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Evaluating Control Protocols for Untrusted AI Agents

✇cs.AI, q-bio.NC updates on arXiv.org
By: Jon Kutasov · Chloe Loughridge · Yuqi Sun · Henry Sleight · Buck Shlegeris · Tyler Tracy · Joe Benton
arXiv:2511.02997v1 Announce Type: new Abstract: As AI systems become more capable and widely deployed as agents, ensuring their safe operation becomes critical. AI control offers one approach to mitigating the risk from untrusted AI agents by monitoring their actions and intervening or auditing when necessary. Evaluating the safety of these protocols requires understanding both their effectiveness against current attacks and their robustness to adaptive adversaries. In this work, we systematically evaluate a range of control protocols in SHADE-Arena, a dataset of diverse agentic environments. First, we evaluate blue team protocols, including deferral to trusted models, resampling, and deferring on critical actions, against a default attack policy. We find that resampling for incrimination and deferring on critical actions perform best, increasing safety from 50% to 96%. We then iterate on red team strategies against these protocols and find that attack policies with additional affordances, such as knowledge of when resampling occurs or the ability to simulate monitors, can substantially improve attack success rates against our resampling strategy, decreasing safety to 17%. However, deferring on critical actions is highly robust to even our strongest red team strategies, demonstrating the importance of denying attack policies access to protocol internals.
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No-Human in the Loop: Agentic Evaluation at Scale for Recommendation

✇cs.AI, q-bio.NC updates on arXiv.org
By: Tao Zhang · Kehui Yao · Luyi Ma · Jiao Chen · Reza Yousefi Maragheh · Kai Zhao · Jianpeng Xu · Evren Korpeoglu · Sushant Kumar · Kannan Achan
arXiv:2511.03051v1 Announce Type: new Abstract: Evaluating large language models (LLMs) as judges is increasingly critical for building scalable and trustworthy evaluation pipelines. We present ScalingEval, a large-scale benchmarking study that systematically compares 36 LLMs, including GPT, Gemini, Claude, and Llama, across multiple product categories using a consensus-driven evaluation protocol. Our multi-agent framework aggregates pattern audits and issue codes into ground-truth labels via scalable majority voting, enabling reproducible comparison of LLM evaluators without human annotation. Applied to large-scale complementary-item recommendation, the benchmark reports four key findings: (i) Anthropic Claude 3.5 Sonnet achieves the highest decision confidence; (ii) Gemini 1.5 Pro offers the best overall performance across categories; (iii) GPT-4o provides the most favorable latency-accuracy-cost tradeoff; and (iv) GPT-OSS 20B leads among open-source models. Category-level analysis shows strong consensus in structured domains (Electronics, Sports) but persistent disagreement in lifestyle categories (Clothing, Food). These results establish ScalingEval as a reproducible benchmark and evaluation protocol for LLMs as judges, with actionable guidance on scaling, reliability, and model family tradeoffs.
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Explaining Decisions in ML Models: a Parameterized Complexity Analysis (Part I)

✇cs.AI, q-bio.NC updates on arXiv.org
By: Sebastian Ordyniak · Giacomo Paesani · Mateusz Rychlicki · Stefan Szeider
arXiv:2511.03545v1 Announce Type: new Abstract: This paper presents a comprehensive theoretical investigation into the parameterized complexity of explanation problems in various machine learning (ML) models. Contrary to the prevalent black-box perception, our study focuses on models with transparent internal mechanisms. We address two principal types of explanation problems: abductive and contrastive, both in their local and global variants. Our analysis encompasses diverse ML models, including Decision Trees, Decision Sets, Decision Lists, Boolean Circuits, and ensembles thereof, each offering unique explanatory challenges. This research fills a significant gap in explainable AI (XAI) by providing a foundational understanding of the complexities of generating explanations for these models. This work provides insights vital for further research in the domain of XAI, contributing to the broader discourse on the necessity of transparency and accountability in AI systems.
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Digital Transformation Chatbot (DTchatbot): Integrating Large Language Model-based Chatbot in Acquiring Digital Transformation Needs

✇cs.AI, q-bio.NC updates on arXiv.org
By: Jiawei Zheng · Gokcen Yilmaz · Ji Han · Saeema Ahmed-Kristensen
arXiv:2511.02842v1 Announce Type: cross Abstract: Many organisations pursue digital transformation to enhance operational efficiency, reduce manual efforts, and optimise processes by automation and digital tools. To achieve this, a comprehensive understanding of their unique needs is required. However, traditional methods, such as expert interviews, while effective, face several challenges, including scheduling conflicts, resource constraints, inconsistency, etc. To tackle these issues, we investigate the use of a Large Language Model (LLM)-powered chatbot to acquire organisations' digital transformation needs. Specifically, the chatbot integrates workflow-based instruction with LLM's planning and reasoning capabilities, enabling it to function as a virtual expert and conduct interviews. We detail the chatbot's features and its implementation. Our preliminary evaluation indicates that the chatbot performs as designed, effectively following predefined workflows and supporting user interactions with areas for improvement. We conclude by discussing the implications of employing chatbots to elicit user information, emphasizing their potential and limitations.
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Mathematical exploration and discovery at scale

✇cs.AI, q-bio.NC updates on arXiv.org
By: Bogdan Georgiev · Javier G\'omez-Serrano · Terence Tao · Adam Zsolt Wagner
arXiv:2511.02864v1 Announce Type: cross Abstract: AlphaEvolve is a generic evolutionary coding agent that combines the generative capabilities of LLMs with automated evaluation in an iterative evolutionary framework that proposes, tests, and refines algorithmic solutions to challenging scientific and practical problems. In this paper we showcase AlphaEvolve as a tool for autonomously discovering novel mathematical constructions and advancing our understanding of long-standing open problems. To demonstrate its breadth, we considered a list of 67 problems spanning mathematical analysis, combinatorics, geometry, and number theory. The system rediscovered the best known solutions in most of the cases and discovered improved solutions in several. In some instances, AlphaEvolve is also able to generalize results for a finite number of input values into a formula valid for all input values. Furthermore, we are able to combine this methodology with Deep Think and AlphaProof in a broader framework where the additional proof-assistants and reasoning systems provide automated proof generation and further mathematical insights. These results demonstrate that large language model-guided evolutionary search can autonomously discover mathematical constructions that complement human intuition, at times matching or even improving the best known results, highlighting the potential for significant new ways of interaction between mathematicians and AI systems. We present AlphaEvolve as a powerful new tool for mathematical discovery, capable of exploring vast search spaces to solve complex optimization problems at scale, often with significantly reduced requirements on preparation and computation time.
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FP-AbDiff: Improving Score-based Antibody Design by Capturing Nonequilibrium Dynamics through the Underlying Fokker-Planck Equation

✇cs.AI, q-bio.NC updates on arXiv.org
By: Jiameng Chen · Yida Xiong · Kun Li · Hongzhi Zhang · Xiantao Cai · Wenbin Hu · Jia Wu
arXiv:2511.03113v1 Announce Type: cross Abstract: Computational antibody design holds immense promise for therapeutic discovery, yet existing generative models are fundamentally limited by two core challenges: (i) a lack of dynamical consistency, which yields physically implausible structures, and (ii) poor generalization due to data scarcity and structural bias. We introduce FP-AbDiff, the first antibody generator to enforce Fokker-Planck Equation (FPE) physics along the entire generative trajectory. Our method minimizes a novel FPE residual loss over the mixed manifold of CDR geometries (R^3 x SO(3)), compelling locally-learned denoising scores to assemble into a globally coherent probability flow. This physics-informed regularizer is synergistically integrated with deep biological priors within a state-of-the-art SE(3)-equivariant diffusion framework. Rigorous evaluation on the RAbD benchmark confirms that FP-AbDiff establishes a new state-of-the-art. In de novo CDR-H3 design, it achieves a mean Root Mean Square Deviation of 0.99 {\AA} when superposing on the variable region, a 25% improvement over the previous state-of-the-art model, AbX, and the highest reported Contact Amino Acid Recovery of 39.91%. This superiority is underscored in the more challenging six-CDR co-design task, where our model delivers consistently superior geometric precision, cutting the average full-chain Root Mean Square Deviation by ~15%, and crucially, achieves the highest full-chain Amino Acid Recovery on the functionally dominant CDR-H3 loop (45.67%). By aligning generative dynamics with physical laws, FP-AbDiff enhances robustness and generalizability, establishing a principled approach for physically faithful and functionally viable antibody design.
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LGM: Enhancing Large Language Models with Conceptual Meta-Relations and Iterative Retrieval

✇cs.AI, q-bio.NC updates on arXiv.org
By: Wenchang Lei · Ping Zou · Yue Wang · Feng Sun · Lei Zhao
arXiv:2511.03214v1 Announce Type: cross Abstract: Large language models (LLMs) exhibit strong semantic understanding, yet struggle when user instructions involve ambiguous or conceptually misaligned terms. We propose the Language Graph Model (LGM) to enhance conceptual clarity by extracting meta-relations-inheritance, alias, and composition-from natural language. The model further employs a reflection mechanism to validate these meta-relations. Leveraging a Concept Iterative Retrieval Algorithm, these relations and related descriptions are dynamically supplied to the LLM, improving its ability to interpret concepts and generate accurate responses. Unlike conventional Retrieval-Augmented Generation (RAG) approaches that rely on extended context windows, our method enables large language models to process texts of any length without the need for truncation. Experiments on standard benchmarks demonstrate that the LGM consistently outperforms existing RAG baselines.
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Hybrid Fact-Checking that Integrates Knowledge Graphs, Large Language Models, and Search-Based Retrieval Agents Improves Interpretable Claim Verification

✇cs.AI, q-bio.NC updates on arXiv.org
By: Shaghayegh Kolli · Richard Rosenbaum · Timo Cavelius · Lasse Strothe · Andrii Lata · Jana Diesner
arXiv:2511.03217v1 Announce Type: cross Abstract: Large language models (LLMs) excel in generating fluent utterances but can lack reliable grounding in verified information. At the same time, knowledge-graph-based fact-checkers deliver precise and interpretable evidence, yet suffer from limited coverage or latency. By integrating LLMs with knowledge graphs and real-time search agents, we introduce a hybrid fact-checking approach that leverages the individual strengths of each component. Our system comprises three autonomous steps: 1) a Knowledge Graph (KG) Retrieval for rapid one - hop lookups in DBpedia, 2) an LM-based classification guided by a task-specific labeling prompt, producing outputs with internal rule-based logic, and 3) a Web Search Agent invoked only when KG coverage is insufficient. Our pipeline achieves an F1 score of 0.93 on the FEVER benchmark on the Supported/Refuted split without task- specific fine - tuning. To address Not enough information cases, we conduct a targeted reannotation study showing that our approach frequently uncovers valid evidence for claims originally labeled as Not Enough Information (NEI), as confirmed by both expert annotators and LLM reviewers. With this paper, we present a modular, opensource fact-checking pipeline with fallback strategies and generalization across datasets.
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Generative Artificial Intelligence in Bioinformatics: A Systematic Review of Models, Applications, and Methodological Advances

✇cs.AI, q-bio.NC updates on arXiv.org
By: Riasad Alvi · Sayeem Been Zaman · Wasimul Karim · Arefin Ittesafun Abian · Mohaimenul Azam Khan Raiaan · Saddam Mukta · Md Rafi Ur Rashid · Md Rafiqul Islam · Yakub Sebastian · Sami Azam
arXiv:2511.03354v1 Announce Type: cross Abstract: Generative artificial intelligence (GenAI) has become a transformative approach in bioinformatics that often enables advancements in genomics, proteomics, transcriptomics, structural biology, and drug discovery. To systematically identify and evaluate these growing developments, this review proposed six research questions (RQs), according to the preferred reporting items for systematic reviews and meta-analysis methods. The objective is to evaluate impactful GenAI strategies in methodological advancement, predictive performance, and specialization, and to identify promising approaches for advanced modeling, data-intensive discovery, and integrative biological analysis. RQ1 highlights diverse applications across multiple bioinformatics subfields (sequence analysis, molecular design, and integrative data modeling), which demonstrate superior performance over traditional methods through pattern recognition and output generation. RQ2 reveals that adapted specialized model architectures outperformed general-purpose models, an advantage attributed to targeted pretraining and context-aware strategies. RQ3 identifies significant benefits in the bioinformatics domains, focusing on molecular analysis and data integration, which improves accuracy and reduces errors in complex analysis. RQ4 indicates improvements in structural modeling, functional prediction, and synthetic data generation, validated by established benchmarks. RQ5 suggests the main constraints, such as the lack of scalability and biases in data that impact generalizability, and proposes future directions focused on robust evaluation and biologically grounded modeling. RQ6 examines that molecular datasets (such as UniProtKB and ProteinNet12), cellular datasets (such as CELLxGENE and GTEx) and textual resources (such as PubMedQA and OMIM) broadly support the training and generalization of GenAI models.
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RAG-IT: Retrieval-Augmented Instruction Tuning for Automated Financial Analysis

✇cs.AI, q-bio.NC updates on arXiv.org
By: Van-Duc Le · Hai-Thien To
arXiv:2412.08179v2 Announce Type: replace-cross Abstract: Financial analysis relies heavily on the interpretation of earnings reports to assess company performance and guide decision-making. Traditional methods for generating such analyses demand significant financial expertise and are often time-consuming. With the rapid advancement of Large Language Models (LLMs), domain-specific adaptations have emerged for financial tasks such as sentiment analysis and entity recognition. This paper introduces RAG-IT (Retrieval-Augmented Instruction Tuning), a novel framework designed to automate the generation of earnings report analyses through an LLM fine-tuned specifically for the financial domain. Our approach integrates retrieval augmentation with instruction-based fine-tuning to enhance factual accuracy, contextual relevance, and domain adaptability. We construct a comprehensive financial instruction dataset derived from extensive financial documents and earnings reports to guide the LLM's adaptation to specialized financial reasoning. Experimental results demonstrate that RAG-IT outperforms general-purpose open-source models and achieves performance comparable to commercial systems like GPT-3.5 on financial report generation tasks. This research highlights the potential of retrieval-augmented instruction tuning to streamline and elevate financial analysis automation, advancing the broader field of intelligent financial reporting.
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REFA: Reference Free Alignment for multi-preference optimization

✇cs.AI, q-bio.NC updates on arXiv.org
By: Taneesh Gupta · Rahul Madhavan · Xuchao Zhang · Chetan Bansal · Saravan Rajmohan
arXiv:2412.16378v4 Announce Type: replace-cross Abstract: To mitigate reward hacking from response verbosity, modern preference optimization methods are increasingly adopting length normalization (e.g., SimPO, ORPO, LN-DPO). While effective against this bias, we demonstrate that length normalization itself introduces a failure mode: the URSLA shortcut. Here models learn to satisfy the alignment objective by prematurely truncating low-quality responses rather than learning from their semantic content. To address this, we introduce REFA, a new alignment framework that proposes probabilistic control on a structural token that controls termination. Our core innovation is a new class of regularizers that operate directly on the probability of the End-of-Sequence (EOS) token, a previously unexploited control lever. This token-level intervention provides a principled solution to the URSLA shortcut, ensuring genuine quality improvements. Furthermore, it unlocks a versatile mechanism for managing the alignment-efficiency tradeoff, enabling practitioners to fine-tune models that adhere to specific token budgets. Empirically, REFA achieves a 60.29% win rate and a 52.17% length-controlled win rate on AlpacaEval2 with Llama-3-8B-Instruct, demonstrating the power of our token-level control paradigm.
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CoTox: Chain-of-Thought-Based Molecular Toxicity Reasoning and Prediction

✇cs.AI, q-bio.NC updates on arXiv.org
By: Jueon Park · Yein Park · Minju Song · Soyon Park · Donghyeon Lee · Seungheun Baek · Jaewoo Kang
arXiv:2508.03159v2 Announce Type: replace-cross Abstract: Drug toxicity remains a major challenge in pharmaceutical development. Recent machine learning models have improved in silico toxicity prediction, but their reliance on annotated data and lack of interpretability limit their applicability. This limits their ability to capture organ-specific toxicities driven by complex biological mechanisms. Large language models (LLMs) offer a promising alternative through step-by-step reasoning and integration of textual data, yet prior approaches lack biological context and transparent rationale. To address this issue, we propose CoTox, a novel framework that integrates LLM with chain-of-thought (CoT) reasoning for multi-toxicity prediction. CoTox combines chemical structure data, biological pathways, and gene ontology (GO) terms to generate interpretable toxicity predictions through step-by-step reasoning. Using GPT-4o, we show that CoTox outperforms both traditional machine learning and deep learning model. We further examine its performance across various LLMs to identify where CoTox is most effective. Additionally, we find that representing chemical structures with IUPAC names, which are easier for LLMs to understand than SMILES, enhances the model's reasoning ability and improves predictive performance. To demonstrate its practical utility in drug development, we simulate the treatment of relevant cell types with drug and incorporated the resulting biological context into the CoTox framework. This approach allow CoTox to generate toxicity predictions aligned with physiological responses, as shown in case study. This result highlights the potential of LLM-based frameworks to improve interpretability and support early-stage drug safety assessment. The code and prompt used in this work are available at https://github.com/dmis-lab/CoTox.
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Evaluating Large Language Models for Detecting Antisemitism

✇cs.AI, q-bio.NC updates on arXiv.org
By: Jay Patel · Hrudayangam Mehta · Jeremy Blackburn
arXiv:2509.18293v2 Announce Type: replace-cross Abstract: Detecting hateful content is a challenging and important problem. Automated tools, like machine-learning models, can help, but they require continuous training to adapt to the ever-changing landscape of social media. In this work, we evaluate eight open-source LLMs' capability to detect antisemitic content, specifically leveraging in-context definition. We also study how LLMs understand and explain their decisions given a moderation policy as a guideline. First, we explore various prompting techniques and design a new CoT-like prompt, Guided-CoT, and find that injecting domain-specific thoughts increases performance and utility. Guided-CoT handles the in-context policy well, improving performance and utility by reducing refusals across all evaluated models, regardless of decoding configuration, model size, or reasoning capability. Notably, Llama 3.1 70B outperforms fine-tuned GPT-3.5. Additionally, we examine LLM errors and introduce metrics to quantify semantic divergence in model-generated rationales, revealing notable differences and paradoxical behaviors among LLMs. Our experiments highlight the differences observed across LLMs' utility, explainability, and reliability. Code and resources available at: https://github.com/idramalab/quantify-llm-explanations
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Site-specific DNA insertion into the human genome with engineered recombinases

✇Nature Biotechnology - Issue - nature.com science feeds
By: Alison Fanton · Liam J. Bartie · Juliana Q. Martins · Vincent Q. Tran · Laine Goudy · Courtney Kernick · Matthew G. Durrant · Jingyi Wei · Zev Armour-Garb · April Pawluk · Silvana Konermann · Alexander Marson · Luke A. Gilbert · Theodore L. Roth · Patrick D. Hsu

Nature Biotechnology, Published online: 06 November 2025; doi:10.1038/s41587-025-02895-3

Engineered DNA recombinases efficiently and specifically insert genetic cargos without the use of landing pads.
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STAT+: What’s FDA plotting for therapy chatbot regulation?

✇STAT
By: Mario Aguilar

You’re reading the web edition of STAT’s Health Tech newsletter, our guide to how technology is transforming the life sciences. Sign up to get it delivered in your inbox every Tuesday and Thursday.

What to know about the FDA’s therapy bots meeting

The Food and Drug Administration is considering whether and how to regulate therapy chatbots that are based on large language models. Today, the agency’s Digital Health Advisory Committee is meeting to consider the topic. In a new story, I explain what’s going on, including some fresh insider intel.

The FDA wants to provide more clarity to developers of generative AI medical devices about what needs regulatory green light and how to get it. The agency is also also worried about LLM-based therapy bots that can provide unpredictable outputs. Regulators are aware about the growing concerns around general purpose bots like ChatGPT, which have been linked to delusions and allegedly to suicides.

Continue to STAT+ to read the full story…

© Sarah Silbiger/Getty Images

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Harnessing multi-omics approaches to decipher tumor evolution and improve diagnosis and therapy in lung cancer

✇Omics In Lung
By: Yicong Cheng · Ling Bai · Jiuwei Cui

Biomark Res. 2025 Nov 5;13(1):140. doi: 10.1186/s40364-025-00859-y.

ABSTRACT

With the advancement of novel technologies such as whole-genome sequencing, single-cell sequencing, and spatial transcriptomics, single-omics analyses have already promoted the research of tumorigenesis as well as development and have partly elucidated the evolutionary processes of lung cancer. However, it is still difficult to distinguish these confounding features via single dimensional approaches due to the complexity, heterogeneity and cell-cell interactions with the immune microenvironment in lung cancer. Multi-omics approaches provide a holistic framework for constructing detailed tumor ecosystem landscapes, thereby facilitating the development of a more robust classification system for precision diagnosis and treatment, and aiding in the discovery of novel cancer biomarkers. In this review, we summarize the potential and applications of multi-omics approaches in characterizing intratumor heterogeneity and the tumor microenvironment throughout the course of lung cancer development. By further discussing the discovery and application of diagnostic and therapeutic biomarkers across precancerous lesions, early-stage lung cancer, tumor progression, metastasis, and therapy resistance, we outline the current challenges and future prospects of using multi-omics to identify reliable biomarkers. Moreover, we emphasize that integrative multi-omics models hold great promise for elucidating the complex interactions within the lung cancer ecosystem, thereby contributing to improved diagnostic accuracy, optimized therapeutic strategies, and better patient outcomes.

PMID:41194170 | PMC:PMC12590604 | DOI:10.1186/s40364-025-00859-y

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Improving dataset transparency in dermatologic Artificial Intelligence using a dataset nutrition label

✇npj Digital Medicine
By: Yingjoy Li · Matthew Taylor · Kasia S. Chmielinski · Allan C. Halpern · Roxana Daneshjou · Jenna C. Lester · Veronica Rotemberg

npj Digital Medicine, Published online: 05 November 2025; doi:10.1038/s41746-025-02125-9

Biased and poorly documented dermatology datasets pose risks to the development of safe and generalizable artificial intelligence (AI) tools. We created a Dataset Nutrition Label (DNL) for multiple dermatology datasets to support transparent and responsible data use. The DNL offers a structured, digestible summary of key attributes, including metadata, limitations, and risks, enabling data users to better assess suitability and proactively address potential sources of bias in datasets.
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Evaluating clinical AI summaries with large language models as judges

✇npj Digital Medicine
By: Emma Croxford · Yanjun Gao · Elliot First · Nicholas Pellegrino · Miranda Schnier · John Caskey · Madeline Oguss · Graham Wills · Guanhua Chen · Dmitriy Dligach · Matthew M. Churpek · Anoop Mayampurath · Frank Liao · Cherodeep Goswami · Karen K. Wong · Brian W. Patterson · Majid Afshar

npj Digital Medicine, Published online: 05 November 2025; doi:10.1038/s41746-025-02005-2

Evaluating clinical AI summaries with large language models as judges
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Liquid biopsy in gastrointestinal oncology: clinical applications and translational integration of ctDNA, CTCs, and sEVs

✇MRD
By: Rita Palieri · Maria De Luca · Francesco Balestra · Giorgia Panzetta · Claudio Lotesoriere · Federica Rizzi · Angela Dalia Ricci · Rita Mastrogiacomo · Maria Lucia Curri · Luigi Andrea Laghi · Gianluigi Giannelli · Nicoletta Depalo · Maria Principia Scavo

Oncol Rev. 2025 Oct 20;19:1702932. doi: 10.3389/or.2025.1702932. eCollection 2025.

ABSTRACT

BACKGROUND AND AIMS: Liquid biopsy offers a minimally invasive tool to detect actionable mutations, monitor minimal residual disease (MRD), and guide therapy in gastrointestinal (GI) cancers. We critically review the clinical utility of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and small extracellular vesicles (sEVs) across GI malignancies and propose a framework for their integration into clinical practice.

METHODS: We synthesized evidence from over 200 studies, including prospective trials and translational research, to assess diagnostic accuracy, prognostic value, and clinical actionability of each biomarker type in esophageal, gastric, colorectal, pancreatic, hepatocellular, and biliary cancers.

RESULTS: ctDNA has shown strong potential for MRD detection and treatment monitoring, particularly in colorectal and pancreatic cancer. CTCs offer insights into metastatic risk and therapeutic resistance, while sEVs provide molecular cargo relevant to immunomodulation and disease progression. Emerging microfluidics and AI-driven multi-omics approaches may overcome current limitations.

CONCLUSION: The integration of liquid biopsy technologies into GI oncology holds promise for early detection and precision therapy. We propose a five-phase clinical roadmap and outine the key research gaps that need to be addressed before widespread implementation in routine care.

PMID:41190015 | PMC:PMC12580207 | DOI:10.3389/or.2025.1702932

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