new

Get trending papers in your email inbox!

Subscribe

Daily Papers

byAK and the research community

Jul 20

Meissa: Multi-modal Medical Agentic Intelligence

Multi-modal large language models (MM-LLMs) have shown strong performance in medical image understanding and clinical reasoning. Recent medical agent systems extend them with tool use and multi-agent collaboration, enabling complex decision-making. However, these systems rely almost entirely on frontier models (e.g., GPT), whose API-based deployment incurs high cost, high latency, and privacy risks that conflict with on-premise clinical requirements. We present Meissa, a lightweight 4B-parameter medical MM-LLM that brings agentic capability offline. Instead of imitating static answers, Meissa learns both when to engage external interaction (strategy selection) and how to execute multi-step interaction (strategy execution) by distilling structured trajectories from frontier models. Specifically, we propose: (1) Unified trajectory modeling: trajectories (reasoning and action traces) are represented within a single state-action-observation formalism, allowing one model to generalize across heterogeneous medical environments. (2) Three-tier stratified supervision: the model's own errors trigger progressive escalation from direct reasoning to tool-augmented and multi-agent interaction, explicitly learning difficulty-aware strategy selection. (3) Prospective-retrospective supervision: pairing exploratory forward traces with hindsight-rationalized execution traces enables stable learning of effective interaction policies. Trained on 40K curated trajectories, Meissa matches or exceeds proprietary frontier agents in 10 of 16 evaluation settings across 13 medical benchmarks spanning radiology, pathology, and clinical reasoning. Using over 25x fewer parameters than typical frontier models like Gemini-3, Meissa operates fully offline with 22x lower end-to-end latency compared to API-based deployment. Data, models, and environments are released at https://github.com/Schuture/Meissa.

A Survey on Medical Large Language Models: Technology, Application, Trustworthiness, and Future Directions

With the advent of Large Language Models (LLMs), medical artificial intelligence (AI) has experienced substantial technological progress and paradigm shifts, highlighting the potential of LLMs to streamline healthcare delivery and improve patient outcomes. Considering this rapid technical progress, in this survey, we trace the recent advances of Medical Large Language Models (Med-LLMs), including the background, key findings, and mainstream techniques, especially for the evolution from general-purpose models to medical-specialized applications. Firstly, we delve into the foundational technology of Med-LLMs, indicating how general models can be progressively adapted and refined for the complicated medical tasks. Secondly, the wide-ranging applications of Med-LLMs are investigated across various healthcare domains, as well as an up-to-date review of existing Med-LLMs. The transformative impact of these models on daily medical practice is evident through their ability to assist clinicians, educators, and patients. Recognizing the importance of responsible innovation, we discuss the challenges associated with ensuring fairness, accountability, privacy, and robustness. Ethical considerations, rigorous evaluation methodologies, and the establishment of regulatory frameworks are crucial for building trustworthiness in the real-world system. We emphasize the need for ongoing scrutiny and development to maintain high standards of safety and reliability. Finally, we anticipate possible future trajectories for Med-LLMs, identifying key avenues for prudent expansion. By consolidating these insights, our review aims to provide professionals and researchers with a thorough understanding of the strengths and limitations of Med-LLMs, fostering a balanced and ethical approach to their integration into the healthcare ecosystem.

  • 9 authors
·
Jun 5, 2024

LAMMI-Pathology: A Tool-Centric Bottom-Up LVLM-Agent Framework for Molecularly Informed Medical Intelligence in Pathology

The emergence of tool-calling-based agent systems introduces a more evidence-driven paradigm for pathology image analysis in contrast to the coarse-grained text-image diagnostic approaches. With the recent large-scale experimental adoption of spatial transcriptomics technologies, molecularly validated pathological diagnosis is becoming increasingly open and accessible. In this work, we propose LAMMI-Pathology (LVLM-Agent System for Molecularly Informed Medical Intelligence in Pathology), a scalable agent framework for domain-specific agent tool-calling. LAMMI-Pathology adopts a tool-centric, bottom-up architecture in which customized domain-adaptive tools serve as the foundation. These tools are clustered by domain style to form component agents, which are then coordinated through a top-level planner hierarchically, avoiding excessively long context lengths that could induce task drift. Based on that, we introduce a novel trajectory construction mechanism based on Atomic Execution Nodes (AENs), which serve as reliable and composable units for building semi-simulated reasoning trajectories that capture credible agent-tool interactions. Building on this foundation, we develop a trajectory-aware fine-tuning strategy that aligns the planner's decision-making process with these multi-step reasoning trajectories, thereby enhancing inference robustness in pathology understanding and its adaptive use of the customized toolset.

  • 3 authors
·
Feb 21

MedReseacher-R1: Expert-Level Medical Deep Researcher via A Knowledge-Informed Trajectory Synthesis Framework

Recent developments in Large Language Model (LLM)-based agents have shown impressive capabilities spanning multiple domains, exemplified by deep research systems that demonstrate superior performance on complex information-seeking and synthesis tasks. While general-purpose deep research agents have shown impressive capabilities, they struggle significantly with medical domain challenges, as evidenced by leading proprietary systems achieving limited accuracy on complex medical benchmarks. The key limitations are: (1) the model lacks sufficient dense medical knowledge for clinical reasoning, and (2) the framework is constrained by the absence of specialized retrieval tools tailored for medical contexts.We present a medical deep research agent that addresses these challenges through two core innovations. First, we develop a novel data synthesis framework using medical knowledge graphs, extracting the longest chains from subgraphs around rare medical entities to generate complex multi-hop question-answer pairs. Second, we integrate a custom-built private medical retrieval engine alongside general-purpose tools, enabling accurate medical information synthesis. Our approach generates 2100+ diverse trajectories across 12 medical specialties, each averaging 4.2 tool interactions.Through a two-stage training paradigm combining supervised fine-tuning and online reinforcement learning with composite rewards, our MedResearcher-R1-32B model demonstrates exceptional performance, establishing new state-of-the-art results on medical benchmarks while maintaining competitive performance on general deep research tasks. Our work demonstrates that strategic domain-specific innovations in architecture, tool design, and training data construction can enable smaller open-source models to outperform much larger proprietary systems in specialized domains.

  • 15 authors
·
Aug 20, 2025 2

Uncertainty-Aware Longitudinal Forecasting of Alzheimer's Disease Progression Using Deep Learning

Longitudinal modelling of Alzheimer's disease progression is clinically useful only if it can describe not just the most likely next diagnosis, but how a patient may evolve over time and how reliable that forecast is. Most deep learning approaches reduce this problem to single-step classification, treating cognitively normal, mild cognitive impairment, and dementia as flat categories while providing limited insight into how uncertainty accumulates across future visits. We propose a probabilistic framework that combines ordinal diagnosis prediction, multi-horizon trajectory generation, and decomposed uncertainty estimation. A Temporal Fusion Transformer encoder is adapted with a CORAL ordinal output layer, asymmetric loss weighting, and converter oversampling to respect disease-stage ordering and improve sensitivity to MCI-to-dementia transitions. Conditioned on the learned patient-context representation, an autoregressive Mixture Density Network generates five-year probabilistic trajectories for diagnosis state, CDR Sum of Boxes, MMSE orientation, and hippocampal volume. On ADNI, the model outperforms linear, recurrent, and transformer baselines for next-visit diagnosis prediction, with the strongest gains on MCI-versus-dementia discrimination. Generated trajectories achieve near-nominal 90% credible interval coverage, widening uncertainty across the forecast horizon, and biomarker dynamics consistent with expected Alzheimer's disease progression. We further separate aleatoric from epistemic uncertainty using analytic mixture variance and a five-member bootstrap ensemble, which provides the strongest encoder diversity and output-level epistemic signal. Epistemic uncertainty is higher for rare progression archetypes, MCI and dementia patients, and under external evaluation on OASIS-3, where it increases alongside prediction error.

  • 3 authors
·
Jun 22

Regions are Who Walk Them: a Large Pre-trained Spatiotemporal Model Based on Human Mobility for Ubiquitous Urban Sensing

User profiling and region analysis are two tasks of significant commercial value. However, in practical applications, modeling different features typically involves four main steps: data preparation, data processing, model establishment, evaluation, and optimization. This process is time-consuming and labor-intensive. Repeating this workflow for each feature results in abundant development time for tasks and a reduced overall volume of task development. Indeed, human mobility data contains a wealth of information. Several successful cases suggest that conducting in-depth analysis of population movement data could potentially yield meaningful profiles about users and areas. Nonetheless, most related works have not thoroughly utilized the semantic information within human mobility data and trained on a fixed number of the regions. To tap into the rich information within population movement, based on the perspective that Regions Are Who walk them, we propose a large spatiotemporal model based on trajectories (RAW). It possesses the following characteristics: 1) Tailored for trajectory data, introducing a GPT-like structure with a parameter count of up to 1B; 2) Introducing a spatiotemporal fine-tuning module, interpreting trajectories as collection of users to derive arbitrary region embedding. This framework allows rapid task development based on the large spatiotemporal model. We conducted extensive experiments to validate the effectiveness of our proposed large spatiotemporal model. It's evident that our proposed method, relying solely on human mobility data without additional features, exhibits a certain level of relevance in user profiling and region analysis. Moreover, our model showcases promising predictive capabilities in trajectory generation tasks based on the current state, offering the potential for further innovative work utilizing this large spatiotemporal model.

  • 6 authors
·
Nov 17, 2023

PIE: Simulating Disease Progression via Progressive Image Editing

Disease progression simulation is a crucial area of research that has significant implications for clinical diagnosis, prognosis, and treatment. One major challenge in this field is the lack of continuous medical imaging monitoring of individual patients over time. To address this issue, we develop a novel framework termed Progressive Image Editing (PIE) that enables controlled manipulation of disease-related image features, facilitating precise and realistic disease progression simulation. Specifically, we leverage recent advancements in text-to-image generative models to simulate disease progression accurately and personalize it for each patient. We theoretically analyze the iterative refining process in our framework as a gradient descent with an exponentially decayed learning rate. To validate our framework, we conduct experiments in three medical imaging domains. Our results demonstrate the superiority of PIE over existing methods such as Stable Diffusion Walk and Style-Based Manifold Extrapolation based on CLIP score (Realism) and Disease Classification Confidence (Alignment). Our user study collected feedback from 35 veteran physicians to assess the generated progressions. Remarkably, 76.2% of the feedback agrees with the fidelity of the generated progressions. To our best knowledge, PIE is the first of its kind to generate disease progression images meeting real-world standards. It is a promising tool for medical research and clinical practice, potentially allowing healthcare providers to model disease trajectories over time, predict future treatment responses, and improve patient outcomes.

  • 6 authors
·
Sep 20, 2023 1

ImageFlowNet: Forecasting Multiscale Image-Level Trajectories of Disease Progression with Irregularly-Sampled Longitudinal Medical Images

Advances in medical imaging technologies have enabled the collection of longitudinal images, which involve repeated scanning of the same patients over time, to monitor disease progression. However, predictive modeling of such data remains challenging due to high dimensionality, irregular sampling, and data sparsity. To address these issues, we propose ImageFlowNet, a novel model designed to forecast disease trajectories from initial images while preserving spatial details. ImageFlowNet first learns multiscale joint representation spaces across patients and time points, then optimizes deterministic or stochastic flow fields within these spaces using a position-parameterized neural ODE/SDE framework. The model leverages a UNet architecture to create robust multiscale representations and mitigates data scarcity by combining knowledge from all patients. We provide theoretical insights that support our formulation of ODEs, and motivate our regularizations involving high-level visual features, latent space organization, and trajectory smoothness. We validate ImageFlowNet on three longitudinal medical image datasets depicting progression in geographic atrophy, multiple sclerosis, and glioblastoma, demonstrating its ability to effectively forecast disease progression and outperform existing methods. Our contributions include the development of ImageFlowNet, its theoretical underpinnings, and empirical validation on real-world datasets. The official implementation is available at https://github.com/KrishnaswamyLab/ImageFlowNet.

  • 11 authors
·
Jun 20, 2024

TrajPrism: A Multi-Task Benchmark for Language-Grounded Urban Trajectory Understanding

Urban mobility is naturally expressed both as trajectories in space and as natural-language descriptions of travel intent, constraints, and preferences. However, prior work rarely evaluates these two modalities together on the same real-world trajectories: trajectory modeling often stays geometry-centric, while language-centric mobility benchmarks frequently target route planning and tool use rather than fine-grained, verifiable alignment between text and the underlying route. We introduce TrajPrism, a multi-task benchmark for language-trajectory alignment that unifies (i) instruction-conditioned trajectory generation, (ii) language-driven semantic trajectory retrieval, and (iii) trajectory captioning, together with an evaluation protocol that measures trajectory fidelity, retrieval quality, and language groundedness. We construct TrajPrism by pairing real urban trajectories with judge-filtered language annotations generated under a four-dimensional travel-intent taxonomy. The benchmark contains 300K selected trajectories across Porto, San Francisco, and Beijing, yielding 2.1M task instances from three instruction variants, three retrieval queries, and one caption per trajectory. We further develop proof-of-concept models for each task: TrajAnchor for instruction-conditioned trajectory generation, TrajFuse for semantic trajectory retrieval, and TrajRap for trajectory captioning. These models instantiate the proposed tasks and show that geometry-only trajectory baselines leave a large gap on our protocol, especially where language is part of the input-output interface. We release TrajPrism with code and a reproducible annotation pipeline that is designed to be portable across cities, given compatible trajectory inputs and map resources.

  • 9 authors
·
May 10

MedMemoryBench: Benchmarking Agent Memory in Personalized Healthcare

The large-scale deployment of personalized healthcare agents demands memory mechanisms that are exceptionally precise, safe, and capable of long-term clinical tracking. However, existing benchmarks primarily focus on daily open-domain conversations, failing to capture the high-stakes complexity of real-world medical applications. Motivated by the stringent production requirements of an industry-leading health management agent serving tens of millions of active users, we introduce MedMemoryBench. We develop a human-agent collaborative pipeline to synthesize highly realistic, long-horizon medical trajectories based on clinically grounded, synthetic patient archetypes. This process yields a massive, expertly validated dataset comprising approximately 2,000 sessions and 16,000 interaction turns. Crucially, MedMemoryBench departs from traditional static evaluations by pioneering an "evaluate-while-constructing" streaming assessment protocol, which precisely mirrors dynamic memory accumulation in production environments. Furthermore, we formalize and systematically investigate the critical phenomenon of memory saturation, where sustained information influx actively degrades retrieval and reasoning robustness. Comprehensive benchmarking reveals severe bottlenecks in mainstream architectures, particularly concerning complex medical reasoning and noise resilience. By exposing these fundamental flaws, MedMemoryBench establishes a vital foundation for developing robust, production-ready medical agents.

  • 13 authors
·
May 11

Unify Change Point Detection and Segment Classification in a Regression Task for Transportation Mode Identification

Identifying travelers' transportation modes is important in transportation science and location-based services. It's appealing for researchers to leverage GPS trajectory data to infer transportation modes with the popularity of GPS-enabled devices, e.g., smart phones. Existing studies frame this problem as classification task. The dominant two-stage studies divide the trip into single-one mode segments first and then categorize these segments. The over segmentation strategy and inevitable error propagation bring difficulties to classification stage and make optimizing the whole system hard. The recent one-stage works throw out trajectory segmentation entirely to avoid these by directly conducting point-wise classification for the trip, whereas leaving predictions dis-continuous. To solve above-mentioned problems, inspired by YOLO and SSD in object detection, we propose to reframe change point detection and segment classification as a unified regression task instead of the existing classification task. We directly regress coordinates of change points and classify associated segments. In this way, our method divides the trip into segments under a supervised manner and leverage more contextual information, obtaining predictions with high accuracy and continuity. Two frameworks, TrajYOLO and TrajSSD, are proposed to solve the regression task and various feature extraction backbones are exploited. Exhaustive experiments on GeoLife dataset show that the proposed method has competitive overall identification accuracy of 0.853 when distinguishing five modes: walk, bike, bus, car, train. As for change point detection, our method increases precision at the cost of drop in recall. All codes are available at https://github.com/RadetzkyLi/TrajYOLO-SSD.

  • 2 authors
·
Dec 7, 2023

Clinically-Inspired Multi-Agent Transformers for Disease Trajectory Forecasting from Multimodal Data

Deep neural networks are often applied to medical images to automate the problem of medical diagnosis. However, a more clinically relevant question that practitioners usually face is how to predict the future trajectory of a disease. Current methods for prognosis or disease trajectory forecasting often require domain knowledge and are complicated to apply. In this paper, we formulate the prognosis prediction problem as a one-to-many prediction problem. Inspired by a clinical decision-making process with two agents -- a radiologist and a general practitioner -- we predict prognosis with two transformer-based components that share information with each other. The first transformer in this framework aims to analyze the imaging data, and the second one leverages its internal states as inputs, also fusing them with auxiliary clinical data. The temporal nature of the problem is modeled within the transformer states, allowing us to treat the forecasting problem as a multi-task classification, for which we propose a novel loss. We show the effectiveness of our approach in predicting the development of structural knee osteoarthritis changes and forecasting Alzheimer's disease clinical status directly from raw multi-modal data. The proposed method outperforms multiple state-of-the-art baselines with respect to performance and calibration, both of which are needed for real-world applications. An open-source implementation of our method is made publicly available at https://github.com/Oulu-IMEDS/CLIMATv2.

  • 4 authors
·
Oct 25, 2022

Foresight -- Generative Pretrained Transformer (GPT) for Modelling of Patient Timelines using EHRs

Background: Electronic Health Records hold detailed longitudinal information about each patient's health status and general clinical history, a large portion of which is stored within the unstructured text. Existing approaches focus mostly on structured data and a subset of single-domain outcomes. We explore how temporal modelling of patients from free text and structured data, using deep generative transformers can be used to forecast a wide range of future disorders, substances, procedures or findings. Methods: We present Foresight, a novel transformer-based pipeline that uses named entity recognition and linking tools to convert document text into structured, coded concepts, followed by providing probabilistic forecasts for future medical events such as disorders, substances, procedures and findings. We processed the entire free-text portion from three different hospital datasets totalling 811336 patients covering both physical and mental health. Findings: On tests in two UK hospitals (King's College Hospital, South London and Maudsley) and the US MIMIC-III dataset precision@10 0.68, 0.76 and 0.88 was achieved for forecasting the next disorder in a patient timeline, while precision@10 of 0.80, 0.81 and 0.91 was achieved for forecasting the next biomedical concept. Foresight was also validated on 34 synthetic patient timelines by five clinicians and achieved relevancy of 97% for the top forecasted candidate disorder. As a generative model, it can forecast follow-on biomedical concepts for as many steps as required. Interpretation: Foresight is a general-purpose model for biomedical concept modelling that can be used for real-world risk forecasting, virtual trials and clinical research to study the progression of disorders, simulate interventions and counterfactuals, and educational purposes.

  • 12 authors
·
Dec 13, 2022

Potential of Multimodal Large Language Models for Data Mining of Medical Images and Free-text Reports

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.

  • 14 authors
·
Jul 8, 2024

Forecasting Clinical Risk from Textual Time Series: Structuring Narratives for Temporal AI in Healthcare

Clinical case reports encode temporal patient trajectories that are often underexploited by traditional machine learning methods relying on structured data. In this work, we introduce the forecasting problem from textual time series, where timestamped clinical findings -- extracted via an LLM-assisted annotation pipeline -- serve as the primary input for prediction. We systematically evaluate a diverse suite of models, including fine-tuned decoder-based large language models and encoder-based transformers, on tasks of event occurrence prediction, temporal ordering, and survival analysis. Our experiments reveal that encoder-based models consistently achieve higher F1 scores and superior temporal concordance for short- and long-horizon event forecasting, while fine-tuned masking approaches enhance ranking performance. In contrast, instruction-tuned decoder models demonstrate a relative advantage in survival analysis, especially in early prognosis settings. Our sensitivity analyses further demonstrate the importance of time ordering, which requires clinical time series construction, as compared to text ordering, the format of the text inputs that LLMs are classically trained on. This highlights the additional benefit that can be ascertained from time-ordered corpora, with implications for temporal tasks in the era of widespread LLM use.

Cost-effectiveness analysis for therapy sequence in advanced cancer: A microsimulation approach with application to metastatic prostate cancer

Purpose. Patients with advanced cancer may undergo multiple lines of treatment, switching therapies as their disease progresses. Motivated by a study of metastatic prostate cancer, we develop a microsimulation framework to study therapy sequence. Methods. We propose a discrete-time state transition model to study two lines of anti-cancer therapy. Based on digitized published progression-free survival (PFS) and overall survival (OS) curves, we infer event types (progression or death), and estimate transition probabilities using cumulative incidence functions with competing risks. Our model incorporates within-patient dependence over time, such that response to first-line therapy informs subsequent event probabilities. Parameters governing the degree of within-patient dependence can be used to calibrate the model-based results to those of a target trial. We demonstrate these methods in a study of two therapy sequences for metastatic prostate cancer, where Docetaxel (DCT) and Abiraterone Acetate (AA) are both appropriate for use in either first or second line treatment. We assess costs, Quality-Adjusted Life Years (QALYs) and Incremental Cost Effectiveness Ratio (ICER) for two treatment strategies: DCT then AA vs AA then DCT. Results. Using digitized survival curves from relevant clinical trials, we identified 8.6-13.9% of PFS times that should be categorized as deaths, allowing for estimation of cumulative incidence functions. Models assuming within-patient independence overestimated OS time, corrected with our calibration approach. Correction resulted in meaningful changes in the difference in QALYs between treatment strategies (0.07 vs 0.15) and the ICER (-\76,836/QALY vs -21,030/QALY). Conclusions. Microsimulation models can be successfully used to study cost-effectiveness of therapy sequences, taking care to account correctly for within-patient dependence.

  • 5 authors
·
Oct 10, 2022

A multimodal and temporal foundation model for virtual patient representations at healthcare system scale

Modern medicine generates vast multimodal data across siloed systems, yet no existing model integrates the full breadth and temporal depth of the clinical record into a unified patient representation. We introduce Apollo, a multimodal temporal foundation model trained and evaluated on over three decades of longitudinal hospital records from a major US hospital system, composed of 25 billion records from 7.2 million patients, representing 28 distinct medical modalities and 12 major medical specialties. Apollo learns a unified representation space integrating over 100 thousand unique medical events in our clinical vocabulary as well as images and clinical text. This "atlas of medical concepts" forms a computational substrate for modeling entire patient care journeys comprised of sequences of structured and unstructured events, which are compressed by Apollo into virtual patient representations. To assess the potential of these whole-patient representations, we created 322 prognosis and retrieval tasks from a held-out test set of 1.4 million patients. We demonstrate the generalized clinical forecasting potential of Apollo embeddings, including predicting new disease onset risk up to five years in advance (95 tasks), disease progression (78 tasks), treatment response (59 tasks), risk of treatment-related adverse events (17 tasks), and hospital operations endpoints (12 tasks). Using feature attribution techniques, we show that model predictions align with clinically-interpretable multimodal biomarkers. We evaluate semantic similarity search on 61 retrieval tasks, and moreover demonstrate the potential of Apollo as a multimodal medical search engine using text and image queries. Together, these modeling capabilities establish the foundation for computable medicine, where the full context of patient care becomes accessible to computational reasoning.

  • 11 authors
·
Apr 20

Think over Trajectories: Leveraging Video Generation to Reconstruct GPS Trajectories from Cellular Signaling

Mobile devices continuously interact with cellular base stations, generating massive volumes of signaling records that provide broad coverage for understanding human mobility. However, such records offer only coarse location cues (e.g., serving-cell identifiers) and therefore limit their direct use in applications that require high-precision GPS trajectories. This paper studies the Sig2GPS problem: reconstructing GPS trajectories from cellular signaling. Inspired by domain experts often lay the signaling trace on the map and sketch the corresponding GPS route, unlike conventional solutions that rely on complex multi-stage engineering pipelines or regress coordinates, Sig2GPS is reframed as an image-to-video generation task that directly operates in the map-visual domain: signaling traces are rendered on a map, and a video generation model is trained to draw a continuous GPS path. To support this paradigm, a paired signaling-to-trajectory video dataset is constructed to fine-tune an open-source video model, and a trajectory-aware reinforcement learning-based optimization method is introduced to improve generation fidelity via rewards. Experiments on large-scale real-world datasets show substantial improvements over strong engineered and learning-based baselines, while additional results on next GPS prediction indicate scalability and cross-city transferability. Overall, these results suggest that map-visual video generation provides a practical interface for trajectory data mining by enabling direct generation and refinement of continuous paths under map constraints.

  • 6 authors
·
Mar 27 2

The Patient is not a Moving Document: A World Model Training Paradigm for Longitudinal EHR

Large language models (LLMs) trained with next-word-prediction have achieved success as clinical foundation models. Representations from these language backbones yield strong linear probe performance across biomedical tasks, suggesting that patient semantics emerge from next-token prediction at scale. However, this paradigm treats patients as a document to be summarized rather than a dynamical system to be simulated; a patient's trajectory emerges from their state evolving under interventions and time, requiring models that simulate dynamics rather than predict tokens. To address this, we introduce SMB-Structure, a world model for structured EHR that grounds a joint-embedding prediction architecture (JEPA) with next-token prediction (SFT). SFT grounds our model to reconstruct future patient states in token space, while JEPA predicts those futures in latent space from the initial patient representation alone, forcing trajectory dynamics to be encoded before the next state is observed. We validate across two large-scale cohorts: Memorial Sloan Kettering (23,319 oncology patients; 323,000+ patient-years) and INSPECT (19,402 pulmonary embolism patients). Using a linear probe evaluated at multiple points along the disease trajectory, we demonstrate that our training paradigm learns embeddings that capture disease dynamics not recoverable by autoregressive baselines, enabling SMB-Structure to achieve competitive performance on complex tasks characterized by high patient heterogeneity. Model weights are available at https://huggingface.co/standardmodelbio/SMB-v1-1.7B-Structure.

  • 8 authors
·
Jan 29

MedSAM-Agent: Empowering Interactive Medical Image Segmentation with Multi-turn Agentic Reinforcement Learning

Medical image segmentation is evolving from task-specific models toward generalizable frameworks. Recent research leverages Multi-modal Large Language Models (MLLMs) as autonomous agents, employing reinforcement learning with verifiable reward (RLVR) to orchestrate specialized tools like the Segment Anything Model (SAM). However, these approaches often rely on single-turn, rigid interaction strategies and lack process-level supervision during training, which hinders their ability to fully exploit the dynamic potential of interactive tools and leads to redundant actions. To bridge this gap, we propose MedSAM-Agent, a framework that reformulates interactive segmentation as a multi-step autonomous decision-making process. First, we introduce a hybrid prompting strategy for expert-curated trajectory generation, enabling the model to internalize human-like decision heuristics and adaptive refinement strategies. Furthermore, we develop a two-stage training pipeline that integrates multi-turn, end-to-end outcome verification with a clinical-fidelity process reward design to promote interaction parsimony and decision efficiency. Extensive experiments across 6 medical modalities and 21 datasets demonstrate that MedSAM-Agent achieves state-of-the-art performance, effectively unifying autonomous medical reasoning with robust, iterative optimization. Code is available https://github.com/CUHK-AIM-Group/MedSAM-Agent{here}.

  • 9 authors
·
Feb 3 3

EigenTrajectory: Low-Rank Descriptors for Multi-Modal Trajectory Forecasting

Capturing high-dimensional social interactions and feasible futures is essential for predicting trajectories. To address this complex nature, several attempts have been devoted to reducing the dimensionality of the output variables via parametric curve fitting such as the B\'ezier curve and B-spline function. However, these functions, which originate in computer graphics fields, are not suitable to account for socially acceptable human dynamics. In this paper, we present EigenTrajectory (ET), a trajectory prediction approach that uses a novel trajectory descriptor to form a compact space, known here as ET space, in place of Euclidean space, for representing pedestrian movements. We first reduce the complexity of the trajectory descriptor via a low-rank approximation. We transform the pedestrians' history paths into our ET space represented by spatio-temporal principle components, and feed them into off-the-shelf trajectory forecasting models. The inputs and outputs of the models as well as social interactions are all gathered and aggregated in the corresponding ET space. Lastly, we propose a trajectory anchor-based refinement method to cover all possible futures in the proposed ET space. Extensive experiments demonstrate that our EigenTrajectory predictor can significantly improve both the prediction accuracy and reliability of existing trajectory forecasting models on public benchmarks, indicating that the proposed descriptor is suited to represent pedestrian behaviors. Code is publicly available at https://github.com/inhwanbae/EigenTrajectory .

  • 3 authors
·
Jul 18, 2023

Advancing Multimodal Medical Capabilities of Gemini

Many clinical tasks require an understanding of specialized data, such as medical images and genomics, which is not typically found in general-purpose large multimodal models. Building upon Gemini's multimodal models, we develop several models within the new Med-Gemini family that inherit core capabilities of Gemini and are optimized for medical use via fine-tuning with 2D and 3D radiology, histopathology, ophthalmology, dermatology and genomic data. Med-Gemini-2D sets a new standard for AI-based chest X-ray (CXR) report generation based on expert evaluation, exceeding previous best results across two separate datasets by an absolute margin of 1% and 12%, where 57% and 96% of AI reports on normal cases, and 43% and 65% on abnormal cases, are evaluated as "equivalent or better" than the original radiologists' reports. We demonstrate the first ever large multimodal model-based report generation for 3D computed tomography (CT) volumes using Med-Gemini-3D, with 53% of AI reports considered clinically acceptable, although additional research is needed to meet expert radiologist reporting quality. Beyond report generation, Med-Gemini-2D surpasses the previous best performance in CXR visual question answering (VQA) and performs well in CXR classification and radiology VQA, exceeding SoTA or baselines on 17 of 20 tasks. In histopathology, ophthalmology, and dermatology image classification, Med-Gemini-2D surpasses baselines across 18 out of 20 tasks and approaches task-specific model performance. Beyond imaging, Med-Gemini-Polygenic outperforms the standard linear polygenic risk score-based approach for disease risk prediction and generalizes to genetically correlated diseases for which it has never been trained. Although further development and evaluation are necessary in the safety-critical medical domain, our results highlight the potential of Med-Gemini across a wide range of medical tasks.

  • 47 authors
·
May 6, 2024

ESL-Bench: An Event-Driven Synthetic Longitudinal Benchmark for Health Agents

Longitudinal health agents must reason across multi-source trajectories that combine continuous device streams, sparse clinical exams, and episodic life events - yet evaluating them is hard: real-world data cannot be released at scale, and temporally grounded attribution questions seldom admit definitive answers without structured ground truth. We present ESL-Bench, an event-driven synthesis framework and benchmark providing 100 synthetic users, each with a 1-5 year trajectory comprising a health profile, a multi-phase narrative plan, daily device measurements, periodic exam records, and an event log with explicit per-indicator impact parameters. Each indicator follows a baseline stochastic process driven by discrete events with sigmoid-onset, exponential-decay kernels under saturation and projection constraints; a hybrid pipeline delegates sparse semantic artifacts to LLM-based planning and dense indicator dynamics to algorithmic simulation with hard physiological bounds. Users are each paired with 100 evaluation queries across five dimensions - Lookup, Trend, Comparison, Anomaly, Explanation - stratified into Easy, Medium, and Hard tiers, with all ground-truth answers programmatically computable from the recorded event-indicator relationships. Evaluating 13 methods spanning LLMs with tools, DB-native agents, and memory-augmented RAG, we find that DB agents (48-58%) substantially outperform memory RAG baselines (30-38%), with the gap concentrated on Comparison and Explanation queries where multi-hop reasoning and evidence attribution are required.

  • 10 authors
·
Apr 2

Artificial Intelligence for Personalized Prediction of Alzheimer's Disease Progression: A Survey of Methods, Data Challenges, and Future Directions

Alzheimer's Disease (AD) is marked by significant inter-individual variability in its progression, complicating accurate prognosis and personalized care planning. This heterogeneity underscores the critical need for predictive models capable of forecasting patient-specific disease trajectories. Artificial Intelligence (AI) offers powerful tools to address this challenge by analyzing complex, multi-modal, and longitudinal patient data. This paper provides a comprehensive survey of AI methodologies applied to personalized AD progression prediction. We review key approaches including state-space models for capturing temporal dynamics, deep learning techniques like Recurrent Neural Networks for sequence modeling, Graph Neural Networks (GNNs) for leveraging network structures, and the emerging concept of AI-driven digital twins for individualized simulation. Recognizing that data limitations often impede progress, we examine common challenges such as high dimensionality, missing data, and dataset imbalance. We further discuss AI-driven mitigation strategies, with a specific focus on synthetic data generation using Variational Autoencoders (VAEs) and Generative Adversarial Networks (GANs) to augment and balance datasets. The survey synthesizes the strengths and limitations of current approaches, emphasizing the trend towards multimodal integration and the persistent need for model interpretability and generalizability. Finally, we identify critical open challenges, including robust external validation, clinical integration, and ethical considerations, and outline promising future research directions such as hybrid models, causal inference, and federated learning. This review aims to consolidate current knowledge and guide future efforts in developing clinically relevant AI tools for personalized AD prognostication.

  • 4 authors
·
Apr 29, 2025

Multi-marginal Schrödinger Bridges with Iterative Reference Refinement

Practitioners frequently aim to infer an unobserved population trajectory using sample snapshots at multiple time points. For instance, in single-cell sequencing, scientists would like to learn how gene expression evolves over time. But sequencing any cell destroys that cell. So we cannot access any cell's full trajectory, but we can access snapshot samples from many cells. Stochastic differential equations are commonly used to analyze systems with full individual-trajectory access; since here we have only sample snapshots, these methods are inapplicable. The deep learning community has recently explored using Schr\"odinger bridges (SBs) and their extensions to estimate these dynamics. However, these methods either (1) interpolate between just two time points or (2) require a single fixed reference dynamic within the SB, which is often just set to be Brownian motion. But learning piecewise from adjacent time points can fail to capture long-term dependencies. And practitioners are typically able to specify a model class for the reference dynamic but not the exact values of the parameters within it. So we propose a new method that (1) learns the unobserved trajectories from sample snapshots across multiple time points and (2) requires specification only of a class of reference dynamics, not a single fixed one. In particular, we suggest an iterative projection method inspired by Schr\"odinger bridges; we alternate between learning a piecewise SB on the unobserved trajectories and using the learned SB to refine our best guess for the dynamics within the reference class. We demonstrate the advantages of our method via a well-known simulated parametric model from ecology, simulated and real data from systems biology, and real motion-capture data.

  • 3 authors
·
Aug 12, 2024

Capabilities of Gemini Models in Medicine

Excellence in a wide variety of medical applications poses considerable challenges for AI, requiring advanced reasoning, access to up-to-date medical knowledge and understanding of complex multimodal data. Gemini models, with strong general capabilities in multimodal and long-context reasoning, offer exciting possibilities in medicine. Building on these core strengths of Gemini, we introduce Med-Gemini, a family of highly capable multimodal models that are specialized in medicine with the ability to seamlessly use web search, and that can be efficiently tailored to novel modalities using custom encoders. We evaluate Med-Gemini on 14 medical benchmarks, establishing new state-of-the-art (SoTA) performance on 10 of them, and surpass the GPT-4 model family on every benchmark where a direct comparison is viable, often by a wide margin. On the popular MedQA (USMLE) benchmark, our best-performing Med-Gemini model achieves SoTA performance of 91.1% accuracy, using a novel uncertainty-guided search strategy. On 7 multimodal benchmarks including NEJM Image Challenges and MMMU (health & medicine), Med-Gemini improves over GPT-4V by an average relative margin of 44.5%. We demonstrate the effectiveness of Med-Gemini's long-context capabilities through SoTA performance on a needle-in-a-haystack retrieval task from long de-identified health records and medical video question answering, surpassing prior bespoke methods using only in-context learning. Finally, Med-Gemini's performance suggests real-world utility by surpassing human experts on tasks such as medical text summarization, alongside demonstrations of promising potential for multimodal medical dialogue, medical research and education. Taken together, our results offer compelling evidence for Med-Gemini's potential, although further rigorous evaluation will be crucial before real-world deployment in this safety-critical domain.

  • 66 authors
·
Apr 29, 2024 3

Geometric Trajectory Diffusion Models

Generative models have shown great promise in generating 3D geometric systems, which is a fundamental problem in many natural science domains such as molecule and protein design. However, existing approaches only operate on static structures, neglecting the fact that physical systems are always dynamic in nature. In this work, we propose geometric trajectory diffusion models (GeoTDM), the first diffusion model for modeling the temporal distribution of 3D geometric trajectories. Modeling such distribution is challenging as it requires capturing both the complex spatial interactions with physical symmetries and temporal correspondence encapsulated in the dynamics. We theoretically justify that diffusion models with equivariant temporal kernels can lead to density with desired symmetry, and develop a novel transition kernel leveraging SE(3)-equivariant spatial convolution and temporal attention. Furthermore, to induce an expressive trajectory distribution for conditional generation, we introduce a generalized learnable geometric prior into the forward diffusion process to enhance temporal conditioning. We conduct extensive experiments on both unconditional and conditional generation in various scenarios, including physical simulation, molecular dynamics, and pedestrian motion. Empirical results on a wide suite of metrics demonstrate that GeoTDM can generate realistic geometric trajectories with significantly higher quality.

  • 5 authors
·
Oct 16, 2024

Causal Longitudinal Prior-Fitted Networks for Counterfactual Outcome Prediction

Longitudinal treatment decisions require predicting potential outcomes under future treatment sequences in the presence of time-varying confounding, heterogeneous patient dynamics, and limited domain-specific data. Existing longitudinal causal estimators typically train a new model for each cohort or simulator. We introduce Causal Longitudinal Prior-Fitted Networks (CausalLongPFN), a prior-fitted in-context predictor for longitudinal causal prediction. The model is pretrained entirely on synthetic episodes sampled from a broad prior over temporal structural causal models, exposing it to treatment-confounder feedback, latent heterogeneity, nonlinear state evolution, delayed effects, and cumulative treatment responses. At test time, CausalLongPFN is frozen: it conditions on support trajectories, a query history, and a proposed future treatment sequence, and returns a predictive distribution over future outcomes without gradient updates or propensity-model fitting. Multi-step predictions are obtained by recursively applying the one-step predictor under the specified treatment sequence. We evaluate on branchable cancer, HIV, and warfarin benchmarks with ground-truth counterfactual labels, and on factual-only rolling-origin prediction in MIMIC-III ICU trajectories. CausalLongPFN is competitive with domain-trained longitudinal baselines on counterfactual benchmarks and performs strongly on factual MIMIC-III prediction, suggesting that broad synthetic causal pretraining can provide a useful frozen alternative when repeated domain-specific training is costly or impractical.

  • 5 authors
·
Jun 3

MedReason: Eliciting Factual Medical Reasoning Steps in LLMs via Knowledge Graphs

Medical tasks such as diagnosis and treatment planning require precise and complex reasoning, particularly in life-critical domains. Unlike mathematical reasoning, medical reasoning demands meticulous, verifiable thought processes to ensure reliability and accuracy. However, there is a notable lack of datasets that provide transparent, step-by-step reasoning to validate and enhance the medical reasoning ability of AI models. To bridge this gap, we introduce MedReason, a large-scale high-quality medical reasoning dataset designed to enable faithful and explainable medical problem-solving in large language models (LLMs). We utilize a structured medical knowledge graph (KG) to convert clinical QA pairs into logical chains of reasoning, or ``thinking paths'', which trace connections from question elements to answers via relevant KG entities. Each path is validated for consistency with clinical logic and evidence-based medicine. Our pipeline generates detailed reasoning for various medical questions from 7 medical datasets, resulting in a dataset of 32,682 question-answer pairs, each with detailed, step-by-step explanations. Experiments demonstrate that fine-tuning with our dataset consistently boosts medical problem-solving capabilities, achieving significant gains of up to 7.7% for DeepSeek-Ditill-8B. Our top-performing model, MedReason-8B, outperforms the Huatuo-o1-8B, a state-of-the-art medical reasoning model, by up to 4.2% on the clinical benchmark MedBullets. We also engage medical professionals from diverse specialties to assess our dataset's quality, ensuring MedReason offers accurate and coherent medical reasoning. Our data, models, and code will be publicly available.

  • 15 authors
·
Apr 1, 2025

TimelyGPT: Extrapolatable Transformer Pre-training for Long-term Time-Series Forecasting in Healthcare

Large-scale pre-trained models (PTMs) such as BERT and GPT have recently achieved great success in Natural Language Processing and Computer Vision domains. However, the development of PTMs on healthcare time-series data is lagging behind.This underscores the limitations of the existing transformer-based architectures, particularly their scalability to handle large-scale time series and ability to capture long-term temporal dependencies. In this study, we present Timely Generative Pre-trained Transformer (TimelyGPT). TimelyGPT employs an extrapolatable position (xPos) embedding to encode trend and periodic patterns into time-series representations. It also integrates recurrent attention and temporal convolution modules to effectively capture global-local temporal dependencies. We evaluated TimelyGPT on two large-scale healthcare time series datasets corresponding to continuous biosignals and irregularly-sampled time series, respectively. Our experiments show that during pre-training, TimelyGPT excels in learning time-series representations from continuously monitored biosignals and irregularly-sampled time series data commonly observed in longitudinal electronic health records (EHRs). In forecasting continuous biosignals, TimelyGPT achieves accurate extrapolation up to 6,000 timesteps of body temperature during the sleep stage transition, given a short look-up window (i.e., prompt) containing only 2,000 timesteps. For irregularly-sampled time series, TimelyGPT with a proposed time-specific inference demonstrates high top recall scores in predicting future diagnoses using early diagnostic records, effectively handling irregular intervals between clinical records. Together, we envision TimelyGPT to be useful in a broad spectrum of health domains, including long-term patient health state forecasting and patient risk trajectory prediction.

  • 6 authors
·
Nov 29, 2023

Mozi: Governed Autonomy for Drug Discovery LLM Agents

Tool-augmented large language model (LLM) agents promise to unify scientific reasoning with computation, yet their deployment in high-stakes domains like drug discovery is bottlenecked by two critical barriers: unconstrained tool-use governance and poor long-horizon reliability. In dependency-heavy pharmaceutical pipelines, autonomous agents often drift into irreproducible trajectories, where early-stage hallucinations multiplicatively compound into downstream failures. To overcome this, we present Mozi, a dual-layer architecture that bridges the flexibility of generative AI with the deterministic rigor of computational biology. Layer A (Control Plane) establishes a governed supervisor--worker hierarchy that enforces role-based tool isolation, limits execution to constrained action spaces, and drives reflection-based replanning. Layer B (Workflow Plane) operationalizes canonical drug discovery stages -- from Target Identification to Lead Optimization -- as stateful, composable skill graphs. This layer integrates strict data contracts and strategic human-in-the-loop (HITL) checkpoints to safeguard scientific validity at high-uncertainty decision boundaries. Operating on the design principle of ``free-form reasoning for safe tasks, structured execution for long-horizon pipelines,'' Mozi provides built-in robustness mechanisms and trace-level audibility to completely mitigate error accumulation. We evaluate Mozi on PharmaBench, a curated benchmark for biomedical agents, demonstrating superior orchestration accuracy over existing baselines. Furthermore, through end-to-end therapeutic case studies, we demonstrate Mozi's ability to navigate massive chemical spaces, enforce stringent toxicity filters, and generate highly competitive in silico candidates, effectively transforming the LLM from a fragile conversationalist into a reliable, governed co-scientist.