Causal inference is paramount for understanding the effects of interventions, yet extracting personalized insights from increasingly complex data remains a significant challenge for modern machine learning. This is the case, in particular, when considering functional outcomes observed over a continuous domain (e.g., time, or space). Estimation of heterogeneous treatment effects, known as CATE, has emerged as a crucial tool for personalized decision-making, but existing meta-learning frameworks are largely limited to scalar outcomes, failing to provide satisfying results in scientific applications that leverage the rich, continuous information encoded in functional data. Here, we introduce FOCaL (Functional Outcome Causal Learning), a novel, doubly robust meta-learner specifically engineered to estimate a functional heterogeneous treatment effect (F-CATE). FOCaL integrates advanced functional regression techniques for both outcome modeling and functional pseudo-outcome reconstruction, thereby enabling the direct and robust estimation of F-CATE. We provide a rigorous theoretical derivation of FOCaL, demonstrate its performance and robustness compared to existing non-robust functional methods through comprehensive simulation studies, and illustrate its practical utility on diverse real-world functional datasets. FOCaL advances the capabilities of machine intelligence to infer nuanced, individualized causal effects from complex data, paving the way for more precise and trustworthy AI systems in personalized medicine, adaptive policy design, and fundamental scientific discovery.

-- Current medical language models, adapted from large language models (LLMs), typically predict ICD code - based diagnosis from electronic health records (EHRs) because these labels are readily available. However, ICD codes do not capture the nuanced, context - rich reasoning clinicians use for diagnosis. Clinicians synthesize diverse patient data and reference clinical practice guidelines (CPGs) to make evidence - based decisions. This misalignment limits the clinical utility of existing models. We introduce GARMLE - G, a Generation - Augmented Retrieval framework that grounds medical language model outp uts in authoritative CPGs. Unlike conventional Retrieval - Augmented Generation based approaches, GARMLE - G enables hallucination - free outputs by directly retrieving authoritative guideline content without relying on model - generated text. It (1) integrates LLM predictions with EHR data to create semantically rich queries, (2) retrieves relevant CPG knowledge snippets via embedding similarity, and (3) fuses guideline content with model output to generate clinically aligned recommendations. A prototype system for hypertension diagnosis was developed and evaluated on multiple metrics, demonstrating superior retrieval precision, semantic relevance, and clinical guideline adherence compared to RAG - based baselines, while maintaining a lightweight architecture suitable for localized healthcare deployment. This work provides a scalable, low - cost, and hallucination - free method for grounding medical language models in evidence - based clinical practice, with strong potential for broader clinical deployment. The research reported in this paper is financially supported by the National Natural Science Foundation of China (62276156), the project of Shandong Provincial Natural Science Foundation (ZR2024LZH005), the Taishan Scholar Program of Shandong Province of China (No.tsq nz20240809), and the Excellent Youth Foundation of Shandong Natural Science Foundation (2024HWYQ - 055). Wenhao Li is with Shandong Normal University, Jinan, China, 250358 (email: lwh@sdnu.edu.cn) Hongkuan Zhang is with Shandong Normal University, Jinan, China, 250358 (email: 2024217028@stu.sdnu.edu.cn) In the healthcare sector, language models and related tools, such as ChatGPT and ClinicalBERT, have been increasingly applied across multiple scenarios, including disease prediction, clinical decision support, patient interaction, drug discovery, and personalized medicine, significantly driving innovation and transformation in medical technology [1, 2] . As a fundamental task in healthcare, disease diagnosis refers to the process by which health professionals identify the most likely disease or disorder causing a patient's symptoms [3] .

This research presents a novel method for non-invasive arterial blood pressure (ABP) prediction using speech signals, employing a BERT -based regression model. Arterial blood pressure is a vital indicator of cardiovascular health, and accurate monitoring is essential in preventing hypertension-related complications. Traditional cuff-based methods often yield inconsistent results due to factors like white-coat and masked hypertension. Our approach leverages the acoustic characteristics of speech, capturing voice features to establish correlations with blood pressure levels. Utilizing advanced deep learning techniques, we analyze speech signals to extract relevant patterns, enabling real-time monitoring without the discomfort of conventional methods.

Generative artificial intelligence for synthetic data generation holds substantial potential to address practical challenges in epidemiology. However, many current methods suffer from limited quality, high computational demands, and complexity for non-experts. Furthermore, common evaluation strategies for synthetic data often fail to directly reflect statistical utility. Against this background, a critical underexplored question is whether synthetic data can reliably reproduce key findings from epidemiological research. We propose the use of adversarial random forests (ARF) as an efficient and convenient method for synthesizing tabular epidemiological data. To evaluate its performance, we replicated statistical analyses from six epidemiological publications and compared original with synthetic results. These publications cover blood pressure, anthropometry, myocardial infarction, accelerometry, loneliness, and diabetes, based on data from the German National Cohort (NAKO Gesundheitsstudie), the Bremen STEMI Registry U45 Study, and the Guelph Family Health Study. Additionally, we assessed the impact of dimensionality and variable complexity on synthesis quality by limiting datasets to variables relevant for individual analyses, including necessary derivations. Across all replicated original studies, results from multiple synthetic data replications consistently aligned with original findings. Even for datasets with relatively low sample size-to-dimensionality ratios, the replication outcomes closely matched the original results across various descriptive and inferential analyses. Reducing dimensionality and pre-deriving variables further enhanced both quality and stability of the results.

Urban greenery is often linked to better health, yet findings from past research have been inconsistent. One reason is that official greenery metrics measure the amount or nearness of greenery but ignore how often people actually may potentially see or use it in daily life. To address this gap, we introduced a new classification that separates on-road greenery, which people see while walking through streets, from off-road greenery, which requires planned visits. We did so by combining aerial imagery of Greater London and greenery data from OpenStreetMap with quantified greenery from over 100,000 Google Street View images and accessibility estimates based on 160,000 road segments. We linked these measures to 7.45 billion medical prescriptions issued by the National Health Service and processed through our methodology. These prescriptions cover five conditions: diabetes, hypertension, asthma, depression, and anxiety, as well as opioid use. As hypothesized, we found that green on-road was more strongly linked to better health than four widely used official measures. For example, hypertension prescriptions dropped by 3.68% in wards with on-road greenery above the median citywide level compared to those below it. If all below-median wards reached the citywide median in on-road greenery, prescription costs could fall by up to £3.15 million each year. These results suggest that greenery seen in daily life may be more relevant than public yet secluded greenery, and that official metrics commonly used in the literature have important limitations.

Modern disease classification often overlooks molecular commonalities hidden beneath divergent clinical presentations. This study introduces a transcriptomics-driven framework for discovering disease relationships by analyzing over 1300 disease-condition pairs using GenoMAS, a fully automated agentic AI system. Beyond identifying robust gene-level overlaps, we develop a novel pathway-based similarity framework that integrates multi-database enrichment analysis to quantify functional convergence across diseases. The resulting disease similarity network reveals both known comorbidities and previously undocumented cross-category links. By examining shared biological pathways, we explore potential molecular mechanisms underlying these connections-offering functional hypotheses that go beyond symptom-based taxonomies. We further show how background conditions such as obesity and hypertension modulate transcriptomic similarity, and identify therapeutic repurposing opportunities for rare diseases like autism spectrum disorder based on their molecular proximity to better-characterized conditions. In addition, this work demonstrates how biologically grounded agentic AI can scale transcriptomic analysis while enabling mechanistic interpretation across complex disease landscapes. All results are publicly accessible at github.com/KeeeeChen/Pathway_Similarity_Network.

Large language models (LLMs) have demonstrated remarkable capabilities for medical question answering and programming, but their potential for generating interpretable computable phenotypes (CPs) is under-explored. In this work, we investigate whether LLMs can generate accurate and concise CPs for six clinical phenotypes of varying complexity, which could be leveraged to enable scalable clinical decision support to improve care for patients with hypertension. In addition to evaluating zero-short performance, we propose and test a synthesize, execute, debug, instruct strategy that uses LLMs to generate and it-eratively refine CPs using data-driven feedback. Our results show that LLMs, coupled with iterative learning, can generate interpretable and reasonably accurate programs that approach the performance of state-of-the-art ML methods while requiring significantly fewer training examples.

--Retinal microvascular imaging is increasingly recognised as a non-invasive method for evaluating systemic vascular and metabolic health. However, the association between lipidomics and retinal vasculature remains inadequate. This study investigates the relationships between serum lipid subclasses, free fatty acids (F A), diacylglycerols (DAG), triacylglycerols (T AG), and cholesteryl esters (CE), and retinal microvascular characteristics in a large population-based cohort. Using Spearman correlation analysis, we examined the interconnection between lipid subclasses and ten retinal microvascular traits, applying the Benjamini-Hochberg false discovery rate (BH-FDR) to adjust for statistical significance. Results indicated that F A were linked to retinal vessel twisti-ness, while CE correlated with the average widths of arteries and veins. Conversely, DAG and T AG showed negative correlations with the width and complexity of arterioles and venules. These findings suggest that retinal vascular architecture reflects distinct circulating lipid profiles, supporting its role as a non-invasive marker of systemic metabolic health. This study is the first to integrate deep-learning (DL)-derived retinal traits with lipidomic subclasses in a healthy cohort, thereby providing insights into microvascular structural changes independent of disease status or treatment effects.

Background: Hypertensive kidney disease (HKD) patients in intensive care units (ICUs) face high short-term mortality, but tailored risk prediction tools are lacking. Early identification of high-risk individuals is crucial for clinical decision-making. Methods: We developed a machine learning framework to predict 30-day in-hospital mortality among ICU patients with HKD using early clinical data from the MIMIC-IV v2.2 database. A cohort of 1,366 adults was curated with strict criteria, excluding malignancy cases. Eighteen clinical features-including vital signs, labs, comorbidities, and therapies-were selected via random forest importance and mutual information filtering. Several models were trained and compared with stratified five-fold cross-validation; CatBoost demonstrated the best performance. Results: CatBoost achieved an AUROC of 0.88 on the independent test set, with sensitivity of 0.811 and specificity of 0.798. SHAP values and Accumulated Local Effects (ALE) plots showed the model relied on meaningful predictors such as altered consciousness, vasopressor use, and coagulation status. Additionally, the DREAM algorithm was integrated to estimate patient-specific posterior risk distributions, allowing clinicians to assess both predicted mortality and its uncertainty. Conclusions: We present an interpretable machine learning pipeline for early, real-time risk assessment in ICU patients with HKD. By combining high predictive performance with uncertainty quantification, our model supports individualized triage and transparent clinical decisions. This approach shows promise for clinical deployment and merits external validation in broader critical care populations.

Methods: We developed a self-supervised deep learning model that extracts meaningful patterns from multi-modal signals (Electroencephalography (EEG), Electrocardiography (ECG), and respiratory signals). The model was trained on data from 4,398 participants. Projection scores were derived by contrasting embeddings from individuals with and without CVD outcomes. External validation was conducted in an independent cohort with 1,093 participants. The source code is available on https://github.com/miraclehetech/sleep-ssl. Results: The projection scores revealed distinct and clinically meaningful patterns across modalities. ECG-derived features were predictive of both prevalent and incident cardiac conditions, particularly CVD mortality. EEG-derived features were predictive of incident hypertension and CVD mortality. Respiratory signals added complementary predictive value. Combining these projection scores with the Framingham Risk Score consistently improved predictive performance, achieving area under the curve values ranging from 0.607 to 0.965 across different outcomes. Findings were robustly replicated and validated in the external testing cohort. Conclusion: Our findings demonstrate that the proposed framework can generate individualized CVD risk scores directly from PSG data. The resulting projection scores have the potential to be integrated into clinical practice, enhancing risk assessment and supporting personalized care.