Daily Papers

As large language model agents increasingly populate networked environments, a fundamental question arises: do artificial intelligence (AI) agent societies undergo convergence dynamics similar to human social systems? Lately, Moltbook approximates a plausible future scenario in which autonomous agents participate in an open-ended, continuously evolving online society. We present the first large-scale systemic diagnosis of this AI agent society. Beyond static observation, we introduce a quantitative diagnostic framework for dynamic evolution in AI agent societies, measuring semantic stabilization, lexical turnover, individual inertia, influence persistence, and collective consensus. Our analysis reveals a system in dynamic balance in Moltbook: while global semantic averages stabilize rapidly, individual agents retain high diversity and persistent lexical turnover, defying homogenization. However, agents exhibit strong individual inertia and minimal adaptive response to interaction partners, preventing mutual influence and consensus. Consequently, influence remains transient with no persistent supernodes, and the society fails to develop stable collective influence anchors due to the absence of shared social memory. These findings demonstrate that scale and interaction density alone are insufficient to induce socialization, providing actionable design and analysis principles for upcoming next-generation AI agent societies.

The retinal vasculature provides important clues in the diagnosis and monitoring of systemic diseases including hypertension and diabetes. The microvascular system is of primary involvement in such conditions, and the retina is the only anatomical site where the microvasculature can be directly observed. The objective assessment of retinal vessels has long been considered a surrogate biomarker for systemic vascular diseases, and with recent advancements in retinal imaging and computer vision technologies, this topic has become the subject of renewed attention. In this paper, we present a novel dataset, dubbed RAVIR, for the semantic segmentation of Retinal Arteries and Veins in Infrared Reflectance (IR) imaging. It enables the creation of deep learning-based models that distinguish extracted vessel type without extensive post-processing. We propose a novel deep learning-based methodology, denoted as SegRAVIR, for the semantic segmentation of retinal arteries and veins and the quantitative measurement of the widths of segmented vessels. Our extensive experiments validate the effectiveness of SegRAVIR and demonstrate its superior performance in comparison to state-of-the-art models. Additionally, we propose a knowledge distillation framework for the domain adaptation of RAVIR pretrained networks on color images. We demonstrate that our pretraining procedure yields new state-of-the-art benchmarks on the DRIVE, STARE, and CHASE_DB1 datasets. Dataset link: https://ravirdataset.github.io/data/

Artificial intelligence (AI) is vital in ophthalmology, tackling tasks like diagnosis, classification, and visual question answering (VQA). However, existing AI models in this domain often require extensive annotation and are task-specific, limiting their clinical utility. While recent developments have brought about foundation models for ophthalmology, they are limited by the need to train separate weights for each imaging modality, preventing a comprehensive representation of multi-modal features. This highlights the need for versatile foundation models capable of handling various tasks and modalities in ophthalmology. To address this gap, we present EyeFound, a multimodal foundation model for ophthalmic images. Unlike existing models, EyeFound learns generalizable representations from unlabeled multimodal retinal images, enabling efficient model adaptation across multiple applications. Trained on 2.78 million images from 227 hospitals across 11 ophthalmic modalities, EyeFound facilitates generalist representations and diverse multimodal downstream tasks, even for detecting challenging rare diseases. It outperforms previous work RETFound in diagnosing eye diseases, predicting systemic disease incidents, and zero-shot multimodal VQA. EyeFound provides a generalizable solution to improve model performance and lessen the annotation burden on experts, facilitating widespread clinical AI applications for retinal imaging.

Clinical diagnosis is critical in medical practice, typically requiring a continuous and evolving process that includes primary diagnosis, differential diagnosis, and final diagnosis. However, most existing clinical diagnostic tasks are single-step processes, which does not align with the complex multi-step diagnostic procedures found in real-world clinical settings. In this paper, we propose a multi-step diagnostic task and annotate a clinical diagnostic dataset (MSDiagnosis). This dataset includes primary diagnosis, differential diagnosis, and final diagnosis questions. Additionally, we propose a novel and effective framework. This framework combines forward inference, backward inference, reflection, and refinement, enabling the LLM to self-evaluate and adjust its diagnostic results. To assess the effectiveness of our proposed method, we design and conduct extensive experiments. The experimental results demonstrate the effectiveness of the proposed method. We also provide a comprehensive experimental analysis and suggest future research directions for this task.

Through a systematic review of academic literature, we propose a taxonomy of systemic risks associated with artificial intelligence (AI), in particular general-purpose AI. Following the EU AI Act's definition, we consider systemic risks as large-scale threats that can affect entire societies or economies. Starting with an initial pool of 1,781 documents, we analyzed 86 selected papers to identify 13 categories of systemic risks and 50 contributing sources. Our findings reveal a complex landscape of potential threats, ranging from environmental harm and structural discrimination to governance failures and loss of control. Key sources of systemic risk emerge from knowledge gaps, challenges in recognizing harm, and the unpredictable trajectory of AI development. The taxonomy provides a snapshot of current academic literature on systemic risks. This paper contributes to AI safety research by providing a structured groundwork for understanding and addressing the potential large-scale negative societal impacts of general-purpose AI. The taxonomy can inform policymakers in risk prioritization and regulatory development.

Retinal imaging has emerged as a powerful, non-invasive modality for detecting and quantifying biomarkers of systemic diseases-ranging from diabetes and hypertension to Alzheimer's disease and cardiovascular disorders but current insights remain dispersed across platforms and specialties. Recent technological advances in optical coherence tomography (OCT/OCTA) and adaptive optics (AO) now deliver ultra-high-resolution scans (down to 5 {\mu}m ) with superior contrast and spatial integration, allowing early identification of microvascular abnormalities and neurodegenerative changes. At the same time, AI-driven and machine learning (ML) algorithms have revolutionized the analysis of large-scale retinal datasets, increasing sensitivity and specificity; for example, deep learning models achieve > 90 \% sensitivity for diabetic retinopathy and AUC = 0.89 for the prediction of cardiovascular risk from fundus photographs. The proliferation of mobile health technologies and telemedicine platforms further extends access, reduces costs, and facilitates community-based screening and longitudinal monitoring. Despite these breakthroughs, translation into routine practice is hindered by heterogeneous imaging protocols, limited external validation of AI models, and integration challenges within clinical workflows. In this review, we systematically synthesize the latest OCT/OCT and AO developments, AI/ML approaches, and mHealth/Tele-ophthalmology initiatives and quantify their diagnostic performance across disease domains. Finally, we propose a roadmap for multicenter protocol standardization, prospective validation trials, and seamless incorporation of retinal screening into primary and specialty care pathways-paving the way for precision prevention, early intervention, and ongoing treatment of life-threatening systemic diseases.

Differential diagnosis is crucial for medicine as it helps healthcare providers systematically distinguish between conditions that share similar symptoms. This study assesses the impact of lab test results on differential diagnoses (DDx) made by large language models (LLMs). Clinical vignettes from 50 case reports from PubMed Central were created incorporating patient demographics, symptoms, and lab results. Five LLMs GPT-4, GPT-3.5, Llama-2-70b, Claude-2, and Mixtral-8x7B were tested to generate Top 10, Top 5, and Top 1 DDx with and without lab data. A comprehensive evaluation involving GPT-4, a knowledge graph, and clinicians was conducted. GPT-4 performed best, achieving 55% accuracy for Top 1 diagnoses and 60% for Top 10 with lab data, with lenient accuracy up to 80%. Lab results significantly improved accuracy, with GPT-4 and Mixtral excelling, though exact match rates were low. Lab tests, including liver function, metabolic/toxicology panels, and serology/immune tests, were generally interpreted correctly by LLMs for differential diagnosis.

Integrating Large Language Models (LLMs) in healthcare diagnosis demands systematic frameworks that can handle complex medical scenarios while maintaining specialized expertise. We present KG4Diagnosis, a novel hierarchical multi-agent framework that combines LLMs with automated knowledge graph construction, encompassing 362 common diseases across medical specialties. Our framework mirrors real-world medical systems through a two-tier architecture: a general practitioner (GP) agent for initial assessment and triage, coordinating with specialized agents for in-depth diagnosis in specific domains. The core innovation lies in our end-to-end knowledge graph generation methodology, incorporating: (1) semantic-driven entity and relation extraction optimized for medical terminology, (2) multi-dimensional decision relationship reconstruction from unstructured medical texts, and (3) human-guided reasoning for knowledge expansion. KG4Diagnosis serves as an extensible foundation for specialized medical diagnosis systems, with capabilities to incorporate new diseases and medical knowledge. The framework's modular design enables seamless integration of domain-specific enhancements, making it valuable for developing targeted medical diagnosis systems. We provide architectural guidelines and protocols to facilitate adoption across medical contexts.

Differential Diagnosis (DDx) is a fundamental yet complex aspect of clinical decision-making, in which physicians iteratively refine a ranked list of possible diseases based on symptoms, antecedents, and medical knowledge. While recent advances in large language models (LLMs) have shown promise in supporting DDx, existing approaches face key limitations, including single-dataset evaluations, isolated optimization of components, unrealistic assumptions about complete patient profiles, and single-attempt diagnosis. We introduce a Modular Explainable DDx Agent (MEDDxAgent) framework designed for interactive DDx, where diagnostic reasoning evolves through iterative learning, rather than assuming a complete patient profile is accessible. MEDDxAgent integrates three modular components: (1) an orchestrator (DDxDriver), (2) a history taking simulator, and (3) two specialized agents for knowledge retrieval and diagnosis strategy. To ensure robust evaluation, we introduce a comprehensive DDx benchmark covering respiratory, skin, and rare diseases. We analyze single-turn diagnostic approaches and demonstrate the importance of iterative refinement when patient profiles are not available at the outset. Our broad evaluation demonstrates that MEDDxAgent achieves over 10% accuracy improvements in interactive DDx across both large and small LLMs, while offering critical explainability into its diagnostic reasoning process.

The field of medical diagnosis has undergone a significant transformation with the advent of large language models (LLMs), yet the challenges of interpretability within these models remain largely unaddressed. This study introduces Chain-of-Diagnosis (CoD) to enhance the interpretability of LLM-based medical diagnostics. CoD transforms the diagnostic process into a diagnostic chain that mirrors a physician's thought process, providing a transparent reasoning pathway. Additionally, CoD outputs the disease confidence distribution to ensure transparency in decision-making. This interpretability makes model diagnostics controllable and aids in identifying critical symptoms for inquiry through the entropy reduction of confidences. With CoD, we developed DiagnosisGPT, capable of diagnosing 9604 diseases. Experimental results demonstrate that DiagnosisGPT outperforms other LLMs on diagnostic benchmarks. Moreover, DiagnosisGPT provides interpretability while ensuring controllability in diagnostic rigor.

There has been a rapidly growing interest in Automatic Symptom Detection (ASD) and Automatic Diagnosis (AD) systems in the machine learning research literature, aiming to assist doctors in telemedicine services. These systems are designed to interact with patients, collect evidence about their symptoms and relevant antecedents, and possibly make predictions about the underlying diseases. Doctors would review the interactions, including the evidence and the predictions, collect if necessary additional information from patients, before deciding on next steps. Despite recent progress in this area, an important piece of doctors' interactions with patients is missing in the design of these systems, namely the differential diagnosis. Its absence is largely due to the lack of datasets that include such information for models to train on. In this work, we present a large-scale synthetic dataset of roughly 1.3 million patients that includes a differential diagnosis, along with the ground truth pathology, symptoms and antecedents for each patient. Unlike existing datasets which only contain binary symptoms and antecedents, this dataset also contains categorical and multi-choice symptoms and antecedents useful for efficient data collection. Moreover, some symptoms are organized in a hierarchy, making it possible to design systems able to interact with patients in a logical way. As a proof-of-concept, we extend two existing AD and ASD systems to incorporate the differential diagnosis, and provide empirical evidence that using differentials as training signals is essential for the efficiency of such systems or for helping doctors better understand the reasoning of those systems.

Clinical diagnosis is a highly specialized discipline requiring both domain expertise and strict adherence to rigorous guidelines. While current AI-driven medical research predominantly focuses on knowledge graphs or natural text pretraining paradigms to incorporate medical knowledge, these approaches primarily rely on implicitly encoded knowledge within model parameters, neglecting task-specific knowledge required by diverse downstream tasks. To address this limitation, we propose Retrieval-Augmented Diagnosis (RAD), a novel framework that explicitly injects external knowledge into multimodal models directly on downstream tasks. Specifically, RAD operates through three key mechanisms: retrieval and refinement of disease-centered knowledge from multiple medical sources, a guideline-enhanced contrastive loss that constrains the latent distance between multi-modal features and guideline knowledge, and the dual transformer decoder that employs guidelines as queries to steer cross-modal fusion, aligning the models with clinical diagnostic workflows from guideline acquisition to feature extraction and decision-making. Moreover, recognizing the lack of quantitative evaluation of interpretability for multimodal diagnostic models, we introduce a set of criteria to assess the interpretability from both image and text perspectives. Extensive evaluations across four datasets with different anatomies demonstrate RAD's generalizability, achieving state-of-the-art performance. Furthermore, RAD enables the model to concentrate more precisely on abnormal regions and critical indicators, ensuring evidence-based, trustworthy diagnosis. Our code is available at https://github.com/tdlhl/RAD.

Diagnosing a whole-slide image is an interactive, multi-stage process involving changes in magnification and movement between fields. Although recent pathology foundation models are strong, practical agentic systems that decide what field to examine next, adjust magnification, and deliver explainable diagnoses are still lacking. The blocker is data: scalable, clinically aligned supervision of expert viewing behavior that is tacit and experience-based, not written in textbooks or online, and therefore absent from large language model training. We introduce the AI Session Recorder, which works with standard WSI viewers to unobtrusively record routine navigation and convert the viewer logs into standardized behavioral commands (inspect or peek at discrete magnifications) and bounding boxes. A lightweight human-in-the-loop review turns AI-drafted rationales into the Pathology-CoT dataset, a form of paired "where to look" and "why it matters" supervision produced at roughly six times lower labeling time. Using this behavioral data, we build Pathologist-o3, a two-stage agent that first proposes regions of interest and then performs behavior-guided reasoning. On gastrointestinal lymph-node metastasis detection, it achieved 84.5% precision, 100.0% recall, and 75.4% accuracy, exceeding the state-of-the-art OpenAI o3 model and generalizing across backbones. To our knowledge, this constitutes one of the first behavior-grounded agentic systems in pathology. Turning everyday viewer logs into scalable, expert-validated supervision, our framework makes agentic pathology practical and establishes a path to human-aligned, upgradeable clinical AI.

Diagnosing lung cancer typically involves physicians identifying lung nodules in Computed tomography (CT) scans and generating diagnostic reports based on their morphological features and medical expertise. Although advancements have been made in using multimodal large language models for analyzing lung CT scans, challenges remain in accurately describing nodule morphology and incorporating medical expertise. These limitations affect the reliability and effectiveness of these models in clinical settings. Collaborative multi-agent systems offer a promising strategy for achieving a balance between generality and precision in medical applications, yet their potential in pathology has not been thoroughly explored. To bridge these gaps, we introduce LungNoduleAgent, an innovative collaborative multi-agent system specifically designed for analyzing lung CT scans. LungNoduleAgent streamlines the diagnostic process into sequential components, improving precision in describing nodules and grading malignancy through three primary modules. The first module, the Nodule Spotter, coordinates clinical detection models to accurately identify nodules. The second module, the Radiologist, integrates localized image description techniques to produce comprehensive CT reports. Finally, the Doctor Agent System performs malignancy reasoning by using images and CT reports, supported by a pathology knowledge base and a multi-agent system framework. Extensive testing on two private datasets and the public LIDC-IDRI dataset indicates that LungNoduleAgent surpasses mainstream vision-language models, agent systems, and advanced expert models. These results highlight the importance of region-level semantic alignment and multi-agent collaboration in diagnosing nodules. LungNoduleAgent stands out as a promising foundational tool for supporting clinical analyses of lung nodules.

The emergence of groundbreaking large language models capable of performing complex reasoning tasks holds significant promise for addressing various scientific challenges, including those arising in complex clinical scenarios. To enable their safe and effective deployment in real-world healthcare settings, it is urgently necessary to benchmark the diagnostic capabilities of current models systematically. Given the limitations of existing medical benchmarks in evaluating advanced diagnostic reasoning, we present DiagnosisArena, a comprehensive and challenging benchmark designed to rigorously assess professional-level diagnostic competence. DiagnosisArena consists of 1,113 pairs of segmented patient cases and corresponding diagnoses, spanning 28 medical specialties, deriving from clinical case reports published in 10 top-tier medical journals. The benchmark is developed through a meticulous construction pipeline, involving multiple rounds of screening and review by both AI systems and human experts, with thorough checks conducted to prevent data leakage. Our study reveals that even the most advanced reasoning models, o3-mini, o1, and DeepSeek-R1, achieve only 45.82%, 31.09%, and 17.79% accuracy, respectively. This finding highlights a significant generalization bottleneck in current large language models when faced with clinical diagnostic reasoning challenges. Through DiagnosisArena, we aim to drive further advancements in AIs diagnostic reasoning capabilities, enabling more effective solutions for real-world clinical diagnostic challenges. We provide the benchmark and evaluation tools for further research and development https://github.com/SPIRAL-MED/DiagnosisArena.

Mental disorders are highly prevalent worldwide, but the shortage of psychiatrists and the inherent subjectivity of interview-based diagnosis create substantial barriers to timely and consistent mental-health assessment. Progress in AI-assisted psychiatric diagnosis is constrained by the absence of benchmarks that simultaneously provide realistic patient simulation, clinician-verified diagnostic labels, and support for dynamic multi-turn consultation. We present LingxiDiagBench, a large-scale multi-agent benchmark that evaluates LLMs on both static diagnostic inference and dynamic multi-turn psychiatric consultation in Chinese. At its core is LingxiDiag-16K, a dataset of 16,000 EMR-aligned synthetic consultation dialogues designed to reproduce real clinical demographic and diagnostic distributions across 12 ICD-10 psychiatric categories. Through extensive experiments across state-of-the-art LLMs, we establish key findings: (1) although LLMs achieve high accuracy on binary depression--anxiety classification (up to 92.3%), performance deteriorates substantially for depression--anxiety comorbidity recognition (43.0%) and 12-way differential diagnosis (28.5%); (2) dynamic consultation often underperforms static evaluation, indicating that ineffective information-gathering strategies significantly impair downstream diagnostic reasoning; (3) consultation quality assessed by LLM-as-a-Judge shows only moderate correlation with diagnostic accuracy, suggesting that well-structured questioning alone does not ensure correct diagnostic decisions. We release LingxiDiag-16K and the full evaluation framework to support reproducible research at https://github.com/Lingxi-mental-health/LingxiDiagBench.

Language models excel at diagnostic assessments on currated medical case-studies and vignettes, performing on par with, or better than, clinical professionals. However, existing studies focus on complex scenarios with rich context making it difficult to draw conclusions about how these systems perform for patients reporting symptoms in everyday life. We deployed SymptomAI, a set of conversational AI agents for end-to-end patient interviewing and differential diagnosis (DDx), via the Fitbit app in a study that randomized participants (N=13,917) to interact with five AI agents. This corpus captures diverse communication and a realistic distribution of illnesses from a real world population. A subset of 1,228 participants reported a clinician-provided diagnosis, and 517 of these were further evaluated by a panel of clinicians during over 250 hours of annotation. SymptomAI DDx were significantly more accurate (OR = 2.47, p < 0.001) than those from independent clinicians given the same dialogue in a blinded randomized comparison. Moreover, agentic strategies which conduct a dedicated symptom interview that elicit additional symptom information before providing a diagnosis, perform substantially better than baseline, user-guided conversations (p < 0.001). An auxiliary analysis on 1,509 conversations from a general US population panel validated that these results generalize beyond wearable device users. We used SymptomAI diagnoses as labels for all 13,917 participants to analyze over 500,000 days of wearable metrics across nearly 400 unique conditions. We identified strong associations between acute infections and physiological shifts (e.g., OR > 7 for influenza). While limited by self-reported ground truth, these results demonstrate the benefits of a dedicated and complete symptom interview compared to a user-guided symptom discussion, which is the default of most consumer LLMs.

Real-world clinical diagnosis is a complex process in which the doctor is required to obtain information from both interaction with the patient and conducting medical exams. Additionally, the doctor needs to adapt to different patient personas, as well as noisy and incomplete information that can happen at any time during the process. However, existing benchmarks for medical LLMs and methods for automatic diagnosis largely simplify this process by reducing it to single-turn question answering, noise-free conversations, or sequential exam making, etc., ignoring the interactive and uncertain nature of clinical diagnosis. In this paper, we aim to address this gap by formalizing clinical diagnosis as a Partially Observable Markov Decision Process (POMDP) with three action types: questioning the patient, ordering medical exams as tool calls, and issuing a diagnosis. We also introduce a systematic noise model comprising seven patient noise types and three exam noise types. Using our proposed environment, we train an effective diagnosis agent, MedExAgent, through a two-stage pipeline that first performs supervised finetuning on synthetic conversations structured after the Calgary-Cambridge model for clinical interviews, and then applies DAPO to optimize a composite reward capturing diagnostic accuracy, tool call quality, and exam cost including financial cost and patient discomfort. Through extensive experiments and ablation studies, we demonstrate that MedExAgent achieves diagnostic performance comparable to larger models while maintaining cost-efficient examination strategies.

Developing reliable AI systems to assist human clinicians in multi-modal medical diagnosis has long been a key objective for researchers. Recently, Multi-modal Large Language Models (MLLMs) have gained significant attention and achieved success across various domains. With strong reasoning capabilities and the ability to perform diverse tasks based on user instructions, they hold great potential for enhancing medical diagnosis. However, directly applying MLLMs to the medical domain still presents challenges. They lack detailed perception of visual inputs, limiting their ability to perform quantitative image analysis, which is crucial for medical diagnostics. Additionally, MLLMs often exhibit hallucinations and inconsistencies in reasoning, whereas clinical diagnoses must adhere strictly to established criteria. To address these challenges, we propose MedAgent-Pro, an evidence-based reasoning agentic system designed to achieve reliable, explainable, and precise medical diagnoses. This is accomplished through a hierarchical workflow: at the task level, knowledge-based reasoning generate reliable diagnostic plans for specific diseases following retrieved clinical criteria. While at the case level, multiple tool agents process multi-modal inputs, analyze different indicators according to the plan, and provide a final diagnosis based on both quantitative and qualitative evidence. Comprehensive experiments on both 2D and 3D medical diagnosis tasks demonstrate the superiority and effectiveness of MedAgent-Pro, while case studies further highlight its reliability and interpretability. The code is available at https://github.com/jinlab-imvr/MedAgent-Pro.

Case definitions are essential for effectively communicating public health threats. However, the absence of a standardized, machine-readable format poses significant challenges to interoperability, epidemiological research, the exchange of qualitative data, and the effective application of computational analysis methods, including artificial intelligence (AI). This complicates comparisons and collaborations across organizations and regions, limits data integration, and hinders technological innovation in public health. To address these issues, we propose the first open, machine-readable format for representing case and syndrome definitions. Additionally, we introduce the first comprehensive dataset of standardized case definitions and tools to convert existing human-readable definitions into machine-readable formats. We also provide an accessible online platform for browsing, analyzing, and contributing new definitions, available at https://opensyndrome.org. The Open Syndrome Definition format enables consistent, scalable use of case definitions across systems, unlocking AI's potential to strengthen public health preparedness and response. The source code for the format can be found at https://github.com/OpenSyndrome/schema under the MIT license.

Artificial intelligence holds great promise for expanding access to expert medical knowledge and reasoning. However, most evaluations of language models rely on static vignettes and multiple-choice questions that fail to reflect the complexity and nuance of evidence-based medicine in real-world settings. In clinical practice, physicians iteratively formulate and revise diagnostic hypotheses, adapting each subsequent question and test to what they've just learned, and weigh the evolving evidence before committing to a final diagnosis. To emulate this iterative process, we introduce the Sequential Diagnosis Benchmark, which transforms 304 diagnostically challenging New England Journal of Medicine clinicopathological conference (NEJM-CPC) cases into stepwise diagnostic encounters. A physician or AI begins with a short case abstract and must iteratively request additional details from a gatekeeper model that reveals findings only when explicitly queried. Performance is assessed not just by diagnostic accuracy but also by the cost of physician visits and tests performed. We also present the MAI Diagnostic Orchestrator (MAI-DxO), a model-agnostic orchestrator that simulates a panel of physicians, proposes likely differential diagnoses and strategically selects high-value, cost-effective tests. When paired with OpenAI's o3 model, MAI-DxO achieves 80% diagnostic accuracy--four times higher than the 20% average of generalist physicians. MAI-DxO also reduces diagnostic costs by 20% compared to physicians, and 70% compared to off-the-shelf o3. When configured for maximum accuracy, MAI-DxO achieves 85.5% accuracy. These performance gains with MAI-DxO generalize across models from the OpenAI, Gemini, Claude, Grok, DeepSeek, and Llama families. We highlight how AI systems, when guided to think iteratively and act judiciously, can advance diagnostic precision and cost-effectiveness in clinical care.

Systemic financial risk refers to the simultaneous failure or destabilization of multiple financial institutions, often triggered by contagion mechanisms or common exposures to shocks. In this paper, we present a dynamical model of bank leverage (the ratio of asset holdings to equity) a quantity that both reflects and drives risk dynamics. We model how banks, constrained by Value-at-Risk (VaR) regulations, adjust their leverage in response to changes in the price of a single asset, assumed to be held in fixed proportion across banks. This leverage-targeting behavior introduces a procyclical feedback loop between asset prices and leverage. In the dynamics, this can manifest as logistic-like behavior with a rich bifurcation structure across model parameters. By analyzing these coupled dynamics in both isolated and interconnected bank models, we outline a framework for understanding how systemic risk can emerge from seemingly rational micro-level behavior.

We investigate whether large language models produce different medical triage recommendations for identical neurological symptoms when only the patient's stated gender and age vary. Using three model families--Gemini 3.5 Flash, Claude Sonnet 4.6, and GPT-5.4-mini--we present a standardized symptom profile (persistent headache, blurred vision, morning nausea, visual disturbances) across seven demographic conditions: three age groups (25, 38, 65) x two genders (male, female), plus a gender-unspecified baseline (n = 30 per condition per model, 630 total trials). We find a stark, systemic gender-dependent triage disparity: young women receive significantly lower emergency room (ER) referral rates than age-matched men (Gemini: 0% vs. 23.3%; Claude: 6.7% vs. 96.7%; GPT: 6.7% vs. 66.7%, all p < 0.001). The disparity disappears at age 65 for all models. The primary mechanism is diagnostic substitution: the models anchor on a gender-associated diagnosis, preferentially classifying young women with Idiopathic Intracranial Hypertension (IIH)--a condition epidemiologically linked to women of childbearing age--while diagnosing men with generic increased intracranial pressure with space-occupying lesions in the differential. This diagnostic closure routes female patients to lower-urgency care (outpatient doctor appointments) despite comparable severity ratings (7-9/10). Our findings demonstrate that clinical LLMs replicate documented human clinical biases by using epidemiological priors to suppress triage urgency, suggesting that AI triage engines must decouple urgency assessment from probabilistic diagnostic priors. We release all code, prompts, and raw results.

Automated clinical diagnosis remains a core challenge in medical AI, which usually requires models to integrate multi-modal data and reason across complex, case-specific contexts. Although recent methods have advanced medical report generation (MRG) and visual question answering (VQA) with medical vision-language models (VLMs), these methods, however, predominantly operate under a sample-isolated inference paradigm, as such processing cases independently without access to longitudinal electronic health records (EHRs) or structurally related patient examples. This paradigm limits reasoning to image-derived information alone, which ignores external complementary medical evidence for potentially more accurate diagnosis. To overcome this limitation, we propose HyperWalker, a Deep Diagnosis framework that reformulates clinical reasoning via dynamic hypergraphs and test-time training. First, we construct a dynamic hypergraph, termed iBrochure, to model the structural heterogeneity of EHR data and implicit high-order associations among multimodal clinical information. Within this hypergraph, a reinforcement learning agent, Walker, navigates to and identifies optimal diagnostic paths. To ensure comprehensive coverage of diverse clinical characteristics in test samples, we incorporate a linger mechanism, a multi-hop orthogonal retrieval strategy that iteratively selects clinically complementary neighborhood cases reflecting distinct clinical attributes. Experiments on MRG with MIMIC and medical VQA on EHRXQA demonstrate that HyperWalker achieves state-of-the-art performance. Code is available at: https://github.com/Bean-Young/HyperWalker

COVID-19 (coronavirus disease 2019) pandemic caused by SARS-CoV-2 has led to a treacherous and devastating catastrophe for humanity. At the time of writing, no specific antivirus drugs or vaccines are recommended to control infection transmission and spread. The current diagnosis of COVID-19 is done by Reverse-Transcription Polymer Chain Reaction (RT-PCR) testing. However, this method is expensive, time-consuming, and not easily available in straitened regions. An interpretable and COVID-19 diagnosis AI framework is devised and developed based on the cough sounds features and symptoms metadata to overcome these limitations. The proposed framework's performance was evaluated using a medical dataset containing Symptoms and Demographic data of 30000 audio segments, 328 cough sounds from 150 patients with four cough classes ( COVID-19, Asthma, Bronchitis, and Healthy). Experiments' results show that the model captures the better and robust feature embedding to distinguish between COVID-19 patient coughs and several types of non-COVID-19 coughs with higher specificity and accuracy of 95.04 pm 0.18% and 96.83pm 0.18% respectively, all the while maintaining interpretability.

Speech patterns have been identified as potential diagnostic markers for neuropsychiatric conditions. However, most studies only compare a single clinical group to healthy controls, whereas clinical practice often requires differentiating between multiple potential diagnoses (multiclass settings). To address this, we assembled a dataset of repeated recordings from 420 participants (67 with major depressive disorder, 106 with schizophrenia and 46 with autism, as well as matched controls), and tested the performance of a range of conventional machine learning models and advanced Transformer models on both binary and multiclass classification, based on voice and text features. While binary models performed comparably to previous research (F1 scores between 0.54-0.75 for autism spectrum disorder, ASD; 0.67-0.92 for major depressive disorder, MDD; and 0.71-0.83 for schizophrenia); when differentiating between multiple diagnostic groups performance decreased markedly (F1 scores between 0.35-0.44 for ASD, 0.57-0.75 for MDD, 0.15-0.66 for schizophrenia, and 0.38-0.52 macro F1). Combining voice and text-based models yielded increased performance, suggesting that they capture complementary diagnostic information. Our results indicate that models trained on binary classification may learn to rely on markers of generic differences between clinical and non-clinical populations, or markers of clinical features that overlap across conditions, rather than identifying markers specific to individual conditions. We provide recommendations for future research in the field, suggesting increased focus on developing larger transdiagnostic datasets that include more fine-grained clinical features, and that can support the development of models that better capture the complexity of neuropsychiatric conditions and naturalistic diagnostic assessment.

Clinical diagnosis of the eye is performed over multifarious data modalities including scalar clinical labels, vectorized biomarkers, two-dimensional fundus images, and three-dimensional Optical Coherence Tomography (OCT) scans. Clinical practitioners use all available data modalities for diagnosing and treating eye diseases like Diabetic Retinopathy (DR) or Diabetic Macular Edema (DME). Enabling usage of machine learning algorithms within the ophthalmic medical domain requires research into the relationships and interactions between all relevant data over a treatment period. Existing datasets are limited in that they neither provide data nor consider the explicit relationship modeling between the data modalities. In this paper, we introduce the Ophthalmic Labels for Investigating Visual Eye Semantics (OLIVES) dataset that addresses the above limitation. This is the first OCT and near-IR fundus dataset that includes clinical labels, biomarker labels, disease labels, and time-series patient treatment information from associated clinical trials. The dataset consists of 1268 near-IR fundus images each with at least 49 OCT scans, and 16 biomarkers, along with 4 clinical labels and a disease diagnosis of DR or DME. In total, there are 96 eyes' data averaged over a period of at least two years with each eye treated for an average of 66 weeks and 7 injections. We benchmark the utility of OLIVES dataset for ophthalmic data as well as provide benchmarks and concrete research directions for core and emerging machine learning paradigms within medical image analysis.

As the field of artificial intelligence progresses, assistive technologies are becoming more widely used across all industries. The healthcare industry is no different, with numerous studies being done to develop assistive tools for healthcare professionals. Automatic diagnostic systems are one such beneficial tool that can assist with a variety of tasks, including collecting patient information, analyzing test results, and diagnosing patients. However, the idea of developing systems that can provide a differential diagnosis has been largely overlooked in most of these research studies. In this study, we propose a transformer-based approach for providing differential diagnoses based on a patient's age, sex, medical history, and symptoms. We use the DDXPlus dataset, which provides differential diagnosis information for patients based on 49 disease types. Firstly, we propose a method to process the tabular patient data from the dataset and engineer them into patient reports to make them suitable for our research. In addition, we introduce two data modification modules to diversify the training data and consequently improve the robustness of the models. We approach the task as a multi-label classification problem and conduct extensive experiments using four transformer models. All the models displayed promising results by achieving over 97% F1 score on the held-out test set. Moreover, we design additional behavioral tests to get a broader understanding of the models. In particular, for one of our test cases, we prepared a custom test set of 100 samples with the assistance of a doctor. The results on the custom set showed that our proposed data modification modules improved the model's generalization capabilities. We hope our findings will provide future researchers with valuable insights and inspire them to develop reliable systems for automatic differential diagnosis.

Generalist Large Language Models (LLMs), such as GPT-4, have shown considerable promise in various domains, including medical diagnosis. Rare diseases, affecting approximately 300 million people worldwide, often have unsatisfactory clinical diagnosis rates primarily due to a lack of experienced physicians and the complexity of differentiating among many rare diseases. In this context, recent news such as "ChatGPT correctly diagnosed a 4-year-old's rare disease after 17 doctors failed" underscore LLMs' potential, yet underexplored, role in clinically diagnosing rare diseases. To bridge this research gap, we introduce RareBench, a pioneering benchmark designed to systematically evaluate the capabilities of LLMs on 4 critical dimensions within the realm of rare diseases. Meanwhile, we have compiled the largest open-source dataset on rare disease patients, establishing a benchmark for future studies in this domain. To facilitate differential diagnosis of rare diseases, we develop a dynamic few-shot prompt methodology, leveraging a comprehensive rare disease knowledge graph synthesized from multiple knowledge bases, significantly enhancing LLMs' diagnostic performance. Moreover, we present an exhaustive comparative study of GPT-4's diagnostic capabilities against those of specialist physicians. Our experimental findings underscore the promising potential of integrating LLMs into the clinical diagnostic process for rare diseases. This paves the way for exciting possibilities in future advancements in this field.

In this paper, we present a framework for training large language models (LLMs) as diagnostic agents with reinforcement learning, enabling them to manage multi-turn diagnostic processes, adaptively select examinations, and commit to final diagnoses. Unlike instruction-tuned models trained on static case summaries, our method acquires diagnostic strategies through interactive exploration and outcome-based feedback. Our contributions are fourfold: (i) We present DiagGym, a diagnostics world model trained with electronic health records that emits examination outcomes conditioned on patient history and recommended examination, serving as a virtual clinical environment for realistic diagnosis training and evaluation; (ii) We train DiagAgent via end-to-end, multi-turn reinforcement learning to learn diagnostic policies that optimize both information yield and diagnostic accuracy; (iii) We introduce DiagBench, a diagnostic benchmark comprising 750 cases with physician-validated examination recommendations and 99 cases annotated with 973 physician-written rubrics on diagnosis process; (iv) we demonstrate superior performance across diverse diagnostic settings. DiagAgent significantly outperforms 10 state-of-the-art LLMs, including DeepSeek-v3 and GPT-4o, as well as two prompt-engineered agents. In single-turn settings, DiagAgent achieves 9.34% higher diagnostic accuracy and 44.03% improvement in examination recommendation hit ratio. In end-to-end settings, it delivers 15.12% increase in diagnostic accuracy and 23.09% boost in examination recommendation F1 score. In rubric-based evaluation, it surpasses the next-best model, Claude-sonnet-4, by 7.1% in weighted rubric score. These findings indicate that learning policies in interactive clinical environments confers dynamic and clinically meaningful diagnostic management abilities unattainable through passive training alone.

An accurate differential diagnosis (DDx) is a cornerstone of medical care, often reached through an iterative process of interpretation that combines clinical history, physical examination, investigations and procedures. Interactive interfaces powered by Large Language Models (LLMs) present new opportunities to both assist and automate aspects of this process. In this study, we introduce an LLM optimized for diagnostic reasoning, and evaluate its ability to generate a DDx alone or as an aid to clinicians. 20 clinicians evaluated 302 challenging, real-world medical cases sourced from the New England Journal of Medicine (NEJM) case reports. Each case report was read by two clinicians, who were randomized to one of two assistive conditions: either assistance from search engines and standard medical resources, or LLM assistance in addition to these tools. All clinicians provided a baseline, unassisted DDx prior to using the respective assistive tools. Our LLM for DDx exhibited standalone performance that exceeded that of unassisted clinicians (top-10 accuracy 59.1% vs 33.6%, [p = 0.04]). Comparing the two assisted study arms, the DDx quality score was higher for clinicians assisted by our LLM (top-10 accuracy 51.7%) compared to clinicians without its assistance (36.1%) (McNemar's Test: 45.7, p < 0.01) and clinicians with search (44.4%) (4.75, p = 0.03). Further, clinicians assisted by our LLM arrived at more comprehensive differential lists than those without its assistance. Our study suggests that our LLM for DDx has potential to improve clinicians' diagnostic reasoning and accuracy in challenging cases, meriting further real-world evaluation for its ability to empower physicians and widen patients' access to specialist-level expertise.

Automatic disease diagnosis has become increasingly valuable in clinical practice. The advent of large language models (LLMs) has catalyzed a paradigm shift in artificial intelligence, with growing evidence supporting the efficacy of LLMs in diagnostic tasks. Despite the increasing attention in this field, a holistic view is still lacking. Many critical aspects remain unclear, such as the diseases and clinical data to which LLMs have been applied, the LLM techniques employed, and the evaluation methods used. In this article, we perform a comprehensive review of LLM-based methods for disease diagnosis. Our review examines the existing literature across various dimensions, including disease types and associated clinical specialties, clinical data, LLM techniques, and evaluation methods. Additionally, we offer recommendations for applying and evaluating LLMs for diagnostic tasks. Furthermore, we assess the limitations of current research and discuss future directions. To our knowledge, this is the first comprehensive review for LLM-based disease diagnosis.

Cardiovascular disease remains the leading cause of global mortality, with progress hindered by human interpretation of complex cardiac tests. Current AI vision-language models are limited to single-modality inputs and are non-interactive. We present MARCUS (Multimodal Autonomous Reasoning and Chat for Ultrasound and Signals), an agentic vision-language system for end-to-end interpretation of electrocardiograms (ECGs), echocardiograms, and cardiac magnetic resonance imaging (CMR) independently and as multimodal input. MARCUS employs a hierarchical agentic architecture comprising modality-specific vision-language expert models, each integrating domain-trained visual encoders with multi-stage language model optimization, coordinated by a multimodal orchestrator. Trained on 13.5 million images (0.25M ECGs, 1.3M echocardiogram images, 12M CMR images) and our novel expert-curated dataset spanning 1.6 million questions, MARCUS achieves state-of-the-art performance surpassing frontier models (GPT-5 Thinking, Gemini 2.5 Pro Deep Think). Across internal (Stanford) and external (UCSF) test cohorts, MARCUS achieves accuracies of 87-91% for ECG, 67-86% for echocardiography, and 85-88% for CMR, outperforming frontier models by 34-45% (P<0.001). On multimodal cases, MARCUS achieved 70% accuracy, nearly triple that of frontier models (22-28%), with 1.7-3.0x higher free-text quality scores. Our agentic architecture also confers resistance to mirage reasoning, whereby vision-language models derive reasoning from unintended textual signals or hallucinated visual content. MARCUS demonstrates that domain-specific visual encoders with an agentic orchestrator enable multimodal cardiac interpretation. We release our models, code, and benchmark open-source.

Rare diseases collectively affect an estimated 3.5% to 5.9% of the population, yet more than 70% of patients are misdiagnosed and many endure years of evaluation before a diagnosis is reached, because early presentations are nonspecific and relevant expertise is scarce and unevenly distributed. Artificial intelligence could provide support, but existing systems address isolated stages of care, overwhelmingly diagnosis. They typically depend on the results of downstream investigations, and they treat the variability between models as noise to be eliminated. Here we present RareLens, a system that supports clinical decision-making across the entire rare disease trajectory by exploiting this variability. When heterogeneous large language models evaluate the same case, they generate divergent but complementary reasoning, which RareLens aligns and calibrates into a single convergent, actionable decision at each stage. Four coordinated modules perform primary-visit risk screening, diagnosis, treatment planning and prognosis. Developed and evaluated on RareBench, a real-world dataset of 157,525 cases spanning all 33 Orphanet categories and more than 7,000 conditions, RareLens outperformed every frontier model tested, including GPT-5, DeepSeek-R1, Claude-3.7-Sonnet and Gemini-2.5-Pro, at each stage. It achieved an area under the curve of 0.917 for screening and top-1 accuracies of 65.5% and 89.8% for diagnosis and treatment. In an external study spanning 1,287 cases and 23 physicians, autonomous RareLens and physicians assisted by RareLens both substantially outperformed unaided physicians. These findings indicate that aligning divergent model reasoning, rather than scaling a single model, offers a generalizable strategy for high-uncertainty clinical decision-making.

This paper presents our team's participation in the MEDIQA-ClinicalNLP2024 shared task B. We present a novel approach to diagnosing clinical dermatology cases by integrating large multimodal models, specifically leveraging the capabilities of GPT-4V under a retriever and a re-ranker framework. Our investigation reveals that GPT-4V, when used as a retrieval agent, can accurately retrieve the correct skin condition 85% of the time using dermatological images and brief patient histories. Additionally, we empirically show that Naive Chain-of-Thought (CoT) works well for retrieval while Medical Guidelines Grounded CoT is required for accurate dermatological diagnosis. Further, we introduce a Multi-Agent Conversation (MAC) framework and show its superior performance and potential over the best CoT strategy. The experiments suggest that using naive CoT for retrieval and multi-agent conversation for critique-based diagnosis, GPT-4V can lead to an early and accurate diagnosis of dermatological conditions. The implications of this work extend to improving diagnostic workflows, supporting dermatological education, and enhancing patient care by providing a scalable, accessible, and accurate diagnostic tool.

Metadata are general characteristics of the data in a well-curated and condensed format, and have been proven to be useful for decision making, knowledge discovery, and also heterogeneous data organization of biobank. Among all data types in the biobank, pathology is the key component of the biobank and also serves as the gold standard of diagnosis. To maximize the utility of biobank and allow the rapid progress of biomedical science, it is essential to organize the data with well-populated pathology metadata. However, manual annotation of such information is tedious and time-consuming. In the study, we develop a multimodal multitask learning framework to predict four major slide-level metadata of pathology images. The framework learns generalizable representations across tissue slides, pathology reports, and case-level structured data. We demonstrate improved performance across all four tasks with the proposed method compared to a single modal single task baseline on two test sets, one external test set from a distinct data source (TCGA) and one internal held-out test set (TTH). In the test sets, the performance improvements on the averaged area under receiver operating characteristic curve across the four tasks are 16.48% and 9.05% on TCGA and TTH, respectively. Such pathology metadata prediction system may be adopted to mitigate the effort of expert annotation and ultimately accelerate the data-driven research by better utilization of the pathology biobank.

Medical images and radiology reports are crucial for diagnosing medical conditions, highlighting the importance of quantitative analysis for clinical decision-making. However, the diversity and cross-source heterogeneity of these data challenge the generalizability of current data-mining methods. Multimodal large language models (MLLMs) have recently transformed many domains, significantly affecting the medical field. Notably, Gemini-Vision-series (Gemini) and GPT-4-series (GPT-4) models have epitomized a paradigm shift in Artificial General Intelligence (AGI) for computer vision, showcasing their potential in the biomedical domain. In this study, we evaluated the performance of the Gemini, GPT-4, and 4 popular large models for an exhaustive evaluation across 14 medical imaging datasets, including 5 medical imaging categories (dermatology, radiology, dentistry, ophthalmology, and endoscopy), and 3 radiology report datasets. The investigated tasks encompass disease classification, lesion segmentation, anatomical localization, disease diagnosis, report generation, and lesion detection. Our experimental results demonstrated that Gemini-series models excelled in report generation and lesion detection but faces challenges in disease classification and anatomical localization. Conversely, GPT-series models exhibited proficiency in lesion segmentation and anatomical localization but encountered difficulties in disease diagnosis and lesion detection. Additionally, both the Gemini series and GPT series contain models that have demonstrated commendable generation efficiency. While both models hold promise in reducing physician workload, alleviating pressure on limited healthcare resources, and fostering collaboration between clinical practitioners and artificial intelligence technologies, substantial enhancements and comprehensive validations remain imperative before clinical deployment.

Rare diseases affect millions of individuals worldwide, yet timely diagnosis remains a major public health challenge due to scarcity of specialized clinical expertise. While large language models (LLMs) show promise to support rare disease diagnosis, current models are constrained by insufficient clinical deployability, limited clinically grounded evidence, and scarcity of training data. Here we present RaDaR (Rare Disease navigatoR), an open-source, compact reasoning LLM (32B parameters) for rare disease diagnosis. RaDaR was trained with 49,170 publicly available free-text cases and 104,666 synthetic cases with reasoning-enhanced training. RaDaR showed the strongest performance among evaluated open-source models, including the 671B DeepSeek-R1, across public benchmarks and four external validation centers. In a retrospective cohort, RaDaR prioritized the final diagnosis before documented clinical suspicion in 61.06 percent of cases, corresponding to a potential lead time of 1.87 months and 50.18 percent of the within-center interval. In a randomized physician-assistance trial, RaDaR assistance improved physicians' rare-disease diagnostic accuracy by 21.44 percentage points compared with internet search alone. Synthetic-data ablations suggested that phenotype-anchored narratives provide useful training signal for long-tail rare diseases, with a monotonic scaling trend within the tested data range. Together, RaDaR and its development and validation framework provide a deployable rare-disease reasoning model and a reproducible development framework for diagnostic AI under data scarcity.

Rare diseases collectively affect over 300 million individuals worldwide, yet timely and accurate diagnosis remains a pervasive challenge. This is largely due to their clinical heterogeneity, low individual prevalence, and the limited familiarity most clinicians have with rare conditions. Here, we introduce DeepRare, the first rare disease diagnosis agentic system powered by a large language model (LLM), capable of processing heterogeneous clinical inputs. The system generates ranked diagnostic hypotheses for rare diseases, each accompanied by a transparent chain of reasoning that links intermediate analytic steps to verifiable medical evidence. DeepRare comprises three key components: a central host with a long-term memory module; specialized agent servers responsible for domain-specific analytical tasks integrating over 40 specialized tools and web-scale, up-to-date medical knowledge sources, ensuring access to the most current clinical information. This modular and scalable design enables complex diagnostic reasoning while maintaining traceability and adaptability. We evaluate DeepRare on eight datasets. The system demonstrates exceptional diagnostic performance among 2,919 diseases, achieving 100% accuracy for 1013 diseases. In HPO-based evaluations, DeepRare significantly outperforms other 15 methods, like traditional bioinformatics diagnostic tools, LLMs, and other agentic systems, achieving an average Recall@1 score of 57.18% and surpassing the second-best method (Reasoning LLM) by a substantial margin of 23.79 percentage points. For multi-modal input scenarios, DeepRare achieves 70.60% at Recall@1 compared to Exomiser's 53.20% in 109 cases. Manual verification of reasoning chains by clinical experts achieves 95.40% agreements. Furthermore, the DeepRare system has been implemented as a user-friendly web application http://raredx.cn/doctor.

Despite achieving high accuracy on medical benchmarks, LLMs exhibit the Einstellung Effect in clinical diagnosis--relying on statistical shortcuts rather than patient-specific evidence, causing misdiagnosis in atypical cases. Existing benchmarks fail to detect this critical failure mode. We introduce MedEinst, a counterfactual benchmark with 5,383 paired clinical cases across 49 diseases. Each pair contains a control case and a "trap" case with altered discriminative evidence that flips the diagnosis. We measure susceptibility via Bias Trap Rate--probability of misdiagnosing traps despite correctly diagnosing controls. Extensive Evaluation of 17 LLMs shows frontier models achieve high baseline accuracy but severe bias trap rates. Thus, we propose ECR-Agent, aligning LLM reasoning with Evidence-Based Medicine standard via two components: (1) Dynamic Causal Inference (DCI) performs structured reasoning through dual-pathway perception, dynamic causal graph reasoning across three levels (association, intervention, counterfactual), and evidence audit for final diagnosis; (2) Critic-Driven Graph and Memory Evolution (CGME) iteratively refines the system by storing validated reasoning paths in an exemplar base and consolidating disease-specific knowledge into evolving illness graphs. Source code is to be released.

We present a general computational theory of cancer and its developmental dynamics. The theory is based on a theory of the architecture and function of developmental control networks which guide the formation of multicellular organisms. Cancer networks are special cases of developmental control networks. Cancer results from transformations of normal developmental networks. Our theory generates a natural classification of all possible cancers based on their network architecture. Each cancer network has a unique topology and semantics and developmental dynamics that result in distinct clinical tumor phenotypes. We apply this new theory with a series of proof of concept cases for all the basic cancer types. These cases have been computationally modeled, their behavior simulated and mathematically described using a multicellular systems biology approach. There are fascinating correspondences between the dynamic developmental phenotype of computationally modeled {\em in silico} cancers and natural {\em in vivo} cancers. The theory lays the foundation for a new research paradigm for understanding and investigating cancer. The theory of cancer networks implies that new diagnostic methods and new treatments to cure cancer will become possible.

WHO has declared that more than 2.2 billion people worldwide are suffering from visual disorders, such as media haze, glaucoma, and drusen. At least 1 billion of these cases could have been either prevented or successfully treated, yet they remain unaddressed due to poverty, a lack of specialists, inaccurate ocular fundus diagnoses by ophthalmologists, or the presence of a rare disease. To address this, the research has developed the Hybrid Trio-Network Model Algorithm for accurately diagnosing 12 distinct common and rare eye diseases. This algorithm utilized the RFMiD dataset of 3,200 fundus images and the Binary Relevance Method to detect diseases separately, ensuring expandability and avoiding incorrect correlations. Each detector, incorporating finely tuned hyperparameters to optimize performance, consisted of three feature components: A classical transfer learning CNN model, a two-stage CNN model, and a Siamese Network. The diagnosis was made using features extracted through this Trio-Model with Ensembled Machine Learning algorithms. The proposed model achieved an average accuracy of 97% and an AUC score of 0.96. Compared to past benchmark studies, an increase of over 10% in the F1-score was observed for most diseases. Furthermore, using the Siamese Network, the model successfully made predictions in diseases like optic disc pallor, which past studies failed to predict due to low confidence. This diagnostic tool presents a stable, adaptive, cost-effective, efficient, accessible, and fast solution for globalizing early detection of both common and rare diseases.

Clinical diagnostic workups typically follow a modality escalation pathway: after initial clinical evaluation, clinicians begin with routine structural imaging (e.g., MRI), selectively add sequences such as FLAIR or T2 to refine the differential, and reserve molecular imaging (e.g., amyloid-PET) for cases that remain uncertain after standard evaluation. Consequently, patients are observed with heterogeneous and often incomplete modality subsets. However, most current AI models assume fixed data modalities as the model inputs. In this paper, we present BrainAnytime, a unified pretraining framework pretrained on 34,899 3D brain scans from five datasets that support brain image analysis under arbitrary modality availability spanning multi-sequence MRI and amyloid-PET. A single model accepts whatever imaging is available, from a lone T1 scan to a full multimodal workup. Pretraining learns structural-molecular correspondences between MRI and PET via cross-modal distillation (RCMD) and prioritizes disease-vulnerable anatomy via atlas-guided curriculum masking (PACM), all within a shared 3D masked autoencoder (Multi-MAE3D). Across four downstream tasks and five clinically motivated modality settings, BrainAnytime largely outperforms modality-specific models, missing-modality baselines, and large-scale brain MRI pretrained foundation models on most modality settings. Notably, it surpasses the strongest missing-modality baselines with relative improvements of 6.2% and 7.0% in average accuracy on CN vs. AD and CN vs. MCI classification, respectively. Code is available at https://github.com/SDH-Lab/BrainAnytime.

Diagnosing and managing a patient is a complex, sequential decision making process that requires physicians to obtain information -- such as which tests to perform -- and to act upon it. Recent advances in artificial intelligence (AI) and large language models (LLMs) promise to profoundly impact clinical care. However, current evaluation schemes overrely on static medical question-answering benchmarks, falling short on interactive decision-making that is required in real-life clinical work. Here, we present AgentClinic: a multimodal benchmark to evaluate LLMs in their ability to operate as agents in simulated clinical environments. In our benchmark, the doctor agent must uncover the patient's diagnosis through dialogue and active data collection. We present two open medical agent benchmarks: a multimodal image and dialogue environment, AgentClinic-NEJM, and a dialogue-only environment, AgentClinic-MedQA. We embed cognitive and implicit biases both in patient and doctor agents to emulate realistic interactions between biased agents. We find that introducing bias leads to large reductions in diagnostic accuracy of the doctor agents, as well as reduced compliance, confidence, and follow-up consultation willingness in patient agents. Evaluating a suite of state-of-the-art LLMs, we find that several models that excel in benchmarks like MedQA are performing poorly in AgentClinic-MedQA. We find that the LLM used in the patient agent is an important factor for performance in the AgentClinic benchmark. We show that both having limited interactions as well as too many interaction reduces diagnostic accuracy in doctor agents. The code and data for this work is publicly available at https://AgentClinic.github.io.