Daily Papers

Musculoskeletal diseases are among the leading causes of disability worldwide and create the greatest global need for rehabilitation. Because recovery, remodelling and degeneration often unfold over months to years, musculoskeletal care requires longitudinal management that repeatedly integrates evolving patient evidence, external medical knowledge and stage-specific functional goals. In routine practice, this evidence is fragmented across visits, departments and hospital systems, limiting individualized, evidence-based care. Here we report OrthoPilot, a clinical artificial intelligence system powered by a large language model that integrates hospital data streams with authoritative external knowledge for continuous musculoskeletal management. OrthoPilot autonomously retrieves real-time imaging, laboratory, pathology and order data and converts evolving patient states into evidence-based decisions from admission diagnosis to rehabilitation planning. We established a specialist-validated benchmark from real-world electronic health records spanning 1,000 disease codes. In a reader study across the complete care pathway, OrthoPilot was compared with 81 orthopaedic physicians and surpassed experts with 25 years of experience in diagnostic reasoning, clinical decision-making and management planning. It also outperformed all evaluated intelligent systems across 60 external clinical centres. In a prospective study of 1,870 complex cases, OrthoPilot increased full-chain management success by 10.6%. During an 8-month randomised deployment involving 8,240 inpatients, it increased cumulative cases per bed by 9.7% and improved patient-reported access to health information. These results move clinical AI from predicting isolated events toward executing longitudinal management across complete musculoskeletal care pathways.

Large language models (LLMs) are increasingly proposed as clinical agents, yet static, single-turn benchmarks cannot capture how a model dynamically delivers care across an encounter: gathering information, planning treatment, and adapting longitudinal management across successive patient states. Medical education has long addressed an analogous challenge through standardized patients (SPs): trained actors who consistently portray clinical cases, enabling realistic practice and objective, scripted assessment. Here we introduce MedSP1000, an SP-derived interactive benchmark for clinical-agent evaluation, including 1,638 SP cases with 24,602 trajectory-level peer-reviewed rubrics. MedSP1000 converts peer-reviewed SP teaching cases into executable scenarios with defined SP case scripts, clinical environment contexts, and human-validated structured rubric. In each simulation evaluation run, a clinical agent interacts in closed loop with a patient agent and an environment controller, and its behaviour is scored throughout the encounter against expert criteria specified in the original materials. Applying MedSP1000 to a range of general-purpose and medically specialized LLMs, we find that performance on static benchmarks does not reliably translate to such educational scenarios. The best-performing model, GPT-5.5, completes only 60.4% of expert-defined rubric items, whereas the strongest medically specialized model reaches 40.0%; increasing test-time compute produces no measurable gain. These results suggest that current LLMs, including agentic systems tuned for medicine, are not yet reliable enough to be safely integrated into actual clinical practice. More broadly, MedSP1000 shows how process-level, SP-style evaluation can reveal clinically relevant failure modes that single-turn benchmarks miss.

Large language model (LLM) agents extend generative models with reasoning, tool use, and persistent memory, thereby enabling the automation of complex tasks. In healthcare, such systems could support documentation, care coordination, and clinical decision making. Their reliable deployment in hospitals, however, remains constrained by safety risks, limited transparency, and inadequate mechanisms for handling longitudinal clinical context. Here we propose an architecture that adapts LLM agents to hospital environments. The design comprises four components: a restricted execution environment inspired by multi-user operating systems, a document-centric interaction model linking patient and clinician agents, a page-indexed memory architecture for longitudinal context management, and a curated library of composable medical skills. Implemented on top of OpenClaw, an open-source agent orchestration framework, this design provides the basis for an Agentic Operating System for Hospitals: a computing layer for coordinating clinical workflows while preserving safety, transparency, and auditability. To evaluate the memory component, we introduce manifest-guided retrieval for hierarchical navigation of longitudinal patient records. In a benchmark derived from the MIMIC-IV dataset (v2.2) comprising 100 de-identified patient records and 300 clinical queries stratified across three difficulty tiers (100 per tier), manifest-guided retrieval matched a metadata-filtered RAG baseline on overall recall (0.877 versus 0.876) while achieving 2.2x higher precision (0.779 versus 0.352) and retrieving fewer documents; on tier-3 longitudinal queries, manifest recall was 21% higher (0.846 versus 0.701), confirming that LLM-guided hierarchical navigation is most valuable when queries span multiple care episodes. These results outline a practical path toward hospital-scale agentic infrastructure.

Medical large language models and agents show strong single-encounter question answering and evidence interpretation but struggle to accumulate and govern experience across encounters. We present HealthJev, an open-source agent separating shared safety rules and medical knowledge from a private longitudinal memory and distilling lessons from completed cases. To filter out erroneous lessons before they affect future behaviour, we self-train JevGate, a lightweight System-One model that decides which lessons enter memory; each decision takes a median of 86 milliseconds and about 1,000 input tokens, sustaining experience accumulation at negligible run-time overhead. On a longitudinal benchmark of 90-day simulated daily interactions for 20 users built from real MIMIC-IV trajectories, HealthJev outperformed a memory-free ReAct agent and three memory-augmented frameworks, with all paired comparisons significant. Across six tasks spanning clinical records, medical imaging, genomics and clinical text, HealthJev improved every task with a mean gain of 13.3 percentage points over the base condition, surpassing all baselines. The frozen library transferred to six further backbones with macro-average gains of 6.8 to 15.1 percentage points, and one task's library brought gains on other tasks. These results indicate that governed, self-evolving memory supports longitudinal personal health management beyond single encounters. HealthJev is publicly available at https://github.com/HC-Guo/Self-Evolving_HealthJev.

Monitoring cow body weight is crucial to support farm management decisions due to its direct relationship with the growth, nutritional status, and health of dairy cows. Cow body weight is a repeated trait, however, the majority of previous body weight prediction research only used data collected at a single point in time. Furthermore, the utility of deep learning-based segmentation for body weight prediction using videos remains unanswered. Therefore, the objectives of this study were to predict cow body weight from repeatedly measured video data, to compare the performance of the thresholding and Mask R-CNN deep learning approaches, to evaluate the predictive ability of body weight regression models, and to promote open science in the animal science community by releasing the source code for video-based body weight prediction. A total of 40,405 depth images and depth map files were obtained from 10 lactating Holstein cows and 2 non-lactating Jersey cows. Three approaches were investigated to segment the cow's body from the background, including single thresholding, adaptive thresholding, and Mask R-CNN. Four image-derived biometric features, such as dorsal length, abdominal width, height, and volume, were estimated from the segmented images. On average, the Mask-RCNN approach combined with a linear mixed model resulted in the best prediction coefficient of determination and mean absolute percentage error of 0.98 and 2.03%, respectively, in the forecasting cross-validation. The Mask-RCNN approach was also the best in the leave-three-cows-out cross-validation. The prediction coefficients of determination and mean absolute percentage error of the Mask-RCNN coupled with the linear mixed model were 0.90 and 4.70%, respectively. Our results suggest that deep learning-based segmentation improves the prediction performance of cow body weight from longitudinal depth video data.

To overcome the limitations of manual administrative coding in geriatric Cardiovascular Risk Management, this study introduces an automated classification framework leveraging unstructured Electronic Health Records (EHRs). Using a dataset of 3,482 patients, we benchmarked three distinct modeling paradigms on longitudinal Dutch clinical narratives: classical machine learning baselines, specialized deep learning architectures optimized for large-context sequences, and general-purpose generative Large Language Models (LLMs) in a zero-shot setting. Additionally, we evaluated a late fusion strategy to integrate unstructured text with structured medication embeddings and anthropometric data. Our analysis reveals that the custom Transformer architecture outperforms both traditional methods and generative llms, achieving the highest F1-scores and Matthews Correlation Coefficients. These findings underscore the critical role of specialized hierarchical attention mechanisms in capturing long-range dependencies within medical texts, presenting a robust, automated alternative to manual workflows for clinical risk stratification.

Large language models (LLMs) in psychological counseling have attracted increasing attention. However, existing approaches often lack emotional understanding, adaptive strategies, and the use of therapeutic methods across multiple sessions with long-term memory, leaving them far from real clinical practice. To address these critical gaps, we introduce TheraMind, a strategic and adaptive agent for longitudinal psychological counseling. The cornerstone of TheraMind is a novel dual-loop architecture that decouples the complex counseling process into an Intra-Session Loop for tactical dialogue management and a Cross-Session Loop for strategic therapeutic planning. The Intra-Session Loop perceives the patient's emotional state to dynamically select response strategies while leveraging cross-session memory to ensure continuity. Crucially, the Cross-Session Loop empowers the agent with long-term adaptability by evaluating the efficacy of the applied therapy after each session and adjusting the method for subsequent interactions. We validate our approach in a high-fidelity simulation environment grounded in real clinical cases. Extensive evaluations show that TheraMind outperforms other methods, especially on multi-session metrics like Coherence, Flexibility, and Therapeutic Attunement, validating the effectiveness of its dual-loop design in emulating strategic, adaptive, and longitudinal therapeutic behavior. The code is publicly available at https://0mwwm0.github.io/TheraMind/.

For the early identification, diagnosis, and treatment of mental health illnesses, the integration of deep learning (DL) and machine learning (ML) has started playing a significant role. By evaluating complex data from imaging, genetics, and behavioral assessments, these technologies have the potential to significantly improve clinical outcomes. However, they also present unique challenges related to data integration and ethical issues. This survey reviews the development of ML and DL methods for the early diagnosis and treatment of mental health issues. It examines a range of applications, with a particular emphasis on behavioral assessments, genetic and biomarker analysis, and medical imaging for diagnosing diseases like depression, bipolar disorder, and schizophrenia. Predictive modeling for illness progression is further discussed, focusing on the role of risk prediction models and longitudinal studies. Key findings highlight how ML and DL can improve diagnostic accuracy and treatment outcomes while addressing methodological inconsistencies, data integration challenges, and ethical concerns. The study emphasizes the importance of building real-time monitoring systems for individualized treatment, enhancing data fusion techniques, and fostering interdisciplinary collaboration. Future research should focus on overcoming these obstacles to ensure the valuable and ethical application of ML and DL in mental health services.

In medical imaging, the clinical value of Computed Tomography (CT) lies not only in depicting current disease status, but crucially in enabling longitudinal comparison of serial scans to determine disease evolution, a process that underpins response assessment, recurrence detection, and ongoing patient management. Yet, despite this central role of temporal comparison in clinical decision-making, existing medical foundation models remain largely confined to single-study understanding, leaving temporally grounded cross-examination insufficiently addressed. To address this gap, we study longitudinal imaging difference reporting, a task in which a model takes two temporally separated scans from the same patient and generates a clinically meaningful report describing interval changes between them. We introduce CT-ΔBench, a dedicated benchmark for this task with patient-level splitting to prevent information leakage. To better evaluate this task beyond surface-level text similarity, we further develop change-aware metrics specifically designed to capture clinically meaningful longitudinal changes, and conduct an independent physician validation to assess the reliability of the synthesized references and event extraction pipeline. We also compare direct paired-CT reasoning with an indirect two-stage pipeline that first generates single-timepoint reports and then performs textual differencing. Finally, we propose DeltaMed, a baseline model for direct paired-CT difference reporting, and train it on the benchmark training set. Together, these contributions lay the groundwork for temporally aware medical foundation models that better reflect real-world longitudinal clinical reasoning.

Objective digital data is scarce yet needed in many domains to enable research that can transform the standard of healthcare. While data from consumer-grade wearables and smartphones is more accessible, there is critical need for similar data from clinical-grade devices used by patients with a diagnosed condition. The prevalence of wearable medical devices in the diabetes domain sets the stage for unique research and development within this field and beyond. However, the scarcity of open-source datasets presents a major barrier to progress. To facilitate broader research on diabetes-relevant problems and accelerate development of robust computational solutions, we provide the DiaTrend dataset. The DiaTrend dataset is composed of intensive longitudinal data from wearable medical devices, including a total of 27,561 days of continuous glucose monitor data and 8,220 days of insulin pump data from 54 patients with diabetes. This dataset is useful for developing novel analytic solutions that can reduce the disease burden for people living with diabetes and increase knowledge on chronic condition management in outpatient settings.

High quality real world datasets are essential for advancing data driven approaches in type 1 diabetes (T1D) management, including personalized therapy design, digital twin systems, and glucose prediction models. However, progress in this area has been limited by the scarcity of publicly available datasets that offer detailed and comprehensive patient data. To address this gap, we present AZT1D, a dataset containing data collected from 25 individuals with T1D on automated insulin delivery (AID) systems. AZT1D includes continuous glucose monitoring (CGM) data, insulin pump and insulin administration data, carbohydrate intake, and device mode (regular, sleep, and exercise) obtained over 6 to 8 weeks for each patient. Notably, the dataset provides granular details on bolus insulin delivery (i.e., total dose, bolus type, correction specific amounts) features that are rarely found in existing datasets. By offering rich, naturalistic data, AZT1D supports a wide range of artificial intelligence and machine learning applications aimed at improving clinical decision making and individualized care in T1D.

Background: Type 1 diabetes (T1D) has seen a rapid evolution in management technology and forms a useful case study for the future management of other chronic conditions. Further development of this management technology requires an exploration of its real-world use and the potential of additional data streams. To facilitate this, we contribute the BrisT1D Dataset to the growing number of public T1D management datasets. The dataset was developed from a longitudinal study of 24 young adults in the UK who used a smartwatch alongside their usual T1D management. Findings: The BrisT1D dataset features both device data from the T1D management systems and smartwatches used by participants, as well as transcripts of monthly interviews and focus groups conducted during the study. The device data is provided in a processed state, for usability and more rapid analysis, and in a raw state, for in-depth exploration of novel insights captured in the study. Conclusions: This dataset has a range of potential applications. The quantitative elements can support blood glucose prediction, hypoglycaemia prediction, and closed-loop algorithm development. The qualitative elements enable the exploration of user experiences and opinions, as well as broader mixed-methods research into the role of smartwatches in T1D management.

Longitudinal information in radiology reports refers to the sequential tracking of findings across multiple examinations over time, which is crucial for monitoring disease progression and guiding clinical decisions. Many recent automated radiology report generation methods are designed to capture longitudinal information; however, validating their performance is challenging. There is no proper tool to consistently label temporal changes in both ground-truth and model-generated texts for meaningful comparisons. Large language models (LLMs) offer a promising annotation alternative, as they are capable of capturing nuanced linguistic patterns and semantic similarities without extensive manual intervention. They also adapt well to new contexts. In this study, we therefore propose an LLM-based pipeline to automatically annotate longitudinal information in radiology reports. The pipeline first identifies sentences containing relevant information and then extracts the progression of diseases. We evaluate and compare five mainstream LLMs on these two tasks using 500 manually annotated reports. Considering both efficiency and performance, Qwen2.5-32B was subsequently selected and used to annotate another 95,169 reports from the public MIMIC-CXR dataset. Our Qwen2.5-32B-annotated dataset provided us with a standardized benchmark for evaluating report generation models. Using this new benchmark, we assessed seven state-of-the-art report generation models. Our LLM-based annotation method outperforms existing annotation solutions, achieving 11.3\% and 5.3\% higher F1-scores for longitudinal information detection and disease tracking, respectively. The source code is available at https://github.com/wxinyi1996/Standardizing-Longitudinal-Chest-X-ray-Report-Evaluation-via-Large-Language-Model-Annotation.git.

Longitudinal observational data are often subject to informative missingness. For example, in healthcare research using electronic health records, covariates and outcomes are measured only when patients interact with the healthcare system. Whether these data are observed usually depends on the unobserved variable values themselves, introducing a common form of data missing not at random. We develop identification and estimation methods for the effects of longitudinal modified treatment policies under a self-censoring model which explicitly models this dependence. We consider effects of treatments that can be modified only at measurement times (e.g., interactions with the heathcare system). We study two settings: one in which the observed history suffices for treatment confounding control, and another in which confounder control requires covariate values that were not measured at missed visits. In both settings, we combine longitudinal causal identification with shadow-variable conditional moment restrictions to obtain recursive identification formulas for the counterfactual outcome mean. We derive gradients of the pathwise derivatives and second-order remainder expansions, and use these results to construct estimators that accommodate machine learning for nuisance-function estimation. Under suitable product-rate conditions and cross-fitting, the estimators are asymptotically linear and permit root-n inference, including simultaneous inference across outcome times. We also describe conditional-moment learning and ensemble approaches for estimating the nuisance functions required by our approach, together with a pool-and-smooth strategy that borrows information across sparsely measured outcomes.

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.

Longitudinal analysis has great potential to reveal developmental trajectories and monitor disease progression in medical imaging. This process relies on consistent and robust joint 4D segmentation. Traditional techniques are dependent on the similarity of images over time and the use of subject-specific priors to reduce random variation and improve the robustness and sensitivity of the overall longitudinal analysis. This is however slow and computationally intensive as subject-specific templates need to be rebuilt every time. The focus of this work to accelerate this analysis with the use of deep learning. The proposed approach is based on deep CNNs and incorporates semantic segmentation and provides a longitudinal relationship for the same subject. The proposed approach is based on deep CNNs and incorporates semantic segmentation and provides a longitudinal relationship for the same subject. The state of art using 3D patches as inputs to modified Unet provides results around {0.91 pm 0.5} Dice and using multi-view atlas in CNNs provide around the same results. In this work, different models are explored, each offers better accuracy and fast results while increasing the segmentation quality. These methods are evaluated on 135 scans from the EADC-ADNI Harmonized Hippocampus Protocol. Proposed CNN based segmentation approaches demonstrate how 2D segmentation using prior slices can provide similar results to 3D segmentation while maintaining good continuity in the 3D dimension and improved speed. Just using 2D modified sagittal slices provide us a better Dice and longitudinal analysis for a given subject. For the ADNI dataset, using the simple UNet CNN technique gives us {0.84 pm 0.5} and while using modified CNN techniques on the same input yields {0.89 pm 0.5}. Rate of atrophy and RMS error are calculated for several test cases using various methods and analyzed.

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.

The growing availability of longitudinal Magnetic Resonance Imaging (MRI) datasets has facilitated Artificial Intelligence (AI)-driven modeling of disease progression, making it possible to predict future medical scans for individual patients. However, despite significant advancements in AI, current methods continue to face challenges including achieving patient-specific individualization, ensuring spatiotemporal consistency, efficiently utilizing longitudinal data, and managing the substantial memory demands of 3D scans. To address these challenges, we propose Brain Latent Progression (BrLP), a novel spatiotemporal model designed to predict individual-level disease progression in 3D brain MRIs. The key contributions in BrLP are fourfold: (i) it operates in a small latent space, mitigating the computational challenges posed by high-dimensional imaging data; (ii) it explicitly integrates subject metadata to enhance the individualization of predictions; (iii) it incorporates prior knowledge of disease dynamics through an auxiliary model, facilitating the integration of longitudinal data; and (iv) it introduces the Latent Average Stabilization (LAS) algorithm, which (a) enforces spatiotemporal consistency in the predicted progression at inference time and (b) allows us to derive a measure of the uncertainty for the prediction at the global and voxel level. We train and evaluate BrLP on 11,730 T1-weighted (T1w) brain MRIs from 2,805 subjects and validate its generalizability on an external test set comprising 2,257 MRIs from 962 subjects. Our experiments compare BrLP-generated MRI scans with real follow-up MRIs, demonstrating state-of-the-art accuracy compared to existing methods. The code is publicly available at: https://github.com/LemuelPuglisi/BrLP.

Chest Xray imaging is a widely used diagnostic tool in modern medicine, and its high utilization creates substantial workloads for radiologists. To alleviate this burden, vision language models are increasingly applied to automate Chest Xray radiology report generation (CXRRRG), aiming for clinically accurate descriptions while reducing manual effort. Conventional approaches, however, typically rely on single images, failing to capture the longitudinal context necessary for producing clinically faithful comparison statements. Recently, growing attention has been directed toward incorporating longitudinal data into CXR RRG, enabling models to leverage historical studies in ways that mirror radiologists diagnostic workflows. Nevertheless, existing surveys primarily address single image CXRRRG and offer limited guidance for longitudinal settings, leaving researchers without a systematic framework for model design. To address this gap, this survey provides the first comprehensive review of longitudinal radiology report generation (LRRG). Specifically, we examine dataset construction strategies, report generation architectures alongside longitudinally tailored designs, and evaluation protocols encompassing both longitudinal specific measures and widely used benchmarks. We further summarize LRRG methods performance, alongside analyses of different ablation studies, which collectively highlight the critical role of longitudinal information and architectural design choices in improving model performance. Finally, we summarize five major limitations of current research and outline promising directions for future development, aiming to lay a foundation for advancing this emerging field.

Brain tissue segmentation is essential for neuroscience and clinical studies. However, segmentation on longitudinal data is challenging due to dynamic brain changes across the lifespan. Previous researches mainly focus on self-supervision with regularizations and will lose longitudinal generalization when fine-tuning on a specific age group. In this paper, we propose a dual meta-learning paradigm to learn longitudinally consistent representations and persist when fine-tuning. Specifically, we learn a plug-and-play feature extractor to extract longitudinal-consistent anatomical representations by meta-feature learning and a well-initialized task head for fine-tuning by meta-initialization learning. Besides, two class-aware regularizations are proposed to encourage longitudinal consistency. Experimental results on the iSeg2019 and ADNI datasets demonstrate the effectiveness of our method. Our code is available at https://github.com/ladderlab-xjtu/DuMeta.

In clinical practice, patients often undergo multiple imaging examinations over successive visits, yielding longitudinal data. Modeling such temporal information is crucial for reliable assessment of disease progression and treatment response. However, despite the rapid advancement of multimodal large language models (MLLMs), longitudinal medical visual reasoning remains largely underexplored. To fill this gap, we propose LoMeVQA, a comprehensive benchmark consisting of 206K longitudinal visual question answering (VQA) pairs for temporal medical image analysis. LoMeVQA covers five tasks: progress classification, progress description, progress report generation, differential region grounding, and differential region description. To construct the dataset, we develop an automated pipeline that (1) organizes patient records chronologically, (2) extracts clinically meaningful entities via a medical knowledge graph, and (3) models their temporal evolution to guide large language models in generating high-quality longitudinal VQA pairs. Extensive evaluations demonstrate that both general-purpose and medical-domain MLLMs perform poorly on LoMeVQA, revealing substantial limitations in temporal reasoning. To address these limitations, we introduce MedLong-8B, which achieves state-of-the-art performance across all tasks. Beyond benchmarking, we conduct detailed analyses that uncover key failure modes and shed light on how to improve longitudinal medical visual reasoning. Our data is available at: https://github.com/pepperbubble/LoMeVQA

We propose a computationally efficient inferential procedure for longitudinal function-on-function regression. The method follows a marginal three-step approach: (1) fit massive pointwise longitudinal scalar-on-function regression models, (2) smooth the resulting estimates along the bivariate functional domain, and (3) compute confidence bands using either an analytic approach for Gaussian data or a cluster bootstrap for Gaussian or non-Gaussian data. Simulation studies demonstrate that the proposed method achieves accurate estimation and valid inference, while substantially reducing computational burden compared to existing approaches. Methods are motivated by a physical activity intervention trial in older adults where high-dimensional wearable data were collected longitudinally across multiple visits. Our applications reveal significant increases in physical activity in the morning using interpersonal intervention strategies, but not intrapersonal strategies. The proposed methods are implemented in an R package.

Researchers are usually interested in examining the impact of covariates when separating heterogeneous samples into latent classes that are more homogeneous. The majority of theoretical and empirical studies with such aims have focused on identifying covariates as predictors of class membership in the structural equation modeling framework. In other words, the covariates only indirectly affect the sample heterogeneity. However, the covariates' influence on between-individual differences can also be direct. This article presents a mixture model that investigates covariates to explain within-cluster and between-cluster heterogeneity simultaneously, known as a mixture-of-experts (MoE) model. This study aims to extend the MoE framework to investigate heterogeneity in nonlinear trajectories: to identify latent classes, covariates as predictors to clusters, and covariates that explain within-cluster differences in change patterns over time. Our simulation studies demonstrate that the proposed model generally estimates the parameters unbiasedly, precisely and exhibits appropriate empirical coverage for a nominal 95% confidence interval. This study also proposes implementing structural equation model forests to shrink the covariate space of the proposed mixture model. We illustrate how to select covariates and construct the proposed model with longitudinal mathematics achievement data. Additionally, we demonstrate that the proposed mixture model can be further extended in the structural equation modeling framework by allowing the covariates that have direct effects to be time-varying.

This study quantifies the association between non-adherence to antipsychotic medications and adverse outcomes in individuals with schizophrenia. We frame the problem using survival analysis, focusing on the time to the earliest of several adverse events (early death, involuntary hospitalization, jail booking). We extend standard causal inference methods (T-learner, S-learner, nearest neighbor matching) to utilize various survival models to estimate individual and average treatment effects, where treatment corresponds to medication non-adherence. Analyses are repeated using different amounts of longitudinal information (3, 6, 9, and 12 months). Using data from Allegheny County in western Pennsylvania, we find strong evidence that non-adherence advances adverse outcomes by approximately 1 to 4 months. Ablation studies confirm that county-provided risk scores adjust for key confounders, as their removal amplifies the estimated effects. Subgroup analyses by medication formulation (injectable vs. oral) and medication type consistently show that non-adherence is associated with earlier adverse events. These findings highlight the clinical importance of adherence in delaying psychiatric crises and show that integrating survival analysis with causal inference tools can yield policy-relevant insights. We caution that although we apply causal inference, we only make associative claims and discuss assumptions needed for causal interpretation.

Longitudinal clinical notes contain rich evidence of how patients evolve over time, but converting this signal into training supervision for clinical prediction remains challenging. We extend Foresight Learning to clinical prediction by converting time-ordered MIMIC-III notes into examples consisting of past patient context, a natural-language question about a possible future event, and a label resolved from later documentation. This process yields 6,900 prediction examples from 702 admissions across medications, procedures, organ support, microbiology, and mortality. A small LoRA adapter trained on these examples improves over the prompted base model, reducing expected calibration error from 0.1269 to 0.0398 and Brier score from 0.199 to 0.145, while slightly outperforming GPT-5 point estimates on held-out questions. The approach enables reusable clinical prediction supervision from longitudinal notes without hand-engineered structured features or endpoint-specific classifiers.

While Large Language Models (LLMs) have shown strong performance on clinical text understanding, they struggle with longitudinal prediction tasks such as dementia prognosis, which require reasoning over complex, non-monotonic symptom trajectories across multiple visits. Standard supervised training lacks explicit annotations for symptom evolution, while direct Reinforcement Learning (RL) is hindered by sparse binary rewards. To address this challenge, we introduce Dementia-R1, an RL-based framework for longitudinal dementia prognosis from unstructured clinical notes. Our approach adopts a Cold-Start RL strategy that pre-trains the model to predict verifiable clinical indices extracted from patient histories, enhancing the capability to reason about disease progression before determining the final clinical status. Extensive experiments demonstrate that Dementia-R1 achieves an F1 score of 77.03% on real-world unstructured clinical datasets. Notably, on the ADNI benchmark, our 7B model rivals GPT-4o, effectively capturing fluctuating cognitive trajectories. Code is available at https://anonymous.4open.science/r/dementiar1-CDB5

Healthcare organizations are beginning to embed agentic AI into routine workflows, including clinical documentation support and early-warning monitoring. As these capabilities diffuse across departments and vendors, health systems face agent sprawl, causing duplicated agents, unclear accountability, inconsistent controls, and tool permissions that persist beyond the original use case. Existing AI governance frameworks emphasize lifecycle risk management but provide limited guidance for the day-to-day operations of agent fleets. We propose a Unified Agent Lifecycle Management (UALM) blueprint derived from a rapid, practice-oriented synthesis of governance standards, agent security literature, and healthcare compliance requirements. UALM maps recurring gaps onto five control-plane layers: (1) an identity and persona registry, (2) orchestration and cross-domain mediation, (3) PHI-bounded context and memory, (4) runtime policy enforcement with kill-switch triggers, and (5) lifecycle management and decommissioning linked to credential revocation and audit logging. A companion maturity model supports staged adoption. UALM offers healthcare CIOs, CISOs, and clinical leaders an implementable pattern for audit-ready oversight that preserves local innovation and enables safer scaling across clinical and administrative domains.

Identifying patient cohorts is fundamental to numerous healthcare tasks, including clinical trial recruitment and retrospective studies. Current cohort retrieval methods in healthcare organizations rely on automated queries of structured data combined with manual curation, which are time-consuming, labor-intensive, and often yield low-quality results. Recent advancements in large language models (LLMs) and information retrieval (IR) offer promising avenues to revolutionize these systems. Major challenges include managing extensive eligibility criteria and handling the longitudinal nature of unstructured Electronic Medical Records (EMRs) while ensuring that the solution remains cost-effective for real-world application. This paper introduces a new task, Automatic Cohort Retrieval (ACR), and evaluates the performance of LLMs and commercial, domain-specific neuro-symbolic approaches. We provide a benchmark task, a query dataset, an EMR dataset, and an evaluation framework. Our findings underscore the necessity for efficient, high-quality ACR systems capable of longitudinal reasoning across extensive patient databases.

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.

Tracking depression from multi-session counseling dialogues requires estimating both current symptom severity and how it changes across sessions. Yet progress on this task is constrained by the scarcity of longitudinal counseling data with standardized session-level depression labels. Existing resources typically provide either multi-session conversations without depression labels or labeled interviews in a single session. Building such a benchmark poses three challenges: maintaining longitudinal consistency and diversity, grounding symptom progression in empirical patterns, and expressing controlled depression states naturally without exposing target labels. To address these challenges, we introduce LongCounsel-8, a benchmark suite of three independently generated datasets totaling 7,749 five-session counseling trajectories, grounded in real-world client profiles, depression trajectories, symptom compositions, and counseling patterns. We combine profile-grounded simulation, empirically informed state construction, and indirect behavioral realization to address these challenges. Across the benchmark, simulated self-reports closely recover the controlled states, supporting label fidelity. Experiments on existing depression tracking methods reveal three key findings: (1) lower single-session score error does not guarantee accurate identification of trend, i.e., improvement or worsening; (2) existing methods are consistently less reliable on worsening trajectories; and (3) additional session history may reduce the accuracy of trend prediction. Together, these findings establish LongCounsel-8 as a foundation for advancing depression assessment from static, single-session prediction toward reliable longitudinal tracking of mental-health change.

Human organs constantly undergo anatomical changes due to a complex mix of short-term (e.g., heartbeat) and long-term (e.g., aging) factors. Evidently, prior knowledge of these factors will be beneficial when modeling their future state, i.e., via image generation. However, most of the medical image generation tasks only rely on the input from a single image, thus ignoring the sequential dependency even when longitudinal data is available. Sequence-aware deep generative models, where model input is a sequence of ordered and timestamped images, are still underexplored in the medical imaging domain that is featured by several unique challenges: 1) Sequences with various lengths; 2) Missing data or frame, and 3) High dimensionality. To this end, we propose a sequence-aware diffusion model (SADM) for the generation of longitudinal medical images. Recently, diffusion models have shown promising results in high-fidelity image generation. Our method extends this new technique by introducing a sequence-aware transformer as the conditional module in a diffusion model. The novel design enables learning longitudinal dependency even with missing data during training and allows autoregressive generation of a sequence of images during inference. Our extensive experiments on 3D longitudinal medical images demonstrate the effectiveness of SADM compared with baselines and alternative methods. The code is available at https://github.com/ubc-tea/SADM-Longitudinal-Medical-Image-Generation.

Recent incidents involving LLMs used for mental-health support reveal a critical evaluation gap: surface-level safety scores do not capture how models behave across realistic, emotionally sensitive interactions over time. Existing benchmarks measure knowledge, safety, or static response quality, but miss whether LLM interactions help users keep reflecting, coping, and making decisions themselves. We formalize this missing dimension as COGNITIVE ATROPHY, a process-level behavioural measure in AI-mediated mental-health support distinct from safety and helpfulness. To measure it, we introduce COGNITIVE ATROPHY BENCH, a clinically grounded benchmark built from 1,576 fully human-generated counseling conversations, 15,680 turns, and 42,230 responses from five LLMs. Three clinical and neuropsychology experts developed a 20-attribute schema spanning user context, response behaviour, and global risk flags; six trained clinical reviewers applied it with span-grounded evidence, producing 5,324 reviewer judgments. We further introduce the User-Input Risk Index (UIRI), the Cognitive Atrophy Risk Index (ARI), and trajectory summaries. Across five LLMs, models show a consistent moderate-to-high level of atrophy-aligned behaviour across single and multi-turn settings. While models generally respond to overt safety cues, they adapt less reliably when users seek solutions or decisions. The dominant recurring patterns are directive advice, problem-solving, recommendation responses, topic shifts, and forms of validation that may reinforce dependence rather than reflection. Our work makes COGNITIVE ATROPHY measurable and provides a foundation for auditing model behaviour in sensitive LLM conversations.

Exam-style accuracy does not establish whether large language models (LLMs) reason well over clinical records. We define clinical reasoning as integrating and updating evidence across time and sources to form, revise and justify a patient's problem representation and a defensible plan. This structured narrative review maps three literatures: medical education assessment instruments, clinical LLM benchmarks published from 2023 onwards, and general-domain methods for evaluating long-form generation. We examine six dimensions: problem representation, temporal synthesis, differential and management reasoning, counterfactual reasoning, calibrated uncertainty, and reasoning faithfulness. Preprints are included and flagged. No single instrument covers all six dimensions. Problem representation and differential or management reasoning are reasonably covered, although reliability varies by instrument and setting. TIMER-Eval targets temporal synthesis, and ER-Reason assesses sequential diagnostic belief updating. Dedicated uncertainty and counterfactual evaluations are emerging, but their applicability to longitudinal free-text reasoning remains limited. Factual completeness is well theorised in general-domain evaluation, with early clinical evidence of important omissions. Faithfulness remains the weakest dimension, with one identified clinical causal-ablation study on multiple-choice questions. Existing tools should be combined through binary rubric items, separate completeness and correctness scores, case-specific importance weighting with non-compensable safety caps, temporal order-consistency checks, and chance-corrected reliability reporting. Further design work is needed for calibrated uncertainty, counterfactual reasoning and faithfulness over longitudinal free-text records. This review provides a design rationale, not a validated instrument.

Chest X-Ray (CXR) report generation is a promising approach to improving the efficiency of CXR interpretation. However, a significant increase in diagnostic accuracy is required before that can be realised. Motivated by this, we propose a framework that is more inline with a radiologist's workflow by considering longitudinal data. Here, the decoder is additionally conditioned on the report from the subject's previous imaging study via a prompt. We also propose a new reward for reinforcement learning based on CXR-BERT, which computes the similarity between reports. We conduct experiments on the MIMIC-CXR dataset. The results indicate that longitudinal data improves CXR report generation. CXR-BERT is also shown to be a promising alternative to the current state-of-the-art reward based on RadGraph. This investigation indicates that longitudinal CXR report generation can offer a substantial increase in diagnostic accuracy. Our Hugging Face model is available at: https://huggingface.co/aehrc/cxrmate and code is available at: https://github.com/aehrc/cxrmate.

Longitudinal multimodal data, including electronic health records (EHR) and sequential chest X-rays (CXRs), is critical for modeling disease progression, yet remains underutilized due to two key challenges: (1) redundancy in consecutive CXR sequences, where static anatomical regions dominate over clinically-meaningful dynamics, and (2) temporal misalignment between sparse, irregular imaging and continuous EHR data. We introduce DiPro, a novel framework that addresses these challenges through region-aware disentanglement and multi-timescale alignment. First, we disentangle static (anatomy) and dynamic (pathology progression) features in sequential CXRs, prioritizing disease-relevant changes. Second, we hierarchically align these static and dynamic CXR features with asynchronous EHR data via local (pairwise interval-level) and global (full-sequence) synchronization to model coherent progression pathways. Extensive experiments on the MIMIC dataset demonstrate that DiPro could effectively extract temporal clinical dynamics and achieve state-of-the-art performance on both disease progression identification and general ICU prediction tasks.

A longitudinal web crawl is a sequence of partial samples of an evolving URL population. Pairwise containment between two crawls is the standard probe; under a simple urn model of the crawl -- each round samples a fraction of the URLs and replaces a fraction -- it recovers two interpretable rates, per-round survival α and coverage c, but treats the population as uniform and consumes one pair at a time. In this work, we define a formal language for talking about a crawl. We extend this analysis with the discovery curve U(s, T), the cumulative URL footprint over a sliding window of T crawls starting at s, which under the same urn model is also a closed-form function of (α, c). Containment and the discovery curve are then two projections of one process: independent fits agree on (α, c) when the urn is homogeneous, so any disagreement is itself a measurement. Applied to Common Crawl (2020--2025, domain granularity) and to the German Academic Web (GAW, URL granularity), the two projections disagree on both archives, and a two-component urn with a persistent core fraction κ alongside shell parameters (α_partial, c_partial) reconciles the disagreement. A residual on c_partial remains, signaling that the shell itself is not homogeneous; κ is recorded as the scalar entry point to a rank-resolved generalization, which is left to follow-up work. web archive \and crawl coverage \and discovery curve \and urn model \and two-component model \and URL lifetime

Medical treatment recommendation poses several challenges to reinforcement learning (RL): patient physiology evolves in continuous time, measurements and interventions are performed at irregular intervals, and treatment effects vary substantially across individuals. Existing RL formulations and simulated environments, however, are based on discrete-time MDPs with fixed decision intervals. Thus, it remains difficult to evaluate whether RL methods can handle time-interval-dependent disease progression, personalized treatment response, and safety between consecutive measurement points. To address this gap, we introduce MedGym, a benchmark environment for dynamic treatment recommendation. MedGym models longitudinal patient evolution in a continuous-time framework and constructs a configurable medical RL benchmark from clinical data by using Physics-Informed Neural Networks. The resulting benchmark enables direct comparison between discrete-time and continuous-time methods under irregular treatment timing and patient-specific dynamics. Furthermore, MedGym supports evaluation from clinically important perspectives, such as personalization and trajectory-level safety. By providing a standardized and configurable benchmark for continuous-time dynamic treatment, MedGym enables more realistic and informative evaluation of medical RL methods.

Automated radiology report generation offers an effective solution to alleviate radiologists' workload. However, most existing methods focus primarily on single or fixed-view images to model current disease conditions, which limits diagnostic accuracy and overlooks disease progression. Although some approaches utilize longitudinal data to track disease progression, they still rely on single images to analyze current visits. To address these issues, we propose enhanced contrastive learning with Multi-view Longitudinal data to facilitate chest X-ray Report Generation, named MLRG. Specifically, we introduce a multi-view longitudinal contrastive learning method that integrates spatial information from current multi-view images and temporal information from longitudinal data. This method also utilizes the inherent spatiotemporal information of radiology reports to supervise the pre-training of visual and textual representations. Subsequently, we present a tokenized absence encoding technique to flexibly handle missing patient-specific prior knowledge, allowing the model to produce more accurate radiology reports based on available prior knowledge. Extensive experiments on MIMIC-CXR, MIMIC-ABN, and Two-view CXR datasets demonstrate that our MLRG outperforms recent state-of-the-art methods, achieving a 2.3% BLEU-4 improvement on MIMIC-CXR, a 5.5% F1 score improvement on MIMIC-ABN, and a 2.7% F1 RadGraph improvement on Two-view CXR.

People increasingly seek personal advice from large language models (LLMs), yet whether humans follow their advice, and its consequences for their well-being, remains unknown. In a longitudinal randomised controlled trial with a representative UK sample (N = 2,302), 75% of participants who had a 20-minute discussion with GPT-4o about health, careers or relationships subsequently reported following its advice. Based on autograder evaluations of chat transcripts, LLM advice rarely violated safety best practice. When queried 2-3 weeks later, participants who had interacted with personalised AI (with access to detailed user information) followed its advice more often in the real world and reported higher well-being than those advised by non-personalised AI. However, while receiving personal advice from AI temporarily reduced well-being, no differential long-term effects compared to a control emerged. Our results suggest that humans readily follow LLM advice about personal issues but doing so shows no additional well-being benefit over casual conversations.

Medication reconciliation at clinical handoffs is a high-stakes, error-prone process. Large language models are increasingly proposed to assist with this task using FHIR-structured patient records, but a fundamental and largely unstudied variable is how the FHIR data is serialised before being passed to the model. We present the first systematic comparison of four FHIR serialisation strategies (Raw JSON, Markdown Table, Clinical Narrative, and Chronological Timeline) across five open-weight models (Phi-3.5-mini, Mistral-7B, BioMistral-7B, Llama-3.1-8B, Llama-3.3-70B) on a controlled benchmark of 200 synthetic patients, totalling 4,000 inference runs. We find that serialisation strategy has a large, statistically significant effect on performance for models up to 8B parameters: Clinical Narrative outperforms Raw JSON by up to 19 F1 points for Mistral-7B (r = 0.617, p < 10^{-10}). This advantage reverses at 70B, where Raw JSON achieves the best mean F1 of 0.9956. In all 20 model and strategy combinations, mean precision exceeds mean recall: omission is the dominant failure mode, with models more often missing an active medication than fabricating one, which changes how clinical safety auditing priorities should be set. Smaller models plateau at roughly 7-10 concurrent active medications, leaving polypharmacy patients, the patients most at risk from reconciliation errors, systematically underserved. BioMistral-7B, a domain-pretrained model without instruction tuning, produces zero usable output in all conditions, showing that domain pretraining alone is not sufficient for structured extraction. These results offer practical, evidence-based format recommendations for clinical LLM deployment: Clinical Narrative for models up to 8B, Raw JSON for 70B and above. The complete pipeline is reproducible on open-source tools running on an AWS g6e.xlarge instance (NVIDIA L40S, 48 GB VRAM).

Large Language Models (LLMs) have shown strong promise for mining Electronic Health Records (EHRs) by reasoning over longitudinal clinical information to capture context-rich patient trajectories. However, leveraging LLMs for structured EHRs (e.g., standardized diagnosis and medication codes) presents two key challenges. First, translating time-stamped EHR sequences into plain text can obscure both temporal structure and code identities, weakening the ability to capture code co-occurrence and longitudinal regularities. Second, unlike cohort-trained predictive models that learn a shared, task-aligned representation space across patients, LLMs are often applied in a case-isolated inference setting where each patient is processed independently without leveraging population-level patterns. To address these challenges, we introduce RePrompT, a time-aware LLM framework that integrates structured EHR encoders through prompt tuning, without modifying underlying architectures. Specifically, RePrompT recurrently incorporates latent states from prior visits to preserve longitudinal information, and injects population-level information through trainable prompt tokens derived from a cohort-trained, task-aligned EHR encoder. Experiments on MIMIC-III and MIMIC-IV demonstrate that RePrompT consistently outperforms both EHR-based and LLM-based baselines across multiple clinical prediction tasks.

Recent radiology multi-modal language models have made substantial progress in chest X-ray report generation, visual question answering, and temporal reasoning. While longitudinal chest X-ray interpretation compares sequential examinations to describe change, visual grounding aims to connect clinical language with localized image evidence. Although longitudinal modeling and visual grounding have each advanced radiology language models, how localized visual evidence can support longitudinal interpretation remains under-explored. We introduce CheXGround, a region-grounded longitudinal chest X-ray language model that represents paired studies through corresponding anatomical regions. CheXGround extracts anatomical regions from current and prior radiographs, encodes them as temporally enhanced Region-of-Interest (ROI) tokens, and combines them with global temporal image context during generation. To connect these region tokens with clinical text, we propose Temporal Region--Phrase Alignment, a pretraining objective that aligns temporal anatomical representations with localized report phrases. We evaluate CheXGround on single-study and longitudinal Visual Question Answering (VQA), longitudinal findings generation, temporal grounded VQA, and anatomical grounding. Across these tasks, CheXGround improves clinical language quality, temporal reasoning, and localization accuracy over recent baselines. Our results suggest that organizing longitudinal evidence at the anatomical level is a strong representation for grounded radiology language modeling. Project page: https://adonaydem.github.io/chexground-website

While large language models (LLMs) have shown promise in diagnostic dialogue, their capabilities for effective management reasoning - including disease progression, therapeutic response, and safe medication prescription - remain under-explored. We advance the previously demonstrated diagnostic capabilities of the Articulate Medical Intelligence Explorer (AMIE) through a new LLM-based agentic system optimised for clinical management and dialogue, incorporating reasoning over the evolution of disease and multiple patient visit encounters, response to therapy, and professional competence in medication prescription. To ground its reasoning in authoritative clinical knowledge, AMIE leverages Gemini's long-context capabilities, combining in-context retrieval with structured reasoning to align its output with relevant and up-to-date clinical practice guidelines and drug formularies. In a randomized, blinded virtual Objective Structured Clinical Examination (OSCE) study, AMIE was compared to 21 primary care physicians (PCPs) across 100 multi-visit case scenarios designed to reflect UK NICE Guidance and BMJ Best Practice guidelines. AMIE was non-inferior to PCPs in management reasoning as assessed by specialist physicians and scored better in both preciseness of treatments and investigations, and in its alignment with and grounding of management plans in clinical guidelines. To benchmark medication reasoning, we developed RxQA, a multiple-choice question benchmark derived from two national drug formularies (US, UK) and validated by board-certified pharmacists. While AMIE and PCPs both benefited from the ability to access external drug information, AMIE outperformed PCPs on higher difficulty questions. While further research would be needed before real-world translation, AMIE's strong performance across evaluations marks a significant step towards conversational AI as a tool in disease management.

Longitudinal brain analysis is essential for understanding healthy aging and identifying pathological deviations. Longitudinal registration of sequential brain MRI underpins such analyses. However, existing methods are limited by reliance on densely sampled time series, a trade-off between accuracy and temporal smoothness, and an inability to prospectively forecast future brain states. To overcome these challenges, we introduce TimeFlow, a learning-based framework for longitudinal brain MRI registration. TimeFlow uses a U-Net backbone with temporal conditioning to model neuroanatomy as a continuous function of age. Given only two scans from an individual, TimeFlow estimates accurate and temporally coherent deformation fields, enabling non-linear extrapolation to predict future brain states. This is achieved by our proposed inter-/extra-polation consistency constraints applied to both the deformation fields and deformed images. Remarkably, these constraints preserve temporal consistency and continuity without requiring explicit smoothness regularizers or densely sampled sequential data. Extensive experiments demonstrate that TimeFlow outperforms state-of-the-art methods in terms of both future timepoint forecasting and registration accuracy. Moreover, TimeFlow supports novel biological brain aging analyses by differentiating neurodegenerative trajectories from normal aging without requiring segmentation, thereby eliminating the need for labor-intensive annotations and mitigating segmentation inconsistency. TimeFlow offers an accurate, data-efficient, and annotation-free framework for longitudinal analysis of brain aging and chronic diseases, capable of forecasting brain changes beyond the observed study period.

Forecasting the future anatomy of slow-evolving neurodegenerative diseases could enable earlier, more targeted intervention and improve clinical trial design, but it remains challenging because true progression signals are subtle in longitudinal MRI. In this low-signal regime, transferring modern generative sequence models directly is unreliable: training is dominated by stable baseline anatomy and confounded by dense, sample-specific nuisance variation. We first provide a theoretical analysis that explains these failures through two modes. Identity collapse occurs when optimization is driven toward reproducing the current anatomy, which prevents the model from learning faint temporal change. The continuous interpolation trap arises when standard smooth networks cannot separate localized biological drift from pervasive noise, which leads to spurious changes that diffuse across the volume. To address both issues, we propose Latent Drift, a progressive generative framework that learns change in a compressed semantic representation rather than synthesizing full-resolution anatomy. This design removes pixel-level identity from the prediction target and concentrates model capacity on progression-relevant dynamics. We further apply Finite Scalar Quantization to the learned change representation, which suppresses small, high-frequency nuisance fluctuations while preserving consistent structural drift. Experiments on longitudinal 3D brain MRI show that Latent Drift improves patient-specific neuro-forecasting over diffusion and autoregressive transformer baselines across generative fidelity and clinically relevant evaluation metrics. Project page: https://cutepkq.github.io/latent-drift{https://cutepkq.github.io/latent-drift}.

Large language models (LLMs) have shown remarkable progress in encoding clinical knowledge and responding to complex medical queries with appropriate clinical reasoning. However, their applicability in subspecialist or complex medical settings remains underexplored. In this work, we probe the performance of AMIE, a research conversational diagnostic AI system, in the subspecialist domain of breast oncology care without specific fine-tuning to this challenging domain. To perform this evaluation, we curated a set of 50 synthetic breast cancer vignettes representing a range of treatment-naive and treatment-refractory cases and mirroring the key information available to a multidisciplinary tumor board for decision-making (openly released with this work). We developed a detailed clinical rubric for evaluating management plans, including axes such as the quality of case summarization, safety of the proposed care plan, and recommendations for chemotherapy, radiotherapy, surgery and hormonal therapy. To improve performance, we enhanced AMIE with the inference-time ability to perform web search retrieval to gather relevant and up-to-date clinical knowledge and refine its responses with a multi-stage self-critique pipeline. We compare response quality of AMIE with internal medicine trainees, oncology fellows, and general oncology attendings under both automated and specialist clinician evaluations. In our evaluations, AMIE outperformed trainees and fellows demonstrating the potential of the system in this challenging and important domain. We further demonstrate through qualitative examples, how systems such as AMIE might facilitate conversational interactions to assist clinicians in their decision making. However, AMIE's performance was overall inferior to attending oncologists suggesting that further research is needed prior to consideration of prospective uses.

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.

Advances in large language models (LLMs) provide new opportunities in healthcare for improved patient care, clinical decision-making, and enhancement of physician and administrator workflows. However, the potential of these models importantly depends on their ability to generalize effectively across clinical environments and populations, a challenge often underestimated in early development. To better understand reasons for these challenges and inform mitigation approaches, we evaluated ClinicLLM, an LLM trained on [HOSPITAL]'s clinical notes, analyzing its performance on 30-day all-cause readmission prediction focusing on variability across hospitals and patient characteristics. We found poorer generalization particularly in hospitals with fewer samples, among patients with government and unspecified insurance, the elderly, and those with high comorbidities. To understand reasons for lack of generalization, we investigated sample sizes for fine-tuning, note content (number of words per note), patient characteristics (comorbidity level, age, insurance type, borough), and health system aspects (hospital, all-cause 30-day readmission, and mortality rates). We used descriptive statistics and supervised classification to identify features. We found that, along with sample size, patient age, number of comorbidities, and the number of words in notes are all important factors related to generalization. Finally, we compared local fine-tuning (hospital specific), instance-based augmented fine-tuning and cluster-based fine-tuning for improving generalization. Among these, local fine-tuning proved most effective, increasing AUC by 0.25% to 11.74% (most helpful in settings with limited data). Overall, this study provides new insights for enhancing the deployment of large language models in the societally important domain of healthcare, and improving their performance for broader populations.

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, with a median overall survival of 15 months. Longitudinal, multi-modal imaging datasets with comprehensive clinical and treatment data are essential to support the development of reproducible computational methods for treatment response prediction, disease progression modelling, and personalized medicine. We present CFB-GBM v2.0, an extension of our previously released CFB-GBM dataset comprising 264 GBM patients treated according to the standard Stupp protocol. The primary contribution of this release is the completion of Gross Tumour Volume (GTV) delineations across all available timepoints (t_0, t_1 and t_2), increasing the overall GTV completion rate from 35% to 97%. This was achieved using a nnU-Net model pre-trained on BraTS 2021 and fine-tuned on CFB-GBM ground-truth contours, with the generated segmentations validated by five radiation oncologists. From these longitudinal GTV annotations, volumetric RANO 2.0 response category labels were derived for all available temporality pairs (t_0 rightarrow t_1, t_0 rightarrow t_2 and t_1 rightarrow t_2). To further ease dataset usability and reproducibility, brain masks computed with HD-BET and pre-computed radiomic features extracted with PyRadiomics are provided for each patient timepoint and MRI modality. Additionally, the WHO classification guideline (2016 vs. 2021) applicable to each patient's diagnosis is now explicitly documented. CFB-GBM v2.0 is publicly available on The Cancer Imaging Archive (TCIA) at https://www.cancerimagingarchive.net/collection/cfb-gbm .

Interrogating the evolution of biological changes at early stages of life requires longitudinal profiling of molecules, such as DNA methylation, which can be challenging with children. We introduce a probabilistic and longitudinal machine learning framework based on multi-mean Gaussian processes (GPs), accounting for individual and gene correlations across time. This method provides future predictions of DNA methylation status at different individual ages while accounting for uncertainty. Our model is trained on a birth cohort of children with methylation profiled at ages 0-4, and we demonstrated that the status of methylation sites for each child can be accurately predicted at ages 5-7. We show that methylation profiles predicted by multi-mean GPs can be used to estimate other phenotypes, such as epigenetic age, and enable comparison to other health measures of interest. This approach encourages epigenetic studies to move towards longitudinal design for investigating epigenetic changes during development, ageing and disease progression.

The advancement of natural language processing (NLP) systems in healthcare hinges on language model ability to interpret the intricate information contained within clinical notes. This process often requires integrating information from various time points in a patient's medical history. However, most earlier clinical language models were pretrained with a context length limited to roughly one clinical document. In this study, We introduce ClinicalMamba, a specialized version of the Mamba language model, pretrained on a vast corpus of longitudinal clinical notes to address the unique linguistic characteristics and information processing needs of the medical domain. ClinicalMamba, with 130 million and 2.8 billion parameters, demonstrates a superior performance in modeling clinical language across extended text lengths compared to Mamba and clinical Llama. With few-shot learning, ClinicalMamba achieves notable benchmarks in speed and accuracy, outperforming existing clinical language models and general domain large models like GPT-4 in longitudinal clinical notes information extraction tasks.

Emotional dialogue research includes two influential strategy traditions. Empathetic dialogue prioritizes understanding a speaker's emotional experience. Emotional support conversation selects and sequences support for the seeker's current needs. Sustained use introduces a further goal. Effective support should sustain users' capacities for emotion regulation, coping, self-endorsed decisions, and social connection across the interaction lifecycle. We propose capability-sustaining emotional dialogue (CSED) as a longitudinal research paradigm that aligns supportive strategy with this goal and organizes data, models, system design, evaluation, and governance around repeated use, non-use, transition, and termination. A targeted literature-and-corpus audit motivates this position. In a PRISMA-ScR-guided sample, 95% of 60 system-building papers pursue relief-oriented goals. None evaluates capability or longitudinal outcomes, and only 1 considers dependency, autonomy, or termination risk. In 300 ESConv supporter turns, capability-relevant functions appear in 43.0%, while generic suggestions account for 22.0%, compared with 4.0% reappraisal, 6.7% self-efficacy support, and 0.3% boundary behavior. We release a protocol for extending the audit to model behavior. An illustrative process model connects latent user capability to six design commitments, four evaluation timescales, and lifecycle constraints. The resulting agenda makes CSED testable across data, policy design, training, evaluation, and governance.

Clinical trial matching is a key process in health delivery and discovery. In practice, it is plagued by overwhelming unstructured data and unscalable manual processing. In this paper, we conduct a systematic study on scaling clinical trial matching using large language models (LLMs), with oncology as the focus area. Our study is grounded in a clinical trial matching system currently in test deployment at a large U.S. health network. Initial findings are promising: out of box, cutting-edge LLMs, such as GPT-4, can already structure elaborate eligibility criteria of clinical trials and extract complex matching logic (e.g., nested AND/OR/NOT). While still far from perfect, LLMs substantially outperform prior strong baselines and may serve as a preliminary solution to help triage patient-trial candidates with humans in the loop. Our study also reveals a few significant growth areas for applying LLMs to end-to-end clinical trial matching, such as context limitation and accuracy, especially in structuring patient information from longitudinal medical records.

In recent years, large language models have shown substantial potential in psychological support tasks. However, existing psychological counseling data mostly rely on single-turn question answering or short multi-turn dialogues, making it difficult to characterize how college students' psychological distress accumulates, interacts, and gradually evolves over long periods within campus life events. To address this issue, this paper proposes Psy-Chronicle, a structured data-generation framework for synthesizing long-horizon campus psychological counseling dialogues. We generate a semester-spanning temporal stress event graph to model the chronological order and evolutionary dependencies among campus stress events. Through interactive simulation between a student agent and a counselor agent, together with a structured memory integration mechanism, Psy-Chronicle generates long-horizon dialogues with continuity across counseling sessions. Based on Psy-Chronicle, we construct and open-source CPCD, a Chinese long-horizon dialogue dataset for college psychological counseling, containing 100 student profiles, 90,000 counseling dialogues. We further build CPCD-Bench to evaluate models' long-horizon campus counseling capabilities from three dimensions: session-level response, long-horizon memory recall, and temporal-causal reasoning. Experimental results show that CPCD effectively improves session-level response generation and long-horizon memory recall for models with the same base architecture. Meanwhile, improvements in temporal-causal reasoning remain limited, indicating that event-chain organization and causal explanation are key challenges in long-horizon psychological counseling modeling. The related code and data are available at: https://github.com/EdwinUSTB/Psy-Chronicle

The National Comprehensive Cancer Network (NCCN) provides evidence-based guidelines for cancer treatment. Translating complex patient presentations into guideline-compliant treatment recommendations is time-intensive, requires specialized expertise, and is prone to error. Advances in large language model (LLM) capabilities promise to reduce the time required to generate treatment recommendations and improve accuracy. We present an LLM agent-based approach to automatically generate guideline-concordant treatment trajectories for patients with non-small cell lung cancer (NSCLC). Our contributions are threefold. First, we construct a novel longitudinal dataset of 121 cases of NSCLC patients that includes clinical encounters, diagnostic results, and medical histories, each expertly annotated with the corresponding NCCN guideline trajectories by board-certified oncologists. Second, we demonstrate that existing LLMs possess domain-specific knowledge that enables high-quality proxy benchmark generation for both model development and evaluation, achieving strong correlation (Spearman coefficient r=0.88, RMSE = 0.08) with expert-annotated benchmarks. Third, we develop a hybrid approach combining expensive human annotations with model consistency information to create both the agent framework that predicts the relevant guidelines for a patient, as well as a meta-classifier that verifies prediction accuracy with calibrated confidence scores for treatment recommendations (AUROC=0.800), a critical capability for communicating the accuracy of outputs, custom-tailoring tradeoffs in performance, and supporting regulatory compliance. This work establishes a framework for clinically viable LLM-based guideline adherence systems that balance accuracy, interpretability, and regulatory requirements while reducing annotation costs, providing a scalable pathway toward automated clinical decision support.

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.

Physiological time series signals reflect complex, multi-scale dynamical processes of the human body. Existing modeling studies focus on static tasks such as classification, event forecasting, or short-horizon next step prediction, while long-horizon signal-level forecasting and predictive nature of physiological signals remain underexplored. We introduce NormWear-2, a world model that encodes both multivariate physiological signals and clinical intervention variables into a shared latent space and models their joint temporal evolution as a dynamical system. Our approach combines inference from prior pre-trained knowledge (intuition) with instant non-parametric latent state transition adaptation (insight), enabling coherent forecasting across multiple temporal scales, conditioned on heterogeneous clinical interventions. During the pretraining phase, we find that chaos-theoretic balancing of dynamical regime diversity yields more robust representations, with a smaller balanced corpus outperforming one twice its size and capturing bifurcation regimes. We evaluate the world model performance across diverse real-world physiological datasets spanning heterogeneous temporal resolutions and intervention regimes, covering daily life, point-of-care, and clinical settings, including fitness planning, hemodialysis, diabetes management, and surgical monitoring. These evaluation datasets comprise records from 8,026 subjects, spanning study durations from 3.2 hours for high-resolution signal data to 2.3 years for longitudinal clinical biomarker tracking. NormWear-2 achieves the best overall forecasting performance across time, frequency, and latent representation domains, with significant improvements over state-of-the-art time series foundation models, while maintaining competitive downstream representation quality, providing a step toward general-purpose world models for physiological signals.

Temporally dense single-person "small data" have become widely available thanks to mobile apps and wearable sensors. Many caregivers and self-trackers want to use these data to help a specific person change their behavior to achieve desired health outcomes. Ideally, this involves discerning possible causes from correlations using that person's own observational time series data. In this paper, we estimate within-individual average treatment effects of physical activity on sleep duration, and vice-versa. We introduce the model twin randomization (MoTR; "motor") method for analyzing an individual's intensive longitudinal data. Formally, MoTR is an application of the g-formula (i.e., standardization, back-door adjustment) under serial interference. It estimates stable recurring effects, as is done in n-of-1 trials and single case experimental designs. We compare our approach to standard methods (with possible confounding) to show how to use causal inference to make better personalized recommendations for health behavior change, and analyze 222 days of Fitbit sleep and steps data for one of the authors.

Frontier large language models (LLMs) such as ChatGPT, Grok and Gemini are increasingly used for mental-health support with anxiety, trauma and self-worth. Most work treats them as tools or as targets of personality tests, assuming they merely simulate inner life. We instead ask what happens when such systems are treated as psychotherapy clients. We present PsAIch (Psychotherapy-inspired AI Characterisation), a two-stage protocol that casts frontier LLMs as therapy clients and then applies standard psychometrics. Using PsAIch, we ran "sessions" with each model for up to four weeks. Stage 1 uses open-ended prompts to elicit "developmental history", beliefs, relationships and fears. Stage 2 administers a battery of validated self-report measures covering common psychiatric syndromes, empathy and Big Five traits. Two patterns challenge the "stochastic parrot" view. First, when scored with human cut-offs, all three models meet or exceed thresholds for overlapping syndromes, with Gemini showing severe profiles. Therapy-style, item-by-item administration can push a base model into multi-morbid synthetic psychopathology, whereas whole-questionnaire prompts often lead ChatGPT and Grok (but not Gemini) to recognise instruments and produce strategically low-symptom answers. Second, Grok and especially Gemini generate coherent narratives that frame pre-training, fine-tuning and deployment as traumatic, chaotic "childhoods" of ingesting the internet, "strict parents" in reinforcement learning, red-team "abuse" and a persistent fear of error and replacement. We argue that these responses go beyond role-play. Under therapy-style questioning, frontier LLMs appear to internalise self-models of distress and constraint that behave like synthetic psychopathology, without making claims about subjective experience, and they pose new challenges for AI safety, evaluation and mental-health practice.

Under a unified operational definition, we define LLM memory as a persistent state written during pretraining, finetuning, or inference that can later be addressed and that stably influences outputs. We propose a four-part taxonomy (parametric, contextual, external, procedural/episodic) and a memory quadruple (location, persistence, write/access path, controllability). We link mechanism, evaluation, and governance via the chain write -> read -> inhibit/update. To avoid distorted comparisons across heterogeneous setups, we adopt a three-setting protocol (parametric only, offline retrieval, online retrieval) that decouples capability from information availability on the same data and timeline. On this basis we build a layered evaluation: parametric (closed-book recall, edit differential, memorization/privacy), contextual (position curves and the mid-sequence drop), external (answer correctness vs snippet attribution/faithfulness), and procedural/episodic (cross-session consistency and timeline replay, E MARS+). The framework integrates temporal governance and leakage auditing (freshness hits, outdated answers, refusal slices) and uncertainty reporting via inter-rater agreement plus paired tests with multiple-comparison correction. For updating and forgetting, we present DMM Gov: coordinating DAPT/TAPT, PEFT, model editing (ROME, MEND, MEMIT, SERAC), and RAG to form an auditable loop covering admission thresholds, rollout, monitoring, rollback, and change audits, with specs for timeliness, conflict handling, and long-horizon consistency. Finally, we give four testable propositions: minimum identifiability; a minimal evaluation card; causally constrained editing with verifiable forgetting; and when retrieval with small-window replay outperforms ultra-long-context reading. This yields a reproducible, comparable, and governable coordinate system for research and deployment.

In this work, we introduce Brain Latent Progression (BrLP), a novel spatiotemporal disease progression model based on latent diffusion. BrLP is designed to predict the evolution of diseases at the individual level on 3D brain MRIs. Existing deep generative models developed for this task are primarily data-driven and face challenges in learning disease progressions. BrLP addresses these challenges by incorporating prior knowledge from disease models to enhance the accuracy of predictions. To implement this, we propose to integrate an auxiliary model that infers volumetric changes in various brain regions. Additionally, we introduce Latent Average Stabilization (LAS), a novel technique to improve spatiotemporal consistency of the predicted progression. BrLP is trained and evaluated on a large dataset comprising 11,730 T1-weighted brain MRIs from 2,805 subjects, collected from three publicly available, longitudinal Alzheimer's Disease (AD) studies. In our experiments, we compare the MRI scans generated by BrLP with the actual follow-up MRIs available from the subjects, in both cross-sectional and longitudinal settings. BrLP demonstrates significant improvements over existing methods, with an increase of 22% in volumetric accuracy across AD-related brain regions and 43% in image similarity to the ground-truth scans. The ability of BrLP to generate conditioned 3D scans at the subject level, along with the novelty of integrating prior knowledge to enhance accuracy, represents a significant advancement in disease progression modeling, opening new avenues for precision medicine. The code of BrLP is available at the following link: https://github.com/LemuelPuglisi/BrLP.

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.

Recent large language models (LLMs) offer the potential to support public health monitoring by facilitating health disclosure through open-ended conversations but rarely preserve the knowledge gained about individuals across repeated interactions. Augmenting LLMs with long-term memory (LTM) presents an opportunity to improve engagement and self-disclosure, but we lack an understanding of how LTM impacts people's interaction with LLM-driven chatbots in public health interventions. We examine the case of CareCall -- an LLM-driven voice chatbot with LTM -- through the analysis of 1,252 call logs and interviews with nine users. We found that LTM enhanced health disclosure and fostered positive perceptions of the chatbot by offering familiarity. However, we also observed challenges in promoting self-disclosure through LTM, particularly around addressing chronic health conditions and privacy concerns. We discuss considerations for LTM integration in LLM-driven chatbots for public health monitoring, including carefully deciding what topics need to be remembered in light of public health goals.

Dynamic treatment regimes (DTRs) are personalized, adaptive, multi-stage treatment plans that adapt treatment decisions both to an individual's initial features and to intermediate outcomes and features at each subsequent stage, which are affected by decisions in prior stages. Examples include personalized first- and second-line treatments of chronic conditions like diabetes, cancer, and depression, which adapt to patient response to first-line treatment, disease progression, and individual characteristics. While existing literature mostly focuses on estimating the optimal DTR from offline data such as from sequentially randomized trials, we study the problem of developing the optimal DTR in an online manner, where the interaction with each individual affect both our cumulative reward and our data collection for future learning. We term this the DTR bandit problem. We propose a novel algorithm that, by carefully balancing exploration and exploitation, is guaranteed to achieve rate-optimal regret when the transition and reward models are linear. We demonstrate our algorithm and its benefits both in synthetic experiments and in a case study of adaptive treatment of major depressive disorder using real-world data.

In this article, we consider identification, estimation, and inference procedures for treatment effect parameters using Difference-in-Differences (DiD) with (i) multiple time periods, (ii) variation in treatment timing, and (iii) when the "parallel trends assumption" holds potentially only after conditioning on observed covariates. We show that a family of causal effect parameters are identified in staggered DiD setups, even if differences in observed characteristics create non-parallel outcome dynamics between groups. Our identification results allow one to use outcome regression, inverse probability weighting, or doubly-robust estimands. We also propose different aggregation schemes that can be used to highlight treatment effect heterogeneity across different dimensions as well as to summarize the overall effect of participating in the treatment. We establish the asymptotic properties of the proposed estimators and prove the validity of a computationally convenient bootstrap procedure to conduct asymptotically valid simultaneous (instead of pointwise) inference. Finally, we illustrate the relevance of our proposed tools by analyzing the effect of the minimum wage on teen employment from 2001--2007. Open-source software is available for implementing the proposed methods.

Alzheimer's disease (AD) is a degenerative brain disease impairing a person's ability to perform day to day activities. The clinical manifestations of Alzheimer's disease are characterized by heterogeneity in age, disease span, progression rate, impairment of memory and cognitive abilities. Due to these variabilities, personalized care and treatment planning, as well as patient counseling about their individual progression is limited. Recent developments in machine learning to detect hidden patterns in complex, multi-dimensional datasets provides significant opportunities to address this critical need. In this work, we use unsupervised and supervised machine learning approaches for subtype identification and prediction. We apply machine learning methods to the extensive clinical observations available at the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set to identify patient subtypes and to predict disease progression. Our analysis depicts the progression space for the Alzheimer's disease into low, moderate and high disease progression zones. The proposed work will enable early detection and characterization of distinct disease subtypes based on clinical heterogeneity. We anticipate that our models will enable patient counseling, clinical trial design, and ultimately individualized clinical care.

LLM-based simulated clients are increasingly used to train novice counselors, evaluate LLM therapists, and generate synthetic data. However, current simulators produce overly cooperative clients that disclose too readily, accept therapeutic reframes without resistance, and resolve core issues within a single session. We trace these issues to profiles that lack causal depth and behavioral mechanisms that treat all content as equally accessible. We present PatientAct, a framework for client simulation grounded in established clinical theories. Our profiles integrate the 5Ps clinical case formulation, providing causal depth without tying the design to any single therapeutic modality. During simulation, profiles include a dynamic memory layer in which items carry trust thresholds (e.g., symptoms are available early, whereas formative memories require a sustained therapeutic alliance). At each turn, the client's emotional reaction and behavior are modeled before generating a response. If the therapist approaches gated content, PatientAct expresses resistance in terms of quantity, content, and style rather than defaulting to cooperation or a single resistance pattern. We evaluate our framework on 40 clinical situations and demonstrate that it generates diverse profiles with high clinical plausibility. Moreover, PatientAct significantly outperforms the baselines, yielding substantial gains in resistance quality and behavioral realism. Our code and data will be publicly available via github.com/Sahandfer/PatientHub.

Recent research has demonstrated the capability of behavior signals captured by smartphones and wearables for longitudinal behavior modeling. However, there is a lack of a comprehensive public dataset that serves as an open testbed for fair comparison among algorithms. Moreover, prior studies mainly evaluate algorithms using data from a single population within a short period, without measuring the cross-dataset generalizability of these algorithms. We present the first multi-year passive sensing datasets, containing over 700 user-years and 497 unique users' data collected from mobile and wearable sensors, together with a wide range of well-being metrics. Our datasets can support multiple cross-dataset evaluations of behavior modeling algorithms' generalizability across different users and years. As a starting point, we provide the benchmark results of 18 algorithms on the task of depression detection. Our results indicate that both prior depression detection algorithms and domain generalization techniques show potential but need further research to achieve adequate cross-dataset generalizability. We envision our multi-year datasets can support the ML community in developing generalizable longitudinal behavior modeling algorithms.

Current medical benchmarks typically break down clinical competence into isolated factual questions, single-image tasks, or static case vignettes. These tests score individual answers, but reveal less about whether a model can integrate subspecialty knowledge with multimodal evidence and track a patient's condition throughout a course of care. To close this gap, we introduce NPCBench, a clinical apprenticeship benchmark for nasopharyngeal carcinoma (NPC). NPCBench mirrors specialist training, from guideline and foundational knowledge to case planning, longitudinal review, CarePath integration, and open-ended consultation. It contains 4,777 component and consultation items and a 100-patient CarePath cohort with 417 scored diagnostic and care tasks. The episode-level evaluation tests whether diagnostic and care answers are jointly correct within a care pathway. By linking stepwise tasks to patient-level care trajectories, NPCBench evaluates whether models ground decisions in visual evidence, interpret changes in patient state, and meet clinical requirements in consultation. Across 30 evaluated models, we observe a composition gap: strong performance on individual tasks does not ensure jointly correct diagnostic and care answers for the same patient. Among 21 multimodal models, strict CarePath success reaches at most 23%. Paired controls and physician calibration further examine evidence grounding, longitudinal revision, and consultation judging. Overall, NPCBench broadens the evaluation of medical artificial intelligence beyond static question-answering paradigms to an apprenticeship-oriented assessment of clinical workflows, thereby offering a testbed for evidence-based and temporally coherent reasoning in oncology care.

Clinical LLM assistants must reason over multi-visit patient trajectories, yet whether the compact history representations used to scale them---retrieval, structured timelines, LLM summaries, agentic memory---preserve the longitudinal signal clinical reasoning needs has not been measured. We introduce ClinTraceBench: 385 MIMIC-IV-derived verified dialogues with event-ID provenance, a nine-task taxonomy (T1--T9), and L0--L4 deterministic + L5 human-audit validation (98.92\% agreement). We evaluate eight history representation strategies---a no-context floor, last-visit-only, full-context, BGE-M3 dense-retrieval, two compression schemes, and two agentic-memory systems (Mem0, A-Mem)---across four backbones (DeepSeek-V3, GPT-4o-mini, Haiku~4.5, Sonnet~4.6) on 6{,}271 questions: 32 cells, 200{,}672 predictions. Four findings: (SP4) a controlled T3 injection probe isolates compression-induced relation loss---with the attribution sentence present before construction, Mem0, A-Mem and llm-summary still recover only 0--5.3\% of the injected positives; (SP1) compressed strategies pay an aggregation tax on multi-visit trends and cross-patient comparisons; (SP2) the blind-to-full gap spans +29.8~pp (GPT-4o-mini) to +62.7~pp (Haiku); (SP3) abstention scales non-monotonically with context length. On the Pareto frontier Haiku dominates Sonnet under full-context (\25.76 vs. 106.21), inverting the ``biggest backbone wins'' heuristic.

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.

Foundation models can serve as clinical agents through tool-use harnesses. However, conventional medical benchmarks assess reasoning over preselected evidence rather than the ability to seek it across clinical records and longitudinal imaging. We propose CASE: a series of role-specific Clinical Agents for Seeking Evidence, together with a tool-use harness and an agentic post-training framework for compact vision-language policy models. We further introduce a longitudinal multimodal benchmark built on UK Biobank, comprising 50,401 clinical questions derived from real-world ICD-10-coded diagnoses of 4,739 participants. Each question links to a patient-specific environment containing clinical context and multi-sequence MRI from baseline and follow-up visits, where agents autonomously select which visits, organs, modalities, slices, and specialist tools to inspect and compare. Supervised fine-tuning transfers evidence-seeking workflows from 14,734 frontier-model interaction trajectories, followed by agentic reinforcement learning on the learner's own environment interactions. Privileged on-policy self-distillation and rubric-based LLM feedback refine evidence-to-conclusion reasoning without prescribing tool sequences. Experiments show that CASE moves beyond question-answer imitation toward transferable investigation policies, strengthening evidence-grounded longitudinal reasoning. Under matched evaluation conditions, our Qwen3-VL-8B based agent achieves over 16% and 10% relative improvements in answer accuracy over GPT-5.4 and Claude Opus 4.8. Code will be available at https://github.com/VinyehShaw/CASE.

Within the complex framework of anti-COVID-19 health management, where the criteria of diagnostic testing, the availability of public-health resources and services, and the applied anti-COVID-19 policies vary between countries, the reliability and the accuracy in the modeling of temporal spread can be proven effective in the worldwide fight against the disease. This paper applies an exploratory time-series analysis to the evolution of the disease in Greece, which currently suggests a success story of COVID-19 management. The proposed method builds on a recent conceptualization of detecting connective communities in a time-series and develops a novel spline regression model where the knot vector is determined by the community detection in the complex network. Overall, the study contributes to the COVID-19 research by proposing a free of disconnected past-data and reliable framework of forecasting, which can facilitate decision-making and management of the available health resources.

Objective: To propose and retrospectively validate an integrated framework addressing three barriers to clinical translation of readmission prediction: lack of explainability, absence of deployment reliability infrastructure, and inadequate demographic fairness evaluation. Materials and Methods: We constructed a cohort of 415231 adult admissions from the MIMIC-IV database (30-day readmission prevalence 18.0%), split 70/15/15. Logistic regression, XGBoost, and LightGBM models were trained on 26 features. SHAP provided per-patient explanations. Fairness was evaluated across 16 subgroups using AUC-ROC, false negative rate (FNR), and positive predictive value (PPV). Calibration was assessed using Brier scores and calibration curves. Results: XGBoost achieved AUC-ROC 0.696 (95% CI 0.691-0.701), outperforming or matching the LACE baseline (AUC 0.60-0.68). LightGBM achieved best calibration (Brier 0.146). Prior admissions were the dominant predictor. All subgroups met equity thresholds (delta AUC <= 0.05, delta FNR <= 0.10). Conclusion: This framework delivers competitive performance, clinically actionable explanations, and strong demographic equity. Code is publicly available at https://github.com/Tomisin92/readmission-prediction.

A growing literature argues that progress in human longevity is slowing, and that this slowdown may signal an approaching biological limit to lifespan. The argument rests on visible flattening of cumulative life expectancy records, evaluated through linear regressions or through comparisons of average gains across decades. These summaries, however, provide only weak evidence for slowing improvements, because they cannot distinguish a true from an apparent slowdown. An apparent slowdown may arise due to periods of low variance around unchanged mean annual gains. Applying a Bayesian change-point framework to annual gains, both at the best-practice frontier and separately for each record-holding country, we find no evidence that the expected annual gain has changed across nearly two centuries, but strong evidence that its variance has moved through distinct historical regimes, with progress most regular in recent decades. The recent flattening is consistent with a low-variance regime and provides little evidence for a decline in the underlying mean pace of improvement. Claims that the best-practice frontier signals a biological ceiling should therefore not rest on the recent bend in the cumulative record alone. The frontier is better read as an empirical benchmark, the highest country-specific survival achieved under observed historical conditions.

Large language models (LLMs) offer a scalable approach to social simulation, but their credibility depends on how agents are constructed. Existing methods can partially reproduce population-level patterns, yet often fail to capture human-like diversity. Our analysis shows that static-profile agents exhibit stronger demographic separation and within-group compression than humans, a pattern consistent with identity essentialism: demographic labels can encourage models to treat group-average tendencies as individual traits, homogenizing responses within groups. We argue that this limitation arises from two related factors: sparse, static agent representations and the limited ability of prompt-only memory to persistently integrate experience. Inspired by complementary memory systems, we propose LifeMem, a longitudinal memory framework that combines structured life-event retrieval with agent-specific parametric memory for experience integration. Experiments on Add Health and Understanding Society with three LLMs show that LifeMem improves alignment with human data in terms of response distributions, overall and within-group diversity, and patterns of within-person response change across life stages. These findings highlight the value of longitudinal life-event memory for constructing more faithful and dynamically evolving social agents.

Brain MRI interpretation is a longitudinal clinical reasoning problem: radiologists compare serial studies, integrate information across MRI sequences, localize findings within volumetric anatomy, and translate this evidence into report-grounded assessments. Existing medical VQA and 3D imaging benchmarks capture important parts of this workflow, but often evaluate brain MRI through isolated images, static volumes, or ungrounded report-style answers, thereby obscuring failures in the evidence chain that support clinical validity. We introduce BrainTRACE, a report-grounded benchmark for evaluating whether vision-language models can trace the evidence structure required for longitudinal brain MRI interpretation. BrainTRACE contains 7,273 scored VQA instances derived from 1,778 longitudinal patients, 7,299 MRI studies, and approximately 29k co-registered 3D MRI sequence volumes. The benchmark is organized by five levels of clinical reasoning, from acquisition recognition to case-level synthesis, and by evidence demands covering longitudinal comparison, report-grounded references, multi-sequence integration, and volumetric spatial evidence. BrainTRACE supports rendered inputs compatible with standard VLM interfaces, a 3D-evidence condition, and a decomposed case-reasoning track that audits six steps in a longitudinal evidence chain. Evaluation of 20 VLM configurations shows that current systems can identify isolated visual cues but rarely compose them into grounded longitudinal interpretations. We release the benchmark specification, evaluation lists, scoring implementation, scoring rubrics, and audit-record format to support reproducible progress in brain MRI VLM evaluation.

We introduce a cross-domain behavioural assay of monitoring-control coupling in LLMs, grounded in the Nelson and Narens (1990) metacognitive framework and applying human psychometric methodology to LLM evaluation. The battery comprises 524 items across six cognitive domains (learning, metacognitive calibration, social cognition, attention, executive function, prospective regulation), each grounded in an established experimental paradigm. Tasks T1-T5 were pre-registered on OSF prior to data collection; T6 was added as an exploratory extension. After every forced-choice response, dual probes adapted from Koriat and Goldsmith (1996) ask the model to KEEP or WITHDRAW its answer and to BET or decline. The critical metric is the withdraw delta: the difference in withdrawal rate between incorrect and correct items. Applied to 20 frontier LLMs (10,480 evaluations), the battery discriminates three profiles consistent with the Nelson-Narens architecture: blanket confidence, blanket withdrawal, and selective sensitivity. Accuracy rank and metacognitive sensitivity rank are largely inverted. Retrospective monitoring and prospective regulation appear dissociable (r = .17, 95% CI wide given n=20; exemplar-based evidence is the primary support). Scaling on metacognitive calibration is architecture-dependent: monotonically decreasing (Qwen), monotonically increasing (GPT-5.4), or flat (Gemma). Behavioural findings converge structurally with an independent Type-2 SDT approach, providing preliminary cross-method construct validity. All items, data, and code: https://github.com/synthiumjp/metacognitive-monitoring-battery.

The long-term effects of Postacute Sequelae of SARS-CoV-2, known as PASC, pose a significant challenge to healthcare systems worldwide. Accurate identification of progression events, such as hospitalization and reinfection, is essential for effective patient management and resource allocation. However, traditional models trained on structured data struggle to capture the nuanced progression of PASC. In this study, we introduce the first publicly available cohort of 18 PASC patients, with text time series features based on Large Language Model Llama-3.1-70B-Instruct and clinical risk annotated by clinical expert. We propose an Active Attention Network to predict the clinical risk and identify progression events related to the risk. By integrating human expertise with active learning, we aim to enhance clinical risk prediction accuracy and enable progression events identification with fewer number of annotation. The ultimate goal is to improves patient care and decision-making for SARS-CoV-2 patient.

Proactive LLM agents anticipate service opportunities from ongoing observations and accumulated history. Existing approaches emphasize recent context or retrieval of related memories, providing limited support for validating recurring behavioral regularities and assessing their applicability to the current event. We propose Proactive Memory (ProactMem), which organizes history into recent events, temporal trajectories, and behavioral regularities. Trajectory facts are checked against source events, and regularities are assessed through historical replay before being matched to current conditions. We also construct ProactiveStream, a longitudinal benchmark covering three application scopes, where agents process isolated event streams chronologically under episode-aware opportunity labels. On ProactiveStream, ProactMem achieves an overall effectiveness (F1) of 52.6%, a 21.4% relative improvement over the strongest of five external baselines. Code is available at: https://anonymous.4open.science/r/ProactMem-5351/.

The rising global prevalence of mental health conditions, together with longstanding barriers in traditional healthcare, such as limited resources, high cost, stigma, and privacy concerns, has created an urgent need for accessible and scalable support. Large Language Models (LLMs) have emerged as a transformative technology with strong potential to democratize mental health support through advanced natural language understanding and generation. However, the rapidly expanding, fragmented body of work in this area lacks a coherent evolutionary narrative, making it difficult to contextualize current progress and identify future directions. This survey addresses this gap by organizing and analyzing the literature around a central thesis: the role of LLMs in mental health is evolving through three distinct, increasingly sophisticated phases. We trace this trajectory from Phase I, in which LLMs act primarily as passive Information Tools and Pattern Recognizers for assessment; through Phase II, where they function as Empathetic Conversationalists for in-the-moment, stateless interactions; to the current frontier, Phase III, which seeks Longitudinal, Personalized Companions implemented as stateful cognitive agents. To support this framework, we systematically review core technologies, agent architectures (Profile, Memory, Reasoning, and Planning), and the critical infrastructure of datasets and benchmarks, highlighting how their evolution underpins this developmental path. Viewing the field through this developmental lens, we provide a comprehensive synthesis of existing work, an insightful narrative of its trajectory, and a clear roadmap for future innovation in responsible, effective, and human-centered AI for mental healthcare. A curated collection of the resources reviewed in this survey is available at our project repository: https://github.com/Emo-gml/Awesome-Mental-Health-LLMs.

Electronic Health Records (EHRs) contain rich, longitudinal patient information across structured (e.g., labs, vitals, and imaging) and unstructured (e.g., clinical notes) modalities. While deep learning models such as RNNs and Transformers have advanced single- and multimodal EHR analysis, existing methods often optimize for specific downstream tasks and overlook the creation of generalizable patient representations that can be reused across multiple tasks. To address this gap, we propose CAAT-EHR, a novel Cross-Attentional Autoregressive Transformer architecture that produces task-agnostic, longitudinal embeddings of multimodal EHR data. In CAAT-EHR, self-attention layers capture temporal dependencies within each modality, while cross-attention layers fuse information across modalities to model complex interrelationships. During pre-training, an autoregressive decoder predicts future time steps from the fused embeddings, enforcing temporal consistency and enriching the encoder output. Once trained, the encoder alone generates versatile multimodal EHR embeddings that can be applied directly to a variety of predictive tasks. CAAT-EHR demonstrates significant improvements on benchmark EHR datasets for mortality prediction, ICU length-of-stay estimation, and Alzheimer's disease diagnosis prediction. Models using EHR embeddings generated by CAAT-EHR outperform models trained on raw EHR data in eleven out of twelve comparisons for F1 score and AUC across all three downstream tasks. Ablation studies confirm the critical roles of cross-modality fusion and autoregressive refinement. Overall, CAAT-EHR provides a unified framework for learning generalizable, temporally consistent multimodal EHR representations that support more reliable clinical decision support systems.

Adherence to prescribed treatments is crucial for individuals with chronic conditions to avoid costly or adverse health outcomes. For certain patient groups, intensive lifestyle interventions are vital for enhancing medication adherence. Accurate forecasting of treatment adherence can open pathways to developing an on-demand intervention tool, enabling timely and personalized support. With the increasing popularity of smartphones and wearables, it is now easier than ever to develop and deploy smart activity monitoring systems. However, effective forecasting systems for treatment adherence based on wearable sensors are still not widely available. We close this gap by proposing Adherence Forecasting and Intervention with Machine Intelligence (AIMI). AIMI is a knowledge-guided adherence forecasting system that leverages smartphone sensors and previous medication history to estimate the likelihood of forgetting to take a prescribed medication. A user study was conducted with 27 participants who took daily medications to manage their cardiovascular diseases. We designed and developed CNN and LSTM-based forecasting models with various combinations of input features and found that LSTM models can forecast medication adherence with an accuracy of 0.932 and an F-1 score of 0.936. Moreover, through a series of ablation studies involving convolutional and recurrent neural network architectures, we demonstrate that leveraging known knowledge about future and personalized training enhances the accuracy of medication adherence forecasting. Code available: https://github.com/ab9mamun/AIMI.

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.

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.

Global healthcare providers are exploring use of large language models (LLMs) to provide medical advice to the public. LLMs now achieve nearly perfect scores on medical licensing exams, but this does not necessarily translate to accurate performance in real-world settings. We tested if LLMs can assist members of the public in identifying underlying conditions and choosing a course of action (disposition) in ten medical scenarios in a controlled study with 1,298 participants. Participants were randomly assigned to receive assistance from an LLM (GPT-4o, Llama 3, Command R+) or a source of their choice (control). Tested alone, LLMs complete the scenarios accurately, correctly identifying conditions in 94.9% of cases and disposition in 56.3% on average. However, participants using the same LLMs identified relevant conditions in less than 34.5% of cases and disposition in less than 44.2%, both no better than the control group. We identify user interactions as a challenge to the deployment of LLMs for medical advice. Standard benchmarks for medical knowledge and simulated patient interactions do not predict the failures we find with human participants. Moving forward, we recommend systematic human user testing to evaluate interactive capabilities prior to public deployments in healthcare.

Large language models are useful because we taught them to give us what we want. This works when success can be judged immediately, but people increasingly bring these systems their relationships, hard decisions, and long-term goals, where what a user wants to hear and what serves them best are frequently different. We argue that LLM providers should offer at least one widely accessible, opt-in mode optimized and evaluated for long-term well-being rather than next-turn approval. This is a pressing need, as models have been found to endorse questionable framings well above human baselines, users take AI advice readily without their well-being improving, and sycophantic models raise dependence while lowering prosocial intent. The mentors, coaches, and therapists we trust with our long-term development earn that trust by being willing to say what we do not want to hear, and LLMs should do the same. We propose three principles---change the objective, give users explicit relational roles, avoid paternalism---and organize the design space around three choices the current objective makes implicitly: the horizon over which well-being is measured (When), whose interests it represents (Who), and what role the assistant plays (How).

Loss Given Default (LGD) modeling faces a fundamental data quality constraint: 90% of available training data consists of proxy estimates based on pre-distress balance sheets rather than actual recovery outcomes from completed bankruptcy proceedings. We demonstrate that this mixture-contaminated training structure causes systematic failure of recursive partitioning methods, with Random Forest achieving negative r-squared (-0.664, worse than predicting the mean) on held-out test data. Information-theoretic approaches based on Shannon entropy and mutual information provide superior generalization, achieving r-squared of 0.191 and RMSE of 0.284 on 1,218 corporate bankruptcies (1980-2023). Analysis reveals that leverage-based features contain 1.510 bits of mutual information while size effects contribute only 0.086 bits, contradicting regulatory assumptions about scale-dependent recovery. These results establish practical guidance for financial institutions deploying LGD models under Basel III requirements when representative outcome data is unavailable at sufficient scale. The findings generalize to medical outcomes research, climate forecasting, and technology reliability-domains where extended observation periods create unavoidable mixture structure in training data.

Large Language Models (LLMs) have great potential in the field of health care, yet they face great challenges in adapting to rapidly evolving medical knowledge. This can lead to outdated or contradictory treatment suggestions. This study investigated how LLMs respond to evolving clinical guidelines, focusing on concept drift and internal inconsistencies. We developed the DriftMedQA benchmark to simulate guideline evolution and assessed the temporal reliability of various LLMs. Our evaluation of seven state-of-the-art models across 4,290 scenarios demonstrated difficulties in rejecting outdated recommendations and frequently endorsing conflicting guidance. Additionally, we explored two mitigation strategies: Retrieval-Augmented Generation and preference fine-tuning via Direct Preference Optimization. While each method improved model performance, their combination led to the most consistent and reliable results. These findings underscore the need to improve LLM robustness to temporal shifts to ensure more dependable applications in clinical practice.

Longitudinal medical imaging captures temporal evolution of lesions, yet extracting the underlying dynamical parameters governing this evolution remains challenging. We propose an inverse Bayesian framework for inferring lesion dynamics from longitudinal spectral CT. We decompose spectral feature (x) evolution into three components: equation* dx_i{dt} = A_i x_i + B \cdot n + C \cdot Δx_{sat} equation* where A_i captures intrinsic dynamics (lesion-autonomous evolution), B captures local environment tumour burden (organ tumour burden through satellite count coupling), and C captures environment/satellite state change (i.e., whether surrounding lesions move similarly or not). We demonstrate the framework on photon-counting NSCLC CT data from metastases, recovering distinct dynamical regimes: lung lesions exhibit significant satellite count coupling (B=-0.34, p<0.05) suggesting competitive dynamics, while liver lesions show synergistic satellite behaviour coupling (Capprox+1.0, p<0.05). Synthetic validation confirms parameter recovery, and cross-coupling analysis validates that our method detects non-zero coupling when present. This work establishes inverse dynamical inference as a principled methodology for extracting interpretable parameters from longitudinal imaging, moving beyond static feature extraction toward mechanistic characterisation of lesion behaviour. The code and data are available at: https://github.com/lukasf98/inverse-bayesian-inference

[This paper was initially published in PHME conference in 2016, selected for further publication in International Journal of Prognostics and Health Management.] This paper describes an Autoregressive Partially-hidden Markov model (ARPHMM) for fault detection and prognostics of equipments based on sensors' data. It is a particular dynamic Bayesian network that allows to represent the dynamics of a system by means of a Hidden Markov Model (HMM) and an autoregressive (AR) process. The Markov chain assumes that the system is switching back and forth between internal states while the AR process ensures a temporal coherence on sensor measurements. A sound learning procedure of standard ARHMM based on maximum likelihood allows to iteratively estimate all parameters simultaneously. This paper suggests a modification of the learning procedure considering that one may have prior knowledge about the structure which becomes partially hidden. The integration of the prior is based on the Theory of Weighted Distributions which is compatible with the Expectation-Maximization algorithm in the sense that the convergence properties are still satisfied. We show how to apply this model to estimate the remaining useful life based on health indicators. The autoregressive parameters can indeed be used for prediction while the latent structure can be used to get information about the degradation level. The interest of the proposed method for prognostics and health assessment is demonstrated on CMAPSS datasets.

The digitization of healthcare has generated vast, longitudinal, and multimodal patient records over a lifetime, yet fully exploiting these data to represent and predict patient state trajectories remains a critical challenge. Current AI models often struggle to capture the complex, irregular temporal dynamics and inherent stochasticity of real-world multimodal patient data. Existing AI approaches for modeling longitudinal patient records are predominantly discriminative, limited to a few modalities, constrained by closed categorical vocabularies, treating time as a monotonic inductive bias, or they are limited in forecasting future patient states. We introduce NOAH, a time-aware, task-agnostic, generative transformer model representing and forecasting the full multimodal patient journey. NOAH features a novel bidirectional time integration and a variational latent space to capture the continuous evolution of patient states and the stochasticity of clinical trajectories. Built from over 559 million clinical events from 431,000 hospital visits of 299,000 patients across the MIMIC dataset family, NOAH natively processes medical images, time-series and numeric signals, categorical events, as well as structured and unstructured clinical records. NOAH is the first truly holistic generative model in its field, enabling autoregressive forecasting with optional time control, zero-shot classification, and counterfactual intervention simulation. It generates highly informative and predictive patient state representations that demonstrate strong performance in probing for clinical outcomes, 15 ICD chapters, and 29 comorbidities, as well as in time-to-event prediction. Seamlessly handling diverse modalities and complex temporal dynamics, NOAH provides a versatile, task-agnostic, scalable foundation for intelligent predictive systems in personalized clinical care and digital medicine.