hospital data teams

Abstract: Random forests (RFs) predict well but are opaque, whereas single decision trees are interpretable but unstable. Artificial representative trees (ARTs) were developed as interpretable surrogate models for RFs, but their use as standalone prediction models with uncertainty quantification has not been systematically investigated. We combine ARTs with leaf-wise Mondrian conformal predictive systems (CPS), enabling a single tree to provide continuous predictions, prediction intervals, and probabilities of exceeding arbitrary thresholds. We compared ARTs with CPS against decision trees with CPS and separate regression and probability trees across five simulation scenarios, 21 benchmark datasets, and a cross-sectional NHANES example data set. Repeated cross-validation assessed predictive performance, interpretability, and stability. ARTs with CPS yield compact, structurally stable trees with substantially more reproducible split-variable selection than decision trees across benchmark datasets and NHANES. Decision trees showed slightly better predictive performance and narrower prediction intervals, while coverage was broadly comparable. CPS-based trees generally achieved lower and less variable Brier scores than multi-model approaches. Combining ARTs with CPS therefore provides a single, interpretable, and stable model for continuous predictions and calibrated probabilities, balancing predictive performance with reproducibility and transparency in settings where stability and interpretability are essential.

Abstract: A medical model's benchmark score does not establish that the same conclusion holds under a different evaluation. This study tests whether claims about model ranking, score reliability and screening performance survive changes in cohort, prompt, negative spectrum, specified prevalence and operating threshold. We audit three medical vision-language models (BioMedCLIP, CheXficient, and MedSigLIP) and a general-domain OpenCLIP comparator on 12,200 chest radiograph records from four datasets (Montgomery, Shenzhen, TBX11K, and VinDr-CXR). Five fixed prompt families yield 244,000 model--image--prompt scores. No model leads every cohort and reliability criterion. Prompt-family changes alter AUROC in 21 of 48 multiplicity-controlled comparisons. Replacing healthy controls with sick non-tuberculosis controls reduces AUROC by 0.075--0.306 across all four models. On VinDr-CXR, the three medical models distinguish tuberculosis from no-finding controls substantially better than from pneumonia or lung tumor; their AUROC point estimates for both named diseases fall below 0.5. CheXficient has documented VinDr-CXR pretraining exposure, which limits the interpretation of its results. Thresholds chosen for 95\% sensitivity on TBX11K training retain that constraint by point estimate in only four of sixteen target evaluations. A five-seed supervised source model reaches 0.999 AUROC on TBX11K validation but 0.629 on each of two external cohorts. Conservative exclusion of perceptual-overlap candidates narrows this gap without closing it. These retrospective, single-task results show that discrimination, score reliability and threshold retention support different portability claims. Evidence for chest X-ray tuberculosis screening should identify the complete evaluation specification rather than attribute clinical portability to a checkpoint alone.

Abstract: Emergency department (ED) decision-making relies on heterogeneous clinical information, including patient history, vital signs, laboratory results, and electrocardiograms (ECGs). Vision--language models (VLMs) can jointly process these modalities, but strong predictive performance does not necessarily imply meaningful use of the correct patient's ECG. We term this failure mode ECG Mirage: apparent multimodal capability without useful dependence on patient-specific ECG information. We distinguish two forms: ECG neglect, where ECGs provide little predictive benefit, and ECG confusion, where matched ECGs outperform no-image inputs but not mismatched ECGs. To evaluate these behaviours, we compare predictions obtained with matched ECGs, outcome-discordant mismatched ECGs, and no-image inputs while holding the clinical text and prediction targets fixed. Across four VLMs on MDS-ED, matched ECGs provide no consistent advantage for either ICU admission or clinical deterioration prediction. We then train four restricted visual prompts using supervised learning followed by conditional direct preference optimisation, while keeping the VLM backbone frozen. The resulting models achieve balanced accuracies of 70.6% for ICU admission and 67.5% for deterioration and increase the matched-versus-mismatched performance gap to approximately 16.5 and 5.5 percentage points, respectively. Overall, our study identifies ECG Mirage in multimodal clinical prediction and introduces visual prompt tuning as an efficient mitigation strategy.

Abstract: Research data quality is multidimensional and purpose-dependent: it emerges from the interplay of data, intended use, contextual knowledge, documentation, intervention decisions, and traceability. This concept paper presents the Data Hospital, a human-in-the-loop control and interaction model for research data quality. Using a hospital metaphor, datasets are admitted, contextualized, assessed, reviewed in specialized stations, modified only through approved interventions, validated, documented, and made replayable where interventions are sufficiently specified. The concept combines deterministic profiling and inspectable evidence with optional evidence-bound explanation by Dr. Data and explicit user decisions. Preserved Raw Data and controlled working states separate observation from intervention. The contribution is not a new cleaning or imputation algorithm, but a ten-stage workflow that makes assessability, uncertainty, intervention authority, provenance, and process reproducibility visible. The prototype is an implementation-backed demonstrator rather than a released research artifact and illustrates selected parts of the concept through representational standardization, imputation, Patient File documentation, and replay. The paper concludes with a staged agenda for subsequent technical and user-centered evaluation.

Abstract: Federated learning enables collaborative training without sharing patient-level data, but most studies remain simulations. Based on five requirements derived from the literature, we analyzed 14 FL frameworks and found that none fully satisfied these requirements. We present FL-Net, a novel federated clinical research framework to fulfill all requirements. It integrates modular data harmonization, data discovery, disclosure control, securely built versioned FL-Net-Tools and containerized federated workflow execution into a persistent network. It enables the re-use of harmonized data and workflows across studies. FL-Net's end-to-end capabilities were evaluated through harmonization, cross-study patient discovery across MIMIC and US-130, and reproducible, audited federated workflows with up to 50 concurrent clients. FL-Net is being developed within the dAIbetes and Microb-AI-ome EU projects and will cover over 800,000 patients across 10 hospitals in 9 countries covering longitudinal and single point in time data, FL-Net provides a practical foundation for interoperable, reproducible, and privacy-preserving multicenter clinical research.

Abstract: One hospital runs bloods and imaging at the same time. Another runs them one after the other, in either order, equally often. Knowing which actually happened, and how it is recorded in data, is critical for all operational managers. In process mining, the standard approach is to construct an event log, and attempt to discover concurrent and sequential processes in a data-driven way. We show this standard approach, built on the stochastic language of an event log, reports only the assumptions of its discovery algorithm, because every such log is explained equally well by a model with no concurrency at all. Further, before any data is acquired, we characterise when data can and cannot distinguish concurrent behaviour. Where it cannot, the distinction is recoverable from evidence the stochastic language discards, such as the times at which activities start and end, or object-centric records that fix an order within an execution. The remedy is therefore a choice of what is recorded, rather than a larger sample. This impacts decision making, as planning resource for truly concurrent services is very different from sequential services.

Abstract: Representation learning from medical code sequences in electronic health records and medical claims data has been successful in various clinical applications, such as those regarding disease prediction. However, significant challenges remain in extending this approach to the discovery of scientific hypotheses. One reason is that many existing BERT-based models fail to adequately capture the hierarchical structure of medical codes and the complex interactions between diagnoses and treatments. To address these limitations, we propose a new unified pre-training framework that explicitly integrates hierarchical sub-token aggregation, partial masking, and cross-reference mechanisms. The proposed model consistently outperformed existing methods on both pre-training objectives and downstream clinical event prediction tasks, including the onset of dementia and hospitalization. We also conducted an in silico drug repositioning case study targeting Alzheimer's disease. In the hypothesis generation step, our approach successfully rediscovered known promising drugs in a data-driven manner without relying on such external knowledge sources as the literature. Subsequently, in the hypothesis prioritization step, we introduced a Task-Adaptive Representation Approach to alleviate the over-encoding of historical prescription information within diagnostic vectors, enabling the robust prioritization of generated hypotheses. This study establishes an exploratory screening workflow for hypothesis generation and prioritization based on observational associations. Importantly, this framework is not intended to provide causal evidence, but rather to identify promising candidates for subsequent rigorous causal inference. Overall, this study demonstrates that domain-informed representation learning combined with task-adaptive representation control can enable a practical hypothesis discovery workflow.

Abstract: In mental health care, reasoning over patient journeys is a key task for clinicians. Yet these journeys, encompassing a longitudinal progression of biological, psychological, and social events, are often spread across disparate unstructured text narratives, making temporal recovery challenging. We present CliniCIRCA, a multi-stage LLM framework for Calendar-anchored, Imprecision-aware Reconstruction of Clinical Annals. To our knowledge, CliniCIRCA is the first to temporally classify clinical events across unstructured discharge summaries without event-level timestamps. From 14,882 MIMIC-III mental health admissions, we first construct a benchmark of 52 discharge summaries on which CliniCIRCA produces 15,891 temporally tagged events. After correcting 629 errors based on a clinician-in-the-loop evaluation, we produce verified gold-standard labels. Finally, the corrected timelines drive a temporally grounded summarization stage that compresses each source 1.52 times into a date-grouped chronological record. We then scale the framework to generate 1,000 silver-standard timelines and evaluate them as training data. Compared with zero- and few-shot prompting, instruction tuning generally improves five open-weight models on event extraction, temporal tagging, and summarization across silver and clinician-verified evaluations.

Abstract: Clinical data abstraction, the process of distilling structured information from patient records, plays a key role in advancing knowledge about diseases such as cancer. Information extraction (IE) with large language models (LLMs) could accelerate this process, but it is unclear whether current frameworks effectively support clinical researchers without AI expertise. To address this, we co-designed an interactive LLM-based abstraction system called Libretto with seven cancer research teams, then evaluated the system's ability to help them answer real-world research questions. We found that while clinicians knew where and how to annotate complex concepts in patient notes, in twelve of fourteen tasks they faced barriers to replicating those intuitions with LLMs. Contextual note reliability judgments, difficulties in steering vibe-coded prompts, and inflexible evaluation strategies necessitated fundamental changes to the IE workflow. Our results highlight open problems for HCI research to bridge the gaps between AI data work tools and clinical users' needs.

Abstract: Longitudinal electronic health records (EHRs) capture years of patient history across notes, codes, labs, and procedures, and contain evidence needed to reason about likely clinical outcomes. However, comprehensive clinician review of these records is impractical, and LLM-based processing is costly and often unreliable, missing some relevant observations while hallucinating others. We therefore propose EviGen, a three-layer framework for verifiable clinical rationale generation that addresses these challenges. The first layer is a patient-conditioned retriever that uses learnable queries to find evidence predictive of, not just textually relevant to, a clinical outcome and ranks it by prediction attribution scores. The second layer is an LLM generator that consumes this ranked evidence as a scaffold to produce a clinical rationale grounded in the retrieved spans. The third layer is a process-supervised verifier that checks the generated rationale at the reasoning-step level, flagging unreliable claims. Across three medical prediction datasets, EviGen improves prediction performance and rationale faithfulness over full-context LLM and RAG baselines, and is preferred by clinical reviewers in a usability evaluation.

Abstract: Biomedical knowledge graphs combine ontology-derived hierarchies with transversal associations among heterogeneous entities such as phenotypes, diseases, genes, proteins, and patients. This hybrid structure raises the question of whether hyperbolic embeddings, which naturally capture tree-like organization, remain useful beyond purely hierarchical graphs. We present a preliminary study of hyperbolic graph representation learning for Mendelian-disease differential diagnosis on a patient-integrated biomedical graph. Experiments on isolated ontology subgraphs show that hyperbolic models achieve strong performance in substantially lower dimensions than Euclidean baselines. We then evaluate the models on a link-prediction task that ranks candidate diseases for each patient. Results suggest that hyperbolic embeddings can exploit biomedical hierarchical structure while supporting diagnostic reasoning over heterogeneous patient-level graphs.

Abstract: Methodological progress in artificial intelligence (AI) for electronic health records (EHRs) depends on our ability to determine which algorithms work better, and under which conditions. However, such progress is thought to be hindered by difficulties in reproducibility and in defining clinically meaningful evaluation tasks. We empirically study these barriers by re-implementing 12 historical and recent algorithms within a shared evaluation framework and evaluating them on two clinical datasets, MIMIC-IV and NWICU. We compare two complementary task families: expert-authored clinically meaningful tasks and generated tasks defined from randomly sampled event codes and prediction horizons. We ask whether relative algorithms comparisons transfer across task families and datasets, whether residual task heterogeneity contains useful methodological structure, and what a controlled comparison reveals about progress over the last decade. We find that aggregate pairwise comparisons transfer strongly across evaluation settings, including from randomly generated tasks to clinically meaningful tasks and across datasets. At the same time, clinically meaningful tasks exhibit greater task-method interaction, providing preliminary evidence that task properties can help explain when particular modeling choices are advantageous. Finally, newer algorithms do not consistently outperform earlier approaches: gradient-boosted trees remain highly competitive when paired with a modern, wide and sparse representation of the EHR. Together, these results suggest that useful methodological knowledge may require less task engineering than commonly assumed, while highlighting the importance of understanding the structured heterogeneity that remains across tasks and methods.

Abstract: Standardizing clinical language to SNOMED CT supports interoperability, analytics, and reusable phenotyping, but concept recommendation remains difficult when relevant concepts are rare or absent from training data. We present a masked-concept recommendation benchmark using the SNOMED CT Entity Linking Challenge v1.2.1 data derived from MIMIC-IV-Note. The dataset contains 75,491 annotations across 272 discharge summaries, with 204 notes used for training and 68 for historical testing. For each unique note-concept pair, the target mention is masked from a local clinical context and the system ranks SNOMED CT concepts observed during training. We compare a popularity baseline, sparse TF-IDF concept prototypes, dense latent semantic analysis embeddings, sparse-dense fusion, retrieved-note evidence, and a retrieval-augmented hybrid. Sparse TF-IDF performs best, achieving Recall@1 of 14.81%, Recall@10 of 33.43%, MRR of 0.2114, and nDCG@10 of 0.2297. Retrieval augmentation does not improve this baseline, with Recall@10 of 31.99% and MRR of 0.1937. Performance is strongly affected by concept frequency: Recall@10 is 7.74% for concepts appearing in only one or two training notes versus 43.90% for concepts appearing in more than ten. In addition, 9.66% of test note-concept pairs contain concepts unseen during training. These findings show that local lexical context and terminology coverage are major determinants of recommendation quality in low-resource settings and provide a reproducible baseline for future ontology-grounded and biomedical-encoder retrieval systems.

Abstract: AI and large language models can recover clinically meaningful features from electronic health records (EHRs), but predictive usefulness does not establish admissibility for causal inference. We introduce information set emulation: an AI typed lift attaches source evidence, clinical and recording times, decision-time availability, representation version, proposed causal roles, and unresolved ambiguity to extracted features under a locked target trial. Causal certificates record auditable evidence for those roles. Features with unresolved downstream roles are routed to compatible reporting or separate analyses. Typed evidence defines an observational fiber of causal worlds consistent with the observed law. The locked scalar estimand maps this fiber to a compatible image whose squared Chebyshev radius equals the residual minimax mean squared error when the image is nonempty and compact. This classical identity provides a target-specific measure of information ambiguity. The contribution is its integration with a joint EHR observation map and an auditable certificate architecture. Under explicit exchangeability, positivity, and nuisance-consistency conditions, we give identification and cross-fitted augmented inverse probability weighted estimation, distinguishing empirical and population targets. An EHR compression-drift identity separates the roles of frame presence, treatment assignment, and outcome observation. Artificial simulations and a common-law finite-world example illustrate estimation failures and information-radius reduction. Synthetic Phase 0 notes demonstrate audit diagnostics; a separate role-specific analysis spread illustrates routing and is not an exact fiber radius. All experiments are synthetic. The framework specifies when reconstructed information can support a point claim and when compatible reporting is required.

Abstract: Medical AI models hold immense potential to improve patient outcomes, but they are also known to unintentionally memorise individual records from their training datasets. While such memorisation has been linked to targeted privacy attacks, its consequences for clinical deployment, where patients may be assessed by a model that saw their historical data during training, remain poorly understood. Here we show that predictions on a patient's unseen future data can change significantly if a model observed that same patient's anonymised historical data during training, a phenomenon we term "memorisation bias". We demonstrate that this bias exists across diverse data modalities and model architectures, and over prolonged time spans: in some cases, memorisation bias persists on future records acquired decades after the historical records used for training. Moreover, in simulated prospective deployment, memorisation bias has asymmetric effects on the diagnostic accuracy of returning data contributors. When a patient returned with a de novo condition absent from their historical records in the training dataset, diagnostic sensitivity decreased significantly compared to an otherwise identical model not trained on their historical data. Conversely, when their health state was unchanged, both sensitivity and specificity were significantly inflated. Our findings reveal a previously uncharacterised risk in medical AI that arises when a model is deployed on patients who contributed to its training data. This exposes a shortcoming of current model development practice: the de-identification measures designed to protect patients' privacy make it difficult to identify returning contributors and exclude them from the AI-assisted interpretation of their own future data. Mitigating memorisation risks may thus require changes to current model training and deployment protocols.

Abstract: Breast histopathology analysis increasingly relies on distributed learning because direct data pooling across institutions is often restricted by privacy, governance, and communication constraints. This study compares server-based Federated Averaging (FedAvg), fully decentralized gossip learning, and Hybrid Gossip-FedAvg for invasive ductal carcinoma (IDC) patch classification. Experiments used 277,524 color image patches with patient-disjoint training, validation, and test partitions and a workload-balanced, Dirichlet-guided allocation across six nodes. Ring, random degree-3, and fully connected gossip topologies were evaluated together with sensitivity analyses for statistical heterogeneity, mixing coefficient, learning rate, model drift, prediction disagreement, calibration, clinically motivated operating points, communication payload, and patient-level IDC burden, together with auxiliary backbone robustness analyses. In the principal alpha=0.3 experiment, Hybrid Gossip-FedAvg achieved a test area under the receiver operating characteristic curve (ROC-AUC) of 0.8811, closely followed by FedAvg at 0.8801 and fully connected gossip at 0.8751. Across three independent patient-level repetitions, FedAvg and Hybrid Gossip-FedAvg obtained the same mean ROC-AUC of 0.9082, with standard deviations of 0.0037 and 0.0043, respectively. Hybrid achieved the highest mean area under the precision-recall curve of 0.8240, whereas FedAvg produced the lowest mean Brier score of 0.1335. Denser gossip graphs improved discrimination but increased theoretical model payload, while ring gossip remained sensitive to learning rate and mixing strength. Overall, FedAvg provided the most consistently reliable server-based baseline, topology-aware gossip offered a viable decentralized alternative, and Hybrid Gossip-FedAvg provided a balanced compromise between peer-to-peer diffusion and periodic global coordination.

Abstract: Federated learning (FL) in healthcare faces pronounced heterogeneity and temporal concept drift across clinical centers, where evolving patient populations and care practices shift data distributions. Existing approaches rely on persistent global communication, incurring substantial bandwidth overhead while risking negative transfer from poorly aligned peers. We propose Adaptive Bayesian Partner Selection (ABPS), a peer-to-peer framework that governs who collaborates, when, and at what cost. Each center maintains a Beta-Bernoulli posterior over prospective peers' Shapley marginal utility, ranks candidates with an Upper Confidence Bound (UCB) criterion, and forms collaborations through a lightweight propose-reject mechanism, with the option to abstain from communication when no mutually beneficial partner exists. The framework admits a stochastic decision interpretation, yielding finite-sample concentration guarantees and O(kappa log T) regret in partner selection, along with conditions under which intentional isolation is optimal under negative transfer. Lightweight extensions (head personalization, bfloat16 quantized communication, and a tunable active-set size) further improve efficiency, and a goal-aware metadata filter enables institution-specific collaboration strategies. On binary in-hospital mortality prediction over the first 24 hours of an ICU stay, with 230 non-IID clinical centers drawn from MIMIC-IV, the full ABPS-X variant matches the strongest federated baseline (FedDyn, AUROC 0.758) at 0.09x the communication cost of FedAvg, with reduced variability. A diversity-driven configuration activates intentional isolation for a substantial fraction of centers. These results show that adaptive, utility-aware collaboration reduces communication without sacrificing accuracy when centers are numerous and small, offering a scalable paradigm for healthcare FL.

Abstract: Diagnostic errors and mislabeling are common in biomedicine, which compromise the reliability of predictive models and data-driven outcomes. Stratifying unlabeled biomedical data based on complex relationships between features eliminates the need for data labels and overcomes the limitations of supervised learning. Traditional clustering methods assume restrictive data distributions, making them suboptimal for capturing complex dependencies in high-dimensional biomedical data. This paper introduces a novel cluster-friendly data presentation framework that integrates the non-Gaussian and non-linear feature dependence of copula models with an ensemble of causal structure discovery (CSD) methods based on Directed Acyclic Graphs (DAGs). While copulas model flexible multivariate distributions by relaxing assumptions related to multivariate normality, linear dependence, and symmetric relationships, an ensemble of DAG-based CSD methods identifies stable causal relationships between features. When clustered using K-means, the new data representation obtained by the proposed copula-adapted DAG (CopDAG) ranks first among the 12 methods in normalized clustering accuracy and adjusted Rand index across 16 biomedical datasets. Our CopDAG method predicts ground-truth class labels directly from feature relationships without data annotations and supervised learning, while also providing cluster visualizations and explainable causal structures of the biomedical data features.

Abstract: Deep networks trained on structural MRI for Alzheimer's disease (AD) staging often reach reasonable accuracy while attending to anatomically irrelevant regions, and multimodal models that add clinical tables frequently rely on variables that were used to assign the diagnostic label in the first place. We study both issues with a deliberately lightweight slice-based encoder (ResNet18 with a one-layer Transformer over slices) on 1,075 baseline T1-weighted scans from ADNI-1. First, we use FastSurfer segmentations as an anatomical reference: YOLOv8 models trained on segmentation-derived labels localize Alzheimer-relevant structures with mAP_50 above 0.96, and a Grad-CAM comparison shows that the image-only classifier frequently attends to the skull, orbits and background. Second, we adapt a CLIP-style image - tabular contrastive framework and organize ADNIMERGE variables along a label-leakage spectrum. Fusion with cognitive scores yields 87.3% three-way accuracy, which we treat as a leakage-driven upper bound rather than an imaging result; fusion with regional volumes yields 73.0%. We observe that the choice of contrastive target changes what the image encoder learns: on MCI vs. CN, the image-only head reaches 52.4% when the encoder is aligned to cognitive scores and 73.8\% when aligned to volumes, although no tabular input is used at inference. Third, restricting the input to a per-subject crop of the medial temporal lobe raises image-only three-way accuracy from 58.7% to 65.1%. All results come from single runs on a small balanced test set, and we report confidence intervals and the protocol differences that prevent direct comparison with published numbers.

Abstract: Extracting informative representations from longitudinal data that can predict future outcomes remains a critical challenge in medicine. Medical datasets are inherently heterogeneous, consisting of a large number of variables collected from different sources, sampled with different temporal spacings, and representing different aspects of human health status. This requires identifying those variables with predictive value, processing longitudinal information, and integrating multiple variables for outcome prediction. Here, we propose a novel agent-based approach, LongAgent, that can autonomously search over combinations of variable sets, temporal windows and longitudinal aggregation functions, and identify candidates with promising predictive performance. LongAgent utilises a history memory of previous searches and numerical evidence to guide subsequent exploration. On synthetic data, LongAgent achieves a mean prediction RMSE of 1.7376 and improves over the strongest non-agent baseline by 0.0151 (95% CI: [0.0045,0.0260]; p=0.0273). On a real clinical dataset, it performs comparably to the best baseline.

Abstract: Recent approaches to 30-day hospital readmission prediction rely on pre-trained language models applied to discharge summaries. Although these methods achieve strong performance, they depend on the availability of clinical notes, incur substantial computational costs, and yield representations that lack interpretability. We propose a knowledge-enriched feature representation that augments structured Electronic Health Record (EHR) data with four medical knowledge sources: disease ontology mapping, procedure classification, drug ingredient vocabulary, and organ system laboratory aggregation, without using clinical notes. Each feature dimension corresponds to a named clinical concept, yielding a sparse and interpretable patient representation. The approach is evaluated with six classifiers on a MIMIC-IV v2.2 cohort. Under 20-fold cross-validation, the best configuration achieves an AUROC of 0.743. This performance is comparable to that of previously reported methods on this dataset, including both those using only structured data and those incorporating clinical notes, while requiring considerably less computational cost. Interpretability analysis shows that demographics, organ system labs, drug ingredient features, and first-level ontology disease categories drive prediction, while deeper hierarchy levels contribute negligibly. These findings indicate that knowledge-enriched structured features offer a competitive and efficient alternative to embeddings from clinical notes for 30-day readmission prediction.

Abstract: As deep learning models become fundamental to modern healthcare, the "Right to be Forgotten" mandated by privacy regulations like GDPR and HIPAA necessitates effective machine unlearning (MU) to remove sensitive patient data from trained models. However, existing MU techniques often struggle with a fundamental "privacy-efficiency-utility" (PEU) trilemma, particularly in medical scenarios where data is frequently characterized by severe class imbalance and long-tailed distributions. In such cases, standard unlearning methods can fail to protect key clinical knowledge or mistakenly delete features essential for diagnosing rare conditions due to the gradient dominance of majority classes. To address these challenges, we propose GRIN+, a novel machine unlearning framework designed for fast and precise data erasure in imbalanced medical scenarios. GRIN+ decouples unlearning-specific knowledge from generalized representations at the parameter level by analyzing the gradient contributions of both "forget" and "retain" sets. It introduces a class-adaptive influence scoring mechanism to rectify gradient dominance and employs a direction-constrained update strategy to prevent the unintended erosion of vital clinical knowledge. Comprehensive benchmarking across multiple medical datasets, including skin cancer (ISIC), brain tumor (MRI), and breast ultrasound (BUSI), demonstrates that GRIN+ achieves an optimal balance of the PEU trilemma. Experimental results show that GRIN+ maintains high diagnostic accuracy and robust privacy while significantly enhancing runtime efficiency compared to existing baselines. We open-source the GRIN+ code and benchmarks to support further research.

Abstract: Vision-language models are increasingly explored for clinical prediction from electronic health records and medical images, where identifying unreliable predictions is important for safe deployment. Uncertainty estimation (UE) enables detecting such predictions, but its evaluation depends on a correctness criterion that determines whether each model output is correct. If this criterion disagrees with human judgement or distorts downstream UE performance, conclusions about model reliability can be misleading. We introduce a two-axis framework that evaluates correctness criteria by their agreement with human judgements and fidelity to human-referenced UE performance. We assess eight criteria across three clinical prediction tasks and three models using 450 predictions annotated by two reviewers. Across the audited tasks, canonical exact matching (EM) achieved the highest observed human agreement and lowest UE distortion, while the BERT-based matching (BEM) and LLM-judge also showed strong human agreement. Across four UE methods and 23,254 clinical predictions, criterion choice changed error-detection AUROC by up to 0.146 and reversed the relative ranking of UE methods. The LLM-judge also selectively accepted invalid or uncertain outputs, accepting 16 of 30 such human-identified errors. These results demonstrate that correctness assessment is an integral component of clinical UE evaluation and should be validated before UE methods are compared.

Abstract: Shapley value (SV)-based methods are the prevailing framework for feature attribution in machine learning, yet existing population-level Shapley estimators generally assume that observations used to evaluate the coalitional game are fully observed under a common feature space. This assumption is routinely violated in multi-site studies across biomedicine, social science, and environmental monitoring, where institutions record different features under different protocols, producing systematic blockwise missingness across sources. We first show that the standard remedy of imputing missing features before computing Shapley values introduces systematic, coalition-dependent bias into the resulting attributions. We then propose \textbf{FUSHAP} (\textbf{Fu}sion \textbf{Sh}apley \textbf{A}ttribution from \textbf{P}artially-observed data), a method that leverages partially-observed auxiliary sites to reduce the variance of a preliminary single-site Shapley estimate without imputation. A permutation-based screening step detects and excludes sites whose data distributions are incompatible with the target population. In synthetic experiments, FUSHAP achieves $3$--$8\times$ lower MSE than the single-site estimator and $2$--$3\times$ lower MSE than imputation baselines without incurring imputation-induced bias, and the screening procedure identifies misaligned sites with $82\%$ power at moderate misalignment and $100\%$ for strong misalignment. On multi-site air quality and multi-center clinical data, FUSHAP reduces MSE by approximately $3$--$7\times$ relative to the single-site estimator; in the clinical application, standard imputation can increase MSE above the single-site baseline.

Abstract: Development and evaluation of computational pathology methods require access to large and diverse datasets. Over the past decade, various initiatives invested significantly into collecting, centralizing, and sharing pathology imaging data. In contrast, sharing of image-derived data such as region-of-interest delineations or segmentation masks is less well developed. In this work, we describe our approach to encoding and sharing image-derived pathology data in a standardized manner within the National Cancer Institute (NCI) Imaging Data Commons (IDC), a platform that hosts and provides public access to de-identified radiology and pathology data. The IDC relies on the Digital Imaging and Communications in Medicine (DICOM) standard for data harmonization, yet the adoption of DICOM for pathology image-derived content has remained largely unexplored until now. Here, we present five representative datasets harmonized by conversion from their original representations into DICOM and shared publicly in the IDC. We demonstrate the benefits of this harmonization, describe contributions to critical open-source tooling, and discuss technical considerations relevant to broader adoption of DICOM for pathology image-derived data.

Abstract: Machine learning models are increasingly deployed in healthcare imaging pipelines for diagnostic support, and training-time attacks against them are a named sector-level concern: healthcare-sector guidance identifies model poisoning and adversarial attacks as threats requiring dedicated defenses, while federal policy directs expanded AI vulnerability-detection tooling to critical infrastructure operators such as rural hospitals. Spectral signature analysis and activation clustering are two established backdoor detection methods routinely evaluated as independent baselines, but their outputs are not ordinarily combined, and reported detection performance on medical imaging benchmarks remains sparse relative to the natural-image setting. This paper contributes three things: a score-level fusion rule combining per-class spectral ranking with activation-clustering flags into a single per-sample poisoning score and a model-level agreement statistic; an open-source implementation of the resulting eight-stage pipeline; and an evaluation of that pipeline against synthetically poisoned variants of a public medical imaging benchmark and CIFAR-10 at four poisoning rates (0%, 1%, 5%, 10%) over five seeds each, measuring each detector alone against the fusion. On the medical benchmark, the fused detector reaches AUROC >= 0.99 at every nonzero poisoning rate tested. On CIFAR-10, fusion does not uniformly help: at 10% poisoning, activation clustering's true-positive rate collapses to 0.000 and spectral AUROC independently degrades to near-chance (0.545), despite a 97.2% attack success rate confirming the backdoor was fully installed. The fused score, a weighted combination of both signals, inherits this joint failure. Detection output is expressed in NIST AI RMF Measure-function and MITRE ATLAS terms, so findings are reported in the vocabulary security and compliance teams already use.

Abstract: Medical image analysis is often hindered by biased datasets, which can lead to biased models and limited clinical applicability. A promising strategy for mitigating such biases is to augment training data with synthetic images. Counterfactual (CF) generation is one such strategy, though the term is used in two different senses: in some works, CFs are produced through causality-based interventions derived from structural causal models, whereas in others, they are produced by non-causal image edits or conventional conditional generative models, such as altering anatomy or adding pathologies. In this work, we study this distinction and evaluate its practical consequences for medical image augmentation. We compare three conditioning strategies: $\textit{Deterministic}$, which changes selected variables while holding the remaining variables fixed; $\textit{Undirected}$, which updates variables according to learned statistical associations without assigning causal directions; and $\textit{Causal}$, which propagates interventions along a directed causal graph. We analyse how these choices affect the resulting images, and explore when causally grounded methods improve dataset augmentation or bring limited benefit. In particular, we assess downstream performance and fairness, where fairness refers to reduced sensitivity to dataset biases across sensitive subgroups. Our experiments demonstrate that using a causal approach to synthetic training data generation can lead to tangible benefits, with these insights offering valuable guidance to machine learning practitioners for the effective design of data generation protocols.

Abstract: Large Language Models (LLMs) have displayed impressive capabilities in handling tasks that require few demonstration examples, making them effective few-shot learners. Despite their potential, LLMs face challenges when it comes to addressing complex real-world tasks that involve multiple modalities or reasoning steps. For example, predicting cancer patients' survival period based on clinical data, cell slides, and genomics poses significant logistical complexities. Although several approaches have been proposed to tackle these challenges, they often fall short in achieving promising performance due to their inability to consider all modalities simultaneously or account for missing modalities, variations in modalities, and the integration of multi-modal data, ultimately compromising their effectiveness. This thesis proposes a novel approach for multi-modal tumor survival prediction to address these limitations. Taking inspiration from recent advancements in LLMs, particularly Mixture of Experts (MoE)-based models, a graph-guided MoE framework is introduced. This framework utilizes a graph structure to manage the predictions effectively and combines multiple models to enhance predictive power. Rather than training a single foundation model for end-to-end survival prediction, the approach leverages a MOE-guided ensemble to manage model callings as tools automatically. By leveraging the strengths of existing models and guiding them through a MOE framework, the aim is to achieve better performance and more accurate predictions in complex real-world tasks. Experiments and analysis on the TCGA-LUAD dataset show improved performance over the individual modal and vanilla ensemble models.

Abstract: Multimodal clinical AI typically assumes that the waveform, report, metadata, and downstream predictions attached to a record belong to the same patient. In practice, linkage failures can silently assemble individually plausible but cross-patient components, creating a safety problem that standard predictive models are not designed to detect. We study this problem as multimodal record integrity triage: given an assembled record, should its modalities be trusted to belong together? We introduce SHIFT-M3, a lightweight text-based pre-fusion screen that measures alignment-based consistency between two separately produced ECG text views: an LLM-generated interpretation and a clinical report summary. On 784,680 MEETI ECG records, SHIFT-M3 achieves 97.6% TPR@5% FPR for full text-view swaps (AUROC 0.996), 90.3% for partial swaps (AUROC 0.974), and 97.7% for label-matched hard negatives (AUROC 0.996) with only 573,569 parameters. Compared with same-dataset lexical baselines, the gains are largest on partial swaps and hard negatives, suggesting that the model is learning more than surface overlap. We also introduce the CMST (Conflict-type Multimodal Stress Test) evaluation taxonomy, a three-seed stability study, a loss ablation, a temporal-tolerance sweep, and a shared-token masking control. The main remaining failure mode is longitudinal ambiguity: at the default operating point, same-patient cross-visit pairs still produce 87.0% Type-II false positives.

Abstract: ICD-10-CM codes are alphanumeric codes used in the US to classify diagnoses and injuries for medical billing and epidemiological reporting. Standard ICD-10-CM benchmarks report aggregate metrics that obscure performance on complex coding scenarios. We evaluate neural, workflow, and agentic systems on a rarity-stratified set of MIMIC-IV discharge summaries and identify two orthogonal failure modes. Neural classifiers exhibit a 0.43 micro-F1 gap between rare and common codes. Workflow systems handle rare codes well but score near zero on injury and external cause codes that require multi-step guideline following. A tool-augmented agentic configuration with structured access to official ICD-10-CM reference materials recovers up to 0.34 micro-F1 on this subset. No single system dominates across all conditions.

Abstract: A clinical agent benchmark can report the same verdict on identical inputs while the agent files a materially different order on each run. Such agents order tests, request medications and place referrals, yet benchmarks typically score one run per task and rarely ask whether identical inputs produce identical actions; MedAgentBench, the benchmark we use, scores a single attempt and says so. To measure this gap we introduce "same-input rerun", which replays a task with every input held fixed and compares the orders rather than the score, with six reliability metrics, and apply it to 1000 MedAgentBench runs across 50 tasks from its five write-capable families, two open-weight models below ten billion parameters quantised to four bits, and two temperatures. The study establishes that action-level divergence exists and can pass unrecorded by the score, not that any rate generalises. Under the 8B model at temperature 0.7, all 43 ordering groups emit a different set of orders across five identical runs, 26 emit the order on some runs and not others, and 28 record a different coded value, dose or analyte. In 22 of those 43 the benchmark reports the same failing verdict for materially different behaviour, as it does for all 10 divergent groups of the 4B model at 0.7. Orders also reach different endpoints across runs, one of which the record server rejects while the agent is told it succeeded. These findings motivate repeated-run evaluation, action-level stability reporting and execution-faithful environment feedback in clinical-agent benchmarks.

Abstract: Discharge summaries are lengthy medical documents that summarize a hospital in-patient visit. Automatically generating them can reduce documentation burden and return clinician time to patient care. Whereas Large Language Model (LLMs) could be used for this task, their Achilles heel is hallucinations, which can have drastic consequences for clinical documentation. We present an evidence-driven alignment framework for discharge summarization at the clinical encounter level, that treats provenance as a first-class constraint, using semantic graphs and deep learning models. Each summary sentence is selected and organized via cross-document semantic alignment and is accompanied by explicit evidence links to its source spans. We show our results on two corpora: a publicly available corpus (MIMIC-III) and clinical notes written by physicians at the University of Illinois Hospital (UIC Health). Additionally, we make source code and trained models available.

Abstract: Existing pipelines for clinical timeline extraction from case reports are evaluated using an expert reference and are limited by imperfect reference annotations and imprecise event alignment. We developed GAVEL, an LLM judge protocol that compares two timelines with the case report and returns a discrepancy type, verdict, and report passage for each difference. We evaluated the event matcher, reviewed 2,738 findings from GPT5.6sol and DeepSeek V3.2, ranked six LLM extractors and two human annotators, and tested GAVEL guided merging. True match rates were 60% immediately below and 48% immediately above the 0.10 cutoff. Manual review confirmed 89.4% and 88.6% of findings. Across 126 reports, merged timelines were preferred in 77.0% of comparisons (95% CI, 69.8 to 84.1%) and reduced discrepancies attributed to the evaluated timeline from 7.63 to 0.85 per report. GAVEL supports report-based comparison and revision without treating either timeline as ground truth.

Abstract: Clinical timelines support treatment-window analysis and leakage-free modeling, but discharge summaries often obscure chronology and structured EHR tables describe only part of the patient course. We present a UID-preserving framework that links each narrative event occurrence to its source span and retains that identity through text-only estimation, structured-evidence retrieval, timestamped source-row grounding, and joint revision. We also present GAVEL, an LLM judge that compares two UID-aligned timelines against the narrative and structured record, to augment prior matching and temporal assessments. Across six open-weight models and 40 mixed-critical-care summaries, the GLM 5.2 multimodal revision, as compared to its text-only variant, improved temporal agreement without reducing event recovery and performed competitively with clinician annotations, while other model revisions showed smaller gains and lower overall performance. Ablations showed that UIDs primarily preserve event retention, whereas source-row linkage supports temporal placement. Blinded human review upheld most GAVEL findings, and controlled adjudication favored multimodal over text-only GLM 5.2 but did not for DeepSeek V3.2. In developing the UID and judge pipeline, we are able to demonstrate 43\% increased event recovery, a framework competitive with clinician annotations, and a system with occurrence-level provenance for both reconstruction and evaluation.

Abstract: Artificial intelligence has shown promise in assisting radiologists in imaging-based diagnosis across a wide range of diseases. Efficient training of large deep learning models is essential to cope with extremely large data sets or dynamically growing disease data, like in a pandemic like situation. In this retrospective study, we collected 300 CT scans from COVID-19 and non-COVID-19 pneumonia patients from three different centers in Germany. We investigated a hybrid CNN-DNN network model based on image decomposition and localization that naturally supports parallel and efficient training of deep learning models. In total, 156 models with three different architectures were trained to capture features at different levels resulting in 12 patient-level COVID-19 diagnosis models. Diagnostic performance as well as time saving were measured. The highest accuracy was obtained from DenseNet121 and 3D CNN models with a parallel CNN-DNN approach, resulting in $88.78\%$ training, $76.67\%$ validation and $76.03\%$ test accuracy for the DenseNet121 with $4\times4\times1$ subdomains and $87.72\%$ training, $76.82\%$ validation and $74.86\%$ test accuracy, respectively, for the 3D CNN with $4\times4\times1$ subdomains. The strongest reduction in parallel training time by a factor of $31$ was observed for the 3D CNN model and $4\times4\times2$ subdomains. Our parallel training approach improves efficiency as well as performance enabling rapid model development, among others crucial for pandemic preparedness.

Abstract: Blinded physician evaluation has been considered by many to be the gold standard for assessing clinical reasoning in large language models (LLMs). This is difficult to scale; thus, prior studies typically rely on small physician panels, often from a single institution or specialty, which both limits the scientific questions investigated and makes it unclear whether findings would be reproduced with a different set of evaluators. To more rigorously and scalably study clinical reasoning in AI models, here we introduce PrecepTron, an LLM fine-tuned for physician-level evaluation of open-ended responses. PrecepTron was trained using low-rank adaptation (LoRA) of a 32-billion-parameter model on a small number of physician examples. We also release GRAND-ROUNDS, a new large-scale physician-annotated benchmark of 9,217 scores by 11 physicians across seven studies. We show that frontier LLMs in typical "LLM-as-a-judge" approaches often disagree with physicians and with each other, but fine-tuning PrecepTron on a small number of cases enables physician-level consistent scoring across tasks. We use PrecepTron to reproduce headline findings from five influential studies assessing LLMs for clinical care in JAMA, Science, and Nature Medicine without new human grading. Using PrecepTron, we then pose new questions about how LLMs reason in medicine that would have been infeasible with human grading alone, including measuring the diagnostic accuracy of frontier LLMs when clinical cases are provided piecemeal, even token by token. Together, PrecepTron and GRAND-ROUNDS provide a foundation for reproducible, large-scale study of how LLMs reason in medicine. All code, data, and labels are made freely available for researchers.

Abstract: Clinical de-identification relies on accurately identifying personally identifiable information (PII). However, manually annotated datasets are costly to construct, while existing synthetic alternatives often provide limited details about their generation process or rely on relatively simple synthesis strategies. We introduce Meddies-PII-Dataset, a corpus of one million synthetic clinical documents spanning seventeen languages and nine PII labels. The documents are generated using attribute-conditioned prompts and validated through thirteen deterministic gates that enforce structural and annotation consistency. To evaluate the dataset's utility, we train Meddies-PII-Model, a BIOES token classifier, and compare it with existing PII extraction systems using exact-match entity-level F1. Meddies-PII-Model achieves the highest performance among the evaluated systems on all reported benchmarks, with a mean F1 of 0.827 across fifteen external benchmarks, compared with 0.658 for the strongest baseline. Upon acceptance, we will publicly release the dataset, benchmark suite, model, generation framework, and evaluation code to support research on multilingual clinical de-identification.

Abstract: Dementia is a major and growing global health burden, with Alzheimer's disease (AD) accounting for most cases. Timely and accurate diagnosis is central to managing this burden and increasingly depends on integrating complementary clinical and imaging information. Multimodal deep learning can combine these modalities for AD diagnosis, but how its explanations behave across modalities, fusion strategies, and cohorts remains unclear. We developed an explainable multimodal framework pairing a 3D CNN encoder for T1-weighted MRI with a feedforward network for harmonized clinical and demographic data, comparing varied model setups on three-way and pairwise diagnostic tasks using 6,479 internal records from the ADNI and 1,703 independent records from the OASIS-3. On ADNI, the tabular-only model achieved the highest three-class AUC-ROC of 0.879 and best discriminated cognitively normal (CN) versus mild cognitive impairment (MCI; 0.903), while cross-attention performed best for MCI versus AD (0.861); CN versus AD was highly discriminative overall. On OASIS-3, the vision-only model performed best (three-class AUC-ROC 0.910); CN versus MCI remained difficult, and no fusion strategy consistently outperformed single modalities across tasks and cohorts. SHAP and Integrated Gradients identified the MMSE as the dominant tabular feature in both cohorts, with global feature rankings agreeing strongly in ADNI ($ρ=0.94$) and OASIS-3 ($ρ=0.96$); CAM-based explanations, however, changed with model configuration and cohort. These findings show that multimodal performance and explanations are task, modality, fusion, and cohort-dependent: a dominant cognitive signal persisted across cohorts, but feature contributions and CAM explanations did not, underscoring the need to evaluate explainability under cohort shift rather than as a stable, intrinsic property.

Abstract: In the VTaC benchmark 71% of ventricular-tachycardia alarms are false, but silencing a real one can delay recognition of a dangerous arrhythmia. We reframe alarm reduction as three-way triage (retain, suppress, or defer) and bound the decision this analysis treats as harmful: among suppressed alarms, the fraction that were genuine stays below a user-set budget with 95% confidence, under i.i.d. event sampling. Alarms sharing a waveform record are dependent, so the clustered analysis is a sensitivity check. On the official split a 5% budget certifies in all three seeds, suppressing 74.8% of false alarms while silencing 1.5% of genuine ones, at AUROC 0.953 and Challenge Score 83.33, numerically comparable to the strongest of the eleven published systems. Our central finding measures what multiplicity costs: the correction charges for every candidate, so a finer grid can certify strictly less. Under held-out calibration the 885-cell grid we declared certifies 1 of 15 fold-runs, while choosing the grid on a separate selection partition certifies 8. We project the calibration volume each budget needs, making an uncertifiable budget a design parameter. Finally, adding a learned reliability dimension to the policy grid did not sharpen the certified frontier.

Abstract: Electronic health record (EHR) foundation models trained on longitudinal patient trajectories have demonstrated strong performance across diverse clinical prediction tasks. However, their clinical reasoning capabilities remain constrained by next-token prediction on limited and incomplete EHR data. To address this, we propose a reinforcement learning (RL) fine-tuning framework that treats EHR foundation models as generative policies over patient trajectories. We formulate common clinical prediction problems (e.g., hospital readmission) as event-conditioned, time-windowed reasoning tasks. We then design time-aware, rollout-sensitive rewards to account for finite rollout lengths and temporally inconclusive outcomes. We find that RL fine-tuning consistently improves over pre-trained backbones and strong baselines. Notably, it enables smaller models to surpass larger pre-trained models in data-limited regimes and induces positive transfer across tasks. Further analysis shows that RL fine-tuned models generate trajectories with stronger structural and semantic alignment to ground truth and greater downstream utility.

Abstract: Clinical electroencephalography (EEG) data are valuable for healthcare research and for developing artificial intelligence (AI)-based clinical decision-support systems, but EEG recordings and derived features may contain sensitive patient-specific information. This creates privacy risks when data are reused, analyzed, or shared across clinical and research environments. Conventional anonymization methods are often insufficient for high-dimensional biomedical signals, since removing direct identifiers does not necessarily prevent re-identification, linkage, or inference risks. At the same time, strong privacy protection may distort clinically relevant signal characteristics and reduce data utility. This paper studies subject-level differential privacy for protecting clinical EEG-derived feature representations using Gaussian and Laplace perturbations. The proposed framework considers three deployment scenarios: client-side anonymization, centralized server-side anonymization, and decentralized local training. Following EEG preprocessing and feature extraction, Gaussian and Laplace perturbations are applied to the resulting patient-level EEG feature representations. The Laplace experiments evaluate the implemented noise scales, while the scales required for formal full-vector calibration are derived separately. The effects of both perturbations are assessed using statistical utility measures and a downstream machine-learning-based utility check. The results show that differentially private perturbation can be integrated into EEG processing workflows, but the selected mechanism, privacy parameters, and sensitivity calibration strongly influence data utility. The study highlights the practical privacy-utility trade-off in DP-based EEG feature anonymization and the challenges of preserving downstream utility in small and imbalanced clinical EEG datasets.

Abstract: Background: To determine whether cross-lingual clinical annotation projection can be formulated as a text-preserving, document-level generative task that produces verifiable character-level annotations for multilingual clinical corpus construction, and to characterize its robustness and computational trade-offs relative to candidate-based projection pipelines. Methods: We developed a constrained LLM projection workflow that inserts entity tags directly into immutable target-language text, followed by deterministic validation and character-offset reconstruction. We evaluated it alongside supervised candidate-span projection and hybrid ML-LLM refinement for transferring Spanish Disease, Symptom, and Procedure annotations into six languages. Evaluation used MultiClinAI gold standard with strict span matching and character-overlap F1 Results: Direct LLM projection achieved the strongest and most consistent performance. GLM 5.2 obtained a mean Strict F1 of 0.9201 across 18 language-entity combinations, while locally deployable Gemma4:31B achieved 0.9133. The best LLM configuration improved Strict F1 over the previous state of the art in all 18 settings, by 0.0564-0.1512, yielding 55,416 grounded mentions with reconstructed offsets. Conclusions: Direct LLM-based projection enables high-quality multilingual clinical annotation transfer and provides a practical approach for extending clinical NLP resources to languages with fewer annotated datasets and language-specific tools. Combined with local inference and deterministic validation, it can substantially reduce expert time and cost for multilingual clinical corpus construction.

Abstract: Background: Emergency Department (ED) return visits are commonly reviewed for quality assurance, but are often limited (e.g., to revisits within 48-72 hours) to increase actionable finding yield while minimizing chart review burden. Those limitations may lead to missed quality improvement opportunities. Methods: We conducted an exploratory, retrospective study of randomly selected ED visits to a multihospital health system having an ED revisit within 1-14 days to the same health system. Given only each visit's primary diagnosis, raters (2-3 clinicians and GPT-4 large language model [LLM]) assessed characteristics of the diagnosis pairs, including the "target": whether a pair warranted further assessment. Informed by rater response analyses, an algorithm leveraging an LLM-populated knowledge graph ("KGA") was created to automatically screen for potentially concerning pairs, then preliminarily assessed. Results: 99 diagnosis pairs were included. GPT-4 responses poorly correlated to clinician raters, rating nearly all (94%) pairs as warranting follow-up (4.4-13.3 times more than clinicians). However, prompt engineering was minimal. Among clinician raters, revisit medical gravity was consistently significantly associated with the target, while a differential diagnosis/complication composite was significantly associated on unadjusted, but not adjusted (though less powered) analysis. The KGA achieved 83-100% positive predictive value for at least one clinician rater determining further assessment was warranted based on the diagnosis pair. Conclusion: These results can inform next steps for improving screening with LLMs like ChatGPT. Further research is warranted to validate this preliminary work's finding that the KGA may enable enhancing the scope and yield of screening without substantially increasing reviewer workload.

Abstract: Simultaneous assessment of medical imaging and patient records is often required in clinical diagnosis. However, standard machine learning algorithms cannot analyze these data types together. Meanwhile, compliance with HIPAA and GDPR can constrain centralized aggregation of sensitive patient data. This leaves a crucial void of secure fusion of visual and textual context across distant networks. Thus, we present OmniMed-FL, a controlled systems study of multimodal federated learning for five-class clinical condition classification (Normal, Pneumonia, COVID-19, Pleural Effusion, Cardiomegaly). Our proxy corpus pairs 3,000 public chest radiographs with 3,000 class-conditioned synthetic notes, matched by class, not by patient. The framework benchmarks eight fusion strategies, three initializations, four missing-text imputation rules, and matched federated baselines under non-IID Dirichlet partitioning across 3 to 20 hospital clients. As all notes are synthetic and pairing is not patient-level, these are descriptive proxy comparisons, not estimates of diagnostic performance or deployment readiness. Within those limits with clients ($K=5$) and severe skew ($α=0.1$), local-only training achieves a macro-F1 score of 0.297, FedAvg achieves $0.662\pm0.074$, FedProx $0.737\pm0.085$, a matched FedMME-style one-shot ensemble $0.647\pm0.080$, and our SCAFFOLD-AdamW adaptation $0.070\pm0.015$, the 0.075 FedProx-FedAvg gap falling inside the wider of the two two-seed standard deviations. Over a $4\times3$ grid, label skew costs up to 0.27 F1 whereas a near-sevenfold client increase costs at most 0.10, while bidirectional volume grows linearly to 183.5 GiB at $K=20$. Multimodal fusion leads on both corpora, scoring 0.956 against 0.934 for text and 0.664 for images on the synthetic corpus and 0.906 against 0.880 and 0.737 on the radiograph corpus, for $2.3\times$ the model state of text alone.

Abstract: Biomedical ontology normalization maps free-text expressions to standardized concepts, enabling consistent integration and analysis of biomedical data. This task remains challenging because lexical variation and subtle distinctions among hierarchically related concepts can obscure concept boundaries. We present OntologyAligner, a three-stage framework that combines ontology-aligned retrieval, large language model candidate reranking, and selective hierarchy-guided refinement. We also construct PhenoNormBench, a unified benchmark comprising 13,390 samples from seven Human Phenotype Ontology datasets. OntologyAligner achieved state-of-the-art performance on HPO normalization, with 88.78% Macro Top-1 Accuracy and 86.75% Micro Top-1 Accuracy, exceeding the strongest baseline by 4.85 and 5.07 percentage points, respectively. Ablation analyses showed complementary contributions from all three stages, and sensitivity analyses demonstrated stability across candidate-set sizes and model backbones. Applications to MONDO, MEDIC, and NCBITaxon further established portability to other ontologies. OntologyAligner offers a generalizable framework for accurate mapping of biomedical text to structured ontology concepts. PhenoNormBench and the code are publicly available at https://github.com/zhelishisongjie/OntologyAligner.

Abstract: Clinical notes contain personally identifiable information (PII), restricting reuse for research and medical AI, especially when data cannot leave an institution. We developed MedDeID, an on-premises framework combining in-house annotation and synthetic-note generation with model training, inference, pseudonymisation and evaluation. On an independently annotated, adjudicated 300-note Dutch hospital benchmark, a hospital-trained compact transformer detected 98.9% of identifying text while redacting 0.24% of text outside annotated identifiers; a synthetic-only counterpart detected 96.1%. On 100 primary-care notes, the synthetic-trained model achieved higher recall than the hospital-trained model (90.3% versus 87.0%) and greater robustness to identifier-format perturbations. An English instantiation trained without real text detected 99.7% and 98.9% of annotated identifier characters on two external synthetic benchmarks. These results demonstrate transfer of the workflow to another language, but not clinical English performance. MedDeID provides a route to locally governed de-identification using real or synthetic training data.

Abstract: Medical claims data comprise the financial details, including the expenses and billing information, as well as the clinical information, such as the diagnoses and treatments, of patients visiting medical facilities. Recently, it has been acknowledged that large databases can be constructed from medical claims data for medical research purposes. However, the clinical information within these datasets is often medically unstructured, limiting its application in comprehensive analyses. This study enhances predictive model performance for major adverse cardiovascular events (MACE), a leading cause of death worldwide. Models that predict MACE are crucial to clinical practice guidelines. We utilize a cross-attention mechanism to develop a method that effectively weights the relationships between diagnoses and treatments. Effectively repre- senting the clinical information contained in medical claims data, this approach generates more representative features for predicting MACE. The ROC-AUC score of our proposed cross-attention-based model was 0.7720, higher than other benchmark models including the conventional atherosclerotic cardiovascular disease model, the light gradient boosting machine, and a self-attention-based model. These results indicate that integrating the clinical structure of medical claims data using a cross-attention mechanism significantly enhances the performance of predictive models.

Abstract: Medical question-answering datasets often contain answer labels, whereas high-quality rationales remain scarce, noisy, or costly to validate. This changes the acquisition question: rather than asking which questions should be labeled, we ask which already-labeled questions should receive rationale supervision under a fixed token budget. We study an offline version of this problem in which candidate rationales are visible to the selector but withheld from downstream training unless selected. We propose root-mean-square Robustness-based Sample Prioritization (RMS-RSP), which perturbs hidden states only at rationale tokens and measures the resulting shift in the gold-versus-best-distractor margin. Across five medical QA datasets, MedGemma-4B-IT, three training seeds, ten budgeted non-RSP selectors, and an unbudgeted full-supervision reference, RMS-RSP provides a deliberately qualified result. Its locked-budget accuracy is 60.61% on average versus 60.08% for Random, with a statistically resolved gain only on AfriMed-QA (+1.44 points). Its full-budget accuracy area is not better than Random. However, after three answer-option reorderings, RMS-RSP improves robust accuracy and semantic consistency by 1.91 and 2.85 points on average, respectively, with the same direction on all five datasets. Training on every pool rationale raises macro accuracy to 63.74%, but consumes 29--254 times more rationale tokens and does not uniformly improve robustness. These findings do not establish universal accuracy gains; they instead suggest that rationale-local boundary sensitivity can identify supervision that improves invariance to semantically equivalent formatting changes.

Abstract: Clinical diagnosis agents must decide not only what test to request next, but also when to diagnose or defer. Existing agent benchmarks largely evaluate accuracy after fixed or unconstrained interaction, leaving autonomous stopping reliability implicit. We present Cros, a risk-constrained stopping layer combining state-wise error ranking, policy design on disjoint development splits, and LTT-style exact tests of selective diagnostic error and minimum autonomous coverage for complete sequential policies. Its finite-sample guarantee requires the candidate family, testing rule, and any randomization to be frozen before calibration labels are accessed. On a 1,834-episode MIMIC-derived abdominal-pain benchmark, the full ranker achieves exploratory state-error AUROC 0.853, compared with 0.715 for maximum class probability and 0.552 for the backbone's native stop score. On the previously viewed 367-episode evaluation split, analytically averaging over the frozen Cros weights yields 16.9% selective error at 78.8% coverage, cost 5.57, and 0.68 tests, versus 30.8% error at 100% coverage, cost 8.14, and 1.53 tests under native stopping. Forced continuation is non-monotone: error is 28.3% with HPI alone and 34.3% after full workup. However, the uniform-weight mixture ablation is cheaper on this viewed split despite missing the locked development margins, and Cros nominally satisfies the joint criterion in only 6 of 20 development resplits. Because evaluation labels were inspected during earlier development, these findings provide exploratory feasibility and audit evidence, not a confirmatory safety certificate.

Abstract: Average treatment effect (ATE) estimation in observational studies is a fundamental statistical tool used frequently in social science, medicine, and other fields. These fields often work with sensitive data where privacy protections are important, so a differentially private mechanism for ATE estimation is highly desirable. Here we present two propensity score-based algorithms for ATE estimation on observational data, one improving the inverse probability weighting (IPW) method used in prior work, and the other using blocking on the propensity score (BPS). Both show lower error and less bias than prior work, with the BPS-based algorithm frequently reducing error by 75% or more compared to prior work.

Abstract: High-risk non-muscle-invasive bladder cancer (HR-NMIBC) carries substantial risks of recurrence and progression, while current clinical risk stratification remains limited. CHIMERA was established as a multimodal AI challenge to benchmark prediction in HR-NMIBC under standardized evaluation. Task BRS predicts RNA-seq-defined BCG Response Subtypes from histopathology and structured clinicopathological data, whereas Task Progression models time-to-progression using histopathology, structured data, and RNA sequencing. A multimodal dataset of 368 patients was divided into public training and hidden validation and test sets. In total, 159 submissions were made, and 13 top-performing models were selected for benchmarking. The best models achieved a weighted F1 score of 0.73 for Task BRS and a C-index of 0.68 for Task Progression. Post-challenge analyses revealed task-dependent modality contributions, cohort-dependent performance degradation, and sensitivity to missing structured data. In Task BRS, histopathology partly compensated for pathology-derived structured variables, whereas progression models showed greater dependence on complementary inputs. Cross-model error analysis further identified patients that were consistently difficult across different architectures, with T1 substage associated with prediction difficulty. These findings highlight barriers to transportability and the importance of missingness-aware modeling and independent multi-institutional validation. CHIMERA provides a standardized multimodal benchmark for bladder cancer and a framework for studying not only model performance, but also robustness, information sufficiency, and patient-level prediction failure.

Abstract: 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.

Abstract: Accurate diagnostic and risk-prediction models are important for supporting clinical decision-making during infectious disease outbreaks. However, privacy and governance requirements may restrict patient-level data sharing across healthcare institutions, and data distributions often vary. Moreover, AUC is widely used to evaluate discriminative performance, motivating its direct optimization in model development. We propose geographically regularized AUC-maximizing personalized federated learning (GrAUC-PFL), which directly optimizes a smooth pairwise AUC surrogate to learn personalized models while keeping patient-level data local and accounting for institutional heterogeneity. Graph-based regularization encourages geographically neighboring institutions to have similar coefficient vectors while retaining a personalized models. Simulations and a real-data application suggest improved discriminative performance, particularly when geographically neighboring institutions have similar data-generating characteristics.

Abstract: Most automated brain parcellation tools are developed and validated on T1-weighted (T1w) MRI. Yet, some clinical workflows for which parcellation is relevant only use contrast-enhanced T1w (T1ce) MRI, on which T1w-trained models are less accurate. We present a unified network that parcellates both pre- and post-contrast agent T1w MRI reliably, trained on a combination of the two with conditioning that spatially modulates its response differently for each. Feature-wise Linear Modulation (FiLM) is a known approach for input-based modulation in networks. It applies a per-channel scale and shift uniformly across the input. However, the appearance change between pre- and post-contrast varies locally across the brain, making FiLM suboptimal for our use case. In this work, we introduce Spatial FiLM (SpFiLM), a conditioning layer whose modulation varies spatially, assembling a voxel-wise scale and shift from image-derived spatial patterns. Using a cohort of 134 patients with paired T1w and T1ce MRI parcellated into 106 classes, the addition of SpFiLM layers in a UNet increased the mean Dice on the test set of 25 patients from 80.2% to 84.1%, a 4.9% relative improvement. Adding SpFiLM layers led to the best performance on both pre- and post-contrast MRI, even when controlling for network parameter counts.

Abstract: We convert black-box clinical prediction models for tabular data into standalone nomograms that can be audited term by term. PRiSM (Partial Responses in Structured Models) takes the shape of each effect and interaction from the source model, not merely which variables mattered, and lets the outcome select and weight them. We tested this in 50,356 heart transplant recipients, with validation in a later era than training. Nomograms from all 5 source models - a public clinical risk score, logistic regression, neural networks, random forests and extreme gradient boosting - met a prespecified noninferiority criterion for discrimination before any further simplification, and generally preserved calibration and clinical net benefit. Those from the 3 machine-learning models showed no detectable difference in discrimination from de novo generalized additive and explainable boosting models, exceeded neural additive models, and carried fewer terms than the explainable boosting model. PRiSM is released as an open-source Python package.

Abstract: The application of large language models (LLMs) to personalized medical assistants has garnered growing interest. However, existing medical benchmarks largely rely on static question answering with pre-selected evidence, leaving unclear whether LLMs can make reliable clinical decisions from real longitudinal electronic health records (EHRs). To bridge this gap, we introduce ObGynLongBench, a rule-grounded long-context EHR benchmark for obstetric and gynecologic decision-making, comprising 1,500 clinical decision-point cases from 976 real pregnancy EHR histories and traceable rules. Each case is anchored to a patient, a pregnancy-timeline point, and a pre-decision information boundary, enabling Evidence-only, Visit-level EHR, and History-level EHR evaluation. Evaluating 17 LLMs reveals a substantial Evidence-to-EHR Gap: models perform well when evidence is directly provided, but accuracy drops when evidence must be extracted from same-day records or full pre-decision EHR histories. Further analyses identify evidence utilization as a key bottleneck: performance decreases with longer EHR contexts and more complex evidence requirements, and earlier failures often predict later failures within the same patient history. Finally, active-search agents perform best among EHR access strategies, highlighting patient-specific evidence utilization as a central challenge for reliable personalized medical assistants. Resources are available at https://github.com/xiangjun2003/ObgynLongbench.

Abstract: Biomedical tables often combine thousands of measured variables with only tens or hundreds of labelled samples, a regime that is poorly represented in general-purpose tabular benchmarks. We introduce TabBench-Bio, a living and interactive benchmark of 43 biomedical datasets spanning multiple domains. Under a shared cross-validation protocol, we compare classical estimators, neural networks, and tabular foundation models across 28 feature-by-sample operating points. At the reference cell of 10,000 features and 100 training samples, RealTabPFN v2.5 has the highest point estimate, followed by Logistic Regression and TabDPT, whose point estimates are nearly identical. A paired bootstrap over the target pool separates RealTabPFN v2.5 from Logistic Regression by 145 Elo (95% interval [59, 232]). Tabular foundation models generally occupy the leading ranks, while the strongest configuration depends on the operating point and biomedical modality. The AutoML framework AutoGluon, using its one-hour "extreme" preset, is configured as a separate resource-intensive reference and is reported here at the reference cell. Fold-level predictions, run status, and deterministic aggregations make every reported result reproducible and reusable. We invite the community to contribute: TabBench-Bio is designed to grow, and we welcome submissions of new biomedical tabular datasets, particularly from underrepresented assays and clinical endpoints, for inclusion in future releases. The interactive leaderboard is available at: https://tabbench-bio.eu

Abstract: Out-of-distribution (OOD) detection is critical for safe deployment of medical AI systems. Recently, test-time adaptation (TTA) has emerged as a new paradigm for OOD detection, automatically adjusting detector behavior during deployment. However, such automatic adaptation mechanisms may raise safety concerns in safety-critical clinical environments. While physician oversight can mitigate these risks, it is resource-intensive and must be judiciously allocated. To reconcile safety with efficiency, we propose CHILD, a training-free framework designed to enhance streaming OOD detection via sparse human feedback. Operating under strict budget constraints, CHILD employs an adaptive risk-aware sample selection mechanism to pinpoint only the most decision-uncertain samples for review. Crucially, it maximizes the utility of this sparse feedback through a retrieval-based score calibration module, which refines model predictions using a compact feature cache without any parameter updates. Extensive experiments on four medical benchmarks demonstrate that CHILD turns limited supervision into significant reliability gains: with a sparse feedback budget of only 5%, it reduces the average FPR95 from 72.63% to 60.26% and improves AUROC from 75.53% to 81.85%, consistently outperforming state-of-the-art baselines. Our code is publicly available at https://github.com/figec/CHILD.

Abstract: Background: Large language models (LLMs) show promise for extracting information from clinical free-text documents, but their outputs are often unstructured and lack traceability, complicating validation and adoption in clinical workflows. In this work we introduce SIFTING, an LLM-based framework designed to address these shortcomings. Methods: SIFTING combines the language comprehension capabilities of LLMs with segment-level processing and structured prompts with strict output control, linking findings to the source text to enable both accurate and transparent information extraction. To demonstrate its capabilities, we applied the framework to the task of extracting tumor T-stage information from 130 lung cancer radiology reports (SIFTING-T-stage). A compact 4-bit quantized version of the open-source LLM Llama-3.3-70B (35 GB) was used in a fully self-hosted setup, providing full control over data and model. Performance was evaluated against a reference standard created by four clinical experts and compared with a range of LLMs as used in a conventional single-prompt approach, using bootstrap resampling to estimate confidence intervals. Results: SIFTING-T-stage achieved an accuracy of 90% (95% CI: 84-95) against the reference standard. We found its performance to be comparable to even the largest state-of-the-art LLMs with reasoning capabilities and to be interchangeable with clinical experts (p < 0.001), while at the same time offering full traceability through source text references. Conclusion: SIFTING enables accurate, structured, and traceable information extraction from clinical free-text documents. It ensures data control, reproducibility, and verifiable outputs that can support clinical validation and workflow integration.

Abstract: Reasoning over privacy-constrained records requires combining structured attributes with evidence from free-text narratives. We introduce CIPHER (Cross-record Inference over Privacy-Hardened Evidence Records), a benchmark of expert-validated questions from consumer-finance, clinical, and law-enforcement records. The questions cover common tabular operations and include executable SQL supervision. We evaluate retrieval, prompting, table-specialist, and hybrid symbolic-neural systems under native redaction and surrogate-based evidence restoration. All system families exhibit substantial failures even when supporting records are provided. Most errors arise from incorrect record selection and predicate interpretation rather than arithmetic execution. Privacy transformations have non-uniform effects, sometimes obscuring necessary evidence and sometimes reducing distraction. CIPHER provides a reproducible testbed for diagnosing these failures and assessing how transformations of sensitive text affect reasoning over hybrid records.