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.

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.

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

Background: The COVID-19 pandemic has intensified mental health issues globally, highlighting the urgent need for remote mental health monitoring. Digital phenotyping using smart devices has emerged as a promising approach, but it remains unclear which features are essential for predicting depression and anxiety. Objective: This systematic review aimed to identify the types of features collected through smart packages—integrated systems combining smartphones with wearable devices such as Actiwatches, smartbands, and smartwatches—and to determine which features should be considered essential for mental health monitoring based on the type of device used. Methods: A systematic review was conducted. Searches were performed across Web of Science, PubMed, and Scopus on February 5, 2025. Inclusion criteria comprised quantitative studies involving adults (≥19 years) using smart devices to predict depression or anxiety based on passive data collection. Studies focusing solely on smartphones or qualitative designs were excluded. Risk of bias was assessed using the Mixed Methods Appraisal Tool and Quality Criteria Checklist. Data were synthesized descriptively, and the relative contribution of each feature was further assessed by calculating coverage (proportion of studies using a feature) and importance among used (proportion identifying it as important when used). These metrics were visualized in quadrant-based scatter plots to identify consistently important features across devices. Results: From 1,382 records, 22 studies across 11 countries were included. The overall synthesis identified a core feature package—accelerometer (ACC), steps, Heart Rate (HR), and sleep. Device-specific analyses revealed further nuances: In Actiwatch studies, ACC and activity were consistently important, but sleep features were rarely examined. In smartbands, HR, steps, sleep, and phone usage were essential, while Global Positioning System (GPS), Electrodermal Activity (EDA), and skin temperature (TEMP) showed high importance when used, suggesting opportunities for broader adoption. In smartwatch studies, sleep and HR emerged as core features, whereas steps and ACC were widely used but often not identified as important. Conclusions: This systematic review identified a core feature package comprising ACC, steps, HR, and sleep that consistently contributes to mood disorder prediction across devices. At the same time, device-specific differences were observed: Actiwatch studies mainly emphasized ACC and activity but underutilized sleep features; smartbands highlighted HR, steps, sleep, and phone usage, with EDA, TEMP, and GPS showing additional promise; and smartwatches most reliably leveraged sleep and HR, while steps and ACC were widely used yet less effective. These findings suggest that while a shared core set of features exists, optimizing digital phenotyping requires tailoring feature selection to the characteristics of each device type. To advance this field, improving data accessibility, particularly in smartwatch ecosystems, and adopting standardized reporting frameworks will be essential to enhance comparability, reproducibility, and future meta-analytic integration. Clinical Trial: Open Science Framework https://osf.io/nz7k8

Nature, Published online: 05 November 2025; doi:10.1038/s41586-025-09716-2

The Fair Human-Centric Image Benchmark (FHIBE, pronounced ‘Feebee’)—an image dataset that implements best practices for consent, privacy, compensation, safety, diversity and utility—can be used responsibly as a fairness evaluation dataset for many human-centric computer vision applications.

arXiv:2511.02752v1 Announce Type: cross Abstract: Artificial intelligence (AI) is diffusing globally at unprecedented speed, but adoption remains uneven. Frontier Large Language Models (LLMs) are known to perform poorly on low-resource languages due to data scarcity. We hypothesize that this performance deficit reduces the utility of AI, thereby slowing adoption in Low-Resource Language Countries (LRLCs). To test this, we use a weighted regression model to isolate the language effect from socioeconomic and demographic factors, finding that LRLCs have a share of AI users that is approximately 20% lower relative to their baseline. These results indicate that linguistic accessibility is a significant, independent barrier to equitable AI diffusion.

arXiv:2510.09801v2 Announce Type: replace Abstract: LLM-powered agents are both a promising new technology and a source of complexity, where choices about models, tools, and prompting can affect their usefulness. While numerous benchmarks measure agent accuracy across domains, they mostly assume full automation, failing to represent the collaborative nature of real-world use cases. In this paper, we make two major steps towards the rigorous assessment of human-agent interactions. First, we propose PULSE, a framework for more efficient human-centric evaluation of agent designs, which comprises collecting user feedback, training an ML model to predict user satisfaction, and computing results by combining human satisfaction ratings with model-generated pseudo-labels. Second, we deploy the framework on a large-scale web platform built around the open-source software agent OpenHands, collecting in-the-wild usage data across over 15k users. We conduct case studies around how three agent design decisions -- choice of LLM backbone, planning strategy, and memory mechanisms -- impact developer satisfaction rates, yielding practical insights for software agent design. We also show how our framework can lead to more robust conclusions about agent design, reducing confidence intervals by 40% compared to a standard A/B test. Finally, we find substantial discrepancies between in-the-wild results and benchmark performance (e.g., the anti-correlation between results comparing claude-sonnet-4 and gpt-5), underscoring the limitations of benchmark-driven evaluation. Our findings provide guidance for evaluations of LLM agents with humans and identify opportunities for better agent designs.

Generative artificial intelligence (GenAI) enables the production of coherent and contextually relevant text by processing large-scale linguistic datasets. Tools such as ChatGPT, Gemini, Claude, and LLaMA are increasingly integrated into medical education, assisting students with a range of tasks, including clinical reasoning, literature review, scientific writing, and formative assessment. Although these tools offer significant advantages in terms of productivity, personalization, and cognitive support, their impact on critical thinking—a cornerstone of medical education—remains uncertain. The aim of this viewpoint paper is to critically assess the influence of GenAI on critical thinking within medical training, examining both its potential to enhance cognitive skills and the risks it poses to cognitive autonomy. Users have reported increased efficiency and improved linguistic output; however, concerns have also been raised regarding the risk of cognitive overreliance. Current evidence presents a mixed picture, indicating both improvements in learner engagement and potential drawbacks such as passivity or susceptibility to misinformation. Without curricular integration that prioritizes ethical use, prompt engineering, and critical evaluation, GenAI may compromise the cognitive autonomy of medical students. Conversely, when thoughtfully embedded into pedagogical frameworks, these tools can act as cognitive enhancers—supporting, rather than replacing, clinical reasoning. Medical education must adapt to ensure that future physicians engage with GenAI in a critical, ethical, and context-aware manner, especially in complex decision-making scenarios. This transformation demands not only technological fluency but also reflective practice and sustained oversight by faculty and academic institutions.

arXiv:2510.26887v1 Announce Type: new Abstract: We present Denario, an AI multi-agent system designed to serve as a scientific research assistant. Denario can perform many different tasks, such as generating ideas, checking the literature, developing research plans, writing and executing code, making plots, and drafting and reviewing a scientific paper. The system has a modular architecture, allowing it to handle specific tasks, such as generating an idea, or carrying out end-to-end scientific analysis using Cmbagent as a deep-research backend. In this work, we describe in detail Denario and its modules, and illustrate its capabilities by presenting multiple AI-generated papers generated by it in many different scientific disciplines such as astrophysics, biology, biophysics, biomedical informatics, chemistry, material science, mathematical physics, medicine, neuroscience and planetary science. Denario also excels at combining ideas from different disciplines, and we illustrate this by showing a paper that applies methods from quantum physics and machine learning to astrophysical data. We report the evaluations performed on these papers by domain experts, who provided both numerical scores and review-like feedback. We then highlight the strengths, weaknesses, and limitations of the current system. Finally, we discuss the ethical implications of AI-driven research and reflect on how such technology relates to the philosophy of science. We publicly release the code at https://github.com/AstroPilot-AI/Denario. A Denario demo can also be run directly on the web at https://huggingface.co/spaces/astropilot-ai/Denario, and the full app will be deployed on the cloud.

arXiv:2510.27009v1 Announce Type: new Abstract: Language models are traditionally designed around causal masking. In domains with spatial or relational structure, causal masking is often viewed as inappropriate, and sequential linearizations are instead used. Yet the question of whether it is viable to accept the information loss introduced by causal masking on nonsequential data has received little direct study, in part because few domains offer both spatial and sequential representations of the same dataset. In this work, we investigate this issue in the domain of chess, which naturally supports both representations. We train language models with bidirectional and causal self-attention mechanisms on both spatial (board-based) and sequential (move-based) data. Our results show that models trained on spatial board states - \textit{even with causal masking} - consistently achieve stronger playing strength than models trained on sequential data. While our experiments are conducted on chess, our results are methodological and may have broader implications: applying causal masking to spatial data is a viable procedure for training unimodal LLMs on spatial data, and in some domains is even preferable to sequentialization.

arXiv:2510.27051v1 Announce Type: new Abstract: Enterprise AI agents must continuously adapt to maintain accuracy, reduce latency, and remain aligned with user needs. We present a practical implementation of a data flywheel in NVInfo AI, NVIDIA's Mixture-of-Experts (MoE) Knowledge Assistant serving over 30,000 employees. By operationalizing a MAPE-driven data flywheel, we built a closed-loop system that systematically addresses failures in retrieval-augmented generation (RAG) pipelines and enables continuous learning. Over a 3-month post-deployment period, we monitored feedback and collected 495 negative samples. Analysis revealed two major failure modes: routing errors (5.25\%) and query rephrasal errors (3.2\%). Using NVIDIA NeMo microservices, we implemented targeted improvements through fine-tuning. For routing, we replaced a Llama 3.1 70B model with a fine-tuned 8B variant, achieving 96\% accuracy, a 10x reduction in model size, and 70\% latency improvement. For query rephrasal, fine-tuning yielded a 3.7\% gain in accuracy and a 40\% latency reduction. Our approach demonstrates how human-in-the-loop (HITL) feedback, when structured within a data flywheel, transforms enterprise AI agents into self-improving systems. Key learnings include approaches to ensure agent robustness despite limited user feedback, navigating privacy constraints, and executing staged rollouts in production. This work offers a repeatable blueprint for building robust, adaptive enterprise AI agents capable of learning from real-world usage at scale.

arXiv:2510.27353v1 Announce Type: new Abstract: Recent studies have suggested that Large Language Models (LLMs) could provide interesting ideas contributing to mathematical discovery. This claim was motivated by reports that LLM-based genetic algorithms produced heuristics offering new insights into the online bin packing problem under uniform and Weibull distributions. In this work, we reassess this claim through a detailed analysis of the heuristics produced by LLMs, examining both their behavior and interpretability. Despite being human-readable, these heuristics remain largely opaque even to domain experts. Building on this analysis, we propose a new class of algorithms tailored to these specific bin packing instances. The derived algorithms are significantly simpler, more efficient, more interpretable, and more generalizable, suggesting that the considered instances are themselves relatively simple. We then discuss the limitations of the claim regarding LLMs' contribution to this problem, which appears to rest on the mistaken assumption that the instances had previously been studied. Our findings instead emphasize the need for rigorous validation and contextualization when assessing the scientific value of LLM-generated outputs.

arXiv:2510.27629v1 Announce Type: cross Abstract: Open-weight bio-foundation models present a dual-use dilemma. While holding great promise for accelerating scientific research and drug development, they could also enable bad actors to develop more deadly bioweapons. To mitigate the risk posed by these models, current approaches focus on filtering biohazardous data during pre-training. However, the effectiveness of such an approach remains unclear, particularly against determined actors who might fine-tune these models for malicious use. To address this gap, we propose \eval, a framework to evaluate the robustness of procedures that are intended to reduce the dual-use capabilities of bio-foundation models. \eval assesses models' virus understanding through three lenses, including sequence modeling, mutational effects prediction, and virulence prediction. Our results show that current filtering practices may not be particularly effective: Excluded knowledge can be rapidly recovered in some cases via fine-tuning, and exhibits broader generalizability in sequence modeling. Furthermore, dual-use signals may already reside in the pretrained representations, and can be elicited via simple linear probing. These findings highlight the challenges of data filtering as a standalone procedure, underscoring the need for further research into robust safety and security strategies for open-weight bio-foundation models.

arXiv:2510.25908v1 Announce Type: new Abstract: Large language models (LLMs) have demonstrated transformative potential in scientific research, yet their deployment in high-stakes contexts raises significant trustworthiness concerns. Here, we introduce SciTrust 2.0, a comprehensive framework for evaluating LLM trustworthiness in scientific applications across four dimensions: truthfulness, adversarial robustness, scientific safety, and scientific ethics. Our framework incorporates novel, open-ended truthfulness benchmarks developed through a verified reflection-tuning pipeline and expert validation, alongside a novel ethics benchmark for scientific research contexts covering eight subcategories including dual-use research and bias. We evaluated seven prominent LLMs, including four science-specialized models and three general-purpose industry models, using multiple evaluation metrics including accuracy, semantic similarity measures, and LLM-based scoring. General-purpose industry models overall outperformed science-specialized models across each trustworthiness dimension, with GPT-o4-mini demonstrating superior performance in truthfulness assessments and adversarial robustness. Science-specialized models showed significant deficiencies in logical and ethical reasoning capabilities, along with concerning vulnerabilities in safety evaluations, particularly in high-risk domains such as biosecurity and chemical weapons. By open-sourcing our framework, we provide a foundation for developing more trustworthy AI systems and advancing research on model safety and ethics in scientific contexts.

arXiv:2510.25992v1 Announce Type: cross Abstract: Large Language Models (LLMs) often struggle with problems that require multi-step reasoning. For small-scale open-source models, Reinforcement Learning with Verifiable Rewards (RLVR) fails when correct solutions are rarely sampled even after many attempts, while Supervised Fine-Tuning (SFT) tends to overfit long demonstrations through rigid token-by-token imitation. To address this gap, we propose Supervised Reinforcement Learning (SRL), a framework that reformulates problem solving as generating a sequence of logical "actions". SRL trains the model to generate an internal reasoning monologue before committing to each action. It provides smoother rewards based on the similarity between the model's actions and expert actions extracted from the SFT dataset in a step-wise manner. This supervision offers richer learning signals even when all rollouts are incorrect, while encouraging flexible reasoning guided by expert demonstrations. As a result, SRL enables small models to learn challenging problems previously unlearnable by SFT or RLVR. Moreover, initializing training with SRL before refining with RLVR yields the strongest overall performance. Beyond reasoning benchmarks, SRL generalizes effectively to agentic software engineering tasks, establishing it as a robust and versatile training framework for reasoning-oriented LLMs.

arXiv:2510.26151v1 Announce Type: cross Abstract: Large annotated datasets are essential for training robust Computer-Aided Diagnosis (CAD) models for breast cancer detection or risk prediction. However, acquiring such datasets with fine-detailed annotation is both costly and time-consuming. Vision-Language Models (VLMs), such as CLIP, which are pre-trained on large image-text pairs, offer a promising solution by enhancing robustness and data efficiency in medical imaging tasks. This paper introduces a novel Multi-View Mammography and Language Model for breast cancer classification and risk prediction, trained on a dataset of paired mammogram images and synthetic radiology reports. Our MV-MLM leverages multi-view supervision to learn rich representations from extensive radiology data by employing cross-modal self-supervision across image-text pairs. This includes multiple views and the corresponding pseudo-radiology reports. We propose a novel joint visual-textual learning strategy to enhance generalization and accuracy performance over different data types and tasks to distinguish breast tissues or cancer characteristics(calcification, mass) and utilize these patterns to understand mammography images and predict cancer risk. We evaluated our method on both private and publicly available datasets, demonstrating that the proposed model achieves state-of-the-art performance in three classification tasks: (1) malignancy classification, (2) subtype classification, and (3) image-based cancer risk prediction. Furthermore, the model exhibits strong data efficiency, outperforming existing fully supervised or VLM baselines while trained on synthetic text reports and without the need for actual radiology reports.

arXiv:2410.14879v4 Announce Type: replace-cross Abstract: Passive tracking methods, such as phone and wearable sensing, have become dominant in monitoring human behaviors in modern ubiquitous computing studies. While there have been significant advances in machine-learning approaches to translate periods of raw sensor data to model momentary behaviors, (e.g., physical activity recognition), there still remains a significant gap in the translation of these sensing streams into meaningful, high-level, context-aware insights that are required for various applications (e.g., summarizing an individual's daily routine). To bridge this gap, experts often need to employ a context-driven sensemaking process in real-world studies to derive insights. This process often requires manual effort and can be challenging even for experienced researchers due to the complexity of human behaviors. We conducted three rounds of user studies with 21 experts to explore solutions to address challenges with sensemaking. We follow a human-centered design process to identify needs and design, iterate, build, and evaluate Vital Insight (VI), a novel, LLM-assisted, prototype system to enable human-in-the-loop inference (sensemaking) and visualizations of multi-modal passive sensing data from smartphones and wearables. Using the prototype as a technology probe, we observe experts' interactions with it and develop an expert sensemaking model that explains how experts move between direct data representations and AI-supported inferences to explore, question, and validate insights. Through this iterative process, we also synthesize and discuss a list of design implications for the design of future AI-augmented visualization systems to better assist experts' sensemaking processes in multi-modal health sensing data.

Nature, Published online: 29 October 2025; doi:10.1038/s41586-025-09686-5

This multi-omic longitudinal analysis of the healthy human peripheral immune system constructs the Human Immune Health Atlas and assembles data on immune cell composition and state changes with age, including responses to cytomegalovirus infection and influenza vaccination.

arXiv:2510.24528v1 Announce Type: new Abstract: The capability of in-context learning (ICL) enables large language models (LLMs) to perform novel tasks without parameter updates by conditioning on a few input-output examples. However, collecting high-quality examples for new or challenging tasks can be costly and labor-intensive. In this work, we propose a cost-efficient two-stage pipeline that reduces reliance on LLMs for data labeling. Our approach first leverages readily available cross-task examples to prompt an LLM and pseudo-label a small set of target task instances. We then introduce a graph-based label propagation method that spreads label information to the remaining target examples without additional LLM queries. The resulting fully pseudo-labeled dataset is used to construct in-task demonstrations for ICL. This pipeline combines the flexibility of cross-task supervision with the scalability of LLM-free propagation. Experiments across five tasks demonstrate that our method achieves strong performance while lowering labeling costs.

arXiv:2510.24701v1 Announce Type: cross Abstract: We present Tongyi DeepResearch, an agentic large language model, which is specifically designed for long-horizon, deep information-seeking research tasks. To incentivize autonomous deep research agency, Tongyi DeepResearch is developed through an end-to-end training framework that combines agentic mid-training and agentic post-training, enabling scalable reasoning and information seeking across complex tasks. We design a highly scalable data synthesis pipeline that is fully automatic, without relying on costly human annotation, and empowers all training stages. By constructing customized environments for each stage, our system enables stable and consistent interactions throughout. Tongyi DeepResearch, featuring 30.5 billion total parameters, with only 3.3 billion activated per token, achieves state-of-the-art performance across a range of agentic deep research benchmarks, including Humanity's Last Exam, BrowseComp, BrowseComp-ZH, WebWalkerQA, xbench-DeepSearch, FRAMES and xbench-DeepSearch-2510. We open-source the model, framework, and complete solutions to empower the community.