights into the roles of these processes in chronic respiratory diseases. High-throughput omics at bulk, single-cell and spatial levels empower the exploration of disease-related changes through untargeted data-driven statistical methods. Multi-omics is the exploration and integration of multiple biological processes, which compared to a single-omics, can provide a substantially greater and more holistic overview of the pathogenic mechanisms that underpin complex diseases. Multi-omics analysis can comprehensively characterise the mechanisms that drive chronic respiratory diseases, capturing unique biological signatures and cellular interactions at different omics levels. Use of these methods has begun to identify key factors and biomarkers in chronic respiratory diseases. Here, we review current omics approaches and highlight recent advances in respiratory research achieved using multi-omics and integrative methods. Our review provides a valuable resource for researchers and clinicians in this area.

PMID:41534886 | DOI:10.1183/16000617.0286-2024

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Complement-secreting CAFs are associated with better prognosis in pancreatic cancer: single-cell multiomics

Gut. 2026 Jan 13:gutjnl-2025-335683. doi: 10.1136/gutjnl-2025-335683. Online ahead of print.

ABSTRACT

BACKGROUND: Accumulating evidence has demonstrated that distinct tumour-promoting and tumour-restraining cancer-associated fibroblast (CAF) subtypes coexist in pancreatic ductal adenocarcinoma.

OBJECTIVE: To develop targeted CAF therapeutic strategies by reprogramming tumour-promoting CAF subtypes.

DESIGN: We leveraged multiomics technologies to systematically identify and characterise CAF subtypes transcriptionally, epigenetically and spatially and correlate them with clinicopathological features.

RESULTS: We found that complement-secreting CAFs (csCAFs), initially identified by our group and inflammatory CAFs (iCAFs) share significant overlap in their transcriptional profiles and chromatin accessibility. iCAFs specifically express transcription factors from the heme and oxidative homeostasis pathway and the activator protein 1 family, which are both involved in cellular response to oxidative stress. Notably, the composition of csCAFs among all CAFs declined during pancreatic carcinogenesis, while trajectory analysis showed that csCAFs could potentially differentiate into iCAFs. Spatially resolved analysis indicated that tumour regions with a higher csCAF composition were associated with lower levels of TGF-β ligands, fewer M2 tumour-associated macrophages and increased levels of lipid mediators. Additionally, we identified a spatially defined CXCL12-CXCR4 ligand-receptor interaction between csCAFs and T cells, but in distinct patterns between different metastatic organs. Patients with a higher composition of csCAFs have significantly longer overall survival and recurrence-free survival through multiplex immunohistochemistry and bulk RNA-seq deconvolution.

CONCLUSION: Our study demonstrates that csCAFs may represent an early-stage iCAF subtype and suggests a promising strategy for reprogramming iCAFs into csCAFs.

PMID:41534892 | DOI:10.1136/gutjnl-2025-335683

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<em>Helicobacter pylori</em> and Cancer: What's the Link?

Clin Exp Gastroenterol. 2026 Jan 7;19:1-11. doi: 10.2147/CEG.S495588. eCollection 2026.

ABSTRACT

Helicobacter pylori (H. pylori) is a human bacterial pathogen that causes one of the most common chronic bacterial infections worldwide. The microorganism has been classified by the International Agency for Research on Cancer as a Group I carcinogen. While the etiological link to gastric cancer is well established, the precise molecular and cellular mechanisms driving this transformation are highly complex and incompletely understood. Fundamentally, the infection results from the chronic presence of acute on chronic gastric mucosal inflammation. H. pylori pathogenicity is increased by bacterial virulence factors including the cytotoxin-associated gene A (CagA) and Vacuolating cytotoxin A (VacA) which may interfere with the host's cell communication and create a pro-tumorigenic microenvironment. Host microRNAs (miRNAs) may amplify these effects by modulating immune responses, enhancing oncogenic signalling. Despite the proven benefits of H. pylori eradication in reducing cancer risk, especially in high-incidence regions, rising antibiotic resistance and host-related variables impede its global implementation. Recent advances in genomics and multi-omics profiling potentially offer new opportunities for targeted prevention. Moreover, emerging evidence suggests H. pylori may also negatively influence immunotherapy outcomes, underscoring its broader relevance in cancer treatment planning. By synthesizing molecular insights, epidemiological trends, and clinical data, this narrative review examines the multifaceted pathways through which H. pylori contributes to gastric carcinogenesis, integrating current knowledge on microbial virulence, host signalling disruption, immune modulation, and epigenetic remodelling.

PMID:41531650 | PMC:PMC12791163 | DOI:10.2147/CEG.S495588

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A nowhere-to-hide mechanism ensures complete piRNA-directed DNA methylation

Nature, Published online: 14 January 2026; doi:10.1038/s41586-025-09940-w

In mice, a SPOCD1–TPR-dependent ‘nowhere-to-hide’ mechanism is required for complete non-stochastic piRNA-directed LINE1 DNA methylation by preventing transposons from escaping surveillance within heterochromatin.
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Semantic Laundering in AI Agent Architectures: Why Tool Boundaries Do Not Confer Epistemic Warrant

arXiv:2601.08333v1 Announce Type: new Abstract: LLM-based agent architectures systematically conflate information transport mechanisms with epistemic justification mechanisms. We formalize this class of architectural failures as semantic laundering: a pattern where propositions with absent or weak warrant are accepted by the system as admissible by crossing architecturally trusted interfaces. We show that semantic laundering constitutes an architectural realization of the Gettier problem: propositions acquire high epistemic status without a connection between their justification and what makes them true. Unlike classical Gettier cases, this effect is not accidental; it is architecturally determined and systematically reproducible. The central result is the Theorem of Inevitable Self-Licensing: under standard architectural assumptions, circular epistemic justification cannot be eliminated. We introduce the Warrant Erosion Principle as the fundamental explanation for this effect and show that scaling, model improvement, and LLM-as-judge schemes are structurally incapable of eliminating a problem that exists at the type level.
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WaterCopilot: An AI-Driven Virtual Assistant for Water Management

arXiv:2601.08559v1 Announce Type: new Abstract: Sustainable water resource management in transboundary river basins is challenged by fragmented data, limited real-time access, and the complexity of integrating diverse information sources. This paper presents WaterCopilot-an AI-driven virtual assistant developed through collaboration between the International Water Management Institute (IWMI) and Microsoft Research for the Limpopo River Basin (LRB) to bridge these gaps through a unified, interactive platform. Built on Retrieval-Augmented Generation (RAG) and tool-calling architectures, WaterCopilot integrates static policy documents and real-time hydrological data via two custom plugins: the iwmi-doc-plugin, which enables semantic search over indexed documents using Azure AI Search, and the iwmi-api-plugin, which queries live databases to deliver dynamic insights such as environmental-flow alerts, rainfall trends, reservoir levels, water accounting, and irrigation data. The system features guided multilingual interactions (English, Portuguese, French), transparent source referencing, automated calculations, and visualization capabilities. Evaluated using the RAGAS framework, WaterCopilot achieves an overall score of 0.8043, with high answer relevancy (0.8571) and context precision (0.8009). Key innovations include automated threshold-based alerts, integration with the LRB Digital Twin, and a scalable deployment pipeline hosted on AWS. While limitations in processing non-English technical documents and API latency remain, WaterCopilot establishes a replicable AI-augmented framework for enhancing water governance in data-scarce, transboundary contexts. The study demonstrates the potential of this AI assistant to support informed, timely decision-making and strengthen water security in complex river basins.
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GI-Bench: A Panoramic Benchmark Revealing the Knowledge-Experience Dissociation of Multimodal Large Language Models in Gastrointestinal Endoscopy Against Clinical Standards

arXiv:2601.08183v1 Announce Type: cross Abstract: Multimodal Large Language Models (MLLMs) show promise in gastroenterology, yet their performance against comprehensive clinical workflows and human benchmarks remains unverified. To systematically evaluate state-of-the-art MLLMs across a panoramic gastrointestinal endoscopy workflow and determine their clinical utility compared with human endoscopists. We constructed GI-Bench, a benchmark encompassing 20 fine-grained lesion categories. Twelve MLLMs were evaluated across a five-stage clinical workflow: anatomical localization, lesion identification, diagnosis, findings description, and management. Model performance was benchmarked against three junior endoscopists and three residency trainees using Macro-F1, mean Intersection-over-Union (mIoU), and multi-dimensional Likert scale. Gemini-3-Pro achieved state-of-the-art performance. In diagnostic reasoning, top-tier models (Macro-F1 0.641) outperformed trainees (0.492) and rivaled junior endoscopists (0.727; p>0.05). However, a critical "spatial grounding bottleneck" persisted; human lesion localization (mIoU >0.506) significantly outperformed the best model (0.345; p
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Moral Lenses, Political Coordinates: Towards Ideological Positioning of Morally Conditioned LLMs

arXiv:2601.08634v1 Announce Type: cross Abstract: While recent research has systematically documented political orientation in large language models (LLMs), existing evaluations rely primarily on direct probing or demographic persona engineering to surface ideological biases. In social psychology, however, political ideology is also understood as a downstream consequence of fundamental moral intuitions. In this work, we investigate the causal relationship between moral values and political positioning by treating moral orientation as a controllable condition. Rather than simply assigning a demographic persona, we condition models to endorse or reject specific moral values and evaluate the resulting shifts on their political orientations, using the Political Compass Test. By treating moral values as lenses, we observe how moral conditioning actively steers model trajectories across economic and social dimensions. Our findings show that such conditioning induces pronounced, value-specific shifts in models' political coordinates. We further notice that these effects are systematically modulated by role framing and model scale, and are robust across alternative assessment instruments instantiating the same moral value. This highlights that effective alignment requires anchoring political assessments within the context of broader social values including morality, paving the way for more socially grounded alignment techniques.
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ISLA: A U-Net for MRI-based acute ischemic stroke lesion segmentation with deep supervision, attention, domain adaptation, and ensemble learning

arXiv:2601.08732v1 Announce Type: cross Abstract: Accurate delineation of acute ischemic stroke lesions in MRI is a key component of stroke diagnosis and management. In recent years, deep learning models have been successfully applied to the automatic segmentation of such lesions. While most proposed architectures are based on the U-Net framework, they primarily differ in their choice of loss functions and in the use of deep supervision, residual connections, and attention mechanisms. Moreover, many implementations are not publicly available, and the optimal configuration for acute ischemic stroke (AIS) lesion segmentation remains unclear. In this work, we introduce ISLA (Ischemic Stroke Lesion Analyzer), a new deep learning model for AIS lesion segmentation from diffusion MRI, trained on three multicenter databases totaling more than 1500 AIS participants. Through systematic optimization of the loss function, convolutional architecture, deep supervision, and attention mechanisms, we developed a robust segmentation framework. We further investigated unsupervised domain adaptation to improve generalization to an external clinical dataset. ISLA outperformed two state-of-the-art approaches for AIS lesion segmentation on an external test set. Codes and trained models will be made publicly available to facilitate reuse and reproducibility.
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MCP Bridge: A Lightweight, LLM-Agnostic RESTful Proxy for Model Context Protocol Servers

arXiv:2504.08999v2 Announce Type: replace-cross Abstract: Large Language Models (LLMs) are increasingly augmented with external tools through standardized interfaces like the Model Context Protocol (MCP). However, current MCP implementations face critical limitations: they typically require local process execution through STDIO transports, making them impractical for resource-constrained environments like mobile devices, web browsers, and edge computing. We present MCP Bridge, a lightweight RESTful proxy that connects to multiple MCP servers and exposes their capabilities through a unified API. Unlike existing solutions, MCP Bridge is fully LLM-agnostic, supporting any backend regardless of vendor. The system implements a risk-based execution model with three security levels-standard execution, confirmation workflow, and Docker isolation - while maintaining backward compatibility with standard MCP clients. However, reliable execution within this framework requires models that can strictly adhere to protocol schemas. To this end, we also fine-tuned the Qwen3 4B and 8B model family on the Agent-Ark/Toucan-1.5M dataset using four Reinforcement Learning techniques: Group Relative Policy Optimization (GRPO), Dr. GRPO, Beta Normalization Policy Optimization (BNPO), and Decoupled Alignment Policy Optimization (DAPO). Evaluated on the MCPToolBench++ benchmark, our optimized model achieves an F1 score of 73.0% that outperforms GPT-OSS-120B (62.17%) and remains competitive with the 70B+ parameter baselines. Evaluation demonstrates that MCP Bridge successfully addresses the constraints of direct MCP connections while providing enhanced security controls and cross-platform compatibility, enabling sophisticated LLM-powered applications in previously inaccessible environments.
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Efficient and Reproducible Biomedical Question Answering using Retrieval Augmented Generation

arXiv:2505.07917v2 Announce Type: replace-cross Abstract: Biomedical question-answering (QA) systems require effective retrieval and generation components to ensure accuracy, efficiency, and scalability. This study systematically examines a Retrieval-Augmented Generation (RAG) system for biomedical QA, evaluating retrieval strategies and response time trade-offs. We first assess state-of-the-art retrieval methods, including BM25, BioBERT, MedCPT, and a hybrid approach, alongside common data stores such as Elasticsearch, MongoDB, and FAISS, on a ~10% subset of PubMed (2.4M documents) to measure indexing efficiency, retrieval latency, and retriever performance in the end-to-end RAG system. Based on these insights, we deploy the final RAG system on the full 24M PubMed corpus, comparing different retrievers' impact on overall performance. Evaluations of the retrieval depth show that retrieving 50 documents with BM25 before reranking with MedCPT optimally balances accuracy (0.90), recall (0.90), and response time (1.91s). BM25 retrieval time remains stable (82ms), while MedCPT incurs the main computational cost. These results highlight previously not well-known trade-offs in retrieval depth, efficiency, and scalability for biomedical QA. With open-source code, the system is fully reproducible and extensible.
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Aligning Trustworthy AI with Democracy: A Dual Taxonomy of Opportunities and Risks

arXiv:2505.13565v2 Announce Type: replace-cross Abstract: Artificial Intelligence (AI) poses both significant risks and valuable opportunities for democratic governance. This paper introduces a dual taxonomy to evaluate AI's complex relationship with democracy: the AI Risks to Democracy (AIRD) taxonomy, which identifies how AI can undermine core democratic principles such as autonomy, fairness, and trust; and the AI's Positive Contributions to Democracy (AIPD) taxonomy, which highlights AI's potential to enhance transparency, participation, efficiency, and evidence-based policymaking. Grounded in the European Union's approach to ethical AI governance, and particularly the seven Trustworthy AI requirements proposed by the European Commission's High-Level Expert Group on AI, each identified risk is aligned with mitigation strategies based on EU regulatory and normative frameworks. Our analysis underscores the transversal importance of transparency and societal well-being across all risk categories and offers a structured lens for aligning AI systems with democratic values. By integrating democratic theory with practical governance tools, this paper offers a normative and actionable framework to guide research, regulation, and institutional design to support trustworthy, democratic AI. It provides scholars with a conceptual foundation to evaluate the democratic implications of AI, equips policymakers with structured criteria for ethical oversight, and helps technologists align system design with democratic principles. In doing so, it bridges the gap between ethical aspirations and operational realities, laying the groundwork for more inclusive, accountable, and resilient democratic systems in the algorithmic age.
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