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The Evaluation Gap in Medicine, AI and LLMs: Navigating Elusive Ground Truth & Uncertainty via a Probabilistic Paradigm

arXiv:2601.05500v1 Announce Type: new Abstract: Benchmarking the relative capabilities of AI systems, including Large Language Models (LLMs) and Vision Models, typically ignores the impact of uncertainty in the underlying ground truth answers from experts. This ambiguity is particularly consequential in medicine where uncertainty is pervasive. In this paper, we introduce a probabilistic paradigm to theoretically explain how high certainty in ground truth answers is almost always necessary for even an expert to achieve high scores, whereas in datasets with high variation in ground truth answers there may be little difference between a random labeller and an expert. Therefore, ignoring uncertainty in ground truth evaluation data can result in the misleading conclusion that a non-expert has similar performance to that of an expert. Using the probabilistic paradigm, we thus bring forth the concepts of expected accuracy and expected F1 to estimate the score an expert human or system can achieve given ground truth answer variability. Our work leads to the recommendation that when establishing the capability of a system, results should be stratified by probability of the ground truth answer, typically measured by the agreement rate of ground truth experts. Stratification becomes critical when the overall performance drops below a threshold of 80%. Under stratified evaluation, performance comparison becomes more reliable in high certainty bins, mitigating the effect of the key confounding factor -- uncertainty.
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A Survey of Agentic AI and Cybersecurity: Challenges, Opportunities and Use-case Prototypes

arXiv:2601.05293v1 Announce Type: cross Abstract: Agentic AI marks an important transition from single-step generative models to systems capable of reasoning, planning, acting, and adapting over long-lasting tasks. By integrating memory, tool use, and iterative decision cycles, these systems enable continuous, autonomous workflows in real-world environments. This survey examines the implications of agentic AI for cybersecurity. On the defensive side, agentic capabilities enable continuous monitoring, autonomous incident response, adaptive threat hunting, and fraud detection at scale. Conversely, the same properties amplify adversarial power by accelerating reconnaissance, exploitation, coordination, and social-engineering attacks. These dual-use dynamics expose fundamental gaps in existing governance, assurance, and accountability mechanisms, which were largely designed for non-autonomous and short-lived AI systems. To address these challenges, we survey emerging threat models, security frameworks, and evaluation pipelines tailored to agentic systems, and analyze systemic risks including agent collusion, cascading failures, oversight evasion, and memory poisoning. Finally, we present three representative use-case implementations that illustrate how agentic AI behaves in practical cybersecurity workflows, and how design choices shape reliability, safety, and operational effectiveness.
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Personalizing Treatment for Pancreatic Ductal Adenocarcinoma: The Emerging Role of Minimal Residual Disease in Perioperative Decision-Making

Cancers (Basel). 2025 Dec 27;18(1):94. doi: 10.3390/cancers18010094.

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with poor long-term survival despite advances in surgical techniques, systemic therapies, and perioperative management. High rates of systemic recurrence following curative-intent resection suggest that many patients harbor minimal residual disease (MRD), microscopic tumor burden that persists postoperatively and remains undetectable by conventional diagnostic tools. Recent advances in liquid biopsy technologies, particularly circulating tumor DNA (ctDNA) analysis, alongside detailed characterization of the PDAC mutational landscape, offer a promising non-invasive approach for MRD detection. Emerging evidence indicates that MRD status can serve as a sensitive prognostic biomarker, identify patients at high risk of relapse, and guide personalized perioperative therapy, including optimization of adjuvant treatment. This review summarizes current knowledge on the biology and detection of MRD in PDAC, its implications for perioperative risk stratification and treatment decision-making, and discusses future directions for integrating MRD assessment into clinical practice to enable more precise, individualized patient management.

PMID:41514607 | PMC:PMC12784771 | DOI:10.3390/cancers18010094

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BCMA-directed mRNA CAR-T cell therapy for myasthenia gravis: exploratory biomarker analysis of a placebo-controlled phase 2b trial

Nature Medicine, Published online: 09 January 2026; doi:10.1038/s41591-025-04170-z

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.
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BCMA-directed mRNA CAR T cell therapy for myasthenia gravis: a randomized, double-blind, placebo-controlled phase 2b trial

Nature Medicine, Published online: 09 January 2026; doi:10.1038/s41591-025-04171-y

In a randomized, double-blind, placebo-controlled trial comparing autologous mRNA-engineered BCMA-targeting CAR T cell therapy versus placebo in patients with generalized myasthenia gravis, a significantly higher percentage of patients exhibited a reduction in disease activity in the treatment arm than in the placebo arm.
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Sci-Reasoning: A Dataset Decoding AI Innovation Patterns

arXiv:2601.04577v1 Announce Type: new Abstract: While AI innovation accelerates rapidly, the intellectual process behind breakthroughs -- how researchers identify gaps, synthesize prior work, and generate insights -- remains poorly understood. The lack of structured data on scientific reasoning hinders systematic analysis and development of AI research agents. We introduce Sci-Reasoning, the first dataset capturing the intellectual synthesis behind high-quality AI research. Using community-validated quality signals and an LLM-accelerated, human-verified pipeline, we trace Oral and Spotlight papers across NeurIPS, ICML, and ICLR (2023-2025) to its key predecessors, articulating specific reasoning links in a structured format. Our analysis identifies 15 distinct thinking patterns, with three dominant strategies accounting for 52.7%: Gap-Driven Reframing (24.2%), Cross-Domain Synthesis (18.0%), and Representation Shift (10.5%). The most powerful innovation recipes combine multiple patterns: Gap-Driven Reframing + Representation Shift, Cross-Domain Synthesis + Representation Shift, and Gap-Driven Reframing + Cross-Domain Synthesis. This dataset enables quantitative studies of scientific progress and provides structured reasoning trajectories for training the next generation AI research agents.
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Beyond Monolithic Architectures: A Multi-Agent Search and Knowledge Optimization Framework for Agentic Search

arXiv:2601.04703v1 Announce Type: new Abstract: Agentic search has emerged as a promising paradigm for complex information seeking by enabling Large Language Models (LLMs) to interleave reasoning with tool use. However, prevailing systems rely on monolithic agents that suffer from structural bottlenecks, including unconstrained reasoning outputs that inflate trajectories, sparse outcome-level rewards that complicate credit assignment, and stochastic search noise that destabilizes learning. To address these challenges, we propose \textbf{M-ASK} (Multi-Agent Search and Knowledge), a framework that explicitly decouples agentic search into two complementary roles: Search Behavior Agents, which plan and execute search actions, and Knowledge Management Agents, which aggregate, filter, and maintain a compact internal context. This decomposition allows each agent to focus on a well-defined subtask and reduces interference between search and context construction. Furthermore, to enable stable coordination, M-ASK employs turn-level rewards to provide granular supervision for both search decisions and knowledge updates. Experiments on multi-hop QA benchmarks demonstrate that M-ASK outperforms strong baselines, achieving not only superior answer accuracy but also significantly more stable training dynamics.\footnote{The source code for M-ASK is available at https://github.com/chenyiqun/M-ASK.}
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Balancing Usability and Compliance in AI Smart Devices: A Privacy-by-Design Audit of Google Home, Alexa, and Siri

arXiv:2601.04403v1 Announce Type: cross Abstract: This paper investigates the privacy and usability of AI-enabled smart devices commonly used by youth, focusing on Google Home Mini, Amazon Alexa, and Apple Siri. While these devices provide convenience and efficiency, they also raise privacy and transparency concerns due to their always-listening design and complex data management processes. The study proposes and applies a combined framework of Heuristic Evaluation, Personal Information Protection and Electronic Documents Act (PIPEDA) Compliance Assessment, and Youth-Centered Usability Testing to assess whether these devices align with Privacy-by-Design principles and support meaningful user control. Results show that Google Home achieved the highest usability score, while Siri scored highest in regulatory compliance, indicating a trade-off between user convenience and privacy protection. Alexa demonstrated clearer task navigation but weaker transparency in data retention. Findings suggest that although youth may feel capable of managing their data, their privacy self-efficacy remains limited by technical design, complex settings, and unclear data policies. The paper concludes that enhancing transparency, embedding privacy guidance during onboarding, and improving policy alignment are critical steps toward ensuring that smart devices are both usable and compliant with privacy standards that protect young users.
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Fast Mining and Dynamic Time-to-Event Prediction over Multi-sensor Data Streams

arXiv:2601.04741v1 Announce Type: cross Abstract: Given real-time sensor data streams obtained from machines, how can we continuously predict when a machine failure will occur? This work aims to continuously forecast the timing of future events by analyzing multi-sensor data streams. A key characteristic of real-world data streams is their dynamic nature, where the underlying patterns evolve over time. To address this, we present TimeCast, a dynamic prediction framework designed to adapt to these changes and provide accurate, real-time predictions of future event time. Our proposed method has the following properties: (a) Dynamic: it identifies the distinct time-evolving patterns (i.e., stages) and learns individual models for each, enabling us to make adaptive predictions based on pattern shifts. (b) Practical: it finds meaningful stages that capture time-varying interdependencies between multiple sensors and improve prediction performance; (c) Scalable: our algorithm scales linearly with the input size and enables online model updates on data streams. Extensive experiments on real datasets demonstrate that TimeCast provides higher prediction accuracy than state-of-the-art methods while finding dynamic changes in data streams with a great reduction in computational time.
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Smart IoT-Based Wearable Device for Detection and Monitoring of Common Cow Diseases Using a Novel Machine Learning Technique

arXiv:2601.04761v1 Announce Type: cross Abstract: Manual observation and monitoring of individual cows for disease detection present significant challenges in large-scale farming operations, as the process is labor-intensive, time-consuming, and prone to reduced accuracy. The reliance on human observation often leads to delays in identifying symptoms, as the sheer number of animals can hinder timely attention to each cow. Consequently, the accuracy and precision of disease detection are significantly compromised, potentially affecting animal health and overall farm productivity. Furthermore, organizing and managing human resources for the manual observation and monitoring of cow health is a complex and economically demanding task. It necessitates the involvement of skilled personnel, thereby contributing to elevated farm maintenance costs and operational inefficiencies. Therefore, the development of an automated, low-cost, and reliable smart system is essential to address these challenges effectively. Although several studies have been conducted in this domain, very few have simultaneously considered the detection of multiple common diseases with high prediction accuracy. However, advancements in Internet of Things (IoT), Machine Learning (ML), and Cyber-Physical Systems have enabled the automation of cow health monitoring with enhanced accuracy and reduced operational costs. This study proposes an IoT-enabled Cyber-Physical System framework designed to monitor the daily activities and health status of cow. A novel ML algorithm is proposed for the diagnosis of common cow diseases using collected physiological and behavioral data. The algorithm is designed to predict multiple diseases by analyzing a comprehensive set of recorded physiological and behavioral features, enabling accurate and efficient health assessment.
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Atlas 2 -- Foundation models for clinical deployment

arXiv:2601.05148v1 Announce Type: cross Abstract: Pathology foundation models substantially advanced the possibilities in computational pathology -- yet tradeoffs in terms of performance, robustness, and computational requirements remained, which limited their clinical deployment. In this report, we present Atlas 2, Atlas 2-B, and Atlas 2-S, three pathology vision foundation models which bridge these shortcomings by showing state-of-the-art performance in prediction performance, robustness, and resource efficiency in a comprehensive evaluation across eighty public benchmarks. Our models were trained on the largest pathology foundation model dataset to date comprising 5.5 million histopathology whole slide images, collected from three medical institutions Charit\'e - Universt\"atsmedizin Berlin, LMU Munich, and Mayo Clinic.
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A Framework for Responsible AI Systems: Building Societal Trust through Domain Definition, Trustworthy AI Design, Auditability, Accountability, and Governance

arXiv:2503.04739v2 Announce Type: replace-cross Abstract: Responsible Artificial Intelligence (RAI) addresses the ethical and regulatory challenges of deploying AI systems in high-risk scenarios. This paper proposes a comprehensive framework for the design of an RAI system (RAIS) that integrates five key dimensions: domain definition, trustworthy AI design, auditability, accountability, and governance. Unlike prior work that treats these components in isolation, our proposal emphasizes their inter-dependencies and iterative feedback loops, enabling proactive and reactive accountability throughout the AI lifecycle. Beyond presenting the framework, we synthesize recent developments in global AI governance and analyze limitations in existing principles-based approaches, highlighting fragmentation, implementation gaps, and the need for participatory governance. The paper also identifies critical challenges and research directions for the RAIS framework, including sector-specific adaptation and operationalization, to support certification, post-deployment monitoring, and risk-based auditing. By bridging technical design and institutional responsibility, this work offers a practical blueprint for embedding responsibility throughout the AI lifecycle, enabling transparent, ethically aligned, and legally compliant AI-based systems.
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SciClaims: An End-to-End Generative System for Biomedical Claim Analysis

arXiv:2503.18526v2 Announce Type: replace-cross Abstract: We present SciClaims, an interactive web-based system for end-to-end scientific claim analysis in the biomedical domain. Designed for high-stakes use cases such as systematic literature reviews and patent validation, SciClaims extracts claims from text, retrieves relevant evidence from PubMed, and verifies their veracity. The system features a user-friendly interface where users can input scientific text and view extracted claims, predictions, supporting or refuting evidence, and justifications in natural language. Unlike prior approaches, SciClaims seamlessly integrates the entire scientific claim analysis process using a single large language model, without requiring additional fine-tuning. SciClaims is optimized to run efficiently on a single GPU and is publicly available for live interaction.
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Multi-Modal AI for Remote Patient Monitoring in Cancer Care

arXiv:2512.00949v2 Announce Type: replace-cross Abstract: For patients undergoing systemic cancer therapy, the time between clinic visits is full of uncertainties and risks of unmonitored side effects. To bridge this gap in care, we developed and prospectively trialed a multi-modal AI framework for remote patient monitoring (RPM). This system integrates multi-modal data from the HALO-X platform, such as demographics, wearable sensors, daily surveys, and clinical events. Our observational trial is one of the largest of its kind and has collected over 2.1 million data points (6,080 patient-days) of monitoring from 84 patients. We developed and adapted a multi-modal AI model to handle the asynchronous and incomplete nature of real-world RPM data, forecasting a continuous risk of future adverse events. The model achieved an accuracy of 83.9% (AUROC=0.70). Notably, the model identified previous treatments, wellness check-ins, and daily maximum heart rate as key predictive features. A case study demonstrated the model's ability to provide early warnings by outputting escalating risk profiles prior to the event. This work establishes the feasibility of multi-modal AI RPM for cancer care and offers a path toward more proactive patient support.(Accepted at Europe NeurIPS 2025 Multimodal Representation Learning for Healthcare Workshop. Best Paper Poster Award.)
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Developing an AI-Assisted Tool That Identifies Patients With Multimorbidity and Complex Polypharmacy to Improve the Process of Medication Reviews: Qualitative Interview and Focus Group Study

Background: Structured medication reviews (SMRs) are an essential component of medication optimization, especially for patients with multimorbidity and polypharmacy. However, the process remains challenging due to the complexities of patient data, time constraints, and the need for coordination among health care professionals (HCPs). This study explores HCPs’ perspectives on the integration of artificial intelligence (AI)–assisted tools to enhance the SMR process, with a focus on the potential benefits of and barriers to adoption. Objective: This study aims to identify the key user requirements for AI-assisted tools to improve the efficiency and effectiveness of SMRs, specifically for patients with multimorbidity, complex polypharmacy, and frailty. Methods: A qualitative study was conducted involving focus groups and semistructured interviews with HCPs and patients in the United Kingdom. Participants included physicians, pharmacists, clinical pharmacologists, psychiatrists from primary and secondary care, a policy maker, and patients with multimorbidity. Data were analyzed using a hybrid inductive and deductive thematic analysis approach to identify themes related to AI-assisted tool functionality, workflow integration, user-interface visualization, and usability in the SMR process. Results: Four major themes emerged from the analysis: innovative AI potential, optimizing electronic patient record visualization, functionality of the AI tool for SMRs, and facilitators of and barriers to AI tool implementation. HCPs identified the potential of AI to support patient identification and prioritizing those at risk of medication-related harm. AI-assisted tools were viewed as essential in detecting prescribing gaps, drug interactions, and patient risk trajectories over time. Participants emphasized the importance of presenting patient data in an intuitive format, with a patient interface for shared decision-making. Suggestions included color-coding blood results, highlighting critical medication reviews, and providing timelines of patient medical histories. HCPs stressed the need for AI tools to integrate seamlessly with existing electronic patient record systems and provide actionable insights without overwhelming users with excessive notifications or “pop-up” alerts. Factors influencing the uptake of AI-assisted tools included the need for user-friendly design, evidence of tool effectiveness (though some were skeptical about the predictive accuracy of AI models), and addressing concerns around digital exclusion. Conclusions: The findings highlight the potential for AI-assisted tools to streamline and optimize the SMR process, particularly for patients with multimorbidity and complex polypharmacy. However, successful implementation depends on addressing concerns related to workflow integration, user acceptance, and evidence of effectiveness. User-centered design is crucial to ensure that AI-assisted tools support HCPs in delivering high-quality, patient-centered care while minimizing cognitive overload and alert fatigue.
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Intervention in Health Misinformation Using Large Language Models for Automated Detection, Thematic Analysis, and Inoculation: Case Study on COVID-19

Background: The rapid growth of social media as an information channel has enabled the swift spread of inaccurate or false health information, significantly impacting public health. This widespread dissemination of misinformation has caused confusion, eroded trust in health authorities, led to noncompliance with health guidelines, and encouraged risky health behaviors. Understanding the dynamics of misinformation on social media is essential for devising effective public health communication strategies. Objective: This study aims to present a comprehensive and automated approach that leverages Large Language Models (LLMs) and Machine Learning (ML) techniques to detect misinformation on social media, uncover the underlying causes and themes, and generate refutation arguments, facilitating control of its spread and promoting public health outcomes by inoculating people against health misinformation. Methods: We use two datasets to train three LLMs, namely BERT, T5, and GPT-2, to classify documents into two categories: misinformation and non-misinformation. Additionally, we employ a separate dataset to identify misinformation topics. To analyze these topics, we applied three topic modeling algorithms—Latent Dirichlet Allocation (LDA), Top2Vec, and BERTopic—and selected the optimal model based on performance evaluated across three metrics. Using a prompting approach, we extract sentence-level representations for the topics to uncover their underlying themes. Finally, we design a prompt text capable of identifying misinformation themes effectively. Codes are available at https://github.com/SamiraMalek/MDIP-MDIS. Results: The trained BERT model demonstrated exceptional performance, achieving 98% accuracy in classifying misinformation and non-misinformation, with a 44% reduction in false positive rates for AI-generated misinformation. Among the three topic modeling approaches employed, BERTopic outperformed the others, achieving the highest metrics with a Coherence Value (CV) of 0.41, Normalized Pointwise Mutual Information (NPMI) of -0.086, and Inverted RBO (IRBO) of 0.99. To address the issue of unclassified documents, we developed an algorithm to assign each document to its closest topic. Additionally, we proposed a novel method using prompt engineering to generate sentence-level representations for each topic, achieving a 99.6% approval rate as "appropriate" or "somewhat appropriate" by three independent raters. We further designed a prompt text to identify themes of misinformation topics and developed another prompt capable of detecting misinformation themes with 82% accuracy. Conclusions: This study presents a comprehensive and automated approach to addressing health misinformation on social media using advanced machine learning and natural language processing techniques. By leveraging large language models (LLMs) and prompt engineering, the system effectively detects misinformation, identifies underlying themes, and provides explanatory responses to combat its spread. The proposed method was tested on an English-language COVID-19–related dataset and has not been evaluated on real-world online social media data; the experiments were conducted offline.
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STAT+: OpenAI invites you to upload medical records to ChatGPT

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.

Millions of people, including me and possibly you, are already asking ChatGPT questions about health. Still others are dumping otherwise inscrutable medical records downloaded from patient portals into the generative AI bot, hoping to glean new insights. 

Now, OpenAI will encourage this behavior with a new health specific tab in the service that the company says has better security and privacy protections so users feel safe pouring sensitive medical data into the bot. In addition to uploading files, users can hook up data from products like Apple Health and Weight Watchers or obtain medical records from providers through b.well’s network. OpenAI promises that it won’t train its models on the data you put into ChatGPT Health. (Reminder: Data that you upload to a consumer service is not covered by HIPAA.)

Continue to STAT+ to read the full story…

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A Web-Based Cancer Prevention Intervention for Rural Emerging Adults: Mixed Methods Development and Pilot-Testing Study

Background: The rapid growth of user-generated web-based health information increases the complexity of cancer information seeking. One promising strategy for promoting high-quality cancer information consumption is through targeted interventions that are intentionally designed to reach individuals in the web-based spaces they occupy. However, there is a paucity of evidence-based information on the best strategies for designing and implementing web-based health behavior change interventions to improve individuals’ cancer-related knowledge and prevent cancer. Objective: This study aimed to develop and pilot test a theory-based intervention via the web to reduce 6 cancer risk factors among rural emerging adults (EAs) through community-engaged research. Methods: This mixed methods evaluation describes the development of a web-based cancer prevention intervention aimed at rural EAs aged 18-26 years in the United States and delivered in Facebook private groups. The intervention was guided by behavior change theory and cocreated with EA and Stakeholder Organization Advisory Boards to ensure relevance, accessibility, and appropriateness. We report on 3 formative surveys, a pilot intervention, protocol development, and the community-engaged process for intervention development. Descriptive statistics were applied to the surveys and pilot intervention baseline results to produce means and SDs using R. Results: We developed posts (n=400) for a Facebook feed aimed at reducing 6 cancer risk behaviors (unhealthy diet, lack of physical activity, tobacco use, alcohol use, sun exposure, and human papillomavirus infection) with iterative input from the EA and stakeholder advisory boards. Formative surveys with rural EAs (n=297) and a pilot study of the intervention with this population (n=26) were conducted. In the pilot study, the intervention reached participants across rural counties, with sustained engagement (post views=1060, reactions=346, comments=72) over a one-month period. Key modifications to the intervention content and design emerged from both advisory boards, the formative surveys, and the pilot intervention, focusing on using perceived reliable sources and direct links to source material. Conclusions: This web-based cancer prevention intervention is scalable and delivers engaging, evidence-informed health information to rural EAs. We offer key insights into the design and implementation of web-based cancer prevention interventions for EAs by describing the resources, timelines, and expertise needed to design and implement the intervention. Considerations for fully engaging EA and community stakeholder partners are presented, and we discuss how their involvement resulted in modifications that strengthened the intervention. Finally, we highlight the importance of theory-based health-behavior messaging, digital messaging skillsets, and platform-tailored dissemination strategies for maximizing web-based intervention acceptability. Trial Registration: ClinicalTrials.gov NCT05618158; https://classic.clinicaltrials.gov/ct2/show/NCT05618158
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A Proposed Paradigm for Imputing Missing Multi-Sensor Data in the Healthcare Domain

arXiv:2601.03565v1 Announce Type: cross Abstract: Chronic diseases such as diabetes pose significant management challenges, particularly due to the risk of complications like hypoglycemia, which require timely detection and intervention. Continuous health monitoring through wearable sensors offers a promising solution for early prediction of glycemic events. However, effective use of multisensor data is hindered by issues such as signal noise and frequent missing values. This study examines the limitations of existing datasets and emphasizes the temporal characteristics of key features relevant to hypoglycemia prediction. A comprehensive analysis of imputation techniques is conducted, focusing on those employed in state-of-the-art studies. Furthermore, imputation methods derived from machine learning and deep learning applications in other healthcare contexts are evaluated for their potential to address longer gaps in time-series data. Based on this analysis, a systematic paradigm is proposed, wherein imputation strategies are tailored to the nature of specific features and the duration of missing intervals. The review concludes by emphasizing the importance of investigating the temporal dynamics of individual features and the implementation of multiple, feature-specific imputation techniques to effectively address heterogeneous temporal patterns inherent in the data.
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