Daily Papers

Retinal imaging has emerged as a powerful, non-invasive modality for detecting and quantifying biomarkers of systemic diseases-ranging from diabetes and hypertension to Alzheimer's disease and cardiovascular disorders but current insights remain dispersed across platforms and specialties. Recent technological advances in optical coherence tomography (OCT/OCTA) and adaptive optics (AO) now deliver ultra-high-resolution scans (down to 5 {\mu}m ) with superior contrast and spatial integration, allowing early identification of microvascular abnormalities and neurodegenerative changes. At the same time, AI-driven and machine learning (ML) algorithms have revolutionized the analysis of large-scale retinal datasets, increasing sensitivity and specificity; for example, deep learning models achieve > 90 \% sensitivity for diabetic retinopathy and AUC = 0.89 for the prediction of cardiovascular risk from fundus photographs. The proliferation of mobile health technologies and telemedicine platforms further extends access, reduces costs, and facilitates community-based screening and longitudinal monitoring. Despite these breakthroughs, translation into routine practice is hindered by heterogeneous imaging protocols, limited external validation of AI models, and integration challenges within clinical workflows. In this review, we systematically synthesize the latest OCT/OCT and AO developments, AI/ML approaches, and mHealth/Tele-ophthalmology initiatives and quantify their diagnostic performance across disease domains. Finally, we propose a roadmap for multicenter protocol standardization, prospective validation trials, and seamless incorporation of retinal screening into primary and specialty care pathways-paving the way for precision prevention, early intervention, and ongoing treatment of life-threatening systemic diseases.

Biologically-informed neural networks typically leverage pathway annotations to enhance performance in biomedical applications. We hypothesized that the benefits of pathway integration does not arise from its biological relevance, but rather from the sparsity it introduces. We conducted a comprehensive analysis of all relevant pathway-based neural network models for predictive tasks, critically evaluating each study's contributions. From this review, we curated a subset of methods for which the source code was publicly available. The comparison of the biologically informed state-of-the-art deep learning models and their randomized counterparts showed that models based on randomized information performed equally well as biologically informed ones across different metrics and datasets. Notably, in 3 out of the 15 analyzed models, the randomized versions even outperformed their biologically informed counterparts. Moreover, pathway-informed models did not show any clear advantage in interpretability, as randomized models were still able to identify relevant disease biomarkers despite lacking explicit pathway information. Our findings suggest that pathway annotations may be too noisy or inadequately explored by current methods. Therefore, we propose a methodology that can be applied to different domains and can serve as a robust benchmark for systematically comparing novel pathway-informed models against their randomized counterparts. This approach enables researchers to rigorously determine whether observed performance improvements can be attributed to biological insights.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that primarily affects the aging population by impairing cognitive and motor functions. Early detection of AD through accessible methodologies like magnetic resonance imaging (MRI) is vital for developing effective interventions to halt or slow the disease's progression. This study aims to perform a comprehensive analysis of machine learning techniques for selecting MRI-based biomarkers and classifying individuals into healthy controls (HC) and unstable controls (uHC) who later show mild cognitive impairment within five years. The research utilizes MRI data from the Alzheimer's Disease Neuroinformatics Initiative (ADNI) and the Open Access Series of Imaging Studies 3 (OASIS-3), focusing on both HC and uHC participants. The study addresses the challenges of imbalanced data by testing classification methods on balanced and unbalanced datasets, and harmonizes data using polynomial regression to mitigate nuisance variables like age, gender, and intracranial volume. Results indicate that Gaussian Naive Bayes and RusBoost classifiers shows an optimal performance, achieving accuracies of up to 76.46% and 72.48% respectively on the ADNI dataset. For the OASIS-3 dataset, Kernel Naive Bayes and RusBoost yield accuracies ranging from 64.66% to 75.71%, improving further in age-matched datasets. Brain regions like the entorhinal cortex, hippocampus, lateral ventricle, and lateral orbitofrontal cortex are identified as significantly impacted during early cognitive decline. Despite limitations such as small sample sizes, the study's harmonization approach enhances the robustness of biomarker selection, suggesting the potential of this semi-automatic machine learning pipeline for early AD detection using MRI.

Parkinsons disease (PD) alters cortical neural dynamics, yet reliable non-invasive electrophysiological biomarkers remain elusive. This study examined whether interpretable EEG features capturing complementary aspects of neural dynamics can discriminate Parkinsonian neural states. A comprehensive set of interpretable features was extracted and grouped into Standard descriptors (spectral power, phase synchronization, time-domain statistics) and Dynamical descriptors (aperiodic activity, cross-frequency coupling, scale-free dynamics, neuronal avalanche statistics, and instantaneous frequency measures). A multi-head attention transformer classifier was trained using strict LOSO validation. Group-level comparisons were performed to identify electrophysiological differences associated with disease and medication state. Standard feature sets achieved strongest performance in discriminating medication states (PDoff vs PDon), whereas Dynamical performed competitively in contrasts between PD patients and healthy controls. Random feature ablation analyses indicated that Dynamical descriptors provide complementary information distributed across features while correlation analysis revealed low redundancy within both feature sets. Group-level comparisons revealed medication-sensitive reductions in delta power and voltage variance, modulation of neuronal avalanche statistics, persistent increases in theta phase synchronization in PD patients, and disease-related alterations in cross-frequency interactions. Traditional spectral and synchronization features primarily reflect medication-related neural modulation, whereas dynamical descriptors reveal broader alterations in cortical network organization associated with disease but also with medication. These findings support multivariate EEG representations as a promising framework for developing non-invasive biomarkers of PD.

We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of biomarkers. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.

Accurate diagnosis of Alzheimer's disease (AD) requires handling tabular biomarker data, yet such data are often small and incomplete, where deep learning models frequently fail to outperform classical methods. Pretrained large language models (LLMs) offer few-shot generalization, structured reasoning, and interpretable outputs, providing a powerful paradigm shift for clinical prediction. We propose TAP-GPT Tabular Alzheimer's Prediction GPT, a domain-adapted tabular LLM framework built on TableGPT2 and fine-tuned for few-shot AD classification using tabular prompts rather than plain texts. We evaluate TAP-GPT across four ADNI-derived datasets, including QT-PAD biomarkers and region-level structural MRI, amyloid PET, and tau PET for binary AD classification. Across multimodal and unimodal settings, TAP-GPT improves upon its backbone models and outperforms traditional machine learning baselines in the few-shot setting while remaining competitive with state-of-the-art general-purpose LLMs. We show that feature selection mitigates degradation in high-dimensional inputs and that TAP-GPT maintains stable performance under simulated and real-world missingness without imputation. Additionally, TAP-GPT produces structured, modality-aware reasoning aligned with established AD biology and shows greater stability under self-reflection, supporting its use in iterative multi-agent systems. To our knowledge, this is the first systematic application of a tabular-specialized LLM to multimodal biomarker-based AD prediction, demonstrating that such pretrained models can effectively address structured clinical prediction tasks and laying the foundation for tabular LLM-driven multi-agent clinical decision-support systems. The source code is publicly available on GitHub: https://github.com/sophie-kearney/TAP-GPT.

Chagas disease screening via ECGs is limited by scarce and noisy labels in existing datasets. We propose a biomarker-based pretraining approach, where an ECG feature extractor is first trained to predict percentile-binned blood biomarkers from the MIMIC-IV-ECG dataset. The pretrained model is then fine-tuned on Brazilian datasets for Chagas detection. Our 5-model ensemble, developed by the Ahus AIM team, achieved a challenge score of 0.269 on the hidden test set, ranking 5th in Detection of Chagas Disease from the ECG: The George B. Moody PhysioNet Challenge 2025. Source code and the model are shared on GitHub: github.com/Ahus-AIM/physionet-challenge-2025

Alzheimer's Disease (AD) is the most common form of dementia and often difficult to diagnose due to the multifactorial etiology of dementia. Recent works on neuroimaging-based computer-aided diagnosis with deep neural networks (DNNs) showed that fusing structural magnetic resonance images (sMRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) leads to improved accuracy in a study population of healthy controls and subjects with AD. However, this result conflicts with the established clinical knowledge that FDG-PET better captures AD-specific pathologies than sMRI. Therefore, we propose a framework for the systematic evaluation of multi-modal DNNs and critically re-evaluate single- and multi-modal DNNs based on FDG-PET and sMRI for binary healthy vs. AD, and three-way healthy/mild cognitive impairment/AD classification. Our experiments demonstrate that a single-modality network using FDG-PET performs better than MRI (accuracy 0.91 vs 0.87) and does not show improvement when combined. This conforms with the established clinical knowledge on AD biomarkers, but raises questions about the true benefit of multi-modal DNNs. We argue that future work on multi-modal fusion should systematically assess the contribution of individual modalities following our proposed evaluation framework. Finally, we encourage the community to go beyond healthy vs. AD classification and focus on differential diagnosis of dementia, where fusing multi-modal image information conforms with a clinical need.

Alongside neuroimaging such as MRI scans and PET, Alzheimer's disease (AD) datasets contain valuable tabular data including AD biomarkers and clinical assessments. Existing computer vision approaches struggle to utilize this additional information. To address these needs, we propose a generalizable framework for multimodal contrastive learning of image data and tabular data, a novel tabular attention module for amplifying and ranking salient features in tables, and the application of these techniques onto Alzheimer's disease prediction. Experimental evaulations demonstrate the strength of our framework by detecting Alzheimer's disease (AD) from over 882 MR image slices from the ADNI database. We take advantage of the high interpretability of tabular data and our novel tabular attention approach and through attribution of the attention scores for each row of the table, we note and rank the most predominant features. Results show that the model is capable of an accuracy of over 83.8%, almost a 10% increase from previous state of the art.

Accurate prediction of knee osteoarthritis (KOA) progression from structural MRI has a potential to enhance disease understanding and support clinical trials. Prior art focused on manually designed imaging biomarkers, which may not fully exploit all disease-related information present in MRI scan. In contrast, our method learns relevant representations from raw data end-to-end using Deep Learning, and uses them for progression prediction. The method employs a 2D CNN to process the data slice-wise and aggregate the extracted features using a Transformer. Evaluated on a large cohort (n=4,866), the proposed method outperforms conventional 2D and 3D CNN-based models and achieves average precision of 0.58pm0.03 and ROC AUC of 0.78pm0.01. This paper sets a baseline on end-to-end KOA progression prediction from structural MRI. Our code is publicly available at https://github.com/MIPT-Oulu/OAProgressionMR.

Clinical diagnosis of the eye is performed over multifarious data modalities including scalar clinical labels, vectorized biomarkers, two-dimensional fundus images, and three-dimensional Optical Coherence Tomography (OCT) scans. Clinical practitioners use all available data modalities for diagnosing and treating eye diseases like Diabetic Retinopathy (DR) or Diabetic Macular Edema (DME). Enabling usage of machine learning algorithms within the ophthalmic medical domain requires research into the relationships and interactions between all relevant data over a treatment period. Existing datasets are limited in that they neither provide data nor consider the explicit relationship modeling between the data modalities. In this paper, we introduce the Ophthalmic Labels for Investigating Visual Eye Semantics (OLIVES) dataset that addresses the above limitation. This is the first OCT and near-IR fundus dataset that includes clinical labels, biomarker labels, disease labels, and time-series patient treatment information from associated clinical trials. The dataset consists of 1268 near-IR fundus images each with at least 49 OCT scans, and 16 biomarkers, along with 4 clinical labels and a disease diagnosis of DR or DME. In total, there are 96 eyes' data averaged over a period of at least two years with each eye treated for an average of 66 weeks and 7 injections. We benchmark the utility of OLIVES dataset for ophthalmic data as well as provide benchmarks and concrete research directions for core and emerging machine learning paradigms within medical image analysis.

A knowledge gap persists between machine learning (ML) developers (e.g., data scientists) and practitioners (e.g., clinicians), hampering the full utilization of ML for clinical data analysis. We investigated the potential of the ChatGPT Advanced Data Analysis (ADA), an extension of GPT-4, to bridge this gap and perform ML analyses efficiently. Real-world clinical datasets and study details from large trials across various medical specialties were presented to ChatGPT ADA without specific guidance. ChatGPT ADA autonomously developed state-of-the-art ML models based on the original study's training data to predict clinical outcomes such as cancer development, cancer progression, disease complications, or biomarkers such as pathogenic gene sequences. Following the re-implementation and optimization of the published models, the head-to-head comparison of the ChatGPT ADA-crafted ML models and their respective manually crafted counterparts revealed no significant differences in traditional performance metrics (P>0.071). Strikingly, the ChatGPT ADA-crafted ML models often outperformed their counterparts. In conclusion, ChatGPT ADA offers a promising avenue to democratize ML in medicine by simplifying complex data analyses, yet should enhance, not replace, specialized training and resources, to promote broader applications in medical research and practice.

Immunotherapy is an effective precision medicine treatment for several cancers. Imaging signatures of the underlying genome (radiogenomics) in glioblastoma patients may serve as preoperative biomarkers of the tumor-host immune apparatus. Validated biomarkers would have the potential to stratify patients during immunotherapy clinical trials, and if trials are beneficial, facilitate personalized neo-adjuvant treatment. The increased use of whole genome sequencing data, and the advances in bioinformatics and machine learning make such developments plausible. We performed a systematic review to determine the extent of development and validation of immune-related radiogenomic biomarkers for glioblastoma. A systematic review was performed following PRISMA guidelines using the PubMed, Medline, and Embase databases. Qualitative analysis was performed by incorporating the QUADAS 2 tool and CLAIM checklist. PROSPERO registered CRD42022340968. Extracted data were insufficiently homogenous to perform a meta-analysis. Results Nine studies, all retrospective, were included. Biomarkers extracted from magnetic resonance imaging volumes of interest included apparent diffusion coefficient values, relative cerebral blood volume values, and image-derived features. These biomarkers correlated with genomic markers from tumor cells or immune cells or with patient survival. The majority of studies had a high risk of bias and applicability concerns regarding the index test performed. Radiogenomic immune biomarkers have the potential to provide early treatment options to patients with glioblastoma. Targeted immunotherapy, stratified by these biomarkers, has the potential to allow individualized neo-adjuvant precision treatment options in clinical trials. However, there are no prospective studies validating these biomarkers, and interpretation is limited due to study bias with little evidence of generalizability.

The prevalence of vision-threatening eye diseases is a significant global burden, with many cases remaining undiagnosed or diagnosed too late for effective treatment. Large vision-language models (LVLMs) have the potential to assist in understanding anatomical information, diagnosing eye diseases, and drafting interpretations and follow-up plans, thereby reducing the burden on clinicians and improving access to eye care. However, limited benchmarks are available to assess LVLMs' performance in ophthalmology-specific applications. In this study, we introduce LMOD, a large-scale multimodal ophthalmology benchmark consisting of 21,993 instances across (1) five ophthalmic imaging modalities: optical coherence tomography, color fundus photographs, scanning laser ophthalmoscopy, lens photographs, and surgical scenes; (2) free-text, demographic, and disease biomarker information; and (3) primary ophthalmology-specific applications such as anatomical information understanding, disease diagnosis, and subgroup analysis. In addition, we benchmarked 13 state-of-the-art LVLM representatives from closed-source, open-source, and medical domains. The results demonstrate a significant performance drop for LVLMs in ophthalmology compared to other domains. Systematic error analysis further identified six major failure modes: misclassification, failure to abstain, inconsistent reasoning, hallucination, assertions without justification, and lack of domain-specific knowledge. In contrast, supervised neural networks specifically trained on these tasks as baselines demonstrated high accuracy. These findings underscore the pressing need for benchmarks in the development and validation of ophthalmology-specific LVLMs.

Retinal imaging is fast, non-invasive, and widely available, offering quantifiable structural and vascular signals for ophthalmic and systemic health assessment. This accessibility creates an opportunity to study how quantitative retinal phenotypes relate to ocular and systemic diseases. However, such analyses remain difficult at scale due to the limited availability of public multi-label datasets and the lack of a unified segmentation-to-quantification pipeline. We present RetSAM, a general retinal segmentation and quantification framework for fundus imaging. It delivers robust multi-target segmentation and standardized biomarker extraction, supporting downstream ophthalmologic studies and oculomics correlation analyses. Trained on over 200,000 fundus images, RetSAM supports three task categories and segments five anatomical structures, four retinal phenotypic patterns, and more than 20 distinct lesion types. It converts these segmentation results into over 30 standardized biomarkers that capture structural morphology, vascular geometry, and degenerative changes. Trained with a multi-stage strategy using both private and public fundus data, RetSAM achieves superior segmentation performance on 17 public datasets. It improves on prior best methods by 3.9 percentage points in DSC on average, with up to 15 percentage points on challenging multi-task benchmarks, and generalizes well across diverse populations, imaging devices, and clinical settings. The resulting biomarkers enable systematic correlation analyses across major ophthalmic diseases, including diabetic retinopathy, age-related macular degeneration, glaucoma, and pathologic myopia. Together, RetSAM transforms fundus images into standardized, interpretable quantitative phenotypes, enabling large-scale ophthalmic research and translation.

Understanding the biological mechanism of disease is critical for medicine, and in particular drug discovery. AI-powered analysis of genome-scale biological data hold great potential in this regard. The increasing availability of single-cell RNA sequencing data has enabled the development of large foundation models for disease biology. However, existing foundation models either do not improve or only modestly improve over task-specific models in downstream applications. Here, we explored two avenues for improving the state-of-the-art. First, we scaled the pre-training dataset to 116 million cells, which is larger than those used by previous models. Second, we leveraged the availability of large-scale biological annotations as a form of supervision during pre-training. We trained the TEDDY family of models comprising six transformer-based state-of-the-art single-cell foundation models with 70 million, 160 million, and 400 million parameters. We vetted our models on two downstream evaluation tasks -- identifying the underlying disease state of held-out donors not seen during training and distinguishing healthy cells from diseased ones for disease conditions and donors not seen during training. Scaling experiments showed that performance improved predictably with both data volume and parameter count. Our models showed substantial improvement over existing work on the first task and more muted improvements on the second.

Scientific discovery in digital health requires converting continuous physiological signals from wearable devices into clinically actionable biomarkers. We introduce CoDaS (AI Co-Data-Scientist), a multi-agent system that structures biomarker discovery as an iterative process combining hypothesis generation, statistical analysis, adversarial validation, and literature-grounded reasoning with human oversight using large-scale wearable datasets. Across three cohorts totaling 9,279 participant-observations, CoDaS identified 41 candidate digital biomarkers for mental health and 25 for metabolic outcomes, each subjected to an internal validation battery spanning replication, stability, robustness, and discriminative power. Across two independent depression cohorts, CoDaS surfaced circadian instability-related features in both datasets, reflected in sleep duration variability (DWB, ρ= 0.252, p < 0.001) and sleep onset variability (GLOBEM, ρ= 0.126, p < 0.001). In a metabolic cohort, CoDaS derived a cardiovascular fitness index (steps/resting heart rate; ρ= -0.374, p < 0.001), and recovered established clinical associations, including the hepatic function ratio (AST/ALT; ρ= -0.375, p < 0.001), a known correlate of insulin resistance. Incorporating CoDaS-derived features alongside demographic variables led to modest but consistent improvements in predictive performance, with cross-validated ΔR^2 increases of 0.040 for depression and 0.021 for insulin resistance. These findings suggest that CoDaS enables systematic and traceable hypothesis generation and prioritization for biomarker discovery from large-scale wearable data.

Metadata are general characteristics of the data in a well-curated and condensed format, and have been proven to be useful for decision making, knowledge discovery, and also heterogeneous data organization of biobank. Among all data types in the biobank, pathology is the key component of the biobank and also serves as the gold standard of diagnosis. To maximize the utility of biobank and allow the rapid progress of biomedical science, it is essential to organize the data with well-populated pathology metadata. However, manual annotation of such information is tedious and time-consuming. In the study, we develop a multimodal multitask learning framework to predict four major slide-level metadata of pathology images. The framework learns generalizable representations across tissue slides, pathology reports, and case-level structured data. We demonstrate improved performance across all four tasks with the proposed method compared to a single modal single task baseline on two test sets, one external test set from a distinct data source (TCGA) and one internal held-out test set (TTH). In the test sets, the performance improvements on the averaged area under receiver operating characteristic curve across the four tasks are 16.48% and 9.05% on TCGA and TTH, respectively. Such pathology metadata prediction system may be adopted to mitigate the effort of expert annotation and ultimately accelerate the data-driven research by better utilization of the pathology biobank.

Heart disease, also known as cardiovascular disease, is a prevalent and critical medical condition characterized by the impairment of the heart and blood vessels, leading to various complications such as coronary artery disease, heart failure, and myocardial infarction. The timely and accurate detection of heart disease is of paramount importance in clinical practice. Early identification of individuals at risk enables proactive interventions, preventive measures, and personalized treatment strategies to mitigate the progression of the disease and reduce adverse outcomes. In recent years, the field of heart disease detection has witnessed notable advancements due to the integration of sophisticated technologies and computational approaches. These include machine learning algorithms, data mining techniques, and predictive modeling frameworks that leverage vast amounts of clinical and physiological data to improve diagnostic accuracy and risk stratification. In this work, we propose to detect heart disease from ECG images using cutting-edge technologies, namely vision transformer models. These models are Google-Vit, Microsoft-Beit, and Swin-Tiny. To the best of our knowledge, this is the initial endeavor concentrating on the detection of heart diseases through image-based ECG data by employing cuttingedge technologies namely, transformer models. To demonstrate the contribution of the proposed framework, the performance of vision transformer models are compared with state-of-the-art studies. Experiment results show that the proposed framework exhibits remarkable classification results.

Accurate prediction of biochemical recurrence (BCR) after radical prostatectomy is critical for guiding adjuvant treatment and surveillance decisions in prostate cancer. However, existing clinicopathological risk models reduce complex morphology to relatively coarse descriptors, leaving substantial prognostic information embedded in routine histopathology underexplored. We present a deep learning-based biomarker that predicts continuous, patient-specific risk of BCR directly from H&E-stained whole-slide prostatectomy specimens. Trained end-to-end on time-to-event outcomes and evaluated across four independent international cohorts, our model demonstrates robust generalization across institutions and patient populations. When integrated with the CAPRA-S clinical risk score, the deep learning risk score consistently improved discrimination for BCR, increasing concordance indices from 0.725-0.772 to 0.749-0.788 across cohorts. To support clinical interpretability, outcome-grounded analyses revealed subtle histomorphological patterns associated with recurrence risk that are not captured by conventional clinicopathological risk scores. This multicohort study demonstrates that deep learning applied to routine prostate histopathology can deliver reproducible and clinically generalizable biomarkers that augment postoperative risk stratification, with potential to support personalized management of prostate cancer in real-world clinical settings.

In recent years, Deep Learning (DL) models are becoming important due to their demonstrated success at overcoming complex learning problems. DL models have been applied effectively for different Natural Language Processing (NLP) tasks such as part-of-Speech (PoS) tagging and Machine Translation (MT). Disease Named Entity Recognition (Disease-NER) is a crucial task which aims at extracting disease Named Entities (NEs) from text. In this paper, a DL model for Disease-NER using dictionary information is proposed and evaluated on National Center for Biotechnology Information (NCBI) disease corpus and BC5CDR dataset. Word embeddings trained over general domain texts as well as biomedical texts have been used to represent input to the proposed model. This study also compares two different Segment Representation (SR) schemes, namely IOB2 and IOBES for Disease-NER. The results illustrate that using dictionary information, pre-trained word embeddings, character embeddings and CRF with global score improves the performance of Disease-NER system.

Introduction: Blood vessels can be non-invasively visualized from a digital fundus image (DFI). Several studies have shown an association between cardiovascular risk and vascular features obtained from DFI. Recent advances in computer vision and image segmentation enable automatising DFI blood vessel segmentation. There is a need for a resource that can automatically compute digital vasculature biomarkers (VBM) from these segmented DFI. Methods: In this paper, we introduce a Python Vasculature BioMarker toolbox, denoted PVBM. A total of 11 VBMs were implemented. In particular, we introduce new algorithmic methods to estimate tortuosity and branching angles. Using PVBM, and as a proof of usability, we analyze geometric vascular differences between glaucomatous patients and healthy controls. Results: We built a fully automated vasculature biomarker toolbox based on DFI segmentations and provided a proof of usability to characterize the vascular changes in glaucoma. For arterioles and venules, all biomarkers were significant and lower in glaucoma patients compared to healthy controls except for tortuosity, venular singularity length and venular branching angles. Conclusion: We have automated the computation of 11 VBMs from retinal blood vessel segmentation. The PVBM toolbox is made open source under a GNU GPL 3 license and is available on physiozoo.com (following publication).

Background Precise prediction of cancer types is vital for cancer diagnosis and therapy. Important cancer marker genes can be inferred through predictive model. Several studies have attempted to build machine learning models for this task however none has taken into consideration the effects of tissue of origin that can potentially bias the identification of cancer markers. Results In this paper, we introduced several Convolutional Neural Network (CNN) models that take unstructured gene expression inputs to classify tumor and non-tumor samples into their designated cancer types or as normal. Based on different designs of gene embeddings and convolution schemes, we implemented three CNN models: 1D-CNN, 2D-Vanilla-CNN, and 2D-Hybrid-CNN. The models were trained and tested on combined 10,340 samples of 33 cancer types and 731 matched normal tissues of The Cancer Genome Atlas (TCGA). Our models achieved excellent prediction accuracies (93.9-95.0%) among 34 classes (33 cancers and normal). Furthermore, we interpreted one of the models, known as 1D-CNN model, with a guided saliency technique and identified a total of 2,090 cancer markers (108 per class). The concordance of differential expression of these markers between the cancer type they represent and others is confirmed. In breast cancer, for instance, our model identified well-known markers, such as GATA3 and ESR1. Finally, we extended the 1D-CNN model for prediction of breast cancer subtypes and achieved an average accuracy of 88.42% among 5 subtypes. The codes can be found at https://github.com/chenlabgccri/CancerTypePrediction.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the leading cause of dementia, significantly impacting cost, mortality, and burden worldwide. The advent of high-throughput omics technologies, such as genomics, transcriptomics, proteomics, and epigenomics, has revolutionized the molecular understanding of AD. Conventional AI approaches typically require the completion of all omics data at the outset to achieve optimal AD diagnosis, which are inefficient and may be unnecessary. To reduce the clinical cost and improve the accuracy of AD diagnosis using multi-omics data, we propose a novel staged graph convolutional network with uncertainty quantification (SGUQ). SGUQ begins with mRNA and progressively incorporates DNA methylation and miRNA data only when necessary, reducing overall costs and exposure to harmful tests. Experimental results indicate that 46.23% of the samples can be reliably predicted using only single-modal omics data (mRNA), while an additional 16.04% of the samples can achieve reliable predictions when combining two omics data types (mRNA + DNA methylation). In addition, the proposed staged SGUQ achieved an accuracy of 0.858 on ROSMAP dataset, which outperformed existing methods significantly. The proposed SGUQ can not only be applied to AD diagnosis using multi-omics data but also has the potential for clinical decision-making using multi-viewed data. Our implementation is publicly available at https://github.com/chenzhao2023/multiomicsuncertainty.

Large language models (LLMs) offer a promising pre-screening tool, improving early disease detection and providing enhanced healthcare access for underprivileged communities. The early diagnosis of various diseases continues to be a significant challenge in healthcare, primarily due to the nonspecific nature of early symptoms, the shortage of expert medical practitioners, and the need for prolonged clinical evaluations, all of which can delay treatment and adversely affect patient outcomes. With impressive accuracy in prediction across a range of diseases, LLMs have the potential to revolutionize clinical pre-screening and decision-making for various medical conditions. In this work, we study the diagnostic capability of LLMs for Rheumatoid Arthritis (RA) with real world patients data. Patient data was collected alongside diagnoses from medical experts, and the performance of LLMs was evaluated in comparison to expert diagnoses for RA disease prediction. We notice an interesting pattern in disease diagnosis and find an unexpected misalignment between prediction and explanation. We conduct a series of multi-round analyses using different LLM agents. The best-performing model accurately predicts rheumatoid arthritis (RA) diseases approximately 95\% of the time. However, when medical experts evaluated the reasoning generated by the model, they found that nearly 68\% of the reasoning was incorrect. This study highlights a clear misalignment between LLMs high prediction accuracy and its flawed reasoning, raising important questions about relying on LLM explanations in clinical settings. LLMs provide incorrect reasoning to arrive at the correct answer for RA disease diagnosis.

Speech patterns have been identified as potential diagnostic markers for neuropsychiatric conditions. However, most studies only compare a single clinical group to healthy controls, whereas clinical practice often requires differentiating between multiple potential diagnoses (multiclass settings). To address this, we assembled a dataset of repeated recordings from 420 participants (67 with major depressive disorder, 106 with schizophrenia and 46 with autism, as well as matched controls), and tested the performance of a range of conventional machine learning models and advanced Transformer models on both binary and multiclass classification, based on voice and text features. While binary models performed comparably to previous research (F1 scores between 0.54-0.75 for autism spectrum disorder, ASD; 0.67-0.92 for major depressive disorder, MDD; and 0.71-0.83 for schizophrenia); when differentiating between multiple diagnostic groups performance decreased markedly (F1 scores between 0.35-0.44 for ASD, 0.57-0.75 for MDD, 0.15-0.66 for schizophrenia, and 0.38-0.52 macro F1). Combining voice and text-based models yielded increased performance, suggesting that they capture complementary diagnostic information. Our results indicate that models trained on binary classification may learn to rely on markers of generic differences between clinical and non-clinical populations, or markers of clinical features that overlap across conditions, rather than identifying markers specific to individual conditions. We provide recommendations for future research in the field, suggesting increased focus on developing larger transdiagnostic datasets that include more fine-grained clinical features, and that can support the development of models that better capture the complexity of neuropsychiatric conditions and naturalistic diagnostic assessment.

In recent years, there is strong emphasis on mining medical data using machine learning techniques. A common problem is to obtain a noiseless set of textual documents, with a relevant content for the research question, and developing a Question Answering (QA) model for a specific medical field. The purpose of this paper is to present a new methodology for building a medical dataset and obtain a QA model for analysis of symptoms and impact on daily life for a specific disease domain. The ``Mental Health'' forum was used, a forum dedicated to people suffering from schizophrenia and different mental disorders. Relevant posts of active users, who regularly participate, were extrapolated providing a new method of obtaining low-bias content and without privacy issues. Furthermore, it is shown how to pre-process the dataset to convert it into a QA dataset. The Bidirectional Encoder Representations from Transformers (BERT), DistilBERT, RoBERTa, and BioBERT models were fine-tuned and evaluated via F1-Score, Exact Match, Precision and Recall. Accurate empirical experiments demonstrated the effectiveness of the proposed method for obtaining an accurate dataset for QA model implementation. By fine-tuning the BioBERT QA model, we achieved an F1 score of 0.885, showing a considerable improvement and outperforming the state-of-the-art model for mental disorders domain.

Early detection of retinal diseases is one of the most important means of preventing partial or permanent blindness in patients. In this research, a novel multi-label classification system is proposed for the detection of multiple retinal diseases, using fundus images collected from a variety of sources. First, a new multi-label retinal disease dataset, the MuReD dataset, is constructed, using a number of publicly available datasets for fundus disease classification. Next, a sequence of post-processing steps is applied to ensure the quality of the image data and the range of diseases, present in the dataset. For the first time in fundus multi-label disease classification, a transformer-based model optimized through extensive experimentation is used for image analysis and decision making. Numerous experiments are performed to optimize the configuration of the proposed system. It is shown that the approach performs better than state-of-the-art works on the same task by 7.9% and 8.1% in terms of AUC score for disease detection and disease classification, respectively. The obtained results further support the potential applications of transformer-based architectures in the medical imaging field.

Machine learning has emerged as a powerful tool for scientific discovery, enabling researchers to extract meaningful insights from complex datasets. For instance, it has facilitated the identification of disease-predictive genes from gene expression data, significantly advancing healthcare. However, the traditional process for analyzing such datasets demands substantial human effort and expertise for the data selection, processing, and analysis. To address this challenge, we introduce a novel framework, a Team of AI-made Scientists (TAIS), designed to streamline the scientific discovery pipeline. TAIS comprises simulated roles, including a project manager, data engineer, and domain expert, each represented by a Large Language Model (LLM). These roles collaborate to replicate the tasks typically performed by data scientists, with a specific focus on identifying disease-predictive genes. Furthermore, we have curated a benchmark dataset to assess TAIS's effectiveness in gene identification, demonstrating our system's potential to significantly enhance the efficiency and scope of scientific exploration. Our findings represent a solid step towards automating scientific discovery through large language models.

Imaging features of knee articular cartilage have been shown to be potential imaging biomarkers for knee osteoarthritis. Despite recent methodological advancements in image analysis techniques like image segmentation, registration, and domain-specific image computing algorithms, only a few works focus on building fully automated pipelines for imaging feature extraction. In this study, we developed a deep-learning-based medical image analysis application for knee cartilage morphometrics, CartiMorph Toolbox (CMT). We proposed a 2-stage joint template learning and registration network, CMT-reg. We trained the model using the OAI-ZIB dataset and assessed its performance in template-to-image registration. The CMT-reg demonstrated competitive results compared to other state-of-the-art models. We integrated the proposed model into an automated pipeline for the quantification of cartilage shape and lesion (full-thickness cartilage loss, specifically). The toolbox provides a comprehensive, user-friendly solution for medical image analysis and data visualization. The software and models are available at https://github.com/YongchengYAO/CMT-AMAI24paper .

Disease risk prediction has attracted increasing attention in the field of modern healthcare, especially with the latest advances in artificial intelligence (AI). Electronic health records (EHRs), which contain heterogeneous patient information, are widely used in disease risk prediction tasks. One challenge of applying AI models for risk prediction lies in generating interpretable evidence to support the prediction results while retaining the prediction ability. In order to address this problem, we propose the method of jointly embedding words and labels whereby attention modules learn the weights of words from medical notes according to their relevance to the names of risk prediction labels. This approach boosts interpretability by employing an attention mechanism and including the names of prediction tasks in the model. However, its application is only limited to the handling of textual inputs such as medical notes. In this paper, we propose a label dependent attention model LDAM to 1) improve the interpretability by exploiting Clinical-BERT (a biomedical language model pre-trained on a large clinical corpus) to encode biomedically meaningful features and labels jointly; 2) extend the idea of joint embedding to the processing of time-series data, and develop a multi-modal learning framework for integrating heterogeneous information from medical notes and time-series health status indicators. To demonstrate our method, we apply LDAM to the MIMIC-III dataset to predict different disease risks. We evaluate our method both quantitatively and qualitatively. Specifically, the predictive power of LDAM will be shown, and case studies will be carried out to illustrate its interpretability.

Deep Learning (DL) in neuroimaging has become increasingly relevant for detecting neurological conditions and neurodegenerative disorders. One of the most predominant biomarkers in neuroimaging is represented by brain age, which has been shown to be a good indicator for different conditions, such as Alzheimer's Disease. Using brain age for weakly supervised pre-training of DL models in transfer learning settings has also recently shown promising results, especially when dealing with data scarcity of different conditions. On the other hand, anatomical information of brain MRIs (e.g. cortical thickness) can provide important information for learning good representations that can be transferred to many downstream tasks. In this work, we propose AnatCL, an anatomical foundation model for brain MRIs that i.) leverages anatomical information in a weakly contrastive learning approach, and ii.) achieves state-of-the-art performances across many different downstream tasks. To validate our approach we consider 12 different downstream tasks for the diagnosis of different conditions such as Alzheimer's Disease, autism spectrum disorder, and schizophrenia. Furthermore, we also target the prediction of 10 different clinical assessment scores using structural MRI data. Our findings show that incorporating anatomical information during pre-training leads to more robust and generalizable representations. Pre-trained models can be found at: https://github.com/EIDOSLAB/AnatCL.

The application of deep learning methods, particularly foundation models, in biological research has surged in recent years. These models can be text-based or trained on underlying biological data, especially omics data of various types. However, comparing the performance of these models consistently has proven to be a challenge due to differences in training data and downstream tasks. To tackle this problem, we developed an architecture-agnostic benchmarking approach that, instead of evaluating the models directly, leverages entity representation vectors from each model and trains simple predictive models for each benchmarking task. This ensures that all types of models are evaluated using the same input and output types. Here we focus on gene properties collected from professionally curated bioinformatics databases. These gene properties are categorized into five major groups: genomic properties, regulatory functions, localization, biological processes, and protein properties. Overall, we define hundreds of tasks based on these databases, which include binary, multi-label, and multi-class classification tasks. We apply these benchmark tasks to evaluate expression-based models, large language models, protein language models, DNA-based models, and traditional baselines. Our findings suggest that text-based models and protein language models generally outperform expression-based models in genomic properties and regulatory functions tasks, whereas expression-based models demonstrate superior performance in localization tasks. These results should aid in the development of more informed artificial intelligence strategies for biological understanding and therapeutic discovery. To ensure the reproducibility and transparency of our findings, we have made the source code and benchmark data publicly accessible for further investigation and expansion at github.com/BiomedSciAI/gene-benchmark.

Structural changes in retinal blood vessels are critical biomarkers for the onset and progression of glaucoma and other ocular diseases. However, current vessel segmentation approaches largely rely on supervised learning and extensive manual annotations, which are costly, error-prone, and difficult to obtain in optical coherence tomography angiography. Here we present BioVessel-Net, an unsupervised generative framework that integrates vessel biostatistics with adversarial refinement and a radius-guided segmentation strategy. Unlike pixel-based methods, BioVessel-Net directly models vascular structures with biostatistical coherence, achieving accurate and explainable vessel extraction without labeled data or high-performance computing. To support training and evaluation, we introduce RetinaMix, a new benchmark dataset of 2D and 3D OCTA images with high-resolution vessel details from diverse populations. Experimental results demonstrate that BioVessel-Net achieves near-perfect segmentation accuracy across RetinaMix and existing datasets, substantially outperforming state-of-the-art supervised and semi-supervised methods. Together, BioVessel-Net and RetinaMix provide a label-free, computationally efficient, and clinically interpretable solution for retinal vessel analysis, with broad potential for glaucoma monitoring, blood flow modeling, and progression prediction. Code and dataset are available: https://github.com/VikiXie/SatMar8.

The drug development pipeline for a new compound can last 10-20 years and cost over 10 billion. Drug repurposing offers a more time- and cost-effective alternative. Computational approaches based on biomedical knowledge graph representations have recently yielded new drug repurposing hypotheses. In this study, we present a novel, disease-specific hypergraph representation learning technique to derive contextual embeddings of biological pathways of various lengths but that all start at any given drug and all end at the disease of interest. Further, we extend this method to multi-disease hypergraphs. To determine the repurposing potential of each of the 1,522 drugs, we derive drug-specific distributions of cosine similarity values and ultimately consider the median for ranking. Cosine similarity values are computed between (1) all biological pathways starting at the considered drug and ending at the disease of interest and (2) all biological pathways starting at drugs currently prescribed against that disease and ending at the disease of interest. We illustrate our approach with Alzheimer's disease (AD) and two of its risk factors: hypertension (HTN) and type 2 diabetes (T2D). We compare each drug's rank across four hypergraph settings (single- or multi-disease): AD only, AD + HTN, AD + T2D, and AD + HTN + T2D. Notably, our framework led to the identification of two promising drugs whose repurposing potential was significantly higher in hypergraphs combining two diseases: dapagliflozin (antidiabetic; moved up, from top 32% to top 7%, across all considered drugs) and debrisoquine (antihypertensive; moved up, from top 76% to top 23%). Our approach serves as a hypothesis generation tool, to be paired with a validation pipeline relying on laboratory experiments and semi-automated parsing of the biomedical literature.

Recent advancements in machine learning have significantly improved the identification of disease-associated genes from gene expression datasets. However, these processes often require extensive expertise and manual effort, limiting their scalability. Large Language Model (LLM)-based agents have shown promise in automating these tasks due to their increasing problem-solving abilities. To support the evaluation and development of such methods, we introduce GenoTEX, a benchmark dataset for the automated analysis of gene expression data. GenoTEX provides annotated code and results for solving a wide range of gene identification problems, encompassing dataset selection, preprocessing, and statistical analysis, in a pipeline that follows computational genomics standards. The benchmark includes expert-curated annotations from bioinformaticians to ensure accuracy and reliability. To provide baselines for these tasks, we present GenoAgent, a team of LLM-based agents that adopt a multi-step programming workflow with flexible self-correction, to collaboratively analyze gene expression datasets. Our experiments demonstrate the potential of LLM-based methods in analyzing genomic data, while error analysis highlights the challenges and areas for future improvement. We propose GenoTEX as a promising resource for benchmarking and enhancing automated methods for gene expression data analysis. The benchmark is available at https://github.com/Liu-Hy/GenoTex.

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

Integrating molecular, morphological, and clinical data is essential for basic and translational biomedical research, yet systematic frameworks for jointly modeling these modalities remain limited. Here we present Haiku, a tri-modal contrastive learning model trained on multiplexed immunofluorescence (mIF). It comprises 26.7 million spatial proteomics patches from 3,218 tissue sections across 1,606 patients spanning 11 organ types, with matched hematoxylin and eosin (H&E) histology and clinical metadata aligned in a shared embedding space. Haiku enables three-way cross-modal retrieval, improves downstream classification and clinical prediction tasks over unimodal baselines, and supports zero-shot biomarker inference through fusion retrieval conditioned on clinical metadata-only text descriptions. Across tasks, Haiku outperforms competing approaches, achieving cross-modal retrieval (Recall@50 up to 0.611 versus near-zero baseline), survival prediction (C-index 0.737, +7.91% relative improvement), and zero-shot biomarker inference (mean Pearson correlation 0.718 across 52 biomarkers). Furthermore, we introduce a counterfactual prediction framework in which modifying only clinical metadata while fixing tissue morphology surfaces niche-specific molecular shifts associated with breast cancer stage progression and lung cancer survival outcomes. In a lung adenocarcinoma case study, the counterfactual analysis recovers niche-specific shifts characterized by increased CD8 and granzyme B, reduced PD-L1, and decreased Ki67, broadly consistent with patterns reported for favorable outcomes. We present these counterfactual results as exploratory, hypothesis-generating signals rather than mechanistic claims. These capabilities demonstrate that tri-modal alignment via Haiku enables integrative analysis of spatial biology, bridging molecular measurements with clinical context for biological exploration.

The World Health Organization added Disease X to their shortlist of blueprint priority diseases to represent a hypothetical, unknown pathogen that could cause a future epidemic. During different virus outbreaks of the past, such as COVID-19, Influenza, Lyme Disease, and Zika virus, researchers from various disciplines utilized Google Trends to mine multimodal components of web behavior to study, investigate, and analyze the global awareness, preparedness, and response associated with these respective virus outbreaks. As the world prepares for Disease X, a dataset on web behavior related to Disease X would be crucial to contribute towards the timely advancement of research in this field. Furthermore, none of the prior works in this field have focused on the development of a dataset to compile relevant web behavior data, which would help to prepare for Disease X. To address these research challenges, this work presents a dataset of web behavior related to Disease X, which emerged from different geographic regions of the world, between February 2018 and August 2023. Specifically, this dataset presents the search interests related to Disease X from 94 geographic regions. The dataset was developed by collecting data using Google Trends. The relevant search interests for all these regions for each month in this time range are available in this dataset. This paper also discusses the compliance of this dataset with the FAIR principles of scientific data management. Finally, an analysis of this dataset is presented to uphold the applicability, relevance, and usefulness of this dataset for the investigation of different research questions in the interrelated fields of Big Data, Data Mining, Healthcare, Epidemiology, and Data Analysis with a specific focus on Disease X.

Early identification of sensitive cancer cell lines is essential for accelerating biomarker discovery and elucidating drug mechanism of action. Given the efficiency and low cost of small-scale drug screens relative to extensive omics profiling, we compared drug-response panel (DRP) descriptors against omics features for predictive capacity using gradient boosting tree models across the GDSC and CCLE drug response datasets. DRP descriptors consistently outperformed omics data across key performance metrics, with variable performance across different drugs. Using complementary explainability approaches, we confirmed known MAPK-inhibitor sensitivity signatures, and identified novel potential biomarker candidates for MEK1/2 and BTK/MNK inhibitors. Lastly, to demonstrate the utility of this approach in distinguishing phenotypes, we applied our models to the breast cancer line MCF7 versus the non-tumorigenic MCF10A, and successfully identified compounds that selectively inhibit MCF7 while sparing the non-tumorigenic MCF10A. This methodology, developed using focused drug and cell line panels, supports early-stage drug development by facilitating rational cell line selection and compound prioritisation, enabling more efficient biomarker identification and candidate assessment.

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

To investigate whether the pleurae, airways and vessels surrounding a nodule on non-contrast computed tomography (CT) can discriminate benign and malignant pulmonary nodules. The LIDC-IDRI dataset, one of the largest publicly available CT database, was exploited for study. A total of 1556 nodules from 694 patients were involved in statistical analysis, where nodules with average scorings <3 and >3 were respectively denoted as benign and malignant. Besides, 339 nodules from 113 patients with diagnosis ground-truth were independently evaluated. Computer algorithms were developed to segment pulmonary structures and quantify the distances to pleural surface, airways and vessels, as well as the counting number and normalized volume of airways and vessels near a nodule. Odds ratio (OR) and Chi-square (\chi^2) testing were performed to demonstrate the correlation between features of surrounding structures and nodule malignancy. A non-parametric receiver operating characteristic (ROC) analysis was conducted in logistic regression to evaluate discrimination ability of each structure. For benign and malignant groups, the average distances from nodules to pleural surface, airways and vessels are respectively (6.56, 5.19), (37.08, 26.43) and (1.42, 1.07) mm. The correlation between nodules and the counting number of airways and vessels that contact or project towards nodules are respectively (OR=22.96, \chi^2=105.04) and (OR=7.06, \chi^2=290.11). The correlation between nodules and the volume of airways and vessels are (OR=9.19, \chi^2=159.02) and (OR=2.29, \chi^2=55.89). The areas-under-curves (AUCs) for pleurae, airways and vessels are respectively 0.5202, 0.6943 and 0.6529. Our results show that malignant nodules are often surrounded by more pulmonary structures compared with benign ones, suggesting that features of these structures could be viewed as lung cancer biomarkers.

Human space exploration beyond low Earth orbit will involve missions of significant distance and duration. To effectively mitigate myriad space health hazards, paradigm shifts in data and space health systems are necessary to enable Earth-independence, rather than Earth-reliance. Promising developments in the fields of artificial intelligence and machine learning for biology and health can address these needs. We propose an appropriately autonomous and intelligent Precision Space Health system that will monitor, aggregate, and assess biomedical statuses; analyze and predict personalized adverse health outcomes; adapt and respond to newly accumulated data; and provide preventive, actionable, and timely insights to individual deep space crew members and iterative decision support to their crew medical officer. Here we present a summary of recommendations from a workshop organized by the National Aeronautics and Space Administration, on future applications of artificial intelligence in space biology and health. In the next decade, biomonitoring technology, biomarker science, spacecraft hardware, intelligent software, and streamlined data management must mature and be woven together into a Precision Space Health system to enable humanity to thrive in deep space.

Recent breakthroughs in self-supervised learning have enabled the use of large unlabeled datasets to train visual foundation models that can generalize to a variety of downstream tasks. While this training paradigm is well suited for the medical domain where annotations are scarce, large-scale pre-training in the medical domain, and in particular pathology, has not been extensively studied. Previous work in self-supervised learning in pathology has leveraged smaller datasets for both pre-training and evaluating downstream performance. The aim of this project is to train the largest academic foundation model and benchmark the most prominent self-supervised learning algorithms by pre-training and evaluating downstream performance on large clinical pathology datasets. We collected the largest pathology dataset to date, consisting of over 3 billion images from over 423 thousand microscopy slides. We compared pre-training of visual transformer models using the masked autoencoder (MAE) and DINO algorithms. We evaluated performance on six clinically relevant tasks from three anatomic sites and two institutions: breast cancer detection, inflammatory bowel disease detection, breast cancer estrogen receptor prediction, lung adenocarcinoma EGFR mutation prediction, and lung cancer immunotherapy response prediction. Our results demonstrate that pre-training on pathology data is beneficial for downstream performance compared to pre-training on natural images. Additionally, the DINO algorithm achieved better generalization performance across all tasks tested. The presented results signify a phase change in computational pathology research, paving the way into a new era of more performant models based on large-scale, parallel pre-training at the billion-image scale.

Background: Health datasets from clinical sources do not reflect the breadth and diversity of disease in the real world, impacting research, medical education, and artificial intelligence (AI) tool development. Dermatology is a suitable area to develop and test a new and scalable method to create representative health datasets. Methods: We used Google Search advertisements to invite contributions to an open access dataset of images of dermatology conditions, demographic and symptom information. With informed contributor consent, we describe and release this dataset containing 10,408 images from 5,033 contributions from internet users in the United States over 8 months starting March 2023. The dataset includes dermatologist condition labels as well as estimated Fitzpatrick Skin Type (eFST) and Monk Skin Tone (eMST) labels for the images. Results: We received a median of 22 submissions/day (IQR 14-30). Female (66.72%) and younger (52% < age 40) contributors had a higher representation in the dataset compared to the US population, and 32.6% of contributors reported a non-White racial or ethnic identity. Over 97.5% of contributions were genuine images of skin conditions. Dermatologist confidence in assigning a differential diagnosis increased with the number of available variables, and showed a weaker correlation with image sharpness (Spearman's P values <0.001 and 0.01 respectively). Most contributions were short-duration (54% with onset < 7 days ago ) and 89% were allergic, infectious, or inflammatory conditions. eFST and eMST distributions reflected the geographical origin of the dataset. The dataset is available at github.com/google-research-datasets/scin . Conclusion: Search ads are effective at crowdsourcing images of health conditions. The SCIN dataset bridges important gaps in the availability of representative images of common skin conditions.

Tracking biosignals is crucial for monitoring wellness and preempting the development of severe medical conditions. Today, wearable devices can conveniently record various biosignals, creating the opportunity to monitor health status without disruption to one's daily routine. Despite widespread use of wearable devices and existing digital biomarkers, the absence of curated data with annotated medical labels hinders the development of new biomarkers to measure common health conditions. In fact, medical datasets are usually small in comparison to other domains, which is an obstacle for developing neural network models for biosignals. To address this challenge, we have employed self-supervised learning using the unlabeled sensor data collected under informed consent from the large longitudinal Apple Heart and Movement Study (AHMS) to train foundation models for two common biosignals: photoplethysmography (PPG) and electrocardiogram (ECG) recorded on Apple Watch. We curated PPG and ECG datasets from AHMS that include data from ~141K participants spanning ~3 years. Our self-supervised learning framework includes participant level positive pair selection, stochastic augmentation module and a regularized contrastive loss optimized with momentum training, and generalizes well to both PPG and ECG modalities. We show that the pre-trained foundation models readily encode information regarding participants' demographics and health conditions. To the best of our knowledge, this is the first study that builds foundation models using large-scale PPG and ECG data collected via wearable consumer devices x2013 prior works have commonly used smaller-size datasets collected in clinical and experimental settings. We believe PPG and ECG foundation models can enhance future wearable devices by reducing the reliance on labeled data and hold the potential to help the users improve their health.

Automatic phenotype concept recognition from unstructured text remains a challenging task in biomedical text mining research. Previous works that address the task typically use dictionary-based matching methods, which can achieve high precision but suffer from lower recall. Recently, machine learning-based methods have been proposed to identify biomedical concepts, which can recognize more unseen concept synonyms by automatic feature learning. However, most methods require large corpora of manually annotated data for model training, which is difficult to obtain due to the high cost of human annotation. In this paper, we propose PhenoTagger, a hybrid method that combines both dictionary and machine learning-based methods to recognize Human Phenotype Ontology (HPO) concepts in unstructured biomedical text. We first use all concepts and synonyms in HPO to construct a dictionary, which is then used to automatically build a distantly supervised training dataset for machine learning. Next, a cutting-edge deep learning model is trained to classify each candidate phrase (n-gram from input sentence) into a corresponding concept label. Finally, the dictionary and machine learning-based prediction results are combined for improved performance. Our method is validated with two HPO corpora, and the results show that PhenoTagger compares favorably to previous methods. In addition, to demonstrate the generalizability of our method, we retrained PhenoTagger using the disease ontology MEDIC for disease concept recognition to investigate the effect of training on different ontologies. Experimental results on the NCBI disease corpus show that PhenoTagger without requiring manually annotated training data achieves competitive performance as compared with state-of-the-art supervised methods.

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

Background:Speech patterns have emerged as potential diagnostic markers for conditions with varying etiologies. Machine learning (ML) presents an opportunity to harness these patterns for accurate disease diagnosis. Objective: This review synthesized findings from studies exploring ML's capability in leveraging speech for the diagnosis of neurological, laryngeal and mental disorders. Methods: A systematic examination of 564 articles was conducted with 91 articles included in the study, which encompassed a wide spectrum of conditions, ranging from voice pathologies to mental and neurological disorders. Methods for speech classifications were assessed based on the relevant studies and scored between 0-10 based on the reported diagnostic accuracy of their ML models. Results: High diagnostic accuracies were consistently observed for laryngeal disorders, dysarthria, and changes related to speech in Parkinsons disease. These findings indicate the robust potential of speech as a diagnostic tool. Disorders like depression, schizophrenia, mild cognitive impairment and Alzheimers dementia also demonstrated high accuracies, albeit with some variability across studies. Meanwhile, disorders like OCD and autism highlighted the need for more extensive research to ascertain the relationship between speech patterns and the respective conditions. Conclusion: ML models utilizing speech patterns demonstrate promising potential in diagnosing a range of mental, laryngeal, and neurological disorders. However, the efficacy varies across conditions, and further research is needed. The integration of these models into clinical practice could potentially revolutionize the evaluation and diagnosis of a number of different medical conditions.

Segmenting biomarkers in medical images is crucial for various biotech applications. Despite advances, Transformer and CNN based methods often struggle with variations in staining and morphology, limiting feature extraction. In medical image segmentation, where datasets often have limited sample availability, recent state-of-the-art (SOTA) methods achieve higher accuracy by leveraging pre-trained encoders, whereas end-to-end methods tend to underperform. This is due to challenges in effectively transferring rich multiscale features from encoders to decoders, as well as limitations in decoder efficiency. To address these issues, we propose an architecture that captures multi-scale local and global contextual information and a novel decoder design, which effectively integrates features from the encoder, emphasizes important channels and regions, and reconstructs spatial dimensions to enhance segmentation accuracy. Our method, compatible with various encoders, outperforms SOTA methods, as demonstrated by experiments on four datasets and ablation studies. Specifically, our method achieves absolute performance gains of 2.76% on MoNuSeg, 3.12% on DSB, 2.87% on Electron Microscopy, and 4.03% on TNBC datasets compared to existing SOTA methods. Code: https://github.com/saadwazir/MCADS-Decoder

Biomedical data is inherently multimodal, consisting of electronic health records, medical imaging, digital pathology, genome sequencing, wearable sensors, and more. The application of artificial intelligence tools to these multifaceted sensing technologies has the potential to revolutionize the prognosis, diagnosis, and management of human health and disease. However, current approaches to biomedical AI typically only train and evaluate with one or a small set of medical modalities and tasks. This limitation hampers the development of comprehensive tools that can leverage the rich interconnected information across many heterogeneous biomedical sensors. To address this challenge, we present MultiMed, a benchmark designed to evaluate and enable large-scale learning across a wide spectrum of medical modalities and tasks. MultiMed consists of 2.56 million samples across ten medical modalities such as medical reports, pathology, genomics, and protein data, and is structured into eleven challenging tasks, including disease prognosis, protein structure prediction, and medical question answering. Using MultiMed, we conduct comprehensive experiments benchmarking state-of-the-art unimodal, multimodal, and multitask models. Our analysis highlights the advantages of training large-scale medical models across many related modalities and tasks. Moreover, MultiMed enables studies of generalization across related medical concepts, robustness to real-world noisy data and distribution shifts, and novel modality combinations to improve prediction performance. MultiMed will be publicly available and regularly updated and welcomes inputs from the community.

Clinical diagnosis is critical in medical practice, typically requiring a continuous and evolving process that includes primary diagnosis, differential diagnosis, and final diagnosis. However, most existing clinical diagnostic tasks are single-step processes, which does not align with the complex multi-step diagnostic procedures found in real-world clinical settings. In this paper, we propose a multi-step diagnostic task and annotate a clinical diagnostic dataset (MSDiagnosis). This dataset includes primary diagnosis, differential diagnosis, and final diagnosis questions. Additionally, we propose a novel and effective framework. This framework combines forward inference, backward inference, reflection, and refinement, enabling the LLM to self-evaluate and adjust its diagnostic results. To assess the effectiveness of our proposed method, we design and conduct extensive experiments. The experimental results demonstrate the effectiveness of the proposed method. We also provide a comprehensive experimental analysis and suggest future research directions for this task.

Large language models (LLMs) have emerged as powerful tools for analyzing complex datasets. Recent studies demonstrate their potential to generate useful, personalized responses when provided with patient-specific health information that encompasses lifestyle, biomarkers, and context. As LLM-driven health applications are increasingly adopted, rigorous and efficient one-sided evaluation methodologies are crucial to ensure response quality across multiple dimensions, including accuracy, personalization and safety. Current evaluation practices for open-ended text responses heavily rely on human experts. This approach introduces human factors and is often cost-prohibitive, labor-intensive, and hinders scalability, especially in complex domains like healthcare where response assessment necessitates domain expertise and considers multifaceted patient data. In this work, we introduce Adaptive Precise Boolean rubrics: an evaluation framework that streamlines human and automated evaluation of open-ended questions by identifying gaps in model responses using a minimal set of targeted rubrics questions. Our approach is based on recent work in more general evaluation settings that contrasts a smaller set of complex evaluation targets with a larger set of more precise, granular targets answerable with simple boolean responses. We validate this approach in metabolic health, a domain encompassing diabetes, cardiovascular disease, and obesity. Our results demonstrate that Adaptive Precise Boolean rubrics yield higher inter-rater agreement among expert and non-expert human evaluators, and in automated assessments, compared to traditional Likert scales, while requiring approximately half the evaluation time of Likert-based methods. This enhanced efficiency, particularly in automated evaluation and non-expert contributions, paves the way for more extensive and cost-effective evaluation of LLMs in health.

Neurological diseases are the leading global cause of disability, yet most lack disease-modifying treatments. We present PROTON, a heterogeneous graph transformer that generates testable hypotheses across molecular, organoid, and clinical systems. To evaluate PROTON, we apply it to Parkinson's disease (PD), bipolar disorder (BD), and Alzheimer's disease (AD). In PD, PROTON linked genetic risk loci to genes essential for dopaminergic neuron survival and predicted pesticides toxic to patient-derived neurons, including the insecticide endosulfan, which ranked within the top 1.29% of predictions. In silico screens performed by PROTON reproduced six genome-wide α-synuclein experiments, including a split-ubiquitin yeast two-hybrid system (normalized enrichment score [NES] = 2.30, FDR-adjusted p < 1 times 10^{-4}), an ascorbate peroxidase proximity labeling assay (NES = 2.16, FDR < 1 times 10^{-4}), and a high-depth targeted exome sequencing study in 496 synucleinopathy patients (NES = 2.13, FDR < 1 times 10^{-4}). In BD, PROTON predicted calcitriol as a candidate drug that reversed proteomic alterations observed in cortical organoids derived from BD patients. In AD, we evaluated PROTON predictions in health records from n = 610,524 patients at Mass General Brigham, confirming that five PROTON-predicted drugs were associated with reduced seven-year dementia risk (minimum hazard ratio = 0.63, 95% CI: 0.53-0.75, p < 1 times 10^{-7}). PROTON generated neurological hypotheses that were evaluated across molecular, organoid, and clinical systems, defining a path for AI-driven discovery in neurological disease.

People with diabetes are at risk of developing an eye disease called diabetic retinopathy (DR). This disease occurs when high blood glucose levels cause damage to blood vessels in the retina. Computer-aided DR diagnosis is a promising tool for early detection of DR and severity grading, due to the great success of deep learning. However, most current DR diagnosis systems do not achieve satisfactory performance or interpretability for ophthalmologists, due to the lack of training data with consistent and fine-grained annotations. To address this problem, we construct a large fine-grained annotated DR dataset containing 2,842 images (FGADR). This dataset has 1,842 images with pixel-level DR-related lesion annotations, and 1,000 images with image-level labels graded by six board-certified ophthalmologists with intra-rater consistency. The proposed dataset will enable extensive studies on DR diagnosis. We set up three benchmark tasks for evaluation: 1. DR lesion segmentation; 2. DR grading by joint classification and segmentation; 3. Transfer learning for ocular multi-disease identification. Moreover, a novel inductive transfer learning method is introduced for the third task. Extensive experiments using different state-of-the-art methods are conducted on our FGADR dataset, which can serve as baselines for future research.

Our research is motivated by the urgent global issue of a large population affected by retinal diseases, which are evenly distributed but underserved by specialized medical expertise, particularly in non-urban areas. Our primary objective is to bridge this healthcare gap by developing a comprehensive diagnostic system capable of accurately predicting retinal diseases solely from fundus images. However, we faced significant challenges due to limited, diverse datasets and imbalanced class distributions. To overcome these issues, we have devised innovative strategies. Our research introduces novel approaches, utilizing hybrid models combining deeper Convolutional Neural Networks (CNNs), Transformer encoders, and ensemble architectures sequentially and in parallel to classify retinal fundus images into 20 disease labels. Our overarching goal is to assess these advanced models' potential in practical applications, with a strong focus on enhancing retinal disease diagnosis accuracy across a broader spectrum of conditions. Importantly, our efforts have surpassed baseline model results, with the C-Tran ensemble model emerging as the leader, achieving a remarkable model score of 0.9166, surpassing the baseline score of 0.9. Additionally, experiments with the IEViT model showcased equally promising outcomes with improved computational efficiency. We've also demonstrated the effectiveness of dynamic patch extraction and the integration of domain knowledge in computer vision tasks. In summary, our research strives to contribute significantly to retinal disease diagnosis, addressing the critical need for accessible healthcare solutions in underserved regions while aiming for comprehensive and accurate disease prediction.

The approval success rate of drug candidates is very low with the majority of failure due to safety and efficacy. Increasingly available high dimensional information on targets, drug molecules and indications provides an opportunity for ML methods to integrate multiple data modalities and better predict clinically promising drug targets. Notably, drug targets with human genetics evidence are shown to have better odds to succeed. However, a recent tensor factorization-based approach found that additional information on targets and indications might not necessarily improve the predictive accuracy. Here we revisit this approach by integrating different types of human genetics evidence collated from publicly available sources to support each target-indication pair. We use Bayesian tensor factorization to show that models incorporating all available human genetics evidence (rare disease, gene burden, common disease) modestly improves the clinical outcome prediction over models using single line of genetics evidence. We provide additional insight into the relative predictive power of different types of human genetics evidence for predicting the success of clinical outcomes.

Foundation models applied to bio-molecular space hold promise to accelerate drug discovery. Molecular representation is key to building such models. Previous works have typically focused on a single representation or view of the molecules. Here, we develop a multi-view foundation model approach, that integrates molecular views of graph, image and text. Single-view foundation models are each pre-trained on a dataset of up to 200M molecules and then aggregated into combined representations. Our multi-view model is validated on a diverse set of 18 tasks, encompassing ligand-protein binding, molecular solubility, metabolism and toxicity. We show that the multi-view models perform robustly and are able to balance the strengths and weaknesses of specific views. We then apply this model to screen compounds against a large (>100 targets) set of G Protein-Coupled receptors (GPCRs). From this library of targets, we identify 33 that are related to Alzheimer's disease. On this subset, we employ our model to identify strong binders, which are validated through structure-based modeling and identification of key binding motifs.

Foundation models in computational pathology promise to unlock the development of new clinical decision support systems and models for precision medicine. However, there is a mismatch between most clinical analysis, which is defined at the level of one or more whole slide images, and foundation models to date, which process the thousands of image tiles contained in a whole slide image separately. The requirement to train a network to aggregate information across a large number of tiles in multiple whole slide images limits these models' impact. In this work, we present a slide-level foundation model for H&E-stained histopathology, PRISM, that builds on Virchow tile embeddings and leverages clinical report text for pre-training. Using the tile embeddings, PRISM produces slide-level embeddings with the ability to generate clinical reports, resulting in several modes of use. Using text prompts, PRISM achieves zero-shot cancer detection and sub-typing performance approaching and surpassing that of a supervised aggregator model. Using the slide embeddings with linear classifiers, PRISM surpasses supervised aggregator models. Furthermore, we demonstrate that fine-tuning of the PRISM slide encoder yields label-efficient training for biomarker prediction, a task that typically suffers from low availability of training data; an aggregator initialized with PRISM and trained on as little as 10% of the training data can outperform a supervised baseline that uses all of the data.

Gastrointestinal (GI) diseases represent a clinically significant burden, necessitating precise diagnostic approaches to optimize patient outcomes. Conventional histopathological diagnosis suffers from limited reproducibility and diagnostic variability. To overcome these limitations, we develop Digepath, a specialized foundation model for GI pathology. Our framework introduces a dual-phase iterative optimization strategy combining pretraining with fine-screening, specifically designed to address the detection of sparsely distributed lesion areas in whole-slide images. Digepath is pretrained on over 353 million multi-scale images from 210,043 H&E-stained slides of GI diseases. It attains state-of-the-art performance on 33 out of 34 tasks related to GI pathology, including pathological diagnosis, protein expression status prediction, gene mutation prediction, and prognosis evaluation. We further translate the intelligent screening module for early GI cancer and achieve near-perfect 99.70% sensitivity across nine independent medical institutions. This work not only advances AI-driven precision pathology for GI diseases but also bridge critical gaps in histopathological practice.

Named-entity recognition (NER) is fundamental to extracting structured information from the >80% of healthcare data that resides in unstructured clinical notes and biomedical literature. Despite recent advances with large language models, achieving state-of-the-art performance across diverse entity types while maintaining computational efficiency remains a significant challenge. We introduce OpenMed NER, a suite of open-source, domain-adapted transformer models that combine lightweight domain-adaptive pre-training (DAPT) with parameter-efficient Low-Rank Adaptation (LoRA). Our approach performs cost-effective DAPT on a 350k-passage corpus compiled from ethically sourced, publicly available research repositories and de-identified clinical notes (PubMed, arXiv, and MIMIC-III) using DeBERTa-v3, PubMedBERT, and BioELECTRA backbones. This is followed by task-specific fine-tuning with LoRA, which updates less than 1.5% of model parameters. We evaluate our models on 12 established biomedical NER benchmarks spanning chemicals, diseases, genes, and species. OpenMed NER achieves new state-of-the-art micro-F1 scores on 10 of these 12 datasets, with substantial gains across diverse entity types. Our models advance the state-of-the-art on foundational disease and chemical benchmarks (e.g., BC5CDR-Disease, +2.70 pp), while delivering even larger improvements of over 5.3 and 9.7 percentage points on more specialized gene and clinical cell line corpora. This work demonstrates that strategically adapted open-source models can surpass closed-source solutions. This performance is achieved with remarkable efficiency: training completes in under 12 hours on a single GPU with a low carbon footprint (< 1.2 kg CO2e), producing permissively licensed, open-source checkpoints designed to help practitioners facilitate compliance with emerging data protection and AI regulations, such as the EU AI Act.

In this paper we present a hybrid method for the automatic detection of dermatological pathologies in medical reports. We use a large language model combined with medical ontologies to predict, given a first appointment or follow-up medical report, the pathology a person may suffer from. The results show that teaching the model to learn the type, severity and location on the body of a dermatological pathology, as well as in which order it has to learn these three features, significantly increases its accuracy. The article presents the demonstration of state-of-the-art results for classification of medical texts with a precision of 0.84, micro and macro F1-score of 0.82 and 0.75, and makes both the method and the data set used available to the community.

Obesity, the leading cause of many non-communicable diseases, occurs mainly for eating more than our body requirements and lack of proper activity. So, being healthy requires heathy diet plans, especially for patients with comorbidities. But it is difficult to figure out the exact quantity of each nutrient because nutrients requirement varies based on physical and disease conditions. In our study we proposed a novel machine learning based system to predict the amount of nutrients one individual requires for being healthy. We applied different machine learning algorithms: linear regression, support vector machine (SVM), decision tree, random forest, XGBoost, LightGBM on fluid and 3 other major micronutrients: carbohydrate, protein, fat consumption prediction. We achieved high accuracy with low root mean square error (RMSE) by using linear regression in fluid prediction, random forest in carbohydrate prediction and LightGBM in protein and fat prediction. We believe our diet recommender system, OBESEYE, is the only of its kind which recommends diet with the consideration of comorbidities and physical conditions and promote encouragement to get rid of obesity.

This study evaluated the effect of BioBERT in medical text processing for the task of medical named entity recognition. Through comparative experiments with models such as BERT, ClinicalBERT, SciBERT, and BlueBERT, the results showed that BioBERT achieved the best performance in both precision and F1 score, verifying its applicability and superiority in the medical field. BioBERT enhances its ability to understand professional terms and complex medical texts through pre-training on biomedical data, providing a powerful tool for medical information extraction and clinical decision support. The study also explored the privacy and compliance challenges of BioBERT when processing medical data, and proposed future research directions for combining other medical-specific models to improve generalization and robustness. With the development of deep learning technology, the potential of BioBERT in application fields such as intelligent medicine, personalized treatment, and disease prediction will be further expanded. Future research can focus on the real-time and interpretability of the model to promote its widespread application in the medical field.

Knowledge Graph (KG) plays a crucial role in Medical Report Generation (MRG) because it reveals the relations among diseases and thus can be utilized to guide the generation process. However, constructing a comprehensive KG is labor-intensive and its applications on the MRG process are under-explored. In this study, we establish a complete KG on chest X-ray imaging that includes 137 types of diseases and abnormalities. Based on this KG, we find that the current MRG data sets exhibit a long-tailed problem in disease distribution. To mitigate this problem, we introduce a novel augmentation strategy that enhances the representation of disease types in the tail-end of the distribution. We further design a two-stage MRG approach, where a classifier is first trained to detect whether the input images exhibit any abnormalities. The classified images are then independently fed into two transformer-based generators, namely, ``disease-specific generator" and ``disease-free generator" to generate the corresponding reports. To enhance the clinical evaluation of whether the generated reports correctly describe the diseases appearing in the input image, we propose diverse sensitivity (DS), a new metric that checks whether generated diseases match ground truth and measures the diversity of all generated diseases. Results show that the proposed two-stage generation framework and augmentation strategies improve DS by a considerable margin, indicating a notable reduction in the long-tailed problem associated with under-represented diseases.

The complexity and variability inherent in high-resolution pathological images present significant challenges in computational pathology. While pathology foundation models leveraging AI have catalyzed transformative advancements, their development demands large-scale datasets, considerable storage capacity, and substantial computational resources. Furthermore, ensuring their clinical applicability and generalizability requires rigorous validation across a broad spectrum of clinical tasks. Here, we present PathOrchestra, a versatile pathology foundation model trained via self-supervised learning on a dataset comprising 300K pathological slides from 20 tissue and organ types across multiple centers. The model was rigorously evaluated on 112 clinical tasks using a combination of 61 private and 51 public datasets. These tasks encompass digital slide preprocessing, pan-cancer classification, lesion identification, multi-cancer subtype classification, biomarker assessment, gene expression prediction, and the generation of structured reports. PathOrchestra demonstrated exceptional performance across 27,755 WSIs and 9,415,729 ROIs, achieving over 0.950 accuracy in 47 tasks, including pan-cancer classification across various organs, lymphoma subtype diagnosis, and bladder cancer screening. Notably, it is the first model to generate structured reports for high-incidence colorectal cancer and diagnostically complex lymphoma-areas that are infrequently addressed by foundational models but hold immense clinical potential. Overall, PathOrchestra exemplifies the feasibility and efficacy of a large-scale, self-supervised pathology foundation model, validated across a broad range of clinical-grade tasks. Its high accuracy and reduced reliance on extensive data annotation underline its potential for clinical integration, offering a pathway toward more efficient and high-quality medical services.

Background: Cancer remains one of the leading causes of morbidity and mortality worldwide. Comprehensive datasets that combine histopathological images with genetic and survival data across various tumour sites are essential for advancing computational pathology and personalised medicine. Results: We present SurGen, a dataset comprising 1,020 H&E-stained whole slide images (WSIs) from 843 colorectal cancer cases. The dataset includes detailed annotations for key genetic mutations (KRAS, NRAS, BRAF) and mismatch repair status, as well as survival data for 426 cases. To demonstrate SurGen's practical utility, we conducted a proof-of-concept machine learning experiment predicting mismatch repair status from the WSIs, achieving a test AUROC of 0.8316. These preliminary results underscore the dataset's potential to facilitate research in biomarker discovery, prognostic modelling, and advanced machine learning applications in colorectal cancer. Conclusions: SurGen offers a valuable resource for the scientific community, enabling studies that require high-quality WSIs linked with comprehensive clinical and genetic information on colorectal cancer. Our initial findings affirm the dataset's capacity to advance diagnostic precision and foster the development of personalised treatment strategies in colorectal oncology. Data available online at https://doi.org/10.6019/S-BIAD1285.

Automated relation extraction (RE) from biomedical literature is critical for many downstream text mining applications in both research and real-world settings. However, most existing benchmarking datasets for bio-medical RE only focus on relations of a single type (e.g., protein-protein interactions) at the sentence level, greatly limiting the development of RE systems in biomedicine. In this work, we first review commonly used named entity recognition (NER) and RE datasets. Then we present BioRED, a first-of-its-kind biomedical RE corpus with multiple entity types (e.g., gene/protein, disease, chemical) and relation pairs (e.g., gene-disease; chemical-chemical) at the document level, on a set of 600 PubMed abstracts. Further, we label each relation as describing either a novel finding or previously known background knowledge, enabling automated algorithms to differentiate between novel and background information. We assess the utility of BioRED by benchmarking several existing state-of-the-art methods, including BERT-based models, on the NER and RE tasks. Our results show that while existing approaches can reach high performance on the NER task (F-score of 89.3%), there is much room for improvement for the RE task, especially when extracting novel relations (F-score of 47.7%). Our experiments also demonstrate that such a rich dataset can successfully facilitate the development of more accurate, efficient, and robust RE systems for biomedicine. The BioRED dataset and annotation guideline are freely available at https://ftp.ncbi.nlm.nih.gov/pub/lu/BioRED/.

Quantitative susceptibility maps from magnetic resonance images can provide both prognostic and diagnostic information in multiple sclerosis, a neurodegenerative disease characterized by the formation of lesions in white matter brain tissue. In particular, susceptibility maps provide adequate contrast to distinguish between "rim" lesions, surrounded by deposited paramagnetic iron, and "non-rim" lesion types. These paramagnetic rim lesions (PRLs) are an emerging biomarker in multiple sclerosis. Much effort has been devoted to both detection and segmentation of such lesions to monitor longitudinal change. As paramagnetic rim lesions are rare, addressing this problem requires confronting the class imbalance between rim and non-rim lesions. We produce synthetic quantitative susceptibility maps of paramagnetic rim lesions and show that inclusion of such synthetic data improves classifier performance and provide a multi-channel extension to generate accompanying contrasts and probabilistic segmentation maps. We exploit the projection capability of our trained generative network to demonstrate a novel denoising approach that allows us to train on ambiguous rim cases and substantially increase the minority class. We show that both synthetic lesion synthesis and our proposed rim lesion label denoising method best approximate the unseen rim lesion distribution and improve detection in a clinically interpretable manner. We release our code and generated data at https://github.com/agr78/PRLx-GAN upon publication.

Traditional diagnosis of aortic valve disease relies on echocardiography, but its cost and required expertise limit its use in large-scale early screening. Photoplethysmography (PPG) has emerged as a promising screening modality due to its widespread availability in wearable devices and its ability to reflect underlying hemodynamic dynamics. However, the extreme scarcity of gold-standard labeled PPG data severely constrains the effectiveness of data-driven approaches. To address this challenge, we propose and validate a new paradigm, Physiology-Guided Self-Supervised Learning (PG-SSL), aimed at unlocking the value of large-scale unlabeled PPG data for efficient screening of Aortic Stenosis (AS) and Aortic Regurgitation (AR). Using over 170,000 unlabeled PPG samples from the UK Biobank, we formalize clinical knowledge into a set of PPG morphological phenotypes and construct a pulse pattern recognition proxy task for self-supervised pre-training. A dual-branch, gated-fusion architecture is then employed for efficient fine-tuning on a small labeled subset. The proposed PG-SSL framework achieves AUCs of 0.765 and 0.776 for AS and AR screening, respectively, significantly outperforming supervised baselines trained on limited labeled data. Multivariable analysis further validates the model output as an independent digital biomarker with sustained prognostic value after adjustment for standard clinical risk factors. This study demonstrates that PG-SSL provides an effective, domain knowledge-driven solution to label scarcity in medical artificial intelligence and shows strong potential for enabling low-cost, large-scale early screening of aortic valve disease.

We present HistoAtlas, a pan-cancer computational atlas that extracts 38 interpretable histomic features from 6,745 diagnostic H&E slides across 21 TCGA cancer types and systematically links every feature to survival, gene expression, somatic mutations, and immune subtypes. All associations are covariate-adjusted, multiple-testing corrected, and classified into evidence-strength tiers. The atlas recovers known biology, from immune infiltration and prognosis to proliferation and kinase signaling, while uncovering compartment-specific immune signals and morphological subtypes with divergent outcomes. Every result is spatially traceable to tissue compartments and individual cells, statistically calibrated, and openly queryable. HistoAtlas enables systematic, large-scale biomarker discovery from routine H&E without specialized staining or sequencing. Data and an interactive web atlas are freely available at https://histoatlas.com .

The effective application of foundation models to translational research in immune-mediated diseases requires multimodal patient-level representations that can capture complex phenotypes emerging from multicellular interactions. Yet most current biological foundation models focus only on single-cell resolution and are evaluated on technical metrics often disconnected from actual drug development tasks and challenges. Here, we introduce EVA, the first cross-species, multimodal foundation model of immunology and inflammation, a therapeutic area where shared pathogenic mechanisms create unique opportunities for transfer learning. EVA harmonizes transcriptomics data across species, platforms, and resolutions, and integrates histology data to produce rich, unified patient representations. We establish clear scaling laws, demonstrating that increasing model size and compute translates to improvements in both pretraining and downstream tasks performance. We introduce a comprehensive evaluation suite of 39 tasks spanning the drug development pipeline: zero-shot target efficacy and gene function prediction for discovery, cross-species or cross-diseases molecular perturbations for preclinical development, and patient stratification with treatment response prediction or disease activity prediction for clinical trials applications. We benchmark EVA against several state-of-the-art biological foundation models and baselines on these tasks, and demonstrate state-of-the-art results on each task category. Using mechanistic interpretability, we further identify biological meaningful features, revealing intertwined representations across species and technologies. We release an open version of EVA for transcriptomics to accelerate research on immune-mediated diseases.

This paper presents a Patherea, a framework for point-based cell detection and classification that provides a complete solution for developing and evaluating state-of-the-art approaches. We introduce a large-scale dataset collected to directly replicate a clinical workflow for Ki-67 proliferation index estimation and use it to develop an efficient point-based approach that directly predicts point-based predictions, without the need for intermediate representations. The proposed approach effectively utilizes point proposal candidates with the hybrid Hungarian matching strategy and a flexible architecture that enables the usage of various backbones and (pre)training strategies. We report state-of-the-art results on existing public datasets - Lizard, BRCA-M2C, BCData, and the newly proposed Patherea dataset. We show that the performance on existing public datasets is saturated and that the newly proposed Patherea dataset represents a significantly harder challenge for the recently proposed approaches. We also demonstrate the effectiveness of recently proposed pathology foundational models that our proposed approach can natively utilize and benefit from. We also revisit the evaluation protocol that is used in the broader field of cell detection and classification and identify the erroneous calculation of performance metrics. Patherea provides a benchmarking utility that addresses the identified issues and enables a fair comparison of different approaches. The dataset and the code will be publicly released upon acceptance.

With the increasing availability of wearable devices, photoplethysmography (PPG) has emerged as a promising non-invasive tool for monitoring human hemodynamics. We propose a deep learning framework to estimate vascular age (AI-vascular age) from PPG signals, incorporating a distribution-aware loss to address biases caused by imbalanced data. The model was developed using data from the UK Biobank (UKB), with 98,672 participants in the development cohort and 113,559 participants (144,683 data pairs) for clinical evaluation. After adjusting for key confounders, individuals with a vascular age gap (AI-vascular age minus calendar age) exceeding 9 years had a significantly higher risk of major adverse cardiovascular and cerebrovascular events (MACCE) (HR = 2.37, p < 0.005) and secondary outcomes, including diabetes (HR = 2.69, p < 0.005), hypertension (HR = 2.88, p < 0.005), coronary heart disease (HR = 2.20, p < 0.005), heart failure (HR = 2.15, p < 0.005), myocardial infarction (HR = 2.51, p < 0.005), stroke (HR = 2.55, p < 0.005), and all-cause mortality (HR = 2.51, p < 0.005). Conversely, participants with a vascular age gap below -9 years exhibited a significantly lower incidence of these outcomes. We further evaluated the longitudinal applicability of AI-vascular age using serial PPG data from the UKB, demonstrating its value in risk stratification by leveraging AI-vascular age at two distinct time points to predict future MACCE incidence. External validation was performed on a MIMIC-III-derived cohort (n = 2,343), where each one-year increase in vascular age gap was significantly associated with elevated in-hospital mortality risk (OR = 1.02, p < 0.005). In conclusion, our study establishes AI-vascular age as a novel, non-invasive digital biomarker for cardiovascular health assessment.

Automatic disease diagnosis has become increasingly valuable in clinical practice. The advent of large language models (LLMs) has catalyzed a paradigm shift in artificial intelligence, with growing evidence supporting the efficacy of LLMs in diagnostic tasks. Despite the increasing attention in this field, a holistic view is still lacking. Many critical aspects remain unclear, such as the diseases and clinical data to which LLMs have been applied, the LLM techniques employed, and the evaluation methods used. In this article, we perform a comprehensive review of LLM-based methods for disease diagnosis. Our review examines the existing literature across various dimensions, including disease types and associated clinical specialties, clinical data, LLM techniques, and evaluation methods. Additionally, we offer recommendations for applying and evaluating LLMs for diagnostic tasks. Furthermore, we assess the limitations of current research and discuss future directions. To our knowledge, this is the first comprehensive review for LLM-based disease diagnosis.

Proteins perform nearly all cellular functions and constitute most drug targets, making their analysis fundamental to understanding human biology in health and disease. Tandem mass spectrometry (MS^2) is the major analytical technique in proteomics that identifies peptides by ionizing them, fragmenting them, and using the resulting mass spectra to identify and quantify proteins in biological samples. In MS^2 analysis, peptide fragment ion probability prediction plays a critical role, enhancing the accuracy of peptide identification from mass spectra as a complement to the intensity information. Current approaches rely on global statistics of fragmentation, which assumes that a fragment's probability is uniform across all peptides. Nevertheless, this assumption is oversimplified from a biochemical principle point of view and limits accurate prediction. To address this gap, we present Pep2Prob, the first comprehensive dataset and benchmark designed for peptide-specific fragment ion probability prediction. The proposed dataset contains fragment ion probability statistics for 608,780 unique precursors (each precursor is a pair of peptide sequence and charge state), summarized from more than 183 million high-quality, high-resolution, HCD MS^2 spectra with validated peptide assignments and fragmentation annotations. We establish baseline performance using simple statistical rules and learning-based methods, and find that models leveraging peptide-specific information significantly outperform previous methods using only global fragmentation statistics. Furthermore, performance across benchmark models with increasing capacities suggests that the peptide-fragmentation relationship exhibits complex nonlinearities requiring sophisticated machine learning approaches.

Generalist Large Language Models (LLMs), such as GPT-4, have shown considerable promise in various domains, including medical diagnosis. Rare diseases, affecting approximately 300 million people worldwide, often have unsatisfactory clinical diagnosis rates primarily due to a lack of experienced physicians and the complexity of differentiating among many rare diseases. In this context, recent news such as "ChatGPT correctly diagnosed a 4-year-old's rare disease after 17 doctors failed" underscore LLMs' potential, yet underexplored, role in clinically diagnosing rare diseases. To bridge this research gap, we introduce RareBench, a pioneering benchmark designed to systematically evaluate the capabilities of LLMs on 4 critical dimensions within the realm of rare diseases. Meanwhile, we have compiled the largest open-source dataset on rare disease patients, establishing a benchmark for future studies in this domain. To facilitate differential diagnosis of rare diseases, we develop a dynamic few-shot prompt methodology, leveraging a comprehensive rare disease knowledge graph synthesized from multiple knowledge bases, significantly enhancing LLMs' diagnostic performance. Moreover, we present an exhaustive comparative study of GPT-4's diagnostic capabilities against those of specialist physicians. Our experimental findings underscore the promising potential of integrating LLMs into the clinical diagnostic process for rare diseases. This paves the way for exciting possibilities in future advancements in this field.

Sepsis is a life-threatening host response to infection associated with high mortality, morbidity, and health costs. Its management is highly time-sensitive since each hour of delayed treatment increases mortality due to irreversible organ damage. Meanwhile, despite decades of clinical research, robust biomarkers for sepsis are missing. Therefore, detecting sepsis early by utilizing the affluence of high-resolution intensive care records has become a challenging machine learning problem. Recent advances in deep learning and data mining promise to deliver a powerful set of tools to efficiently address this task. This empirical study proposes two novel approaches for the early detection of sepsis: a deep learning model and a lazy learner based on time series distances. Our deep learning model employs a temporal convolutional network that is embedded in a Multi-task Gaussian Process Adapter framework, making it directly applicable to irregularly-spaced time series data. Our lazy learner, by contrast, is an ensemble approach that employs dynamic time warping. We frame the timely detection of sepsis as a supervised time series classification task. For this, we derive the most recent sepsis definition in an hourly resolution to provide the first fully accessible early sepsis detection environment. Seven hours before sepsis onset, our methods improve area under the precision--recall curve from 0.25 to 0.35/0.40 over the state of the art. This demonstrates that they are well-suited for detecting sepsis in the crucial earlier stages when management is most effective.

The rapid growth of biomedical literature and curated databases has made it increasingly difficult for researchers to systematically connect biomarker mechanisms to actionable drug combination hypotheses. We present AI Co-Scientist (CoDHy), an interactive, human-in-the-loop system for biomarker-guided drug combination hypothesis generation in cancer research. CoDHy integrates structured biomedical databases and unstructured literature evidence into a task-specific knowledge graph, which serves as the basis for graph-based reasoning and hypothesis construction. The system combines knowledge graph embeddings with agent-based reasoning to generate, validate, and rank candidate drug combinations, while explicitly grounding each hypothesis in retrievable evidence. Through a web-based interface, users can configure the scientific context, inspect intermediate results, and iteratively refine hypotheses, enabling transparent and researcher-steerable exploration rather than automated decision-making. We demonstrate CoDHy as a system for exploratory hypothesis generation and decision support in translational oncology, highlighting its design, interaction workflow, and practical use cases.

Healthcare data now span EHRs, medical imaging, genomics, and wearable sensors, but most diagnostic models still process these modalities in isolation. This limits their ability to capture early, cross-modal disease signatures. This paper introduces a multimodal foundation model built on a transformer architecture that integrates heterogeneous clinical data through modality-specific encoders and cross-modal attention. Each modality is mapped into a shared latent space and fused using multi-head attention with residual normalization. We implement the framework using a multimodal dataset that simulates early-stage disease patterns across EHR sequences, imaging patches, genomic profiles, and wearable signals, including missing-modality scenarios and label noise. The model is trained using supervised classification together with self-supervised reconstruction and contrastive alignment to improve robustness. Experimental evaluation demonstrates strong performance in early-detection settings, with stable classification metrics, reliable uncertainty estimates, and interpretable attention patterns. The approach moves toward a flexible, pretrain-and-fine-tune foundation model that supports precision diagnostics, handles incomplete inputs, and improves early disease detection across oncology, cardiology, and neurology applications.

We present DM-Bench, the first benchmark designed to evaluate large language model (LLM) performance across real-world decision-making tasks faced by individuals managing diabetes in their daily lives. Unlike prior health benchmarks that are either generic, clinician-facing or focused on clinical tasks (e.g., diagnosis, triage), DM-Bench introduces a comprehensive evaluation framework tailored to the unique challenges of prototyping patient-facing AI solutions in diabetes, glucose management, metabolic health and related domains. Our benchmark encompasses 7 distinct task categories, reflecting the breadth of real-world questions individuals with diabetes ask, including basic glucose interpretation, educational queries, behavioral associations, advanced decision making and long term planning. Towards this end, we compile a rich dataset comprising one month of time-series data encompassing glucose traces and metrics from continuous glucose monitors (CGMs) and behavioral logs (e.g., eating and activity patterns) from 15,000 individuals across three different diabetes populations (type 1, type 2, pre-diabetes/general health and wellness). Using this data, we generate a total of 360,600 personalized, contextual questions across the 7 tasks. We evaluate model performance on these tasks across 5 metrics: accuracy, groundedness, safety, clarity and actionability. Our analysis of 8 recent LLMs reveals substantial variability across tasks and metrics; no single model consistently outperforms others across all dimensions. By establishing this benchmark, we aim to advance the reliability, safety, effectiveness and practical utility of AI solutions in diabetes care.

Clinical diagnosis prediction models, when provided with a patient's medical history, aim to detect potential diseases early, facilitating timely intervention and improving prognostic outcomes. However, the inherent scarcity of patient data and large disease candidate space often pose challenges in developing satisfactory models for this intricate task. The exploration of leveraging Large Language Models (LLMs) for encapsulating clinical decision processes has been limited. We introduce MERA, a clinical diagnosis prediction model that bridges pertaining natural language knowledge with medical practice. We apply hierarchical contrastive learning on a disease candidate ranking list to alleviate the large decision space issue. With concept memorization through fine-tuning, we bridge the natural language clinical knowledge with medical codes. Experimental results on MIMIC-III and IV datasets show that MERA achieves the state-of-the-art diagnosis prediction performance and dramatically elevates the diagnosis prediction capabilities of generative LMs.

Tumor protein P53 is believed to be involved in over half of human cancers cases, the prediction of malignancies plays essential roles not only in advance detection for cancer, but also in discovering effective prevention and treatment of cancer, till now there isn't approach be able in prediction the mutated in tumor protein P53 which is caused high ratio of human cancers like breast, Blood, skin, liver, lung, bladder etc. This research proposed a new approach for prediction pre-cancer via detection malignant mutations in tumor protein P53 using bioinformatics tools like FASTA, BLAST, CLUSTALW and TP53 databases worldwide. Implement and apply this new approach of prediction pre-cancer through mutations at tumor protein P53 shows an effective result when used more specific parameters/features to extract the prediction result that means when the user increase the number of filters of the results which obtained from the database gives more specific diagnosis and classify, addition that the detecting pre-cancer via prediction mutated tumor protein P53 will reduces a person's cancers in the future by avoiding exposure to toxins, radiation or monitoring themselves at older ages by change their food, environment, even the pace of living. Also that new approach of prediction pre-cancer will help if there is any treatment can give for that person to therapy the mutated tumor protein P53. Index Terms (Normal Homology TP53 gene, Tumor Protein P53, Oncogene Labs, GC and AT content, FASTA, BLAST, ClustalW)

Human medical data can be challenging to obtain due to data privacy concerns, difficulties conducting certain types of experiments, or prohibitive associated costs. In many settings, data from animal models or in-vitro cell lines are available to help augment our understanding of human data. However, this data is known for having low etiological validity in comparison to human data. In this work, we augment small human medical datasets with in-vitro data and animal models. We use Invariant Risk Minimisation (IRM) to elucidate invariant features by considering cross-organism data as belonging to different data-generating environments. Our models identify genes of relevance to human cancer development. We observe a degree of consistency between varying the amounts of human and mouse data used, however, further work is required to obtain conclusive insights. As a secondary contribution, we enhance existing open source datasets and provide two uniformly processed, cross-organism, homologue gene-matched datasets to the community.

Pathology Foundation Models (FMs) hold great promise for healthcare. Before they can be used in clinical practice, it is essential to ensure they are robust to variations between medical centers. We measure whether pathology FMs focus on biological features like tissue and cancer type, or on the well known confounding medical center signatures introduced by staining procedure and other differences. We introduce the Robustness Index. This novel robustness metric reflects to what degree biological features dominate confounding features. Ten current publicly available pathology FMs are evaluated. We find that all current pathology foundation models evaluated represent the medical center to a strong degree. Significant differences in the robustness index are observed. Only one model so far has a robustness index greater than one, meaning biological features dominate confounding features, but only slightly. A quantitative approach to measure the influence of medical center differences on FM-based prediction performance is described. We analyze the impact of unrobustness on classification performance of downstream models, and find that cancer-type classification errors are not random, but specifically attributable to same-center confounders: images of other classes from the same medical center. We visualize FM embedding spaces, and find these are more strongly organized by medical centers than by biological factors. As a consequence, the medical center of origin is predicted more accurately than the tissue source and cancer type. The robustness index introduced here is provided with the aim of advancing progress towards clinical adoption of robust and reliable pathology FMs.

Efficient Human Epithelial-2 (HEp-2) cell image classification can facilitate the diagnosis of many autoimmune diseases. This paper presents an automatic framework for this classification task, by utilizing the deep convolutional neural networks (CNNs) which have recently attracted intensive attention in visual recognition. This paper elaborates the important components of this framework, discusses multiple key factors that impact the efficiency of training a deep CNN, and systematically compares this framework with the well-established image classification models in the literature. Experiments on benchmark datasets show that i) the proposed framework can effectively outperform existing models by properly applying data augmentation; ii) our CNN-based framework demonstrates excellent adaptability across different datasets, which is highly desirable for classification under varying laboratory settings. Our system is ranked high in the cell image classification competition hosted by ICPR 2014.

Hepato-pancreato-biliary (HPB) disorders represent a global public health challenge due to their high morbidity and mortality. Although large language models (LLMs) have shown promising performance in general medical question-answering tasks, the current evaluation benchmarks are mostly derived from standardized examinations or manually designed questions, lacking HPB coverage and clinical cases. To address these issues, we systematically eatablish an HPB disease evaluation benchmark comprising 3,535 closed-ended multiple-choice questions and 337 open-ended real diagnosis cases, which encompasses all the 33 main categories and 465 subcategories of HPB diseases defined in the International Statistical Classification of Diseases, 10th Revision (ICD-10). The multiple-choice questions are curated from public datasets and synthesized data, and the clinical cases are collected from prestigious medical journals, case-sharing platforms, and collaborating hospitals. By evalauting commercial and open-source general and medical LLMs on our established benchmark, namely ClinBench-HBP, we find that while commercial LLMs perform competently on medical exam questions, they exhibit substantial performance degradation on HPB diagnosis tasks, especially on complex, inpatient clinical cases. Those medical LLMs also show limited generalizability to HPB diseases. Our results reveal the critical limitations of current LLMs in the domain of HPB diseases, underscoring the imperative need for future medical LLMs to handle real, complex clinical diagnostics rather than simple medical exam questions. The benchmark will be released at https://clinbench-hpb.github.io.

We introduce a new visual-interactive tool: Explainable Labeling Assistant (XLabel) that takes an explainable machine learning approach to data labeling. The main component of XLabel is the Explainable Boosting Machine (EBM), a predictive model that can calculate the contribution of each input feature towards the final prediction. As a case study, we use XLabel to predict the labels of four non-communicable diseases (NCDs): diabetes, hypertension, chronic kidney disease, and dyslipidemia. We demonstrate that EBM is an excellent choice of predictive model by comparing it against a rule-based and four other machine learning models. By performing 5-fold cross-validation on 427 medical records, EBM's prediction accuracy, precision, and F1-score are greater than 0.95 in all four NCDs. It performed as well as two black-box models and outperformed the other models in these metrics. In an additional experiment, when 40% of the records were intentionally mislabeled, EBM could recall the correct labels of more than 90% of these records.

Following the global COVID-19 pandemic, the number of scientific papers studying the virus has grown massively, leading to increased interest in automated literate review. We present a clinical text mining system that improves on previous efforts in three ways. First, it can recognize over 100 different entity types including social determinants of health, anatomy, risk factors, and adverse events in addition to other commonly used clinical and biomedical entities. Second, the text processing pipeline includes assertion status detection, to distinguish between clinical facts that are present, absent, conditional, or about someone other than the patient. Third, the deep learning models used are more accurate than previously available, leveraging an integrated pipeline of state-of-the-art pretrained named entity recognition models, and improving on the previous best performing benchmarks for assertion status detection. We illustrate extracting trends and insights, e.g. most frequent disorders and symptoms, and most common vital signs and EKG findings, from the COVID-19 Open Research Dataset (CORD-19). The system is built using the Spark NLP library which natively supports scaling to use distributed clusters, leveraging GPUs, configurable and reusable NLP pipelines, healthcare specific embeddings, and the ability to train models to support new entity types or human languages with no code changes.

Hypertension, defined as blood pressure (BP) that is above normal, holds paramount significance in the realm of public health, as it serves as a critical precursor to various cardiovascular diseases (CVDs) and significantly contributes to elevated mortality rates worldwide. However, many existing BP measurement technologies and standards might be biased because they do not consider clinical outcomes, comorbidities, or demographic factors, making them inconclusive for diagnostic purposes. There is limited data-driven research focused on studying the variance in BP measurements across these variables. In this work, we employed GPT-35-turbo, a large language model (LLM), to automatically extract the mean and standard deviation values of BP for both males and females from a dataset comprising 25 million abstracts sourced from PubMed. 993 article abstracts met our predefined inclusion criteria (i.e., presence of references to blood pressure, units of blood pressure such as mmHg, and mention of biological sex). Based on the automatically-extracted information from these articles, we conducted an analysis of the variations of BP values across biological sex. Our results showed the viability of utilizing LLMs to study the BP variations across different demographic factors.

Lung diseases remain a critical global health concern, and it's crucial to have accurate and quick ways to diagnose them. This work focuses on classifying different lung diseases into five groups: viral pneumonia, bacterial pneumonia, COVID, tuberculosis, and normal lungs. Employing advanced deep learning techniques, we explore a diverse range of models including CNN, hybrid models, ensembles, transformers, and Big Transfer. The research encompasses comprehensive methodologies such as hyperparameter tuning, stratified k-fold cross-validation, and transfer learning with fine-tuning.Remarkably, our findings reveal that the Xception model, fine-tuned through 5-fold cross-validation, achieves the highest accuracy of 96.21\%. This success shows that our methods work well in accurately identifying different lung diseases. The exploration of explainable artificial intelligence (XAI) methodologies further enhances our understanding of the decision-making processes employed by these models, contributing to increased trust in their clinical applications.

Machine learning techniques are effective for building predictive models because they identify patterns in large datasets. Development of a model for complex real-life problems often stop at the point of publication, proof of concept or when made accessible through some mode of deployment. However, a model in the medical domain risks becoming obsolete as patient demographics, systems and clinical practices change. The maintenance and monitoring of predictive model performance post-publication is crucial to enable their safe and effective long-term use. We will assess the infrastructure required to monitor the outputs of a machine learning algorithm, and present two scenarios with examples of monitoring and updates of models, firstly on a breast cancer prognosis model trained on public longitudinal data, and secondly on a neurodegenerative stratification algorithm that is currently being developed and tested in clinic.

Despite the impressive capabilities of Large Language Models (LLMs) in general medical domains, questions remain about their performance in diagnosing rare diseases. To answer this question, we aim to assess the diagnostic performance of LLMs in rare diseases, and explore methods to enhance their effectiveness in this area. In this work, we introduce a rare disease question-answering (ReDis-QA) dataset to evaluate the performance of LLMs in diagnosing rare diseases. Specifically, we collected 1360 high-quality question-answer pairs within the ReDis-QA dataset, covering 205 rare diseases. Additionally, we annotated meta-data for each question, facilitating the extraction of subsets specific to any given disease and its property. Based on the ReDis-QA dataset, we benchmarked several open-source LLMs, revealing that diagnosing rare diseases remains a significant challenge for these models. To facilitate retrieval augmentation generation for rare disease diagnosis, we collect the first rare diseases corpus (ReCOP), sourced from the National Organization for Rare Disorders (NORD) database. Specifically, we split the report of each rare disease into multiple chunks, each representing a different property of the disease, including their overview, symptoms, causes, effects, related disorders, diagnosis, and standard therapies. This structure ensures that the information within each chunk aligns consistently with a question. Experiment results demonstrate that ReCOP can effectively improve the accuracy of LLMs on the ReDis-QA dataset by an average of 8%. Moreover, it significantly guides LLMs to generate trustworthy answers and explanations that can be traced back to existing literature.

The recent surge in performance for image analysis of digitised pathology slides can largely be attributed to the advances in deep learning. Deep models can be used to initially localise various structures in the tissue and hence facilitate the extraction of interpretable features for biomarker discovery. However, these models are typically trained for a single task and therefore scale poorly as we wish to adapt the model for an increasing number of different tasks. Also, supervised deep learning models are very data hungry and therefore rely on large amounts of training data to perform well. In this paper, we present a multi-task learning approach for segmentation and classification of nuclei, glands, lumina and different tissue regions that leverages data from multiple independent data sources. While ensuring that our tasks are aligned by the same tissue type and resolution, we enable meaningful simultaneous prediction with a single network. As a result of feature sharing, we also show that the learned representation can be used to improve the performance of additional tasks via transfer learning, including nuclear classification and signet ring cell detection. As part of this work, we train our developed Cerberus model on a huge amount of data, consisting of over 600K objects for segmentation and 440K patches for classification. We use our approach to process 599 colorectal whole-slide images from TCGA, where we localise 377 million, 900K and 2.1 million nuclei, glands and lumina, respectively and make the results available to the community for downstream analysis.

Drug discovery typically consists of multiple steps, including identifying a target protein key to a disease's etiology, validating that interacting with this target could prevent symptoms or cure the disease, discovering a small molecule or biologic therapeutic to interact with it, and optimizing the candidate molecule through a complex landscape of required properties. Drug discovery related tasks often involve prediction and generation while considering multiple entities that potentially interact, which poses a challenge for typical AI models. For this purpose we present MAMMAL - Molecular Aligned Multi-Modal Architecture and Language - a method that we applied to create a versatile multi-task foundation model ibm/biomed.omics.bl.sm.ma-ted-458m that learns from large-scale biological datasets (2 billion samples) across diverse modalities, including proteins, small molecules, and genes. We introduce a prompt syntax that supports a wide range of classification, regression, and generation tasks. It allows combining different modalities and entity types as inputs and/or outputs. Our model handles combinations of tokens and scalars and enables the generation of small molecules and proteins, property prediction, and transcriptomic lab test predictions. We evaluated the model on 11 diverse downstream tasks spanning different steps within a typical drug discovery pipeline, where it reaches new SOTA in 9 tasks and is comparable to SOTA in 2 tasks. This performance is achieved while using a unified architecture serving all tasks, in contrast to the original SOTA performance achieved using tailored architectures. The model code and pretrained weights are publicly available at https://github.com/BiomedSciAI/biomed-multi-alignment and https://huggingface.co/ibm/biomed.omics.bl.sm.ma-ted-458m.

Deep Learning based models are currently dominating most state-of-the-art solutions for disease prediction. Existing works employ RNNs along with multiple levels of attention mechanisms to provide interpretability. These deep learning models, with trainable parameters running into millions, require huge amounts of compute and data to train and deploy. These requirements are sometimes so huge that they render usage of such models as unfeasible. We address these challenges by developing a simpler yet interpretable non-deep learning based model for application to EHR data. We model and showcase our work's results on the task of predicting first occurrence of a diagnosis, often overlooked in existing works. We push the capabilities of a tree based model and come up with a strong baseline for more sophisticated models. Its performance shows an improvement over deep learning based solutions (both, with and without the first-occurrence constraint) all the while maintaining interpretability.

Controlling the COVID-19 pandemic largely hinges upon the existence of fast, safe, and highly-available diagnostic tools. Ultrasound, in contrast to CT or X-Ray, has many practical advantages and can serve as a globally-applicable first-line examination technique. We provide the largest publicly available lung ultrasound (US) dataset for COVID-19 consisting of 106 videos from three classes (COVID-19, bacterial pneumonia, and healthy controls); curated and approved by medical experts. On this dataset, we perform an in-depth study of the value of deep learning methods for differential diagnosis of COVID-19. We propose a frame-based convolutional neural network that correctly classifies COVID-19 US videos with a sensitivity of 0.98+-0.04 and a specificity of 0.91+-08 (frame-based sensitivity 0.93+-0.05, specificity 0.87+-0.07). We further employ class activation maps for the spatio-temporal localization of pulmonary biomarkers, which we subsequently validate for human-in-the-loop scenarios in a blindfolded study with medical experts. Aiming for scalability and robustness, we perform ablation studies comparing mobile-friendly, frame- and video-based architectures and show reliability of the best model by aleatoric and epistemic uncertainty estimates. We hope to pave the road for a community effort toward an accessible, efficient and interpretable screening method and we have started to work on a clinical validation of the proposed method. Data and code are publicly available.

Foodborne gastrointestinal (GI) illness is a common cause of ill health in the UK. However, many cases do not interact with the healthcare system, posing significant challenges for traditional surveillance methods. The growth of publicly available online restaurant reviews and advancements in large language models (LLMs) present potential opportunities to extend disease surveillance by identifying public reports of GI illness. In this study, we introduce a novel annotation schema, developed with experts in GI illness, applied to the Yelp Open Dataset of reviews. Our annotations extend beyond binary disease detection, to include detailed extraction of information on symptoms and foods. We evaluate the performance of open-weight LLMs across these three tasks: GI illness detection, symptom extraction, and food extraction. We compare this performance to RoBERTa-based classification models fine-tuned specifically for these tasks. Our results show that using prompt-based approaches, LLMs achieve micro-F1 scores of over 90% for all three of our tasks. Using prompting alone, we achieve micro-F1 scores that exceed those of smaller fine-tuned models. We further demonstrate the robustness of LLMs in GI illness detection across three bias-focused experiments. Our results suggest that publicly available review text and LLMs offer substantial potential for public health surveillance of GI illness by enabling highly effective extraction of key information. While LLMs appear to exhibit minimal bias in processing, the inherent limitations of restaurant review data highlight the need for cautious interpretation of results.

Medical images and radiology reports are crucial for diagnosing medical conditions, highlighting the importance of quantitative analysis for clinical decision-making. However, the diversity and cross-source heterogeneity of these data challenge the generalizability of current data-mining methods. Multimodal large language models (MLLMs) have recently transformed many domains, significantly affecting the medical field. Notably, Gemini-Vision-series (Gemini) and GPT-4-series (GPT-4) models have epitomized a paradigm shift in Artificial General Intelligence (AGI) for computer vision, showcasing their potential in the biomedical domain. In this study, we evaluated the performance of the Gemini, GPT-4, and 4 popular large models for an exhaustive evaluation across 14 medical imaging datasets, including 5 medical imaging categories (dermatology, radiology, dentistry, ophthalmology, and endoscopy), and 3 radiology report datasets. The investigated tasks encompass disease classification, lesion segmentation, anatomical localization, disease diagnosis, report generation, and lesion detection. Our experimental results demonstrated that Gemini-series models excelled in report generation and lesion detection but faces challenges in disease classification and anatomical localization. Conversely, GPT-series models exhibited proficiency in lesion segmentation and anatomical localization but encountered difficulties in disease diagnosis and lesion detection. Additionally, both the Gemini series and GPT series contain models that have demonstrated commendable generation efficiency. While both models hold promise in reducing physician workload, alleviating pressure on limited healthcare resources, and fostering collaboration between clinical practitioners and artificial intelligence technologies, substantial enhancements and comprehensive validations remain imperative before clinical deployment.

Diabetes is a chronic disorder identified by the high sugar level in the blood that can cause various different disorders such as kidney failure, heart attack, sightlessness, and stroke. Developments in the healthcare domain by facilitating the early detection of diabetes risk can help not only caregivers but also patients. AIoMT is a recent technology that integrates IoT and machine learning methods to give services for medical purposes, which is a powerful technology for the early detection of diabetes. In this paper, we take advantage of AIoMT and propose a hybrid diabetes risk detection method, DiabML, which uses the BWO algorithm and ML methods. BWO is utilized for feature selection and SMOTE for imbalance handling in the pre-processing procedure. The simulation results prove the superiority of the proposed DiabML method compared to the existing works. DiabML achieves 86.1\% classification accuracy by AdaBoost classifier outperforms the relevant existing methods.

Gene expression can be used to subtype breast cancer with improved prediction of risk of recurrence and treatment responsiveness over that obtained using routine immunohistochemistry (IHC). However, in the clinic, molecular profiling is primarily used for ER+ breast cancer, which is costly, tissue destructive, requires specialized platforms and takes several weeks to obtain a result. Deep learning algorithms can effectively extract morphological patterns in digital histopathology images to predict molecular phenotypes quickly and cost-effectively. We propose a new, computationally efficient approach called hist2RNA inspired by bulk RNA-sequencing techniques to predict the expression of 138 genes (incorporated from six commercially available molecular profiling tests), including luminal PAM50 subtype, from hematoxylin and eosin (H&E) stained whole slide images (WSIs). The training phase involves the aggregation of extracted features for each patient from a pretrained model to predict gene expression at the patient level using annotated H&E images from The Cancer Genome Atlas (TCGA, n=335). We demonstrate successful gene prediction on a held-out test set (n = 160, corr = 0.82 across patients, corr = 0.29 across genes) and perform exploratory analysis on an external tissue microarray (TMA) dataset (n = 498) with known IHC and survival information. Our model is able to predict gene expression and luminal PAM50 subtype (Luminal A versus Luminal B) on the TMA dataset with prognostic significance for overall survival in univariate analysis (c-index = 0.56, hazard ratio = 2.16 (95% CI 1.12-3.06), p < 5 x 10-3), and independent significance in multivariate analysis incorporating standard clinicopathological variables (c-index = 0.65, hazard ratio = 1.85 (95% CI 1.30-2.68), p < 5 x 10-3).

WHO has declared that more than 2.2 billion people worldwide are suffering from visual disorders, such as media haze, glaucoma, and drusen. At least 1 billion of these cases could have been either prevented or successfully treated, yet they remain unaddressed due to poverty, a lack of specialists, inaccurate ocular fundus diagnoses by ophthalmologists, or the presence of a rare disease. To address this, the research has developed the Hybrid Trio-Network Model Algorithm for accurately diagnosing 12 distinct common and rare eye diseases. This algorithm utilized the RFMiD dataset of 3,200 fundus images and the Binary Relevance Method to detect diseases separately, ensuring expandability and avoiding incorrect correlations. Each detector, incorporating finely tuned hyperparameters to optimize performance, consisted of three feature components: A classical transfer learning CNN model, a two-stage CNN model, and a Siamese Network. The diagnosis was made using features extracted through this Trio-Model with Ensembled Machine Learning algorithms. The proposed model achieved an average accuracy of 97% and an AUC score of 0.96. Compared to past benchmark studies, an increase of over 10% in the F1-score was observed for most diseases. Furthermore, using the Siamese Network, the model successfully made predictions in diseases like optic disc pallor, which past studies failed to predict due to low confidence. This diagnostic tool presents a stable, adaptive, cost-effective, efficient, accessible, and fast solution for globalizing early detection of both common and rare diseases.

Objective: Data unavailability has been one of the biggest barriers in clinical natural language processing. This paper is aimed at providing a large-scale and publicly available patient note dataset, named PMC-Patients, with relevant articles and similar patients annotations. The ultimate goal of PMC-Patients is to facilitate the development of retrieval-based clinical decision support systems. Materials and Methods: To collect PMC-Patients, we extract patient notes from case reports in PubMed Central by recognizing certain section patterns. Patient-article relevance and patient-patient similarity are annotated by citation relationships in PubMed. In addition, we perform three tasks with PMC-Patients to demonstrate its utility in providing clinical decision support for a given patient, including (1) classifying whether another patient is similar, (2) retrieving similar patients in PMC-Patients, and (3) retrieving relevant articles in PubMed. Results: We collect and release PMC-Patients under the CC BY-NC-SA license, which becomes the largest publicly available patient note dataset so far. PMC-Patients contains 167k patient notes that are annotated with 3.1M relevant articles and 293k similar patients. Qualitative and quantitative analyses reveal the high quality and richness of our dataset. Experiments show that classifying the similarity of patient pairs is relatively easy, but it is hard to retrieve similar patients or relevant articles for a given patient from a large set of candidates. Conclusion: We present PMC-Patients, a large-scale dataset of patient notes with high quality, easy access, diverse conditions, and rich annotations. The proposed dataset can also serve as a hard benchmark for evaluating retrieval-based clinical decision support systems.

Digital pathology enables automatic analysis of histopathological sections using artificial intelligence (AI). Automatic evaluation could improve diagnostic efficiency and help find associations between morphological features and clinical outcome. For development of such prediction models, identifying invasive epithelial cells, and separating these from benign epithelial cells and in situ lesions would be the first step. In this study, we aimed to develop an AI model for segmentation of epithelial cells in sections from breast cancer. We generated epithelial ground truth masks by restaining hematoxylin and eosin (HE) sections with cytokeratin (CK) AE1/AE3, and by pathologists' annotations. HE/CK image pairs were used to train a convolutional neural network, and data augmentation was used to make the model more robust. Tissue microarrays (TMAs) from 839 patients, and whole slide images from two patients were used for training and evaluation of the models. The sections were derived from four cohorts of breast cancer patients. TMAs from 21 patients from a fifth cohort was used as a second test set. In quantitative evaluation, a mean Dice score of 0.70, 0.79, and 0.75 for invasive epithelial cells, benign epithelial cells, and in situ lesions, respectively, were achieved. In qualitative scoring (0-5) by pathologists, results were best for all epithelium and invasive epithelium, with scores of 4.7 and 4.4. Scores for benign epithelium and in situ lesions were 3.7 and 2.0. The proposed model segmented epithelial cells in HE stained breast cancer slides well, but further work is needed for accurate division between the classes. Immunohistochemistry, together with pathologists' annotations, enabled the creation of accurate ground truths. The model is made freely available in FastPathology and the code is available at https://github.com/AICAN-Research/breast-epithelium-segmentation

Timely and accurate lymphoma diagnosis is essential for guiding cancer treatment. Standard diagnostic practice combines hematoxylin and eosin (HE)-stained whole slide images with immunohistochemistry, flow cytometry, and molecular genetic tests to determine lymphoma subtypes, a process requiring costly equipment, skilled personnel, and causing treatment delays. Deep learning methods could assist pathologists by extracting diagnostic information from routinely available HE-stained slides, yet comprehensive benchmarks for lymphoma subtyping on multicenter data are lacking. In this work, we present the first multicenter lymphoma benchmarking dataset covering four common lymphoma subtypes and healthy control tissue. We systematically evaluate five publicly available pathology foundation models (H-optimus-1, H0-mini, Virchow2, UNI2, Titan) combined with attention-based (AB-MIL) and transformer-based (TransMIL) multiple instance learning aggregators across three magnifications (10x, 20x, 40x). On in-distribution test sets, models achieve multiclass balanced accuracies exceeding 80% across all magnifications, with all foundation models performing similarly and both aggregation methods showing comparable results. The magnification study reveals that 40x resolution is sufficient, with no performance gains from higher resolutions or cross-magnification aggregation. However, on out-of-distribution test sets, performance drops substantially to around 60%, highlighting significant generalization challenges. To advance the field, larger multicenter studies covering additional rare lymphoma subtypes are needed. We provide an automated benchmarking pipeline to facilitate such future research.

Contrast agents in dynamic contrast enhanced magnetic resonance imaging allow to localize tumors and observe their contrast kinetics, which is essential for cancer characterization and respective treatment decision-making. However, contrast agent administration is not only associated with adverse health risks, but also restricted for patients during pregnancy, and for those with kidney malfunction, or other adverse reactions. With contrast uptake as key biomarker for lesion malignancy, cancer recurrence risk, and treatment response, it becomes pivotal to reduce the dependency on intravenous contrast agent administration. To this end, we propose a multi-conditional latent diffusion model capable of acquisition time-conditioned image synthesis of DCE-MRI temporal sequences. To evaluate medical image synthesis, we additionally propose and validate the Fréchet radiomics distance as an image quality measure based on biomarker variability between synthetic and real imaging data. Our results demonstrate our method's ability to generate realistic multi-sequence fat-saturated breast DCE-MRI and uncover the emerging potential of deep learning based contrast kinetics simulation. We publicly share our accessible codebase at https://github.com/RichardObi/ccnet and provide a user-friendly library for Fréchet radiomics distance calculation at https://pypi.org/project/frd-score.

Background: This study aimed to evaluate and compare the performance of classical machine learning models (CMLs) and large language models (LLMs) in predicting mortality associated with COVID-19 by utilizing a high-dimensional tabular dataset. Materials and Methods: We analyzed data from 9,134 COVID-19 patients collected across four hospitals. Seven CML models, including XGBoost and random forest (RF), were trained and evaluated. The structured data was converted into text for zero-shot classification by eight LLMs, including GPT-4 and Mistral-7b. Additionally, Mistral-7b was fine-tuned using the QLoRA approach to enhance its predictive capabilities. Results: Among the CML models, XGBoost and RF achieved the highest accuracy, with F1 scores of 0.87 for internal validation and 0.83 for external validation. In the LLM category, GPT-4 was the top performer with an F1 score of 0.43. Fine-tuning Mistral-7b significantly improved its recall from 1% to 79%, resulting in an F1 score of 0.74, which was stable during external validation. Conclusion: While LLMs show moderate performance in zero-shot classification, fine-tuning can significantly enhance their effectiveness, potentially aligning them closer to CML models. However, CMLs still outperform LLMs in high-dimensional tabular data tasks.

Multimodal large language models (MLLMs) have advanced clinical tasks for common conditions, but their performance on rare diseases remains largely untested. In rare-disease scenarios, clinicians often lack prior clinical knowledge, forcing them to rely strictly on case-level evidence for clinical judgments. Existing benchmarks predominantly evaluate common-condition, single-image settings, leaving multimodal and multi-image evidence integration under rare-disease data scarcity systematically unevaluated. We introduce MMRareBench, to our knowledge the first rare-disease benchmark jointly evaluating multimodal and multi-image clinical capability across four workflow-aligned tracks: diagnosis, treatment planning, cross-image evidence alignment, and examination suggestion. The benchmark comprises 1,756 question-answer pairs with 7,958 associated medical images curated from PMC case reports, with Orphanet-anchored ontology alignment, track-specific leakage control, evidence-grounded annotations, and a two-level evaluation protocol. A systematic evaluation of 23 MLLMs reveals fragmented capability profiles and universally low treatment-planning performance, with medical-domain models trailing general-purpose MLLMs substantially on multi-image tracks despite competitive diagnostic scores. These patterns are consistent with a capacity dilution effect: medical fine-tuning can narrow the diagnostic gap but may erode the compositional multi-image capability that rare-disease evidence integration demands.

Color fundus photography and Optical Coherence Tomography (OCT) are the two most cost-effective tools for glaucoma screening. Both two modalities of images have prominent biomarkers to indicate glaucoma suspected. Clinically, it is often recommended to take both of the screenings for a more accurate and reliable diagnosis. However, although numerous algorithms are proposed based on fundus images or OCT volumes in computer-aided diagnosis, there are still few methods leveraging both of the modalities for the glaucoma assessment. Inspired by the success of Retinal Fundus Glaucoma Challenge (REFUGE) we held previously, we set up the Glaucoma grAding from Multi-Modality imAges (GAMMA) Challenge to encourage the development of fundus \& OCT-based glaucoma grading. The primary task of the challenge is to grade glaucoma from both the 2D fundus images and 3D OCT scanning volumes. As part of GAMMA, we have publicly released a glaucoma annotated dataset with both 2D fundus color photography and 3D OCT volumes, which is the first multi-modality dataset for glaucoma grading. In addition, an evaluation framework is also established to evaluate the performance of the submitted methods. During the challenge, 1272 results were submitted, and finally, top-10 teams were selected to the final stage. We analysis their results and summarize their methods in the paper. Since all these teams submitted their source code in the challenge, a detailed ablation study is also conducted to verify the effectiveness of the particular modules proposed. We find many of the proposed techniques are practical for the clinical diagnosis of glaucoma. As the first in-depth study of fundus \& OCT multi-modality glaucoma grading, we believe the GAMMA Challenge will be an essential starting point for future research.

Antibodies have become an important class of therapeutic agents to treat human diseases. To accelerate therapeutic antibody discovery, computational methods, especially machine learning, have attracted considerable interest for predicting specific interactions between antibody candidates and target antigens such as viruses and bacteria. However, the publicly available datasets in existing works have notable limitations, such as small sizes and the lack of non-binding samples and exact amino acid sequences. To overcome these limitations, we have developed AVIDa-hIL6, a large-scale dataset for predicting antigen-antibody interactions in the variable domain of heavy chain of heavy chain antibodies (VHHs), produced from an alpaca immunized with the human interleukin-6 (IL-6) protein, as antigens. By leveraging the simple structure of VHHs, which facilitates identification of full-length amino acid sequences by DNA sequencing technology, AVIDa-hIL6 contains 573,891 antigen-VHH pairs with amino acid sequences. All the antigen-VHH pairs have reliable labels for binding or non-binding, as generated by a novel labeling method. Furthermore, via introduction of artificial mutations, AVIDa-hIL6 contains 30 different mutants in addition to wild-type IL-6 protein. This characteristic provides opportunities to develop machine learning models for predicting changes in antibody binding by antigen mutations. We report experimental benchmark results on AVIDa-hIL6 by using neural network-based baseline models. The results indicate that the existing models have potential, but further research is needed to generalize them to predict effective antibodies against unknown mutants. The dataset is available at https://avida-hil6.cognanous.com.

Deep learning has enabled the development of highly robust foundation models for various pathological tasks across diverse diseases and patient cohorts. Among these models, vision-language pre-training, which leverages large-scale paired data to align pathology image and text embedding spaces, and provides a novel zero-shot paradigm for downstream tasks. However, existing models have been primarily data-driven and lack the incorporation of domain-specific knowledge, which limits their performance in cancer diagnosis, especially for rare tumor subtypes. To address this limitation, we establish a Knowledge-enhanced Pathology (KEEP) foundation model that harnesses disease knowledge to facilitate vision-language pre-training. Specifically, we first construct a disease knowledge graph (KG) that covers 11,454 human diseases with 139,143 disease attributes, including synonyms, definitions, and hypernym relations. We then systematically reorganize the millions of publicly available noisy pathology image-text pairs, into 143K well-structured semantic groups linked through the hierarchical relations of the disease KG. To derive more nuanced image and text representations, we propose a novel knowledge-enhanced vision-language pre-training approach that integrates disease knowledge into the alignment within hierarchical semantic groups instead of unstructured image-text pairs. Validated on 18 diverse benchmarks with more than 14,000 whole slide images (WSIs), KEEP achieves state-of-the-art performance in zero-shot cancer diagnostic tasks. Notably, for cancer detection, KEEP demonstrates an average sensitivity of 89.8% at a specificity of 95.0% across 7 cancer types. For cancer subtyping, KEEP achieves a median balanced accuracy of 0.456 in subtyping 30 rare brain cancers, indicating strong generalizability for diagnosing rare tumors.

Predicting drug-target interactions (DTI) is an essential part of the drug discovery process, which is an expensive process in terms of time and cost. Therefore, reducing DTI cost could lead to reduced healthcare costs for a patient. In addition, a precisely learned molecule representation in a DTI model could contribute to developing personalized medicine, which will help many patient cohorts. In this paper, we propose a new molecule representation based on the self-attention mechanism, and a new DTI model using our molecule representation. The experiments show that our DTI model outperforms the state of the art by up to 4.9% points in terms of area under the precision-recall curve. Moreover, a study using the DrugBank database proves that our model effectively lists all known drugs targeting a specific cancer biomarker in the top-30 candidate list.

Foundation models, often pre-trained with large-scale data, have achieved paramount success in jump-starting various vision and language applications. Recent advances further enable adapting foundation models in downstream tasks efficiently using only a few training samples, e.g., in-context learning. Yet, the application of such learning paradigms in medical image analysis remains scarce due to the shortage of publicly accessible data and benchmarks. In this paper, we aim at approaches adapting the foundation models for medical image classification and present a novel dataset and benchmark for the evaluation, i.e., examining the overall performance of accommodating the large-scale foundation models downstream on a set of diverse real-world clinical tasks. We collect five sets of medical imaging data from multiple institutes targeting a variety of real-world clinical tasks (22,349 images in total), i.e., thoracic diseases screening in X-rays, pathological lesion tissue screening, lesion detection in endoscopy images, neonatal jaundice evaluation, and diabetic retinopathy grading. Results of multiple baseline methods are demonstrated using the proposed dataset from both accuracy and cost-effective perspectives.

Medical benchmark datasets significantly contribute to developing Large Language Models (LLMs) for medical knowledge extraction, diagnosis, summarization, and other uses. Yet, current benchmarks are mainly derived from exam questions given to medical students or cases described in the medical literature, lacking the complexity of real-world patient cases that deviate from classic textbook abstractions. These include rare diseases, uncommon presentations of common diseases, and unexpected treatment responses. Here, we construct Clinically Uncommon Patient Cases and Diagnosis Dataset (CUPCase) based on 3,562 real-world case reports from BMC, including diagnoses in open-ended textual format and as multiple-choice options with distractors. Using this dataset, we evaluate the ability of state-of-the-art LLMs, including both general-purpose and Clinical LLMs, to identify and correctly diagnose a patient case, and test models' performance when only partial information about cases is available. Our findings show that general-purpose GPT-4o attains the best performance in both the multiple-choice task (average accuracy of 87.9%) and the open-ended task (BERTScore F1 of 0.764), outperforming several LLMs with a focus on the medical domain such as Meditron-70B and MedLM-Large. Moreover, GPT-4o was able to maintain 87% and 88% of its performance with only the first 20% of tokens of the case presentation in multiple-choice and free text, respectively, highlighting the potential of LLMs to aid in early diagnosis in real-world cases. CUPCase expands our ability to evaluate LLMs for clinical decision support in an open and reproducible manner.

Progress in remote PhotoPlethysmoGraphy (rPPG) is limited by the critical issues of existing publicly available datasets: small size, privacy concerns with facial videos, and lack of diversity in conditions. The paper introduces a novel comprehensive large-scale multi-view video dataset for rPPG and health biomarkers estimation. Our dataset comprises 3600 synchronized video recordings from 600 subjects, captured under varied conditions (resting and post-exercise) using multiple consumer-grade cameras at different angles. To enable multimodal analysis of physiological states, each recording is paired with a 100 Hz PPG signal and extended health metrics, such as electrocardiogram, arterial blood pressure, biomarkers, temperature, oxygen saturation, respiratory rate, and stress level. Using this data, we train an efficient rPPG model and compare its quality with existing approaches in cross-dataset scenarios. The public release of our dataset and model should significantly speed up the progress in the development of AI medical assistants.

The medical domain is vast and diverse, with many existing embedding models focused on general healthcare applications. However, these models often struggle to capture a deep understanding of diseases due to their broad generalization across the entire medical field. To address this gap, I present DisEmbed, a disease-focused embedding model. DisEmbed is trained on a synthetic dataset specifically curated to include disease descriptions, symptoms, and disease-related Q\&A pairs, making it uniquely suited for disease-related tasks. For evaluation, I benchmarked DisEmbed against existing medical models using disease-specific datasets and the triplet evaluation method. My results demonstrate that DisEmbed outperforms other models, particularly in identifying disease-related contexts and distinguishing between similar diseases. This makes DisEmbed highly valuable for disease-specific use cases, including retrieval-augmented generation (RAG) tasks, where its performance is particularly robust.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease affecting 35% of extremely low birth weight infants. Defined by oxygen dependence at 36 weeks postmenstrual age, it causes lifelong respiratory complications. However, preventive interventions carry severe risks, including neurodevelopmental impairment, ventilator-induced lung injury, and systemic complications. Therefore, early BPD prognosis and prediction of BPD outcome is crucial to avoid unnecessary toxicity in low risk infants. Admission radiographs of extremely preterm infants are routinely acquired within 24h of life and could serve as a non-invasive prognostic tool. In this work, we developed and investigated a deep learning approach using chest X-rays from 163 extremely low-birth-weight infants (leq32 weeks gestation, 401-999g) obtained within 24 hours of birth. We fine-tuned a ResNet-50 pretrained specifically on adult chest radiographs, employing progressive layer freezing with discriminative learning rates to prevent overfitting and evaluated a CutMix augmentation and linear probing. For moderate/severe BPD outcome prediction, our best performing model with progressive freezing, linear probing and CutMix achieved an AUROC of 0.78 pm 0.10, balanced accuracy of 0.69 pm 0.10, and an F1-score of 0.67 pm 0.11. In-domain pre-training significantly outperformed ImageNet initialization (p = 0.031) which confirms domain-specific pretraining to be important for BPD outcome prediction. Routine IRDS grades showed limited prognostic value (AUROC 0.57 pm 0.11), confirming the need of learned markers. Our approach demonstrates that domain-specific pretraining enables accurate BPD prediction from routine day-1 radiographs. Through progressive freezing and linear probing, the method remains computationally feasible for site-level implementation and future federated learning deployments.

This technical report introduces a Named Clinical Entity Recognition Benchmark for evaluating language models in healthcare, addressing the crucial natural language processing (NLP) task of extracting structured information from clinical narratives to support applications like automated coding, clinical trial cohort identification, and clinical decision support. The leaderboard provides a standardized platform for assessing diverse language models, including encoder and decoder architectures, on their ability to identify and classify clinical entities across multiple medical domains. A curated collection of openly available clinical datasets is utilized, encompassing entities such as diseases, symptoms, medications, procedures, and laboratory measurements. Importantly, these entities are standardized according to the Observational Medical Outcomes Partnership (OMOP) Common Data Model, ensuring consistency and interoperability across different healthcare systems and datasets, and a comprehensive evaluation of model performance. Performance of models is primarily assessed using the F1-score, and it is complemented by various assessment modes to provide comprehensive insights into model performance. The report also includes a brief analysis of models evaluated to date, highlighting observed trends and limitations. By establishing this benchmarking framework, the leaderboard aims to promote transparency, facilitate comparative analyses, and drive innovation in clinical entity recognition tasks, addressing the need for robust evaluation methods in healthcare NLP.

Accurate prognosis for an individual patient is a key component of precision oncology. Recent advances in machine learning have enabled the development of models using a wider range of data, including imaging. Radiomics aims to extract quantitative predictive and prognostic biomarkers from routine medical imaging, but evidence for computed tomography radiomics for prognosis remains inconclusive. We have conducted an institutional machine learning challenge to develop an accurate model for overall survival prediction in head and neck cancer using clinical data etxracted from electronic medical records and pre-treatment radiological images, as well as to evaluate the true added benefit of radiomics for head and neck cancer prognosis. Using a large, retrospective dataset of 2,552 patients and a rigorous evaluation framework, we compared 12 different submissions using imaging and clinical data, separately or in combination. The winning approach used non-linear, multitask learning on clinical data and tumour volume, achieving high prognostic accuracy for 2-year and lifetime survival prediction and outperforming models relying on clinical data only, engineered radiomics and deep learning. Combining all submissions in an ensemble model resulted in improved accuracy, with the highest gain from a image-based deep learning model. Our results show the potential of machine learning and simple, informative prognostic factors in combination with large datasets as a tool to guide personalized cancer care.

Large language models (LLMs) have demonstrated impressive capabilities in disease diagnosis. However, their effectiveness in identifying rarer diseases, which are inherently more challenging to diagnose, remains an open question. Rare disease performance is critical with the increasing use of LLMs in healthcare settings. This is especially true if a primary care physician needs to make a rarer prognosis from only a patient conversation so that they can take the appropriate next step. To that end, several clinical decision support systems are designed to support providers in rare disease identification. Yet their utility is limited due to their lack of knowledge of common disorders and difficulty of use. In this paper, we propose RareScale to combine the knowledge LLMs with expert systems. We use jointly use an expert system and LLM to simulate rare disease chats. This data is used to train a rare disease candidate predictor model. Candidates from this smaller model are then used as additional inputs to black-box LLM to make the final differential diagnosis. Thus, RareScale allows for a balance between rare and common diagnoses. We present results on over 575 rare diseases, beginning with Abdominal Actinomycosis and ending with Wilson's Disease. Our approach significantly improves the baseline performance of black-box LLMs by over 17% in Top-5 accuracy. We also find that our candidate generation performance is high (e.g. 88.8% on gpt-4o generated chats).