Clinical Risk Prediction

Predicting complex human traits from genetic data is challenging because different genetic, clinical, and molecular data sources often contain different parts of the signal. Here, we present EFGPP, a reproducible framework for generating, ranking, and combining multiple types of data for genotype-to-phenotype prediction. We applied EFGPP to migraine prediction using UK Biobank data from 733 individuals. The framework combined genotype-derived features, principal components, clinical and metabolomic covariates, and polygenic risk scores generated from migraine and depression GWAS using PLINK, PRSice-2, AnnoPred, and LDAK-GWAS. The best single data type achieved a test AUC of 0.644, while combining multiple data types improved performance to 0.688 using migraine-focused inputs and 0.663 using cross-trait depression-derived inputs. Genetic features alone did not outperform the covariates-only baseline, but genotype-derived features performed better than PRS alone, and depression-derived PRS showed useful predictive signal. Overall, EFGPP provides a practical proof-of-concept framework for prioritising and integrating heterogeneous genetic data sources for complex phenotype prediction.

With the proliferation of Electronic Health Records (EHRs), a critical challenge in building predictive models is determining the optimal historical data time window to maximize accuracy. This study investigates the impact of various observation windows ranging from the day of surgery to three years prior on predicting 30-day readmission following hip and knee arthroplasties. The dataset encompasses both structured encounter records (over 4 million) and unstructured clinical notes (80,000) from 7,174 patients. To extract meaning from the clinical notes, we employed a suite of non neural (BOW, count BOW, TF IDF, LDA) and neural encoders (BERT, 1D CNN, BiLSTM, Average). We subsequently evaluated models utilizing clinical notes alone, structured data alone, and a combination of both modalities. Our results demonstrate that the optimal time window for unstructured clinical notes is significantly shorter than for structured data, maximum predictive performance was achieved using notes from just three to six months prior to surgery. In contrast, performance using structured data improved as the time window lengthened, but strictly plateaued after twelve months. These modality-specific temporal patterns remained consistent regardless of model complexity or encoder type. Ultimately, these findings challenge the general assumption that more historical data inherently yields better machine learning predictions, establishing targeted time-window guidelines for optimizing readmission prediction models.

Effectively stratifying patient risk in chronic diseases like glaucoma is a major clinical challenge. Clinicians need tools to identify patients at high risk of progression from sparse and irregularly-sampled electronic health records (EHRs). We propose a novel deep kernel learning (DKL) architecture that leverages a Gaussian Process (GP) backend. The GP's kernel is defined by a transformer-based feature extractor applied to clinical-BERT embeddings to model glaucoma patient trajectories from multimodal EHR data. Our method successfully identifies three clinically distinct patient subgroups. Crucially, the model learns to decouple disease progression from current severity, identifying a high-risk group with a worsening trajectory despite having better average visual acuity than a second, stably poor group. This reveals that the model learns to identify progression risk rather than just the current disease state. This ability to stratify patients based on their risk trajectory progression offers a powerful tool for clinical decision support, enabling targeted interventions for high-risk individuals and improving the management of glaucoma care.

Clinical time-series forecasting is increasingly studied for decision support, yet standard aggregate metrics can obscure whether a model is actually useful for the task it is meant to serve. In safety-critical settings, low average error can coexist with dangerous failures in exactly the high-risk regimes that matter most. We present a task-aware evaluation framework for blood glucose forecasting built around two downstream uses: hypoglycemia early warning and insulin dosing decision support. For early warning, we evaluate on real data from three clinical cohorts using event-level recall and false alarms per patient-day, metrics that reflect operational alarm burden rather than aggregate accuracy. We show that models appearing acceptable overall, with recall above 0.9 on the full test set, can fail badly in the post-bolus slice, where insulin-on-board is elevated and missed warnings carry the greatest clinical consequences. Standard forecasting evaluation, however, does not test whether a model can reason about the effects of actions, a requirement for supporting insulin dosing decisions. We therefore add a second, interventional arm using the FDA-accepted UVA/Padova simulator, where we evaluate whether forecasters can predict glucose responses to altered insulin plans in paired factual/counterfactual scenarios. We show that models that look strong on real-data forecasting often fail to predict the direction, magnitude, or ranking of intervention effects, and choose poor insulin doses when evaluated under a clinically motivated cost. Taken together, the two arms reveal a consistent gap between forecasting accuracy and task-relevant usefulness. We release the benchmark, the standardized preprocessing pipeline for public cohorts, and the simulator-based interventional dataset as a reproducible toolkit.

Individualized Alzheimer's disease (AD) progression prediction requires models that use irregular visits, account for censoring, avoid diagnostic leakage, and provide calibrated horizon risks. We propose PROgression-aware MultI-horizon Survival Estimation for Alzheimer's Disease (PROMISE-AD), a leakage-safe survival framework for predicting conversion from cognitively normal (CN) to mild cognitive impairment (MCI) and from MCI to AD dementia using ADNI/TADPOLE tabular histories. PROMISE-AD converts pre-index visits into tokens with standardized measurements, missingness masks, longitudinal changes, time-normalized slopes, visit timing, and non-diagnostic categorical attributes. A temporal Transformer fuses global, attention-pooled, and latest-visit representations to estimate a progression score and latent discrete-time mixture hazards. Training combines survival likelihood, horizon-specific focal risk loss, progression ranking, hazard smoothness, and mixture-balance regularization, followed by validation-set isotonic calibration for 1-, 2-, 3-, and 5-year risks. In held-out testing across three seeds, PROMISE-AD achieved an integrated Brier score (IBS) of 0.085 $\pm$ 0.012, C-index of 0.808 $\pm$ 0.015, and mean time-dependent AUC of 0.840 $\pm$ 0.081 for CN-to-MCI conversion, yielding the lowest IBS among compared methods. For MCI-to-AD conversion, PROMISE-AD achieved the highest C-index (0.894 $\pm$ 0.018) and near-ceiling 5-year discrimination (AUROC 0.997 $\pm$ 0.003; AUPRC 0.999 $\pm$ 0.001), although some baselines had lower IBS. Ablations and interpretability supported longitudinal change features, fused temporal representations, mixture hazards, cognitive and functional measures, APOE4 status, and recent conversion-proximal visits. These findings suggest that progression-aware survival modeling can provide interpretable multi-horizon AD conversion risk estimates.

Understanding how human health changes over time, and why responses to interventions vary between individuals, remains a central challenge in medicine. Here we present HealthFormer, a decoder-only transformer that models the human physiological trajectory generatively, by training on data from the Human Phenotype Project, a multi-visit cohort of over 15,000 deeply phenotyped individuals. We tokenise each participant's health trajectory across 667 measurements spanning seven domains: blood biomarkers, body composition, sleep physiology, continuous glucose monitoring, gut microbiome, wearable-derived physiology, and behaviour and medication exposure. We train HealthFormer to forecast individual physiological trajectories across these domains, and from this single generative objective a range of clinically relevant tasks can be expressed as queries on the model. We show that, without task-specific training, HealthFormer transfers to four independent cohorts and improves prediction for 27 of 30 incident-disease and mortality endpoints, exceeding established clinical risk scores in every comparison. We further show that the model can simulate interventions in silico: in a held-out personalised-nutrition trial, intervention-conditioned predictions recover individual six-month biomarker changes (e.g., Pearson r = 0.78 for diastolic blood pressure). Across 41 randomised intervention-outcome comparisons drawn from published trials, our results show that the predicted direction of effect agrees in every case, and the predicted mean falls within the reported 95% confidence interval in 30 cases. We position HealthFormer as an initial health world model, from which forecasting, risk stratification, and intervention-conditioned simulation arise as queries, providing a basis for clinical digital twins.

Progression to dialysis or end-stage renal disease is a rare but clinically important outcome. Clinicians need evidence on how medication exposures influence downstream risk. We constructed a fixed-window EHR cohort (90-day observation, 730-day prediction; N=81401; dialysis/ESRD prevalence: 1.1%) and modeled sequences of diagnoses, procedures, and medications with kidney laboratory trends (creatinine, BUN, eGFR). A transformer-based causal multi-head model was trained to estimate drug- and ingredient-level average treatment effects (ATEs) using counterfactual exposure removal and insertion under a full medication history setup. On test set, predictive performance reached an AUC of 0.694 and PR-AUC of 0.094. At the selected decision threshold (0.883), the model achieved an F1 score of 0.201 with a Brier score of 0.018. Post-hoc causal analyses of lab changes (eGFR, creatinine, BUN) using IPTW, AIPW, naive, and covariate-adjusted OLS methods assessed clinical directionality. Results showed partial protective-direction support for ACE/ARB exposures and worsening-direction signals for loop diuretics.

Multimodal artificial intelligence models for endometrial cancer (EC) risk stratification typically optimize aggregate predictive performance but provide limited mechanisms for enforcing mandatory guideline overrides, such as assigning POLE-mutated tumors to the low-risk group despite high-grade morphology. We present EndoGov, a two-tier multi-agent expert system that factorizes the decision process as D(x) = G(P(x), R), where specialist agents P extract structured evidence and a governance agent G applies an executable rule set R. Tier 1 comprises pathology, molecular, and clinical agents that independently generate schema-constrained reports from frozen foundation-model features or structured records. Tier 2 queries an evidence-level-weighted Guideline Knowledge Graph, using deterministic hard-path rules for high-priority overrides and constrained soft-path reasoning for ambiguous cases. In TCGA-UCEC (n=541), EndoGov achieved 0.943 accuracy, 0.973 macro AUC, and a conditional logic-violation rate (C-LVR) of 0.93% among trigger-exposed cases. In CPTAC-UCEC (n=95), where reference labels are guideline-derived, EndoGov reached 0.842 accuracy compared with < 0.31 for locked-transfer neural baselines, supporting governance-pathway transfer under distribution shift rather than validation against independent clinical truth. End-to-end safety decomposition localized residual failures primarily to upstream molecular detection rather than downstream governance. Backend-swap experiments further showed that hard-path compliance is invariant to the LLM backend. These findings indicate that explicit clinical-rule governance can provide guideline-compliant, auditable EC risk assignment while preserving competitive discrimination.

Disease progression varies with age and is influenced by underlying genetic, biochemical, and hormonal etiologies, suggesting the need for tailored monitoring, care, and medication beyond standard clinical guidelines. Specifically, in autoimmune diseases like type 1 diabetes (T1D), where patients depend on exogenous insulin to compensate for insulin deficiency, medication dosing and the physiological response reflected in vital signs can differ. Insulin therapy can lead to hypoglycemia, a dangerous condition characterized by decreased blood glucose levels ($\leq$70). This risk can be mitigated through improved diabetes management supported by data analytics. Notably, leveraging data from continuous glucose monitoring (CGM) devices, hypoglycemia onset can be predicted. However, while glucose variability, auto-antibody levels, and hypoglycemia occurrence differ across age groups, hypoglycemia classification most often only relies on population-based models specialized in specific age ranges. In this work, we classify hypoglycemia 0, 5-15, 20-45, and 50-120 minutes before onset using DiaData, a large CGM dataset of patients with T1D ranging from children to seniors. In particular, we investigate: 1) the generalizability of a population-based model including all age groups, 2) the impact of age-segmented models trained separately per age group, and 3) the effect of model individualization through transfer learning. The results show that a global population-based model yields similar or superior performance compared to age-segmented models. These findings suggest that data from children, teenagers, and adults can be combined for training models on hypoglycemia classification. While glucose variation differs across age groups, short-term hypoglycemic patterns are similar. However, data of children obtain their best recall with age specialized model.

Emerging AI systems in behavioral health and psychiatry use multi-step or multi-agent LLM pipelines for tasks like assessing self-harm risk and screening for depression. However, common evaluation approaches, like LLM-as-a-judge, do not indicate when a decision is reliable or how errors may accumulate across multiple LLM judgements, limiting their suitability for safety-critical settings. We present a statistical framework for multi-agent pipelines structured as directed acyclic graphs (DAGs) that provides an alternative to heuristic voting with principled, adaptive decision-making. We model each agent as a stochastic categorical decision and introduce (1) tighter agent-level performance confidence bounds, (2) a bandit-based adaptive sampling strategy based on input difficulty, and (3) regret guarantees over the multi-agent system that shows logarithmic error growth when deployed. We evaluate our system on two labeled datasets in behavioral health : the AEGIS 2.0 behavioral health subset (N=161) and a stratified sample of SWMH Reddit posts (N=250). Empirically, our adaptive sampling strategy achieves the lowest false positive rate of any condition across both datasets, 0.095 on AEGIS 2.0 compared to 0.159 for single-agent models, reducing incorrect flagging of safe content by 40% and still having similar false negative rates across all conditions. These results suggest that principled adaptive sampling offers a meaningful improvement in precision without reducing recall in this setting.

Large language models (LLMs) are increasingly utilized in clinical reasoning and risk assessment. However, their interpretive reliability in critical and indeterminate domains such as psychiatry remains unclear. Prior work has identified algorithmic biases and prompt sensitivity in these systems, raising concerns about how contextual information may influence model outputs, but there remains no systematic way to assess these, especially in the psychiatric domain. We propose an approach for reliability auditing downstream LLM tasks by structuring evaluation around the impact of prompt design and the inclusion of medically insignificant inputs on predicted hospitalization risk scores, which is often the first downstream AI clinical-decision-making task. In our audit, a cohort of synthetic patient profiles (n = 50) is generated, each consisting of 15 clinically relevant features and up to 50 clinically insignificant features, across four prompt reframings (neutral, logical, human impact, clinical judgment). We audit four LLMs (Gemini 2.5 Flash, LLaMa 3.3 70b, Claude Sonnet 4.6, GPT-4o mini), and our results show that including medically insignificant variables resulted in a statistically significant increase in the absolute mean predicted hospitalization risk and output variability across all models and prompts, indicating reduced predictive stability as contextual noise increased. Clinically insignificant features had an effect on instability across many model-prompt conditions, and prompt variations independently affected the trajectory of instability in a model-dependent manner. These findings quantify how LLM-based psychiatric risk assessments are sensitive to non-clinical information, highlighting the need for systematic evaluations of attributional stability and uncertainty behavior like this before clinical deployments.

Accurate early prediction of Acute Kidney Injury (AKI) is critical for timely clinical intervention. However, existing deep learning models struggle with irregularly sampled data and suffer from the opaque "black-box" nature of sequential architectures, strictly limiting clinical trust. To address these challenges, we propose CT-Former, integrating continuous-time modeling with a Causal-Transformer. To handle data irregularity without biased artificial imputation, our framework utilizes a continuous-time state evolution mechanism to naturally track patient temporal trajectories. To resolve the black-box problem, our Causal-Attention module abandons uninterpretable hidden state aggregation. Instead, it generates a directed structural causal matrix to identify and trace the exact historical onset of severe physiological shocks. By establishing clear causal pathways between historical anomalies and current risk predictions, CT-Former provides native clinical interpretability. Training follows a decoupled two-stage protocol to optimize the causal-fusion process independently. Extensive experiments on the MIMIC-IV cohort (N=18,419) demonstrate that CT-Former significantly outperforms state-of-the-art baselines. The results confirm that our explicitly transparent architecture offers an accurate and trustworthy tool for clinical decision-making.

Timely and interpretable early warning of sepsis remains a major clinical challenge due to the complex temporal dynamics of physiological deterioration. Traditional data-driven models often provide accurate yet opaque predictions, limiting physicians' confidence and clinical applicability. To address this limitation, we propose a Large Language Model (LLM)-guided temporal simulation framework that explicitly models physiological trajectories prior to disease onset for clinically interpretable prediction. The framework consists of a spatiotemporal feature extraction module that captures dynamic dependencies among multivariate vital signs, a Medical Prompt-as-Prefix module that embeds clinical reasoning cues into LLMs, and an agent-based post-processing component that constrains predictions within physiologically plausible ranges. By first simulating the evolution of key physiological indicators and then classifying sepsis onset, our model offers transparent prediction mechanisms that align with clinical judgment. Evaluated on the MIMIC-IV and eICU databases, the proposed method achieves superior AUC scores (0.861-0.903) across 24-4-hour pre-onset prediction tasks, outperforming conventional deep learning and rule-based approaches. More importantly, it provides interpretable trajectories and risk trends that can assist clinicians in early intervention and personalized decision-making in intensive care environments.

We evaluated whether a glaucoma risk assessment (GRA) model trained on All of Us national data can identify patients at high probability of glaucoma using only systemic electronic health records (EHR) at an independent institution. In this cross-sectional study, 20,636 Stanford patients seen from November 2013 to January 2024 were included (15% with glaucoma). A pretrained GRA model was fine-tuned on the Stanford cohort and tested on a held-out set using demographics, systemic diagnoses, medications, laboratory results, and physical examination measurements as inputs. The best model achieved AUROC 0.883 and PPV 0.657. Calibration was consistent with clinical risk: the highest prediction decile showed the greatest glaucoma diagnosis rate (65.7%) and treatment rate (57.0%). Performance improved with more trainable layers up to 15 and with additional data. An EHR-only GRA model may enable scalable and accessible pre-screening without specialized imaging.

Coronary artery disease (CAD) remains one of the leading causes of death globally, highlighting the need for reliable predictive systems to support early diagnosis and risk assessment. While traditional machine learning models perform well on structured clinical data, large language models (LLMs) present new possibilities to interpret medical information expressed in natural language. In this work, we develop a hybrid framework that bridges structured clinical data and natural-language representations for CAD prediction. Using a publicly available dataset of 1,190 patient records with 11 clinical attributes, structured variables are converted into interpretable feature representations and synthetic clinical narratives using LLMs. A validation pipeline performs reverse extraction of clinical variables and computes a consistency score with the original records, achieving an average fidelity of 94.61%. We then evaluate four conventional machine learning models and compare their performance with LLM-based classification under zero-shot and few-shot prompting settings. We use two LLMs here, GPT and Gemini. Experimental results show that Random Forest achieves the highest accuracy. Despite this advantage, LLM-based classification remains beneficial in real-world clinical settings. This is because LLMs operate directly on natural language patient descriptions, meaning that sensitive numerical patient data such as exact lab values, blood pressure readings, and diagnostic codes are kept private. Findings suggest that combining structured clinical data with LLM-generated narratives can enable new directions for hybrid clinical prediction systems.

The retina provides a unique, noninvasive window into Alzheimer's disease (AD) and dementia, capturing early structural changes through morphometric features, while systemic and lifestyle risk factors reflect well-established contributors to disease susceptibility long before clinical symptom onset. However, current retinal analysis frameworks typically model imaging and risk factors separately, limiting their ability to capture joint multimodal patterns critical for early risk prediction. Moreover, existing methods rarely incorporate mechanisms to organize or align patients with similar retinal and clinical characteristics, constraining the learning of coherent cross-modal associations. To address these limitations, we introduce REVEAL (REtinal-risk Vision-Language Early Alzheimer's Learning), a framework that aligns color fundus photographs with individualized disease-specific risk profiles for predicting incident AD and dementia, on average 8 years before diagnosis (range: 1-11 years). Because real-world risk factors are structured questionnaire data, we translate them into clinically interpretable narratives compatible with pretrained vision-language models (VLMs). We further propose a group-aware contrastive learning (GACL) strategy that clusters patients with similar retinal morphometry and risk factors as positive pairs, strengthening multimodal alignment. This unified representation learning framework substantially outperforms state-of-the-art retinal imaging models paired with clinical text encoders, as well as general-purpose VLMs, demonstrating the value of jointly modeling retinal biomarkers and clinical risk factors. By providing a generalizable and noninvasive approach for early AD and dementia risk stratification, REVEAL has the potential to enable earlier intervention and improve preventive care at the population level.

Early prediction of severe clinical deterioration and remaining length of stay can enable timely intervention and better resource allocation in high-acuity settings such as the ICU. This has driven the development of machine learning models that leverage continuous streams of vital signs and other physiological signals for real-time risk prediction. Despite their promise, existing methods have important limitations. Contrastive pretraining treats all patients as equally strong negatives, failing to capture clinically meaningful similarity between patients with related diagnoses. Meanwhile, downstream fine-tuning typically ignores complementary modalities such as clinical notes, which provide rich contextual information unavailable in physiological signals alone. To address these challenges, we propose OC-Distill, a two-stage framework that leverages multimodal supervision during training while requiring only vital signs at inference. In the first stage, we introduce an ontology-aware contrastive objective that exploits the ICD hierarchy to quantify patient similarity and learn clinically grounded representations. In the second stage, we fine-tune the pretrained encoder via cross-modal knowledge distillation, transferring complementary information from clinical notes into the model. Across multiple ICU prediction tasks on MIMIC, OC-Distill demonstrates improved label efficiency and achieves state-of-the-art performance among methods that use only vital signs at inference.

Chronic rhinosinusitis (CRS) is a common heterogeneous inflammatory disorder that causes substantial morbidity and healthcare costs. CRS is difficult to identify early from routine encounters, as symptom presentations overlap with common conditions such as allergic rhinitis, and heterogeneous phenotypes further obscure risk patterns. Prior predictive studies often rely on single-institutional cohorts , which reduce population-level generalizability. To overcome this, we leveraged nationwide longitudinal EHR data from the All of Us Research Program to predict CRS diagnosis using two years of pre-diagnostic history. To address extreme feature sparsity and dimensionality in coded EHR data, we implemented a hybrid feature-selection pipeline that combines prevalence-based statistical screening with model-based importance ranking, compressing approximately 110,000 candidate codes into 100 interpretable features. To capture demographic heterogeneity, we trained demographic stratified models across six adult sex and life-stage subgroups with subgroup-specific hyperparameter tuning. Our framework achieved an overall AUC of 0.8461, improving discrimination by 0.0168 over the best baseline. These results demonstrate that routinely collected EHR data may support population-representative CRS risk stratification and inform earlier triage and referral prioritization in primary care.

Clinical language models (LMs) are increasingly applied to support clinical risk prediction from free-text notes, yet their uncertainty estimates often remain poorly calibrated and clinically unreliable. In this work, we propose Clinical Uncertainty Risk Alignment (CURA), a framework that aligns clinical LM-based risk estimates and uncertainty with both individual error likelihoods and cohort-level ambiguities. CURA first fine-tunes domain-specific clinical LMs to obtain task-adapted patient embeddings, and then performs uncertainty fine-tuning of a multi-head classifier using a bi-level uncertainty objective. Specifically, an individual-level calibration term aligns predictive uncertainty with each patient's likelihood of error, while a cohort-aware regularizer pulls risk estimates toward event rates in their local neighborhoods in the embedding space and places extra weight on ambiguous cohorts near the decision boundary. We further show that this cohort-aware term can be interpreted as a cross-entropy loss with neighborhood-informed soft labels, providing a label-smoothing view of our method. Extensive experiments on MIMIC-IV clinical risk prediction tasks across various clinical LMs show that CURA consistently improves calibration metrics without substantially compromising discrimination. Further analysis illustrates that CURA reduces overconfident false reassurance and yields more trustworthy uncertainty estimates for downstream clinical decision support.

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.

Accurate prediction of future risk and disease progression in sepsis is clinically important for early warning and timely intervention in intensive care. However, short-window sepsis prediction remains challenging, because shorter observation windows provide limited historical evidence, whereas longer prediction horizons reduce the number of patient trajectories with valid future supervision. To address this problem, we propose CSRA, a Controlled Spectral Residual Augmentation framework for short-window multi-system ICU time series. CSRA first groups variables by clinical systems and extracts system-level and global representations. It then performs input-adaptive residual perturbation in the spectral domain to generate structured and clinically plausible trajectory variations. To improve augmentation stability and controllability, CSRA is trained end-to-end with the downstream predictor under a unified objective, together with anchor consistency loss and controller regularization. Experiments on a MIMIC-IV sepsis cohort across multiple downstream models show that CSRA is consistently competitive and often superior, reducing regression error by 10.2% in MSE and 3.7% in MAE over the non-augmentation baseline, while also yielding consistent gains on classification. CSRA further maintains more favorable performance under shorter observation windows, longer prediction horizons, and smaller training data scales, while also remaining effective on an external clinical dataset~(ZiGongICUinfection), indicating stronger robustness and generalizability in clinically constrained settings.

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.

Gait assessment is a key clinical indicator of fall risk and overall health in older adults. However, standard clinical practice is largely limited to stopwatch-measured gait speed. We present a pipeline that leverages a 3D Human Mesh Recovery (HMR) model to extract gait parameters from recordings of older adults completing the Timed Up and Go (TUG) test. From videos recorded across different community centers, we extract and analyze spatiotemporal gait parameters, including step time, sit-to-stand duration, and step length. We found that video-derived step time was significantly correlated with IMU-based insole measurements. Using linear mixed effects models, we confirmed that shorter, more variable step lengths and longer sit-to-stand durations were predicted by higher self-rated fall risk and fear of falling. These findings demonstrate that our pipeline can enable accessible and ecologically valid gait analysis in community settings.

Efficient and explainable breast cancer (BC) risk prediction is critical for large-scale population-based screening. Breast MRI provides functional information for personalized risk assessment. Yet effective modeling remains challenging as fully 3D CNNs capture volumetric context at high computational cost, whereas lightweight 2D CNNs fail to model inter-slice continuity. Importantly, breast MRI modeling for shor- and long-term BC risk stratification remains underexplored. In this study, we propose LoGo-MR, a 2.5D local-global structural modeling framework for five-year BC risk prediction. Aligned with clinical interpretation, our framework first employs neighbor-slice encoding to capture subtle local cues linked to short-term risk. It then integrates transformer-enhanced multiple-instance learning (MIL) to model distributed global patterns related to long-term risk and provide interpretable slice importance. We further apply this framework across axial, sagittal, and coronal planes as LoGo3-MR to capture complementary volumetric information. This multi-plane formulation enables voxel-level risk saliency mapping, which may assist radiologists in localizing risk-relevant regions during breast MRI interpretation. Evaluated on a large breast MRI screening cohort (~7.5K), our method outperforms 2D/3D baselines and existing SOTA MIL methods, achieving AUCs of 0.77-0.69 for 1- to 5-year prediction and improving C-index by ~6% over 3D CNNs. LoGo3-MR further improves overall performance with interpretable localization across three planes, and validation across seven backbones shows consistent gains. These results highlight the clinical potential of efficient MRI-based BC risk stratification for large-scale screening. Code will be released publicly.

Accurate estimation of cancer risk from longitudinal electronic health records (EHRs) could support earlier detection and improved care, but modeling such complex patient trajectories remains challenging. We present TrajOnco, a training-free, multi-agent large language model (LLM) framework designed for scalable multi-cancer early detection. Using a chain-of-agents architecture with long-term memory, TrajOnco performs temporal reasoning over sequential clinical events to generate patient-level summaries, evidence-linked rationales, and predicted risk scores. We evaluated TrajOnco on de-identified Truveta EHR data across 15 cancer types using matched case-control cohorts, predicting risk of cancer diagnosis at 1 year. In zero-shot evaluation, TrajOnco achieved AUROCs of 0.64-0.80, performing comparably to supervised machine learning in a lung cancer benchmark while demonstrating better temporal reasoning than single-agent LLMs. The multi-agent design also enabled effective temporal reasoning with smaller-capacity models such as GPT-4.1-mini. The fidelity of TrajOnco's output was validated through human evaluation. Furthermore, TrajOnco's interpretable reasoning outputs can be aggregated to reveal population-level risk patterns that align with established clinical knowledge. These findings highlight the potential of multi-agent LLMs to execute interpretable temporal reasoning over longitudinal EHRs, advancing both scalable multi-cancer early detection and clinical insight generation.

Frailty and functional decline strongly influence treatment tolerance and outcomes in older patients with cancer, yet assessment is typically limited to infrequent clinic visits. We propose a multimodal wearable framework to estimate frailty-related functional change between visits in elderly breast cancer patients enrolled in the multicenter CARDIOCARE study. Free-living smartwatch physical activity and sleep features are combined with ECG-derived heart rate variability (HRV) features from a chest strap and organized into patient-horizon bags aligned to month 3 (M3) and month 6 (M6) follow-ups. Our innovation is an attention-based multiple instance learning (MIL) formulation that fuses irregular, multimodal wearable instances under real-world missingness and weak supervision. An attention-based MIL model with modality-specific multilayer perceptron (MLP) encoders with embedding dimension 128 aggregates variable-length and partially missing longitudinal instances to predict discretized change-from-baseline classes (worsened, stable, improved) for FACIT-F and handgrip strength. Under subject-independent leave-one-subject-out (LOSO) evaluation, the full multimodal model achieved balanced accuracy/F1 of 0.68 +/- 0.08/0.67 +/- 0.09 at M3 and 0.70 +/- 0.10/0.69 +/- 0.08 at M6 for handgrip, and 0.59 +/- 0.04/0.58 +/- 0.06 at M3 and 0.64 +/- 0.05/0.63 +/- 0.07 at M6 for FACIT-F. Ablation results indicated that smartwatch activity and sleep provide the strongest predictive information for frailty-related functional changes, while HRV contributes complementary information when fused with smartwatch streams.

Deep learning-based modeling of multimodal Electronic Health Records (EHRs) has become an important approach for clinical diagnosis and risk prediction. However, due to diverse clinical workflows and privacy constraints, raw EHRs are inherently multi-level incomplete, including irregular sampling, missing modalities, and sparse labels. These issues cause temporal misalignment, modality imbalance, and limited supervision. Most existing multimodal methods assume relatively complete data, and even methods designed for incompleteness usually address only one or two of these issues in isolation. As a result, they often rely on rigid temporal/modal alignment or discard incomplete data, which may distort raw clinical semantics. To address this problem, we propose HealthPoint (HP), a unified clinical point cloud paradigm for multi-level incomplete EHRs. HP represents heterogeneous clinical events as points in a continuous 4D space defined by content, time, modality, and case. To model interactions between arbitrary point pairs, we introduce a Low-Rank Relational Attention mechanism that efficiently captures high-order dependencies across these four dimensions. We further develop a hierarchical interaction and sampling strategy to balance fine-grained modeling and computational efficiency. Built on this framework, HP enables flexible event-level interaction and fine-grained self-supervision, supporting robust modality recovery and effective use of unlabeled data. Experiments on large-scale EHR datasets for risk prediction show that HP consistently achieves state-of-the-art performance and strong robustness under varying degrees of incompleteness.

Clinical prediction from structured electronic health records (EHRs) is challenging due to high dimensionality, heterogeneity, class imbalance, and distribution shift. While tabular in-context learning (TICL) and retrieval-augmented methods perform well on generic benchmarks, their behavior in clinical settings remains unclear. We present a multi-cohort EHR benchmark comparing classical, deep tabular, and TICL models across varying data scale, feature dimensionality, outcome rarity, and cross-cohort generalization. PFN-based TICL models are sample-efficient in low-data regimes but degrade under naive distance-based retrieval as heterogeneity and imbalance increase. We propose AWARE, a task-aligned retrieval framework using supervised embedding learning and lightweight adapters. AWARE improves AUPRC by up to 12.2% under extreme imbalance, with gains increasing with data complexity. Our results identify retrieval quality and retrieval-inference alignment as key bottlenecks for deploying tabular in-context learning in clinical prediction.

Forecasting evolving clinical risks relies on intrinsic pathological dependencies rather than mere chronological proximity, yet current methods struggle with coarse binary supervision and physical timestamps. To align predictive modeling with clinical logic, we propose the Medical-semantics Aware Time-ALiBi Transformer (MATA-Former), utilizing event semantics to dynamically parameterize attention weights to prioritize causal validity over time lags. Furthermore, we introduce Plateau-Gaussian Soft Labeling (PSL), reformulating binary classification into continuous multi-horizon regression for full-trajectory risk modeling. Evaluated on SIICU -- a newly constructed dataset featuring over 506k events with rigorous expert-verified, fine-grained annotations -- and the MIMIC-IV dataset, our framework demonstrates superior efficacy and robust generalization in capturing risks from text-intensive, irregular clinical time series.

Large language model (LLM) systems are increasingly used to support high-stakes decision-making, but they typically perform worse when the available evidence is internally inconsistent. Such a scenario exists in real-world healthcare settings, with patient-reported symptoms contradicting medical signs. To study this problem, we introduce MIMIC-DOS, a dataset for short-horizon organ dysfunction worsening prediction in the intensive care unit (ICU) setting. We derive this dataset from the widely recognized MIMIC-IV, a publicly available electronic health record dataset, and construct it exclusively from cases in which discordance between signs and symptoms exists. This setting poses a substantial challenge for existing LLM-based approaches, with single-pass LLMs and agentic pipelines often struggling to reconcile such conflicting signals. To address this problem, we propose CARE: a multi-stage privacy-compliant agentic reasoning framework in which a proprietary LLM provides guidance by generating structured categories and transitions without accessing sensitive patient data, while a local LLM uses these categories and transitions to support evidence acquisition and final decision-making. Empirically, under controlled retrospective evaluation on MIMIC-DOS, CARE achieves the best overall performance across key metrics among the evaluated LLMs and agentic workflows, showing that it can more robustly handle conflicting clinical evidence while preserving privacy.