Clinical Outcome Prediction

Objective: Post-traumatic epilepsy (PTE) is a debilitating neurological disorder that develops after traumatic brain injury (TBI). Early prediction of PTE remains challenging due to heterogeneous clinical data, limited positive cases, and reliance on resource-intensive neuroimaging data. We investigate whether routinely collected acute clinical records alone can support early PTE prediction using language model-based approaches. Methods: Using a curated subset of the TRACK-TBI cohort, we developed an automated PTE prediction framework that implements pretrained large language models (LLMs) as fixed feature extractors to encode clinical records. Tabular features, LLM-generated embeddings, and hybrid feature representations were evaluated using gradient-boosted tree classifiers under stratified cross-validation. Results: LLM embeddings achieved performance improvements by capturing contextual clinical information compared to using tabular features alone. The best performance was achieved by a modality-aware feature fusion strategy combining tabular features and LLM embeddings, achieving an AUC-ROC of 0.892 and AUPRC of 0.798. Acute post-traumatic seizures, injury severity, neurosurgical intervention, and ICU stay are key contributors to the predictive performance. Significance: These findings demonstrate that routine acute clinical records contain information suitable for early PTE risk prediction using LLM embeddings in conjunction with gradient-boosted tree classifiers. This approach represents a promising complement to imaging-based prediction.

This study evaluates colorectal risk factors and compares classical models against Quantum Neural Networks (QNNs) for anastomotic leak prediction. Analyzing clinical data with 14% leak prevalence, we tested ZZFeatureMap encodings with RealAmplitudes and EfficientSU2 ansatze under simulated noise. $F_β$-optimized quantum configurations yielded significantly higher sensitivity (83.3%) than classical baselines (66.7%). This demonstrates that quantum feature spaces better prioritize minority class identification, which is critical for low-prevalence clinical risk prediction. Our work explores various optimizers under noisy conditions, highlighting key trade-offs and future directions for hardware deployment.

Sparse autoencoders (SAEs) have been applied to large language models and protein language models, but not systematically to electronic health record (EHR) foundation models. We train TopK SAEs on FlatASCEND, a 14.5-million-parameter autoregressive clinical sequence model, at all 10 residual stream extraction points on INSPECT (outpatient) and MIMIC-IV (ICU). SAE decomposition reveals progressive abstraction across transformer depth: layer-0 features are near-perfect token detectors (45.7% singleton), while layer-6 features span approximately 30 token types across multiple clinical categories (0.5% singleton). Under full-sequence simple linear probes, SAE features outperform dense representations for discrete event prediction (mortality) while dense representations outperform for continuous magnitude prediction (length of stay) - a probe-level representational phenomenon that does not extend to clinically relevant leakage-safe windows, where dense representations match or exceed SAE features across all tested settings (eICU-CRD 48-hour AUC: SAE 0.871 versus dense 0.880; base model zero-shot, SAE dictionaries trained on eICU activations; MIMIC-IV: 0.836 versus 0.914; INSPECT 1-year/3-year: 0.697 versus 0.800). A delta-mode intervention method reduces SAE perturbation noise by 86x, enabling cleaner feature-level experiments, though the resulting perturbation effects are larger than random controls in 3 of 4 conditions but not formally significant. Feature reproducibility across random seeds is 21%, and individual features should be interpreted as illustrative rather than stable.

Predicting post-surgical seizure outcomes in pharmacoresistant epilepsy is a clinical challenge. Conventional deep-learning approaches operate on static, single-timepoint pre-operative scans, omitting longitudinal morphological changes. We propose Neuro-Oracle, a three-stage framework that: (i) distils pre-to-post-operative MRI changes into a compact 512-dimensional trajectory vector using a 3D Siamese contrastive encoder; (ii) retrieves historically similar surgical trajectories from a population archive via nearest-neighbour search; and (iii) synthesises a natural-language prognosis grounded in the retrieved evidence using a quantized Llama-3-8B reasoning agent. Evaluations are conducted on the public EPISURG dataset ($N{=}268$ longitudinally paired cases) using five-fold stratified cross-validation. Since ground-truth seizure-freedom scores are unavailable, we utilize a clinical proxy label based on the resection type. We acknowledge that the network representations may potentially learn the anatomical features of the resection cavities (i.e., temporal versus non-temporal locations) rather than true prognostic morphometry. Our current evaluation thus serves mainly as a proof-of-concept for the trajectory-aware retrieval architecture. Trajectory-based classifiers achieve AUC values between 0.834 and 0.905, compared with 0.793 for a single-timepoint ResNet-50 baseline. The Neuro-Oracle agent (M5) matches the AUC of purely discriminative trajectory classifiers (0.867) while producing structured justifications with zero observed hallucinations under our audit protocol. A Siamese Diversity Ensemble (M6) of trajectory-space classifiers attains an AUC of 0.905 without language-model overhead.

Extranodal extension (ENE) is an emerging prognostic factor in human papillomavirus (HPV)-associated oropharyngeal cancer (OPC), although it is currently omitted as a clinical staging criteria. Recent works have advocated for the inclusion of iENE as a prognostic marker in HPV-positive OPC staging. However, several practical limitations continue to hinder its clinical integration, including inconsistencies in segmentation, low contrast in the periphery of metastatic lymph nodes on CT imaging, and laborious manual annotations. To address these limitations, we propose a fully automated end-to-end pipeline that uses computed tomography (CT) images with clinical data to assess the status of nodal ENE and predict treatment outcomes. Our approach includes a hierarchical 3D semi-supervised segmentation model designed to detect and delineate relevant iENE from radiotherapy planning CT scans. From these segmentations, a set of radiomics and deep features are extracted to train an imaging-detected ENE grading classifier. The predicted ENE status is then evaluated for its prognostic value and compared with existing staging criteria. Furthermore, we integrate these nodal features with primary tumor characteristics in a multimodal, attention-based outcome prediction model, providing a dynamic framework for outcome prediction. Our method is validated in an internal cohort of 397 HPV-positive OPC patients treated with radiation therapy or chemoradiotherapy between 2009 and 2020. For outcome prediction at the 2-year mark, our pipeline surpassed baseline models with 88.2% (4.8) in AUC for metastatic recurrence, 79.2% (7.4) for overall survival, and 78.1% (8.6) for disease-free survival. We also obtain a concordance index of 83.3% (6.5) for metastatic recurrence, 71.3% (8.9) for overall survival, and 70.0% (8.1) for disease-free survival, making it feasible for clinical decision making.

Purpose. High-grade serous ovarian carcinoma (HGSOC) is characterized by pronounced biological and spatial heterogeneity and is frequently diagnosed at an advanced stage. Neoadjuvant chemotherapy (NACT) followed by delayed primary surgery is commonly employed in patients unsuitable for primary cytoreduction. The Chemotherapy Response Score (CRS) is a validated histopathological biomarker of response to NACT, but it is only available postoperatively. In this study, we investigate whether pre-treatment computed tomography (CT) imaging and clinical data can be used to predict CRS as an investigational decision-support adjunct to inform multidisciplinary team (MDT) discussions regarding expected treatment response. Methods. We proposed a 2.5D multimodal deep learning framework that processes lesion-dense omental slices using a pre-trained Vision Transformer encoder and integrates the resulting visual representations with clinical variables through an intermediate fusion module to predict CRS. Results. Our multimodal model, integrating imaging and clinical data, achieved a ROC-AUC of 0.95 alongside 95% accuracy and 80% precision on the internal test cohort (IEO, n=41 patients). On the external test set (OV04, n=70 patients), it achieved a ROC-AUC of 0.68, alongside 67% accuracy and 75% precision. Conclusion. These preliminary results demonstrate the feasibility of transformer-based deep learning for preoperative prediction of CRS in HGSOC using routine clinical data and CT imaging. As an investigational, pre-treatment decision-support tool, this approach may assist MDT discussions by providing early, non-invasive estimates of treatment response.

Large language models (LLMs) hold significant promise for healthcare, yet their reliability in high-stakes clinical settings is often compromised by hallucinations and a lack of granular medical context. While Retrieval Augmented Generation (RAG) can mitigate these issues, standard supervised pipelines require computationally intensive searches over massive external knowledge bases, leading to high latency that is impractical for time-sensitive care. To address this, we introduce Keys to Knowledge (K2K), a novel framework that replaces external retrieval with internal, key-based knowledge access. By encoding essential clinical information directly into the model's parameter space, K2K enables rapid retrieval from internal key-value memory without inference-time overhead. We further enhance retrieval quality through activation-guided probe construction and cross-attention reranking. Experimental results demonstrate that K2K achieves state-of-the-art performance across four benchmark healthcare outcome prediction datasets.

Recent advances in Artificial Intelligence (AI) and the exploration of noninvasive, objective biomarkers, such as speech signals, have encouraged the development of algorithms to support the early diagnosis of neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS). Voice changes in subjects suffering from ALS typically manifest as progressive dysarthria, which is a prominent neurodegenerative symptom because it affects patients as the disease progresses. Since voice signals are complex data, the development and use of advanced AI techniques are fundamental to extracting distinctive patterns from them. Validating AI algorithms for ALS diagnosis and monitoring using voice signals is challenging, particularly due to the lack of annotated reference datasets. In this work, we present the outcome of a collaboration between a multidisciplinary team of clinicians and Machine Learning experts to create both a clinically annotated validation dataset and the "Speech Analysis for Neurodegenerative Diseases" (SAND) challenge based on it. Specifically, by analyzing voice disorders, the SAND challenge provides an opportunity to develop, test, and evaluate AI models for the automatic early identification and prediction of ALS disease progression.

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy; yet substantial proportion of patients exhibit intrinsic or acquired resistance, making accurate pre-treatment response prediction a critical unmet need. Transcriptomics-based biomarkers derived from bulk and single-cell RNA sequencing (scRNA-seq) offer a promising avenue for capturing tumour-immune interactions, yet the cross-cohort generalisability of existing prediction models remains unclear.We systematically benchmark nine state-of-the-art transcriptomic ICI response predictors, five bulk RNA-seq-based models (COMPASS, IRNet, NetBio, IKCScore, and TNBC-ICI) and four scRNA-seq-based models (PRECISE, DeepGeneX, Tres and scCURE), using publicly available independent datasets unseen during model development. Overall, predictive performance was modest: bulk RNA-seq models performed at or near chance level across most cohorts, while scRNA-seq models showed only marginal improvements. Pathway-level analyses revealed sparse and inconsistent biomarker signals across models. Although scRNA-seq-based predictors converged on immune-related programs such as allograft rejection, bulk RNA-seq-based models exhibited little reproducible overlap. PRECISE and NetBio identified the most coherent immune-related themes, whereas IRNet predominantly captured metabolic pathways weakly aligned with ICI biology. Together, these findings demonstrate the limited cross-cohort robustness and biological consistency of current transcriptomic ICI prediction models, underscoring the need for improved domain adaptation, standardised preprocessing, and biologically grounded model design.

We develop and analyze explainable machine learning (ML) models for sepsis outcome prediction using a novel Electronic Health Record (EHR) dataset from 12,286 hospitalizations at a large emergency hospital in Romania. The dataset includes demographics, International Classification of Diseases (ICD-10) diagnostics, and 600 types of laboratory tests. This study aims to identify clinically strong predictors while achieving state-of-the-art results across three classification tasks: (1)deceased vs. discharged, (2)deceased vs. recovered, and (3)recovered vs. ameliorated. We trained five ML models to capture complex distributions while preserving clinical interpretability. Experiments explored the trade-off between feature richness and patient coverage, using subsets of the 10--50 most frequent laboratory tests. Model performance was evaluated using accuracy and area under the curve (AUC), and explainability was assessed using SHapley Additive exPlanations (SHAP). The highest performance was obtained for the deceased vs. recovered case study (AUC=0.983, accuracy=0.93). SHAP analysis identified several strong predictors such as cardiovascular comorbidities, urea levels, aspartate aminotransferase, platelet count, and eosinophil percentage. Eosinopenia emerged as a top predictor, highlighting its value as an underutilized marker that is not included in current assessment standards, while the high performance suggests the applicability of these models in clinical settings.

Spatial transcriptomics (ST) enables gene expression mapping within anatomical context but remains costly and low-throughput. Hematoxylin and eosin (H&E) staining offers rich morphology yet lacks molecular resolution. We present \ours (Spatial Transcriptomics and histOlogy Representation Model), a foundation model trained on 1.2 million spatially resolved transcriptomic profiles with matched histology across 18 organs. Using a hierarchical architecture integrating morphological features, gene expression, and spatial context, STORM bridges imaging and omics through robust molecular--morphological representations. STORM enhances spatial domain discovery, producing biologically coherent tissue maps, and outperforms existing methods in predicting spatial gene expression from H&E images across 11 tumor types. The model is platform-agnostic, performing consistently across Visium, Xenium, Visium HD, and CosMx. Applied to 23 independent cohorts comprising 7,245 patients, STORM significantly improves immunotherapy response prediction and prognostication over established biomarkers, providing a scalable framework for spatially informed discovery and clinical precision medicine.

Timely discharge prediction is essential for optimizing bed turnover and resource allocation in elective spine surgery units. This study evaluates the feasibility of lightweight, fine-tuned large language models (LLMs) and traditional text-based models for predicting next-day discharge using postoperative clinical notes. We compared 13 models, including TF-IDF with XGBoost and LGBM, and compact LLMs (DistilGPT-2, Bio_ClinicalBERT) fine-tuned via LoRA. TF-IDF with LGBM achieved the best balance, with an F1-score of 0.47 for the discharge class, a recall of 0.51, and the highest AUC-ROC (0.80). While LoRA improved recall in DistilGPT2, overall transformer-based and generative models underperformed. These findings suggest interpretable, resource-efficient models may outperform compact LLMs in real-world, imbalanced clinical prediction tasks.

Datasets used in immunotherapy response prediction are typically small in size, as well as diverse in cancer type, drug administered, and sequencer used. Models often drop in performance when tested on patient cohorts that are not included in the training process. Recent work has shown that transformer-based models along with self-supervised learning show better generalisation performance than threshold-based biomarkers, but is still suboptimal. We present BioCOMPASS, an extension of a transformer-based model called COMPASS, that integrates biomarkers and treatment information to further improve its generalisability. Instead of feeding biomarker data as input, we built loss components to align them with the model's intermediate representations. We found that components such as treatment gating and pathway consistency loss improved generalisability when evaluated with Leave-one-cohort-out, Leave-one-cancer-type-out and Leave-one-treatment-out strategies. Results show that building components that exploit biomarker and treatment information can help in generalisability of immunotherapy response prediction. Careful curation of additional components that leverage complementary clinical information and domain knowledge represents a promising direction for future research.

Objective: This study aimed to evaluate which voice features can predict health deterioration in patients with chronic HF. Background: Heart failure (HF) is a chronic condition with progressive deterioration and acute decompensations, often requiring hospitalization and imposing substantial healthcare and economic burdens. Current standard-of-care (SoC) home monitoring, such as weight tracking, lacks predictive accuracy and requires high patient engagement. Voice is a promising non-invasive biomarker, though prior studies have mainly focused on acute HF stages. Methods: In a 2-month longitudinal study, 32 patients with HF collected daily voice recordings and SoC measures of weight and blood pressure at home, with biweekly questionnaires for health status. Acoustic analysis generated detailed vowel and speech features. Time-series features were extracted from aggregated lookback windows (e.g., 7 days) to predict next-day health status. Explainable machine learning with nested cross-validation identified top vocal biomarkers, and a case study illustrated model application. Results: A total of 21,863 recordings were analyzed. Acoustic vowel features showed strong correlations with health status. Time-series voice features within the lookback window outperformed corresponding standard care measures, achieving peak sensitivity and specificity of 0.826 and 0.782 versus 0.783 and 0.567 for SoC metrics. Key prognostic voice features identifying deterioration included delayed energy shift, low energy variability, and higher shimmer variability in vowels, along with reduced speaking and articulation rate, lower phonation ratio, decreased voice quality, and increased formant variability in speech. Conclusion: Voice-based monitoring offers a non-invasive approach to detect early health changes in chronic HF, supporting proactive and personalized care.

Multimodal Machine Learning offers a holistic view of a patient's status, integrating structured and unstructured data from electronic health records (EHR). We propose a framework to predict metastasis risk one month prior to diagnosis, using six months of clinical history from EHR data. Data from four cancer cohorts collected at Karolinska University Hospital (Stockholm, Sweden) were analyzed: breast (n = 743), colon (n = 387), lung (n = 870), and prostate (n = 1890). The dataset included demographics, comorbidities, laboratory results, medications, and clinical text. We compared traditional and deep learning classifiers across single modalities and multimodal combinations, using various fusion strategies and a Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) 2a design, with an 80-20 development-validation split to ensure a rigorous, repeatable evaluation. Performance was evaluated using AUROC, AUPRC, F1 score, sensitivity, and specificity. We then employed a multimodal adaptation of SHAP to analyze the classifiers' reasoning. Intermediate fusion achieved the highest F1 scores on breast (0.845), colon (0.786), and prostate cancer (0.845), demonstrating strong predictive performance. For lung cancer, the intermediate fusion achieved an F1 score of 0.819, while the text-only model achieved the highest, with an F1 score of 0.829. Deep learning classifiers consistently outperformed traditional models. Colon cancer, the smallest cohort, had the lowest performance, highlighting the importance of sufficient training data. SHAP analysis showed that the relative importance of modalities varied across cancer types. Fusion strategies offer distinct strengths and weaknesses. Intermediate fusion consistently delivered the best results, but strategy choices should align with data characteristics and organizational needs.

Parkinson's disease (PD) affects over ten million people worldwide. Although temporal interference (TI) and deep brain stimulation (DBS) are promising therapies, inter-individual variability limits empirical treatment selection, increasing non-negligible surgical risk and cost. Previous explorations either resort to limited statistical biomarkers that are insufficient to characterize variability, or employ AI-driven methods which is prone to overfitting and opacity. We bridge this gap with a pretraining-finetuning framework to predict outcomes directly from resting-state fMRI. Critically, a generative virtual brain foundation model, pretrained on a collective dataset (2707 subjects, 5621 sessions) to capture universal disorder patterns, was finetuned on PD cohorts receiving TI (n=51) or DBS (n=55) to yield individualized virtual brains with high fidelity to empirical functional connectivity (r=0.935). By constructing counterfactual estimations between pathological and healthy neural states within these personalized models, we predicted clinical responses (TI: AUPR=0.853; DBS: AUPR=0.915), substantially outperforming baselines. External and prospective validations (n=14, n=11) highlight the feasibility of clinical translation. Moreover, our framework provides state-dependent regional patterns linked to response, offering hypothesis-generating mechanistic insights.

This study presents a fully automated methodology for early prediction studies in clinical settings, leveraging information extracted from unstructured discharge reports. The proposed pipeline uses discharge reports to support the three main steps of early prediction: cohort selection, dataset generation, and outcome labeling. By processing discharge reports with natural language processing techniques, we can efficiently identify relevant patient cohorts, enrich structured datasets with additional clinical variables, and generate high-quality labels without manual intervention. This approach addresses the frequent issue of missing or incomplete data in codified electronic health records (EHR), capturing clinically relevant information that is often underrepresented. We evaluate the methodology in the context of predicting atrial fibrillation (AF) progression, showing that predictive models trained on datasets enriched with discharge report information achieve higher accuracy and correlation with true outcomes compared to models trained solely on structured EHR data, while also surpassing traditional clinical scores. These results demonstrate that automating the integration of unstructured clinical text can streamline early prediction studies, improve data quality, and enhance the reliability of predictive models for clinical decision-making.

Hypertrophic cardiomyopathy (HCM) requires accurate risk stratification to inform decisions regarding ICD therapy and follow-up management. Current established models, such as the European Society of Cardiology (ESC) score, exhibit moderate discriminative performance. This study develops a robust, explainable machine learning (ML) risk score leveraging routinely collected echocardiographic, clinical, and medication data, typically contained within Electronic Health Records (EHRs), to predict a 5-year composite cardiovascular outcome in HCM patients. The model was trained and internally validated using a large cohort (N=1,201) from the SHARE registry (Florence Hospital) and externally validated on an independent cohort (N=382) from Rennes Hospital. The final Random Forest ensemble model achieved a high internal Area Under the Curve (AUC) of 0.85 +- 0.02, significantly outperforming the ESC score (0.56 +- 0.03). Critically, survival curve analysis on the external validation set showed superior risk separation for the ML score (Log-rank p = 8.62 x 10^(-4) compared to the ESC score (p = 0.0559). Furthermore, longitudinal analyses demonstrate that the proposed risk score remains stable over time in event-free patients. The model high interpretability and its capacity for longitudinal risk monitoring represent promising tools for the personalized clinical management of HCM.

Deep learning models have shown promise in EEG-based outcome prediction for comatose patients after cardiac arrest, but their reliability is often compromised by subtle forms of data leakage. In particular, when long EEG recordings are segmented into short windows and reused across multiple training stages, models may implicitly encode and propagate label information, leading to overly optimistic validation performance and poor generalization. In this study, we identify a previously overlooked form of data leakage in multi-stage EEG modeling pipelines. We demonstrate that violating strict patient-level separation can significantly inflate validation metrics while causing substantial degradation on independent test data. To address this issue, we propose a leakage-aware two-stage framework. In the first stage, short EEG segments are transformed into embedding representations using a convolutional neural network with an ArcFace objective. In the second stage, a Transformer-based model aggregates these embeddings to produce patient-level predictions, with strict isolation between training cohorts to eliminate leakage pathways. Experiments on a large-scale EEG dataset of post-cardiac-arrest patients show that the proposed framework achieves stable and generalizable performance under clinically relevant constraints, particularly in maintaining high sensitivity at stringent specificity thresholds. These results highlight the importance of rigorous data partitioning and provide a practical solution for reliable EEG-based outcome prediction.

This study assesses whether self-supervised learning (SSL) improves knee osteoarthritis (OA) modeling for diagnosis and prognosis relative to ImageNet-pretrained initialization. We compared (i) image-only SSL pretrained on knee radiographs from the OAI, MOST, and NYU cohorts, and (ii) multimodal image-text SSL pretrained on hospital knee radiographs paired with radiologist impressions. For diagnostic Kellgren-Lawrence (KL) grade prediction, SSL yielded mixed results. While image-only SSL improved accuracy during linear probing (frozen encoder), it did not outperform ImageNet pretraining during full fine-tuning. Similarly, multimodal SSL failed to improve grading performance. A likely explanation is mismatch between the hospital pretraining corpus and the downstream diagnostic task: the hospital image-text dataset was restricted to knees from patients with clinically identified OA in routine care, rather than a cohort spanning the full spectrum from normal to severe disease needed for balanced KL grading. In addition, radiology impressions do not explicitly encode KL grade, limiting supervision for learning KL-specific decision boundaries. In contrast, this same multimodal initialization significantly improved prognostic modeling. It outperformed ImageNet baselines in predicting 4-year structural incidence and progression, including on external validation (MOST AUROC: 0.701 vs. 0.599 at 10% labeled data). Overall, these results suggest that our hospital image-text data may be less effective for diagnostic grading when the pretraining cohort is limited to OA knees, but can provide a strong signal for prognostic modeling when the downstream task is better aligned with the pretraining data distribution.

While large-scale pretraining has revolutionized language modeling, its potential remains underexplored in healthcare with structured electronic health records (EHRs). We present RAVEN, a novel generative pretraining strategy for sequential EHR data based on Recurrence-Aware next-Visit EveNt prediction. Leveraging a dataset of over one million unique individuals, our model learns to autoregressively generate tokenized clinical events for the next visit conditioned on patient history. We introduce regularization on predicting repeated events and highlight a key pitfall in EHR-based foundation model evaluations: repeated event tokens can inflate performance metrics when new onsets are not distinguished from subsequent occurrences. Furthermore, we empirically investigate the scaling behaviors in a data-constrained, compute-saturated regime, showing that simply increasing model size is suboptimal without commensurate increases in data volume. We evaluate our model via zero-shot prediction for forecasting the incidence of a diverse set of diseases, where it rivals fully fine-tuned representation-based Transformer models and outperforms both standard simulation-based next-token approaches and a prompted medical large language model baseline. Finally, without additional parameter updates, we show that RAVEN can generalize to an external patient cohort under lossy clinical code mappings and feature coverage gaps.

Deploying clinical ML is slow and brittle: models that work at one hospital often degrade under distribution shifts at the next. In this work, we study a simple question -- can large language models (LLMs) create portable patient embeddings i.e. representations of patients enable a downstream predictor built on one hospital to be used elsewhere with minimal-to-no retraining and fine-tuning. To do so, we map from irregular ICU time series onto concise natural language summaries using a frozen LLM, then embed each summary with a frozen text embedding model to obtain a fixed length vector capable of serving as input to a variety of downstream predictors. Across three cohorts (MIMIC-IV, HIRID, PPICU), on multiple clinically grounded forecasting and classification tasks, we find that our approach is simple, easy to use and competitive with in-distribution with grid imputation, self-supervised representation learning, and time series foundation models, while exhibiting smaller relative performance drops when transferring to new hospitals. We study the variation in performance across prompt design, with structured prompts being crucial to reducing the variance of the predictive models without altering mean accuracy. We find that using these portable representations improves few-shot learning and does not increase demographic recoverability of age or sex relative to baselines, suggesting little additional privacy risk. Our work points to the potential that LLMs hold as tools to enable the scalable deployment of production grade predictive models by reducing the engineering overhead.

Foundation models in healthcare have largely adopted self supervised pretraining objectives inherited from natural language processing and computer vision, emphasizing reconstruction and large scale representation learning prior to downstream adaptation. We revisit this paradigm in outcome centric clinical prediction settings and argue that, when high quality supervision is available, direct outcome alignment may provide a stronger inductive bias than generative pretraining. We propose a supervised deep learning framework that explicitly shapes representation geometry by maximizing inter class separation relative to within class variance, thereby concentrating model capacity along clinically meaningful axes. Across multiple longitudinal electronic health record tasks, including mortality and readmission prediction, our approach consistently outperforms masked, autoregressive, and contrastive pretraining baselines under matched model capacity. The proposed method improves discrimination, calibration, and sample efficiency, while simplifying the training pipeline to a single stage optimization. These findings suggest that in low entropy, outcome driven healthcare domains, supervision can act as the statistically optimal driver of representation learning, challenging the assumption that large scale self supervised pretraining is a prerequisite for strong clinical performance.

Longitudinal neuroimaging is essential for modeling disease progression in Alzheimer's disease (AD), yet irregular sampling and missing visits pose substantial challenges for learning reliable temporal representations. To address this challenge, we propose SDE-HGNN, a stochastic differential equation (SDE)-driven spatio-temporal hypergraph neural network for irregular longitudinal fMRI connectome modeling. The framework first employs an SDE-based reconstruction module to recover continuous latent trajectories from irregular observations. Based on these reconstructed representations, dynamic hypergraphs are constructed to capture higher-order interactions among brain regions over time. To further model temporal evolution, hypergraph convolution parameters evolve through SDE-controlled recurrent dynamics conditioned on inter-visit intervals, enabling disease-stage-adaptive connectivity modeling. We also incorporate a sparsity-based importance learning mechanism to identify salient brain regions and discriminative connectivity patterns. Extensive experiments on the OASIS-3 and ADNI cohorts demonstrate consistent improvements over state-of-the-art graph and hypergraph baselines in AD progression prediction. The source code is available at https://anonymous.4open.science/r/SDE-HGNN-017F.

Early prediction of Post-Acute Sequelae of SARS-CoV-2 severity is a critical challenge for women's health, particularly given the diagnostic overlap between PASC and common hormonal transitions such as menopause. Identifying and accounting for these confounding factors is essential for accurate long-term trajectory prediction. We conducted a retrospective study of 1,155 women (mean age 61) from the NIH RECOVER dataset. By integrating static clinical profiles with four weeks of longitudinal wearable data (monitoring cardiac activity and sleep), we developed a causal network based on a Large Language Model to predict future PASC scores. Our framework achieved a precision of 86.7% in clinical severity prediction. Our causal attribution analysis demonstrate the model's ability to differentiate between active pathology and baseline noise: direct indicators such as breathlessness and malaise reached maximum saliency (1.00), while confounding factors like menopause and diabetes were successfully suppressed with saliency scores below 0.27.

Background: This study aims to develop and validate federated learning models for predicting major postoperative complications and mortality using a large multicenter dataset from the OneFlorida Data Trust. We hypothesize that federated learning models will offer robust generalizability while preserving data privacy and security. Methods: This retrospective, longitudinal, multicenter cohort study included 358,644 adult patients admitted to five healthcare institutions, who underwent 494,163 inpatient major surgical procedures from 2012-2023. We developed and internally and externally validated federated learning models to predict the postoperative risk of intensive care unit (ICU) admission, mechanical ventilation (MV) therapy, acute kidney injury (AKI), and in-hospital mortality. These models were compared with local models trained on data from a single center and central models trained on a pooled dataset from all centers. Performance was primarily evaluated using area under the receiver operating characteristics curve (AUROC) and the area under the precision-recall curve (AUPRC) values. Results: Our federated learning models demonstrated strong predictive performance, with AUROC scores consistently comparable or superior performance in terms of AUROC and AUPRC across all outcomes and sites. Our federated learning models also demonstrated strong generalizability, with comparable or superior performance in terms of both AUROC and AUPRC compared to the best local learning model at each site. Conclusions: By leveraging multicenter data, we developed robust, generalizable, and privacy-preserving predictive models for major postoperative complications and mortality. These findings support the feasibility of federated learning in clinical decision support systems.

Prostate cancer is among the most frequently diagnosed malignancies in men worldwide. However, precise prediction of biochemical recurrence (BCR) after radical prostatectomy remains challenging. Here, we propose a computationally efficient multi section whole slide image analysis framework designed to capture the whole gland tumor landscape. We curated a large scale dataset comprising 23,451 slides from 789 patients and systematically optimized patch and slide sub sampling to substantially reduce the computational cost of training and inference. Under this efficient configuration, the framework achieved strong predictive performance for 1- and 2-year BCR, with discrimination and clinical net benefit comparable to or exceeding those of established clinical benchmarks. In multivariable Cox proportional hazards analysis, the AI derived risk score remained an independent prognostic factor among the covariates examined, and its integration with clinical variables further improved prognostic performance. External validation in an independent cohort provided preliminary evidence of transferability. Finally, attention-dispersion analysis showed that the model drew prognostic information from multiple sections, consistent with the multifocal nature of prostate cancer. Collectively, these findings support the potential of multi section slide analysis as a scalable approach for postoperative BCR risk assessment in prostate cancer.

Major pathological response (pR) following neoadjuvant therapy is a clinically meaningful endpoint in non-small cell lung cancer, strongly associated with improved survival. However, accurate preoperative prediction of pR remains challenging, particularly in real-world clinical settings characterized by limited data availability and incomplete clinical profiles. In this study, we propose a multimodal deep learning framework designed to address these constraints by integrating foundation model-based CT feature extraction with a missing-aware architecture for clinical variables. This approach enables robust learning from small cohorts while explicitly modeling missing clinical information, without relying on conventional imputation strategies. A weighted fusion mechanism is employed to leverage the complementary contributions of imaging and clinical modalities, yielding a multimodal model that consistently outperforms both unimodal imaging and clinical baselines. These findings underscore the added value of integrating heterogeneous data sources and highlight the potential of multimodal, missing-aware systems to support pR prediction under realistic clinical conditions.

Ophthalmic decision-making depends on subtle lesion-scale cues interpreted across multimodal imaging and over time, yet most medical foundation models remain static and degrade under modality and acquisition shifts. Here we introduce EyeWorld, a generative world model that conceptualizes the eye as a partially observed dynamical system grounded in clinical imaging. EyeWorld learns an observation-stable latent ocular state shared across modalities, unifying fine-grained parsing, structure-preserving cross-modality translation and quality-robust enhancement within a single framework. Longitudinal supervision further enables time-conditioned state transitions, supporting forecasting of clinically meaningful progression while preserving stable anatomy. By moving from static representation learning to explicit dynamical modeling, EyeWorld provides a unified approach to robust multimodal interpretation and prognosis-oriented simulation in medicine.

Response variability limits the clinical utility of transcutaneous auricular vagus nerve stimulation (taVNS) for negative symptoms in treatment-resistant schizophrenia (TRS). This study aimed to develop an electroencephalography (EEG)-based machine learning (ML) model to predict individual response and explore associated neurophysiological mechanisms. We used ML to develop and validate predictive models based on pre-treatment EEG data features (power, coherence, and dynamic functional connectivity) from 50 TRS patients enrolled in the taVNS trial, within a nested cross-validation framework. Participants received 20 sessions of active or sham taVNS (n = 25 each) over two weeks, followed by a two-week follow-up. The prediction target was the percentage change in the positive and negative syndrome scale-factor score for negative symptoms (PANSS-FSNS) from baseline to post-treatment, with further evaluation of model specificity and neurophysiological relevance.The optimal model accurately predicted taVNS response in the active group, with predicted PANSS-FSNS changes strongly correlated with observed changes (r = 0.87, p < .001); permutation testing confirmed performance above chance (p < .001). Nine consistently retained features were identified, predominantly fronto-parietal and fronto-temporal coherence features. Negligible predictive performance in the sham group and failure to predict positive symptom change support the predictive specificity of this oscillatory signature for taVNS-related negative symptom improvement. Two coherence features within fronto-parietal-temporal networks showed post-taVNS changes significantly associated with symptom improvement, suggesting dual roles as predictors and potential therapeutic targets. EEG oscillatory neuromarkers enable accurate prediction of individual taVNS response in TRS, supporting mechanism-informed precision neuromodulation strategies.