Daily Papers

Foundation Models (FMs) trained on Electronic Health Records (EHRs) have achieved state-of-the-art results on numerous clinical prediction tasks. However, most existing EHR FMs have context windows of <1k tokens. This prevents them from modeling full patient EHRs which can exceed 10k's of events. Recent advancements in subquadratic long-context architectures (e.g., Mamba) offer a promising solution. However, their application to EHR data has not been well-studied. We address this gap by presenting the first systematic evaluation of the effect of context length on modeling EHR data. We find that longer context models improve predictive performance -- our Mamba-based model surpasses the prior state-of-the-art on 9/14 tasks on the EHRSHOT prediction benchmark. For clinical applications, however, model performance alone is insufficient -- robustness to the unique properties of EHR is crucial. Thus, we also evaluate models across three previously underexplored properties of EHR data: (1) the prevalence of "copy-forwarded" diagnoses which creates artificial repetition of tokens within EHR sequences; (2) the irregular time intervals between EHR events which can lead to a wide range of timespans within a context window; and (3) the natural increase in disease complexity over time which makes later tokens in the EHR harder to predict than earlier ones. Stratifying our EHRSHOT results, we find that higher levels of each property correlate negatively with model performance, but that longer context models are more robust to more extreme levels of these properties. Our work highlights the potential for using long-context architectures to model EHR data, and offers a case study for identifying new challenges in modeling sequential data motivated by domains outside of natural language. We release our models and code at: https://github.com/som-shahlab/long_context_clues

Idiopathic pulmonary fibrosis (IPF) is a progressive disease that irreversibly transforms lung tissue into rigid fibrotic structures, leading to debilitating symptoms such as shortness of breath and chronic fatigue. The heterogeneity and complexity of this disease, particularly regarding its severity and progression rate, have made predicting its future course a complex and challenging task. Besides, traditional diagnostic methods based on clinical evaluations and imaging have limitations in capturing the disease's complexity. Using the Kaggle Pulmonary Fibrosis Progression dataset, which includes computed tomography images, and clinical information, the model predicts changes in forced vital capacity (FVC), a key progression indicator. Our method uses a proposed context-aware sequential-parallel hybrid transformer model and clinical information enrichment for its prediction. The proposed method achieved a Laplace Log-Likelihood score of -6.508, outperforming prior methods and demonstrating superior predictive capabilities. These results highlight the potential of advanced deep learning techniques to provide more accurate and timely predictions, offering a transformative approach to the diagnosis and management of IPF, with implications for improved patient outcomes and therapeutic advancements.

In this work, we introduce LightCNN, a minimalist Convolutional Neural Network (CNN) architecture designed for Parkinson's disease (PD) classification using EEG data. LightCNN's strength lies in its simplicity, utilizing just a single convolutional layer. Embracing Leonardo da Vinci's principle that "simplicity is the ultimate sophistication," LightCNN demonstrates that complexity is not required to achieve outstanding results. We benchmarked LightCNN against several state-of-the-art deep learning models known for their effectiveness in EEG-based PD classification. Remarkably, LightCNN outperformed all these complex architectures, with a 2.3% improvement in recall, a 4.6% increase in precision, a 0.1% edge in AUC, a 4% boost in F1-score, and a 3.3% higher accuracy compared to the closest competitor. Furthermore, LightCNN identifies known pathological brain rhythms associated with PD and effectively captures clinically relevant neurophysiological changes in EEG. Its simplicity and interpretability make it ideal for deployment in resource-constrained environments, such as mobile or embedded systems for EEG analysis. In conclusion, LightCNN represents a significant step forward in efficient EEG-based PD classification, demonstrating that a well-designed, lightweight model can achieve superior performance over more complex architectures. This work underscores the potential for minimalist models to meet the needs of modern healthcare applications, particularly where resources are limited.

As the global food security landscape continues to evolve, the need for accurate and reliable crop disease diagnosis has never been more pressing. To address global food security concerns, we extend the widely used PlantVillage dataset with additional apple leaf disease classes, enhancing diversity and complexity. Experimental evaluations on both original and extended datasets reveal that existing models struggle with the new additions, highlighting the need for more robust and generalizable computer vision models. Test F1 scores of 99.63% and 97.87% were obtained on the original and extended datasets, respectively. Our study provides a more challenging and diverse benchmark, paving the way for the development of accurate and reliable models for identifying apple leaf diseases under varying imaging conditions. The expanded dataset is available at https://www.kaggle.com/datasets/akinyemijoseph/apple-leaf-disease-dataset-6-classes-v2 enabling future research to build upon our findings.

Plant diseases pose significant threats to agriculture. It necessitates proper diagnosis and effective treatment to safeguard crop yields. To automate the diagnosis process, image segmentation is usually adopted for precisely identifying diseased regions, thereby advancing precision agriculture. Developing robust image segmentation models for plant diseases demands high-quality annotations across numerous images. However, existing plant disease datasets typically lack segmentation labels and are often confined to controlled laboratory settings, which do not adequately reflect the complexity of natural environments. Motivated by this fact, we established PlantSeg, a large-scale segmentation dataset for plant diseases. PlantSeg distinguishes itself from existing datasets in three key aspects. (1) Annotation type: Unlike the majority of existing datasets that only contain class labels or bounding boxes, each image in PlantSeg includes detailed and high-quality segmentation masks, associated with plant types and disease names. (2) Image source: Unlike typical datasets that contain images from laboratory settings, PlantSeg primarily comprises in-the-wild plant disease images. This choice enhances the practical applicability, as the trained models can be applied for integrated disease management. (3) Scale: PlantSeg is extensive, featuring 11,400 images with disease segmentation masks and an additional 8,000 healthy plant images categorized by plant type. Extensive technical experiments validate the high quality of PlantSeg's annotations. This dataset not only allows researchers to evaluate their image classification methods but also provides a critical foundation for developing and benchmarking advanced plant disease segmentation algorithms.

In clinical practice, electrocardiography (ECG) remains the gold standard for cardiac monitoring, providing crucial insights for diagnosing a wide range of cardiovascular diseases (CVDs). However, its reliance on specialized equipment and trained personnel limits feasibility for continuous routine monitoring. Photoplethysmography (PPG) offers accessible, continuous monitoring but lacks definitive electrophysiological information, preventing conclusive diagnosis. Generative models present a promising approach to translate PPG into clinically valuable ECG signals, yet current methods face substantial challenges, including the misalignment of physiological semantics in generative models and the complexity of modeling in high-dimensional signals. To this end, we propose PPGFlowECG, a two-stage framework that aligns PPG and ECG in a shared latent space via the CardioAlign Encoder and employs latent rectified flow to generate ECGs with high fidelity and interpretability. To the best of our knowledge, this is the first study to experiment on MCMED, a newly released clinical-grade dataset comprising over 10 million paired PPG-ECG samples from more than 118,000 emergency department visits with expert-labeled cardiovascular disease annotations. Results demonstrate the effectiveness of our method for PPG-to-ECG translation and cardiovascular disease detection. Moreover, cardiologist-led evaluations confirm that the synthesized ECGs achieve high fidelity and improve diagnostic reliability, underscoring our method's potential for real-world cardiovascular screening.

Artificial intelligence is poised to augment dermatological care by enabling scalable image-based diagnostics. Yet, the development of robust and equitable models remains hindered by datasets that fail to capture the clinical and demographic complexity of real-world practice. This complexity stems from region-specific disease distributions, wide variation in skin tones, and the underrepresentation of outpatient scenarios from non-Western populations. We introduce DermaCon-IN, a prospectively curated dermatology dataset comprising over 5,450 clinical images from approximately 3,000 patients across outpatient clinics in South India. Each image is annotated by board-certified dermatologists with over 240 distinct diagnoses, structured under a hierarchical, etiology-based taxonomy adapted from Rook's classification. The dataset captures a wide spectrum of dermatologic conditions and tonal variation commonly seen in Indian outpatient care. We benchmark a range of architectures including convolutional models (ResNet, DenseNet, EfficientNet), transformer-based models (ViT, MaxViT, Swin), and Concept Bottleneck Models to establish baseline performance and explore how anatomical and concept-level cues may be integrated. These results are intended to guide future efforts toward interpretable and clinically realistic models. DermaCon-IN provides a scalable and representative foundation for advancing dermatology AI in real-world settings.

Cardiac MRI allows for a comprehensive assessment of myocardial structure, function, and tissue characteristics. Here we describe a foundational vision system for cardiac MRI, capable of representing the breadth of human cardiovascular disease and health. Our deep learning model is trained via self-supervised contrastive learning, by which visual concepts in cine-sequence cardiac MRI scans are learned from the raw text of the accompanying radiology reports. We train and evaluate our model on data from four large academic clinical institutions in the United States. We additionally showcase the performance of our models on the UK BioBank, and two additional publicly available external datasets. We explore emergent zero-shot capabilities of our system, and demonstrate remarkable performance across a range of tasks; including the problem of left ventricular ejection fraction regression, and the diagnosis of 35 different conditions such as cardiac amyloidosis and hypertrophic cardiomyopathy. We show that our deep learning system is capable of not only understanding the staggering complexity of human cardiovascular disease, but can be directed towards clinical problems of interest yielding impressive, clinical grade diagnostic accuracy with a fraction of the training data typically required for such tasks.

The evaluation of generated reports remains a critical challenge in Computed Tomography (CT) report generation, due to the large volume of text, the diversity and complexity of findings, and the presence of fine-grained, disease-oriented attributes. Conventional evaluation metrics offer only coarse measures of lexical overlap or entity matching and fail to reflect the granular diagnostic accuracy required for clinical use. To address this gap, we propose CT-FineBench, a benchmark built from CT-RATE and Merlin to evaluate the fine-grained factual consistency of CT reports, constructed from CT-RATE and Merlin. Our benchmark is constructed through a meticulous, Question-Answering (QA) based process: first, we identify and structure key, finding-specific clinical attributes (like location, size, margin). Second, we systematically transform these attributes into a QA dataset, where questions probe for specific clinical details grounded in gold-standard reports. The evaluation protocol for CT-FineBench involves using this QA dataset to query a machine-generated report and scoring the correctness of the answers. This allows for a comprehensive, interpretable, and clinically-relevant assessment, moving beyond superficial lexical overlap to pinpoint specific clinical errors. Experiments show that CT-FineBench correlates better with expert clinical assessment and is substantially more sensitive to fine-grained factual errors than prior metrics.

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.

Rare diseases present unique challenges in healthcare, often suffering from delayed diagnosis and fragmented information landscapes. The scarcity of reliable knowledge in these conditions poses a distinct challenge for Large Language Models (LLMs) in supporting clinical management and delivering precise patient information underscoring the need for focused training on these 'zebra' cases. We present Zebra-Llama, a specialized context-aware language model with high precision Retrieval Augmented Generation (RAG) capability, focusing on Ehlers-Danlos Syndrome (EDS) as our case study. EDS, affecting 1 in 5,000 individuals, exemplifies the complexities of rare diseases with its diverse symptoms, multiple subtypes, and evolving diagnostic criteria. By implementing a novel context-aware fine-tuning methodology trained on questions derived from medical literature, patient experiences, and clinical resources, along with expertly curated responses, Zebra-Llama demonstrates unprecedented capabilities in handling EDS-related queries. On a test set of real-world questions collected from EDS patients and clinicians, medical experts evaluated the responses generated by both models, revealing Zebra-Llama's substantial improvements over base model (Llama 3.1-8B-Instruct) in thoroughness (77.5% vs. 70.1%), accuracy (83.0% vs. 78.8%), clarity (74.7% vs. 72.0%) and citation reliability (70.6% vs. 52.3%). Released as an open-source resource, Zebra-Llama not only provides more accessible and reliable EDS information but also establishes a framework for developing specialized AI solutions for other rare conditions. This work represents a crucial step towards democratizing expert-level knowledge in rare disease management, potentially transforming how healthcare providers and patients navigate the complex landscape of rare diseases.

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).

The complexity of a graph is the number of its labeled spanning trees. In this work complexity is studied in settings that admit regular graphs. An exact formula is established linking complexity of the complement of a regular graph to numbers of closed walks in the graph by way of an infinite alternating series. Some consequences of this result yield infinite classes of lower and upper bounds on the complexity of such graphs. Applications of these mathematical results to biological problems on neuronal activity are described.

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.

The increasing complexity of Artificial Intelligence models poses challenges to interpretability, particularly in the healthcare sector. This study investigates the impact of deep learning model complexity and Explainable AI (XAI) efficacy, utilizing four ResNet architectures (ResNet-18, 34, 50, 101). Through methodical experimentation on 4,369 lung X-ray images of COVID-19-infected and healthy patients, the research evaluates models' classification performance and the relevance of corresponding XAI explanations with respect to the ground-truth disease masks. Results indicate that the increase in model complexity is associated with a decrease in classification accuracy and AUC-ROC scores (ResNet-18: 98.4%, 0.997; ResNet-101: 95.9%, 0.988). Notably, in eleven out of twelve statistical tests performed, no statistically significant differences occurred between XAI quantitative metrics - Relevance Rank Accuracy and the proposed Positive Attribution Ratio - across trained models. These results suggest that increased model complexity does not consistently lead to higher performance or relevance of explanations for models' decision-making processes.

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.

Rare diseases collectively affect over 300 million individuals worldwide, yet timely and accurate diagnosis remains a pervasive challenge. This is largely due to their clinical heterogeneity, low individual prevalence, and the limited familiarity most clinicians have with rare conditions. Here, we introduce DeepRare, the first rare disease diagnosis agentic system powered by a large language model (LLM), capable of processing heterogeneous clinical inputs. The system generates ranked diagnostic hypotheses for rare diseases, each accompanied by a transparent chain of reasoning that links intermediate analytic steps to verifiable medical evidence. DeepRare comprises three key components: a central host with a long-term memory module; specialized agent servers responsible for domain-specific analytical tasks integrating over 40 specialized tools and web-scale, up-to-date medical knowledge sources, ensuring access to the most current clinical information. This modular and scalable design enables complex diagnostic reasoning while maintaining traceability and adaptability. We evaluate DeepRare on eight datasets. The system demonstrates exceptional diagnostic performance among 2,919 diseases, achieving 100% accuracy for 1013 diseases. In HPO-based evaluations, DeepRare significantly outperforms other 15 methods, like traditional bioinformatics diagnostic tools, LLMs, and other agentic systems, achieving an average Recall@1 score of 57.18% and surpassing the second-best method (Reasoning LLM) by a substantial margin of 23.79 percentage points. For multi-modal input scenarios, DeepRare achieves 70.60% at Recall@1 compared to Exomiser's 53.20% in 109 cases. Manual verification of reasoning chains by clinical experts achieves 95.40% agreements. Furthermore, the DeepRare system has been implemented as a user-friendly web application http://raredx.cn/doctor.

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.

Rare diseases collectively affect an estimated 3.5% to 5.9% of the population, yet more than 70% of patients are misdiagnosed and many endure years of evaluation before a diagnosis is reached, because early presentations are nonspecific and relevant expertise is scarce and unevenly distributed. Artificial intelligence could provide support, but existing systems address isolated stages of care, overwhelmingly diagnosis. They typically depend on the results of downstream investigations, and they treat the variability between models as noise to be eliminated. Here we present RareLens, a system that supports clinical decision-making across the entire rare disease trajectory by exploiting this variability. When heterogeneous large language models evaluate the same case, they generate divergent but complementary reasoning, which RareLens aligns and calibrates into a single convergent, actionable decision at each stage. Four coordinated modules perform primary-visit risk screening, diagnosis, treatment planning and prognosis. Developed and evaluated on RareBench, a real-world dataset of 157,525 cases spanning all 33 Orphanet categories and more than 7,000 conditions, RareLens outperformed every frontier model tested, including GPT-5, DeepSeek-R1, Claude-3.7-Sonnet and Gemini-2.5-Pro, at each stage. It achieved an area under the curve of 0.917 for screening and top-1 accuracies of 65.5% and 89.8% for diagnosis and treatment. In an external study spanning 1,287 cases and 23 physicians, autonomous RareLens and physicians assisted by RareLens both substantially outperformed unaided physicians. These findings indicate that aligning divergent model reasoning, rather than scaling a single model, offers a generalizable strategy for high-uncertainty clinical decision-making.

Data scarcity is a common obstacle in medical research due to the high costs associated with data collection and the complexity of gaining access to and utilizing data. Synthesizing health data may provide an efficient and cost-effective solution to this shortage, enabling researchers to explore distributions and populations that are not represented in existing observations or difficult to access due to privacy considerations. To that end, we have developed a multi-task self-attention model that produces realistic wearable activity data. We examine the characteristics of the generated data and quantify its similarity to genuine samples with both quantitative and qualitative approaches.

Cancer is a complex disease, the understanding and treatment of which are being aided through increases in the volume of collected data and in the scale of deployed computing power. Consequently, there is a growing need for the development of data-driven and, in particular, deep learning methods for various tasks such as cancer diagnosis, detection, prognosis, and prediction. Despite recent successes, however, designing high-performing deep learning models for nonimage and nontext cancer data is a time-consuming, trial-and-error, manual task that requires both cancer domain and deep learning expertise. To that end, we develop a reinforcement-learning-based neural architecture search to automate deep-learning-based predictive model development for a class of representative cancer data. We develop custom building blocks that allow domain experts to incorporate the cancer-data-specific characteristics. We show that our approach discovers deep neural network architectures that have significantly fewer trainable parameters, shorter training time, and accuracy similar to or higher than those of manually designed architectures. We study and demonstrate the scalability of our approach on up to 1,024 Intel Knights Landing nodes of the Theta supercomputer at the Argonne Leadership Computing Facility.

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.

Identifying disease phenotypes from electronic health records (EHRs) is critical for numerous secondary uses. Manually encoding physician knowledge into rules is particularly challenging for rare diseases due to inadequate EHR coding, necessitating review of clinical notes. Large language models (LLMs) offer promise in text understanding but may not efficiently handle real-world clinical documentation. We propose a zero-shot LLM-based method enriched by retrieval-augmented generation and MapReduce, which pre-identifies disease-related text snippets to be used in parallel as queries for the LLM to establish diagnosis. We show that this method as applied to pulmonary hypertension (PH), a rare disease characterized by elevated arterial pressures in the lungs, significantly outperforms physician logic rules (F_1 score of 0.62 vs. 0.75). This method has the potential to enhance rare disease cohort identification, expanding the scope of robust clinical research and care gap identification.

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.

Disease progression simulation is a crucial area of research that has significant implications for clinical diagnosis, prognosis, and treatment. One major challenge in this field is the lack of continuous medical imaging monitoring of individual patients over time. To address this issue, we develop a novel framework termed Progressive Image Editing (PIE) that enables controlled manipulation of disease-related image features, facilitating precise and realistic disease progression simulation. Specifically, we leverage recent advancements in text-to-image generative models to simulate disease progression accurately and personalize it for each patient. We theoretically analyze the iterative refining process in our framework as a gradient descent with an exponentially decayed learning rate. To validate our framework, we conduct experiments in three medical imaging domains. Our results demonstrate the superiority of PIE over existing methods such as Stable Diffusion Walk and Style-Based Manifold Extrapolation based on CLIP score (Realism) and Disease Classification Confidence (Alignment). Our user study collected feedback from 35 veteran physicians to assess the generated progressions. Remarkably, 76.2% of the feedback agrees with the fidelity of the generated progressions. To our best knowledge, PIE is the first of its kind to generate disease progression images meeting real-world standards. It is a promising tool for medical research and clinical practice, potentially allowing healthcare providers to model disease trajectories over time, predict future treatment responses, and improve patient outcomes.

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.

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.

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.

Medical coding translates clinical documentation into standardized codes for billing, research, and public health, but manual coding is time-consuming and error-prone. Existing automation efforts rely on small datasets that poorly represent real-world patient heterogeneity. We trained a language model on 5.8 million electronic health records from 1.8 million patients across nearly all specialties in Eastern Denmark (2006--2016) to predict ICD-10 codes from clinical notes, medications, and laboratory results. Evaluated on 270,000 held-out patients, the model achieved a micro F1 of 71.8% and a top-10 recall of 95.5%. Performance varied by specialty (F1: 53--91%), with higher scores in specialties with well-defined diagnostic criteria. Codes appearing predominantly as secondary diagnoses had markedly lower F1 scores. For three such codes (suicide-related behaviors, weight disorders, and hypertension), the model identified thousands of uncoded cases, of which 76-86% were confirmed valid upon manual review, suggesting systematic under-coding rather than model error. These findings suggest under-coding of secondary diagnoses in Eastern Denmark during this period, with potential implications for epidemiological research, public health surveillance, and understanding of multimorbidity. Similar time constraints and reimbursement structures in other healthcare systems suggest this may not be isolated to this dataset. The model can automate coding for approximately 50% of cases and provide accurate suggestions for most others, and may offer a practical solution to help capture missed secondary conditions.

The timely identification of socio-economic sectors vulnerable to a disease outbreak presents an important challenge to the civic authorities and healthcare workers interested in outbreak mitigation measures. This problem was traditionally solved by studying the aberrances in small-scale healthcare data. In this paper, we leverage data driven models to determine the relationship between the trends of World Development Indicators and occurrence of disease outbreaks using worldwide historical data from 2000-2019, and treat it as a classic supervised classification problem. CART based feature selection was employed in an unorthodox fashion to determine the covariates getting affected by the disease outbreak, thus giving the most vulnerable sectors. The result involves a comprehensive analysis of different classification algorithms and is indicative of the relationship between the disease outbreak occurrence and the magnitudes of various development indicators.

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.

Genomic alterations lead to cancer complexity and form a major hurdle for a comprehensive understanding of the molecular mechanisms underlying oncogenesis. In this review, we describe the recent advances in studying cancer-associated genes from a systems biological point of view. The integration of known cancer genes onto protein and signaling networks reveals the characteristics of cancer genes within networks. This approach shows that cancer genes often function as network hub proteins which are involved in many cellular processes and form focal nodes in the information exchange between many signaling pathways. Literature mining allows constructing gene-gene networks, in which new cancer genes can be identified. The gene expression profiles of cancer cells are used for reconstructing gene regulatory networks. By doing so, the genes, which are involved in the regulation of cancer progression, can be picked up from these networks after which their functions can be further confirmed in the laboratory.

Building upon our previous investigations of O1 replication (Part 1: Journey Learning [Qin et al., 2024] and Part 2: Distillation [Huang et al., 2024]), this work explores the potential of inference-time scaling in large language models (LLMs) for medical reasoning tasks, ranging from diagnostic decision-making to treatment planning. Through extensive experiments on medical benchmarks of varying complexity (MedQA, Medbullets, and JAMA Clinical Challenges), our investigation reveals several key insights: (1) Increasing inference time does lead to improved performance. With a modest training set of 500 samples, our model yields substantial performance improvements of 6%-11%. (2) Task complexity directly correlates with the required length of reasoning chains, confirming the necessity of extended thought processes for challenging problems. (3) The differential diagnoses generated by our model adhere to the principles of the hypothetico-deductive method, producing a list of potential conditions that may explain a patient's symptoms and systematically narrowing these possibilities by evaluating the evidence. These findings demonstrate the promising synergy between inference-time scaling and journey learning in advancing LLMs' real-world clinical reasoning capabilities.

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.

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.

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.

Existing plant disease classification models have achieved remarkable performance in recognizing in-laboratory diseased images. However, their performance often significantly degrades in classifying in-the-wild images. Furthermore, we observed that in-the-wild plant images may exhibit similar appearances across various diseases (i.e., small inter-class discrepancy) while the same diseases may look quite different (i.e., large intra-class variance). Motivated by this observation, we propose an in-the-wild multimodal plant disease recognition dataset that contains the largest number of disease classes but also text-based descriptions for each disease. Particularly, the newly provided text descriptions are introduced to provide rich information in textual modality and facilitate in-the-wild disease classification with small inter-class discrepancy and large intra-class variance issues. Therefore, our proposed dataset can be regarded as an ideal testbed for evaluating disease recognition methods in the real world. In addition, we further present a strong yet versatile baseline that models text descriptions and visual data through multiple prototypes for a given class. By fusing the contributions of multimodal prototypes in classification, our baseline can effectively address the small inter-class discrepancy and large intra-class variance issues. Remarkably, our baseline model can not only classify diseases but also recognize diseases in few-shot or training-free scenarios. Extensive benchmarking results demonstrate that our proposed in-the-wild multimodal dataset sets many new challenges to the plant disease recognition task and there is a large space to improve for future works.

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.

Medical research generates a large number of publications with the PubMed database already containing >35 million research articles. Integration of the knowledge scattered across this large body of literature could provide key insights into physiological mechanisms and disease processes leading to novel medical interventions. However, it is a great challenge for researchers to utilize this information in full since the scale and complexity of the data greatly surpasses human processing abilities. This becomes especially problematic in cases of extreme urgency like the COVID-19 pandemic. Automated text mining can help extract and connect information from the large body of medical research articles. The first step in text mining is typically the identification of specific classes of keywords (e.g., all protein or disease names), so called Named Entity Recognition (NER). Here we present an end-to-end pipeline for NER of typical entities found in medical research articles, including diseases, cells, chemicals, genes/proteins, and species. The pipeline can access and process large medical research article collections (PubMed, CORD-19) or raw text and incorporates a series of deep learning models fine-tuned on the HUNER corpora collection. In addition, the pipeline can perform dictionary-based NER related to COVID-19 and other medical topics. Users can also load their own NER models and dictionaries to include additional entities. The output consists of publication-ready ranked lists and graphs of detected entities and files containing the annotated texts. An associated script allows rapid inspection of the results for specific entities of interest. As model use cases, the pipeline was deployed on two collections of autophagy-related abstracts from PubMed and on the CORD19 dataset, a collection of 764 398 research article abstracts related to COVID-19.

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.

Skin diseases are a major public health concern worldwide, and their detection is often challenging without access to dermatological expertise. In countries like Bangladesh, which is highly populated, the number of qualified skin specialists and diagnostic instruments is insufficient to meet the demand. Due to the lack of proper detection and treatment of skin diseases, that may lead to severe health consequences including death. Common properties of skin diseases are, changing the color, texture, and pattern of skin and in this era of artificial intelligence and machine learning, we are able to detect skin diseases by using image processing and computer vision techniques. In response to this challenge, we develop a publicly available dataset focused on common skin disease detection using machine learning techniques. We focus on five prevalent skin diseases in Bangladesh: Contact Dermatitis, Vitiligo, Eczema, Scabies, and Tinea Ringworm. The dataset consists of 1612 images (of which, 250 are distinct while others are augmented), collected directly from patients at the outpatient department of Faridpur Medical College, Faridpur, Bangladesh. The data comprises of 302, 381, 301, 316, and 312 images of Dermatitis, Eczema, Scabies, Tinea Ringworm, and Vitiligo, respectively. Although the data are collected regionally, the selected diseases are common across many countries especially in South Asia, making the dataset potentially valuable for global applications in machine learning-based dermatology. We also apply several machine learning and deep learning models on the dataset and report classification performance. We expect that this research would garner attention from machine learning and deep learning researchers and practitioners working in the field of automated disease diagnosis.

Rare diseases affect hundreds of millions worldwide, yet diagnosis often spans years. Convectional pipelines decouple noisy evidence extraction from downstream inferential diagnosis, and general/medical large language models (LLMs) face scarce real world electronic health records (EHRs), stale domain knowledge, and hallucinations. We assemble a large, domain specialized clinical corpus and a clinician validated reasoning set, and develop RareSeek R1 via staged instruction tuning, chain of thought learning, and graph grounded retrieval. Across multicenter EHR narratives and public benchmarks, RareSeek R1 attains state of the art accuracy, robust generalization, and stability under noisy or overlapping phenotypes. Augmented retrieval yields the largest gains when narratives pair with prioritized variants by resolving ambiguity and aligning candidates to mechanisms. Human studies show performance on par with experienced physicians and consistent gains in assistive use. Notably, transparent reasoning highlights decisive non phenotypic evidence (median 23.1%, such as imaging, interventions, functional tests) underpinning many correct diagnoses. This work advances a narrative first, knowledge integrated reasoning paradigm that shortens the diagnostic odyssey and enables auditable, clinically translatable decision support.

Vision-threatening eye diseases pose a major global health burden, with timely diagnosis limited by workforce shortages and restricted access to specialized care. While multimodal large language models (MLLMs) show promise for medical image interpretation, advancing MLLMs for ophthalmology is hindered by the lack of comprehensive benchmark datasets suitable for evaluating generative models. We present a large-scale multimodal ophthalmology benchmark comprising 32,633 instances with multi-granular annotations across 12 common ophthalmic conditions and 5 imaging modalities. The dataset integrates imaging, anatomical structures, demographics, and free-text annotations, supporting anatomical structure recognition, disease screening, disease staging, and demographic prediction for bias evaluation. This work extends our preliminary LMOD benchmark with three major enhancements: (1) nearly 50% dataset expansion with substantial enlargement of color fundus photography; (2) broadened task coverage including binary disease diagnosis, multi-class diagnosis, severity classification with international grading standards, and demographic prediction; and (3) systematic evaluation of 24 state-of-the-art MLLMs. Our evaluations reveal both promise and limitations. Top-performing models achieved ~58% accuracy in disease screening under zero-shot settings, and performance remained suboptimal for challenging tasks like disease staging. We will publicly release the dataset, curation pipeline, and leaderboard to potentially advance ophthalmic AI applications and reduce the global burden of vision-threatening diseases.

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.

Objective: The reading level of health educational materials significantly influences the understandability and accessibility of the information, particularly for minoritized populations. Many patient educational resources surpass the reading level and complexity of widely accepted standards. There is a critical need for high-performing text simplification models in health information to enhance dissemination and literacy. This need is particularly acute in cancer education, where effective prevention and screening education can substantially reduce morbidity and mortality. Methods: We introduce Simplified Digestive Cancer (SimpleDC), a parallel corpus of cancer education materials tailored for health text simplification research, comprising educational content from the American Cancer Society, Centers for Disease Control and Prevention, and National Cancer Institute. Utilizing SimpleDC alongside the existing Med-EASi corpus, we explore Large Language Model (LLM)-based simplification methods, including fine-tuning, reinforcement learning (RL), reinforcement learning with human feedback (RLHF), domain adaptation, and prompt-based approaches. Our experimentation encompasses Llama 2 and GPT-4. A novel RLHF reward function is introduced, featuring a lightweight model adept at distinguishing between original and simplified texts, thereby enhancing the model's effectiveness with unlabeled data. Results: Fine-tuned Llama 2 models demonstrated high performance across various metrics. Our innovative RLHF reward function surpassed existing RL text simplification reward functions in effectiveness. The results underscore that RL/RLHF can augment fine-tuning, facilitating model training on unlabeled text and improving performance.

Graphs have often been used to answer questions about the interaction between real-world entities by taking advantage of their capacity to represent complex topologies. Complex networks are known to be graphs that capture such non-trivial topologies; they are able to represent human phenomena such as epidemic processes, the dynamics of populations, and the urbanization of cities. The investigation of complex networks has been extrapolated to many fields of science, with particular emphasis on computing techniques, including artificial intelligence. In such a case, the analysis of the interaction between entities of interest is transposed to the internal learning of algorithms, a paradigm whose investigation is able to expand the state of the art in Computer Science. By exploring this paradigm, this thesis puts together complex networks and machine learning techniques to improve the understanding of the human phenomena observed in pandemics, pendular migration, and street networks. Accordingly, we contribute with: (i) a new neural network architecture capable of modeling dynamic processes observed in spatial and temporal data with applications in epidemics propagation, weather forecasting, and patient monitoring in intensive care units; (ii) a machine-learning methodology for analyzing and predicting links in the scope of human mobility between all the cities of Brazil; and, (iii) techniques for identifying inconsistencies in the urban planning of cities while tracking the most influential vertices, with applications over Brazilian and worldwide cities. We obtained results sustained by sound evidence of advances to the state of the art in artificial intelligence, rigorous formalisms, and ample experimentation. Our findings rely upon real-world applications in a range of domains, demonstrating the applicability of our methodologies.

In contrast to entropy, which increases monotonically, the "complexity" or "interestingness" of closed systems seems intuitively to increase at first and then decrease as equilibrium is approached. For example, our universe lacked complex structures at the Big Bang and will also lack them after black holes evaporate and particles are dispersed. This paper makes an initial attempt to quantify this pattern. As a model system, we use a simple, two-dimensional cellular automaton that simulates the mixing of two liquids ("coffee" and "cream"). A plausible complexity measure is then the Kolmogorov complexity of a coarse-grained approximation of the automaton's state, which we dub the "apparent complexity." We study this complexity measure, and show analytically that it never becomes large when the liquid particles are non-interacting. By contrast, when the particles do interact, we give numerical evidence that the complexity reaches a maximum comparable to the "coffee cup's" horizontal dimension. We raise the problem of proving this behavior analytically.

A compartmental deterministic model that allows (1) immunity from two stages of infection and carriage, and (2) disease induced death, is used in studying the dynamics of meningitis epidemic process in a closed population. It allows for difference in the transmission rate of infection to a susceptible by a carrier and an infective. It is generalized to allow a proportion ({\phi}) of those susceptibles infected to progress directly to infectives in stage I. Both models are used in this study. The threshold conditions for the spread of carrier and infectives in stage I are derived for the two models. Sensitivity analysis is performed on the reproductive number derived from the next generation matrix. The case-carrier ratio profile for various parameters and threshold values are shown. So also are the graphs of the total number ever infected as influenced by {\epsilon} and {\phi}. The infection transmission rate (eta), the odds in favor of a carrier, over an infective, in transmitting an infection to a susceptible ({\epsilon}) and the carrier conversion rate ({\phi}) to an infective in stage I, are identified as key parameters that should be subject of attention for any control intervention strategy. The case-carrier ratio profiles provide evidence of a critical case-carrier ratio attained before the number of reported cases grows to an epidemic level. They also provide visual evidence of epidemiological context, in this case, epidemic incidence (in later part of dry season) and endemic incidence (during rainy season). Results from total proportion ever infected suggest that the model, in which {\phi}=0 obtained, can adequately represent, in essence, the generalized model for this study.

Histopathology plays a central role in clinical medicine and biomedical research. While artificial intelligence shows promising results on many pathological tasks, generalization and dealing with rare diseases, where training data is scarce, remains a challenge. Distilling knowledge from unlabeled data into a foundation model before learning from, potentially limited, labeled data provides a viable path to address these challenges. In this work, we extend the state of the art of foundation models for digital pathology whole slide images by semi-automated data curation and incorporating pathologist domain knowledge. Specifically, we combine computational and pathologist domain knowledge (1) to curate a diverse dataset of 103k slides corresponding to 750 million image patches covering data from different fixation, staining, and scanning protocols as well as data from different indications and labs across the EU and US, (2) for grouping semantically similar slides and tissue patches, and (3) to augment the input images during training. We evaluate the resulting model on a set of public and internal benchmarks and show that although our foundation model is trained with an order of magnitude less slides, it performs on par or better than competing models. We expect that scaling our approach to more data and larger models will further increase its performance and capacity to deal with increasingly complex real world tasks in diagnostics and biomedical research.

Understanding how humans perceive visual complexity is a key area of study in visual cognition. Previous approaches to modeling visual complexity assessments have often resulted in intricate, difficult-to-interpret algorithms that employ numerous features or sophisticated deep learning architectures. While these complex models achieve high performance on specific datasets, they often sacrifice interpretability, making it challenging to understand the factors driving human perception of complexity. Recently (Shen, et al. 2024) proposed an interpretable segmentation-based model that accurately predicted complexity across various datasets, supporting the idea that complexity can be explained simply. In this work, we investigate the failure of their model to capture structural, color and surprisal contributions to complexity. To this end, we propose Multi-Scale Sobel Gradient (MSG) which measures spatial intensity variations, Multi-Scale Unique Color (MUC) which quantifies colorfulness across multiple scales, and surprise scores generated using a Large Language Model. We test our features on existing benchmarks and a novel dataset (Surprising Visual Genome) containing surprising images from Visual Genome. Our experiments demonstrate that modeling complexity accurately is not as simple as previously thought, requiring additional perceptual and semantic factors to address dataset biases. Our model improves predictive performance while maintaining interpretability, offering deeper insights into how visual complexity is perceived and assessed. Our code, analysis and data are available at https://github.com/Complexity-Project/Complexity-in-Complexity.

Diabetes is a chronic disease that poses a significant global health burden, and optimizing diabetes management requires multi-stakeholder collaboration. Large language models (LLMs) have shown promise in various healthcare scenarios, but their effectiveness across a diverse range of diabetes tasks remains unproven. In this study, we introduced a framework to train and validate diabetes-specific LLMs. We first developed a comprehensive data processing pipeline that includes data collection, filtering, augmentation and refinement. This approach contributes to creating a high-quality, diabetes-specific dataset, and several evaluation benchmarks entirely from scratch. Utilizing the collected training dataset, we fine-tuned a diabetes-specific LLM family that demonstrated state-of-the-art proficiency in understanding and processing various diabetes tasks compared to other LLMs. Furthermore, clinical studies showed the potential applications of our models in diabetes care, including providing personalized healthcare, assisting medical education, and streamlining clinical tasks. In conclusion, our study introduced a framework to develop and evaluate a diabetes-specific LLM family, and highlighted its potential to enhance clinical practice and provide personalized, data-driven support for diabetes support when facing different end users. The code is provided via GitHub at https://github.com/waltonfuture/Diabetica.

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.

The abundance of intestinal flora is closely related to human diseases, but diseases are not caused by a single gut microbe. Instead, they result from the complex interplay of numerous microbial entities. This intricate and implicit connection among gut microbes poses a significant challenge for disease prediction using abundance information from OTU data. Recently, several methods have shown potential in predicting corresponding diseases. However, these methods fail to learn the inner association among gut microbes from different hosts, leading to unsatisfactory performance. In this paper, we present a novel architecture, Unsupervised Multi-graph Merge Adversarial Network (UMMAN). UMMAN can obtain the embeddings of nodes in the Multi-Graph in an unsupervised scenario, so that it helps learn the multiplex association. Our method is the first to combine Graph Neural Network with the task of intestinal flora disease prediction. We employ complex relation-types to construct the Original-Graph and disrupt the relationships among nodes to generate corresponding Shuffled-Graph. We introduce the Node Feature Global Integration (NFGI) module to represent the global features of the graph. Furthermore, we design a joint loss comprising adversarial loss and hybrid attention loss to ensure that the real graph embedding aligns closely with the Original-Graph and diverges from the Shuffled-Graph. Comprehensive experiments on five classical OTU gut microbiome datasets demonstrate the effectiveness and stability of our method. (We will release our code soon.)

Whole-Slide Image (WSI) is an important tool for evaluating the prognosis of cancer patients. Present WSI-based prognosis studies generally follow a conventional paradigm -- cancer-specific model development -- where one cancer disease corresponds to one model and this model cannot make use of the prognostic knowledge from others. Despite its notable success in recent years, this paradigm has inherent limitations and has always been struggling with practical requirements: (i) scaling to the rare tumor diseases with very limited samples and (ii) benefiting from the generalizable prognostic knowledge in other cancers. To this end, this paper presents the first systematic study on Prognostic Knowledge Transfer in Pathology, called Path-PKT. It comprises three main parts. (1) We curate a large dataset (UNI2-h-DSS) with 13 cancers and use it to evaluate the transferability of prognostic knowledge between different cancers computationally. (2) We design experiments to understand what factors affect knowledge transfer and what causes positive transfers. (3) Motivated by empirical findings, we propose a new baseline approach (MoE-PKT) with a routing mechanism to utilize the generalizable prognostic knowledge in other cancers. Finally, we show the transferability of source models to rare tumor diseases. This study could lay solid foundations for the study of knowledge transfer in WSI-based cancer prognosis. Source code is available at https://github.com/liupei101/Path-PKT.

Rare diseases, including Inborn Errors of Metabolism (IEM), pose significant diagnostic challenges. Case reports serve as key but computationally underutilized resources to inform diagnosis. Clinical dense information extraction refers to organizing medical information into structured predefined categories. Large Language Models (LLMs) may enable scalable information extraction from case reports but are rarely evaluated for this task. We introduce CaseReportBench, an expert-annotated dataset for dense information extraction of case reports, focusing on IEMs. Using this dataset, we assess various models and prompting strategies, introducing novel approaches such as category-specific prompting and subheading-filtered data integration. Zero-shot chain-of-thought prompting offers little advantage over standard zero-shot prompting. Category-specific prompting improves alignment with the benchmark. The open-source model Qwen2.5-7B outperforms GPT-4o for this task. Our clinician evaluations show that LLMs can extract clinically relevant details from case reports, supporting rare disease diagnosis and management. We also highlight areas for improvement, such as LLMs' limitations in recognizing negative findings important for differential diagnosis. This work advances LLM-driven clinical natural language processing and paves the way for scalable medical AI applications.

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.

The field of medical diagnosis has undergone a significant transformation with the advent of large language models (LLMs), yet the challenges of interpretability within these models remain largely unaddressed. This study introduces Chain-of-Diagnosis (CoD) to enhance the interpretability of LLM-based medical diagnostics. CoD transforms the diagnostic process into a diagnostic chain that mirrors a physician's thought process, providing a transparent reasoning pathway. Additionally, CoD outputs the disease confidence distribution to ensure transparency in decision-making. This interpretability makes model diagnostics controllable and aids in identifying critical symptoms for inquiry through the entropy reduction of confidences. With CoD, we developed DiagnosisGPT, capable of diagnosing 9604 diseases. Experimental results demonstrate that DiagnosisGPT outperforms other LLMs on diagnostic benchmarks. Moreover, DiagnosisGPT provides interpretability while ensuring controllability in diagnostic rigor.

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.

Diabetes is a prevalent chronic disease with significant health and economic burdens worldwide. Early prediction and diagnosis can aid in effective management and prevention of complications. This study explores the use of machine learning models to predict diabetes based on lifestyle factors using data from the Behavioral Risk Factor Surveillance System (BRFSS) 2015 survey. The dataset consists of 21 lifestyle and health-related features, capturing aspects such as physical activity, diet, mental health, and socioeconomic status. Three classification models, Decision Tree, K-Nearest Neighbors (KNN), and Logistic Regression, are implemented and evaluated to determine their predictive performance. The models are trained and tested using a balanced dataset, and their performances are assessed based on accuracy, precision, recall, and F1-score. The results indicate that the Decision Tree, KNN, and Logistic Regression achieve an accuracy of 0.74, 0.72, and 0.75, respectively, with varying strengths in precision and recall. The findings highlight the potential of machine learning in diabetes prediction and suggest future improvements through feature selection and ensemble learning techniques.

Epidemiologists aiming to model the dynamics of global events face a significant challenge in identifying the factors linked with anomalies such as disease outbreaks. In this paper, we present a novel method for identifying the most important development sectors sensitive to disease outbreaks by using global development indicators as markers. We use statistical methods to assess the causative linkages between these indicators and disease outbreaks, as well as to find the most often ranked indicators. We used data imputation techniques in addition to statistical analysis to convert raw real-world data sets into meaningful data for causal inference. The application of various algorithms for the detection of causal linkages between the indicators is the subject of this research. Despite the fact that disparities in governmental policies between countries account for differences in causal linkages, several indicators emerge as important determinants sensitive to disease outbreaks over the world in the 21st Century.

Foundation models are becoming valuable tools in medicine. Yet despite their promise, the best way to leverage Large Language Models (LLMs) in complex medical tasks remains an open question. We introduce a novel multi-agent framework, named Medical Decision-making Agents (MDAgents) that helps address this gap by automatically assigning a collaboration structure to a team of LLMs. The assigned solo or group collaboration structure is tailored to the medical task at hand, emulating real-world medical decision-making processes adapted to tasks of varying complexities. We evaluate our framework and baseline methods using state-of-the-art LLMs across a suite of real-world medical knowledge and medical diagnosis benchmarks, including a comparison of LLMs' medical complexity classification against human physicians. MDAgents achieved the best performance in seven out of ten benchmarks on tasks requiring an understanding of medical knowledge and multi-modal reasoning, showing a significant improvement of up to 4.2% (p < 0.05) compared to previous methods' best performances. Ablation studies reveal that MDAgents effectively determines medical complexity to optimize for efficiency and accuracy across diverse medical tasks. Notably, the combination of moderator review and external medical knowledge in group collaboration resulted in an average accuracy improvement of 11.8%. Our code can be found at https://github.com/mitmedialab/MDAgents.

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.

Accurate and interpretable multi-disease diagnosis remains a critical challenge in medical research, particularly when leveraging heterogeneous multimodal medical data. Current approaches often rely on single-modal data, limiting their ability to comprehensively understand complex diseases. To address this, we propose MedTVT-R1, a novel Multimodal Large Language Model (MLLM) framework designed to integrate clinical multimodal data for reasoning and diagnosing multiple diseases. We construct MedTVT-QA, a curated instruction dataset that provides question-answer pairs for physiological-level interpretations and disease-level diagnoses with a Chain of Evidence approach. MedTVT-R1 incorporates a modality perception layer to capture inter-modal dependencies and adaptively weight modality contributions. Additionally, we employ Group Relative Policy Optimization (GRPO)-based Reinforcement Fine-Tuning with a Jaccard Reward function to enhance diagnostic reasoning. Experimental results demonstrate MedTVT-R1's superiority in multimodal feature utilization and multi-disease diagnosis, offering significant potential for clinical applications such as diagnostic report generation and comorbidity reasoning. The dataset and code are available at https://github.com/keke-nice/MedTVT-R1.

Automatic coding of International Classification of Diseases (ICD) is a multi-label text categorization task that involves extracting disease or procedure codes from clinical notes. Despite the application of state-of-the-art natural language processing (NLP) techniques, there are still challenges including limited availability of data due to privacy constraints and the high variability of clinical notes caused by different writing habits of medical professionals and various pathological features of patients. In this work, we investigate the semi-structured nature of clinical notes and propose an automatic algorithm to segment them into sections. To address the variability issues in existing ICD coding models with limited data, we introduce a contrastive pre-training approach on sections using a soft multi-label similarity metric based on tree edit distance. Additionally, we design a masked section training strategy to enable ICD coding models to locate sections related to ICD codes. Extensive experimental results demonstrate that our proposed training strategies effectively enhance the performance of existing ICD coding methods.

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.

Predicting disease trajectories from electronic health records (EHRs) is a complex task due to major challenges such as data non-stationarity, high granularity of medical codes, and integration of multimodal data. EHRs contain both structured data, such as diagnostic codes, and unstructured data, such as clinical notes, which hold essential information often overlooked. Current models, primarily based on structured data, struggle to capture the complete medical context of patients, resulting in a loss of valuable information. To address this issue, we propose an approach that integrates unstructured clinical notes into transformer-based deep learning models for sequential disease prediction. This integration enriches the representation of patients' medical histories, thereby improving the accuracy of diagnosis predictions. Experiments on MIMIC-IV datasets demonstrate that the proposed approach outperforms traditional models relying solely on structured data.

Recent large language models (LLMs) in the general domain, such as ChatGPT, have shown remarkable success in following instructions and producing human-like responses. However, such language models have not been learned individually and carefully for the medical domain, resulting in poor diagnostic accuracy and inability to give correct recommendations for medical diagnosis, medications, etc. To address this issue, we collected more than 700 diseases and their corresponding symptoms, recommended medications, and required medical tests, and then generated 5K doctor-patient conversations. By fine-tuning models of doctor-patient conversations, these models emerge with great potential to understand patients' needs, provide informed advice, and offer valuable assistance in a variety of medical-related fields. The integration of these advanced language models into healthcare can revolutionize the way healthcare professionals and patients communicate, ultimately improving the overall quality of care and patient outcomes. In addition, we will open all source code, datasets and model weights to advance the further development of dialogue models in the medical field. In addition, the training data, code, and weights of this project are available at: https://github.com/Kent0n-Li/ChatDoctor.

Recent advances in generative AI have brought incredible breakthroughs in several areas, including medical imaging. These generative models have tremendous potential not only to help safely share medical data via synthetic datasets but also to perform an array of diverse applications, such as anomaly detection, image-to-image translation, denoising, and MRI reconstruction. However, due to the complexity of these models, their implementation and reproducibility can be difficult. This complexity can hinder progress, act as a use barrier, and dissuade the comparison of new methods with existing works. In this study, we present MONAI Generative Models, a freely available open-source platform that allows researchers and developers to easily train, evaluate, and deploy generative models and related applications. Our platform reproduces state-of-art studies in a standardised way involving different architectures (such as diffusion models, autoregressive transformers, and GANs), and provides pre-trained models for the community. We have implemented these models in a generalisable fashion, illustrating that their results can be extended to 2D or 3D scenarios, including medical images with different modalities (like CT, MRI, and X-Ray data) and from different anatomical areas. Finally, we adopt a modular and extensible approach, ensuring long-term maintainability and the extension of current applications for future features.

Medical report generation has achieved remarkable advancements yet has still been faced with several challenges. First, the inherent imbalance in the distribution of normal and abnormal cases may lead models to exhibit a biased focus on normal samples, resulting in unreliable diagnoses. Second, the frequent occurrence of common template sentences in the reports may overwhelm the critical abnormal information. Moreover, existing works focus on 2D chest X-rays, leaving CT report generation underexplored due to the high-dimensional nature of CT images and the limited availability of CT-report pairs. Recently, LLM has shown a great ability to generate reliable answers with appropriate prompts, which shed light on addressing the aforementioned challenges. In this paper, we propose Dia-LLaMA, a framework to adapt the LLaMA2-7B for CT report generation by incorporating diagnostic information as guidance prompts. Considering the high dimension of CT, we leverage a pre-trained ViT3D with perceiver to extract the visual information. To tailor the LLM for report generation and emphasize abnormality, we extract additional diagnostic information by referring to a disease prototype memory bank, which is updated during training to capture common disease representations. Furthermore, we introduce disease-aware attention to enable the model to adjust attention for different diseases. Experiments on the chest CT dataset demonstrated that our proposed method outperformed previous methods and achieved state-of-the-art on both clinical efficacy performance and natural language generation metrics. The code will be made publically available.

Digital twin technology has is anticipated to transform healthcare, enabling personalized medicines and support, earlier diagnoses, simulated treatment outcomes, and optimized surgical plans. Digital twins are readily gaining traction in industries like manufacturing, supply chain logistics, and civil infrastructure. Not in patient care, however. The challenge of modeling complex diseases with multimodal patient data and the computational complexities of analyzing it have stifled digital twin adoption in the biomedical vertical. Yet, these major obstacles can potentially be handled by approaching these models in a different way. This paper proposes a novel framework for addressing the barriers to clinical twin modeling created by computational costs and modeling complexities. We propose structuring patient health data as a knowledge graph and using closed-form continuous-time liquid neural networks, for real-time analytics. By synthesizing multimodal patient data and leveraging the flexibility and efficiency of closed form continuous time networks and knowledge graph ontologies, our approach enables real time insights, personalized medicine, early diagnosis and intervention, and optimal surgical planning. This novel approach provides a comprehensive and adaptable view of patient health along with real-time analytics, paving the way for digital twin simulations and other anticipated benefits in healthcare.

While hundreds of artificial intelligence (AI) algorithms are now approved or cleared by the US Food and Drugs Administration (FDA), many studies have shown inconsistent generalization or latent bias, particularly for underrepresented populations. Some have proposed that generative AI could reduce the need for real data, but its utility in model development remains unclear. Skin disease serves as a useful case study in synthetic image generation due to the diversity of disease appearance, particularly across the protected attribute of skin tone. Here we show that latent diffusion models can scalably generate images of skin disease and that augmenting model training with these data improves performance in data-limited settings. These performance gains saturate at synthetic-to-real image ratios above 10:1 and are substantially smaller than the gains obtained from adding real images. As part of our analysis, we generate and analyze a new dataset of 458,920 synthetic images produced using several generation strategies. Our results suggest that synthetic data could serve as a force-multiplier for model development, but the collection of diverse real-world data remains the most important step to improve medical AI algorithms.

Automatic International Classification of Diseases (ICD) coding aims to assign multiple ICD codes to a medical note with average length of 3,000+ tokens. This task is challenging due to a high-dimensional space of multi-label assignment (tens of thousands of ICD codes) and the long-tail challenge: only a few codes (common diseases) are frequently assigned while most codes (rare diseases) are infrequently assigned. This study addresses the long-tail challenge by adapting a prompt-based fine-tuning technique with label semantics, which has been shown to be effective under few-shot setting. To further enhance the performance in medical domain, we propose a knowledge-enhanced longformer by injecting three domain-specific knowledge: hierarchy, synonym, and abbreviation with additional pretraining using contrastive learning. Experiments on MIMIC-III-full, a benchmark dataset of code assignment, show that our proposed method outperforms previous state-of-the-art method in 14.5% in marco F1 (from 10.3 to 11.8, P<0.001). To further test our model on few-shot setting, we created a new rare diseases coding dataset, MIMIC-III-rare50, on which our model improves marco F1 from 17.1 to 30.4 and micro F1 from 17.2 to 32.6 compared to previous method.

The cycle of scientific discovery is frequently bottlenecked by the slow, manual creation of software to support computational experiments. To address this, we present an AI system that creates expert-level scientific software whose goal is to maximize a quality metric. The system uses a Large Language Model (LLM) and Tree Search (TS) to systematically improve the quality metric and intelligently navigate the large space of possible solutions. The system achieves expert-level results when it explores and integrates complex research ideas from external sources. The effectiveness of tree search is demonstrated across a wide range of benchmarks. In bioinformatics, it discovered 40 novel methods for single-cell data analysis that outperformed the top human-developed methods on a public leaderboard. In epidemiology, it generated 14 models that outperformed the CDC ensemble and all other individual models for forecasting COVID-19 hospitalizations. Our method also produced state-of-the-art software for geospatial analysis, neural activity prediction in zebrafish, time series forecasting and numerical solution of integrals. By devising and implementing novel solutions to diverse tasks, the system represents a significant step towards accelerating scientific progress.

Advances in large language models (LLMs) provide new opportunities in healthcare for improved patient care, clinical decision-making, and enhancement of physician and administrator workflows. However, the potential of these models importantly depends on their ability to generalize effectively across clinical environments and populations, a challenge often underestimated in early development. To better understand reasons for these challenges and inform mitigation approaches, we evaluated ClinicLLM, an LLM trained on [HOSPITAL]'s clinical notes, analyzing its performance on 30-day all-cause readmission prediction focusing on variability across hospitals and patient characteristics. We found poorer generalization particularly in hospitals with fewer samples, among patients with government and unspecified insurance, the elderly, and those with high comorbidities. To understand reasons for lack of generalization, we investigated sample sizes for fine-tuning, note content (number of words per note), patient characteristics (comorbidity level, age, insurance type, borough), and health system aspects (hospital, all-cause 30-day readmission, and mortality rates). We used descriptive statistics and supervised classification to identify features. We found that, along with sample size, patient age, number of comorbidities, and the number of words in notes are all important factors related to generalization. Finally, we compared local fine-tuning (hospital specific), instance-based augmented fine-tuning and cluster-based fine-tuning for improving generalization. Among these, local fine-tuning proved most effective, increasing AUC by 0.25% to 11.74% (most helpful in settings with limited data). Overall, this study provides new insights for enhancing the deployment of large language models in the societally important domain of healthcare, and improving their performance for broader populations.

Automatic medical report generation (MRG) is of great research value as it has the potential to relieve radiologists from the heavy burden of report writing. Despite recent advancements, accurate MRG remains challenging due to the need for precise clinical understanding and the identification of clinical findings. Moreover, the imbalanced distribution of diseases makes the challenge even more pronounced, as rare diseases are underrepresented in training data, making their diagnostic performance unreliable. To address these challenges, we propose diagnosis-driven prompts for medical report generation (PromptMRG), a novel framework that aims to improve the diagnostic accuracy of MRG with the guidance of diagnosis-aware prompts. Specifically, PromptMRG is based on encoder-decoder architecture with an extra disease classification branch. When generating reports, the diagnostic results from the classification branch are converted into token prompts to explicitly guide the generation process. To further improve the diagnostic accuracy, we design cross-modal feature enhancement, which retrieves similar reports from the database to assist the diagnosis of a query image by leveraging the knowledge from a pre-trained CLIP. Moreover, the disease imbalanced issue is addressed by applying an adaptive logit-adjusted loss to the classification branch based on the individual learning status of each disease, which overcomes the barrier of text decoder's inability to manipulate disease distributions. Experiments on two MRG benchmarks show the effectiveness of the proposed method, where it obtains state-of-the-art clinical efficacy performance on both datasets.

While large language models hold promise for complex medical applications, their development is hindered by the scarcity of high-quality reasoning data. To address this issue, existing approaches typically distill chain-of-thought reasoning traces from large proprietary models via supervised fine-tuning, then conduct reinforcement learning (RL). These methods exhibit limited improvement on underrepresented domains like rare diseases while incurring substantial costs from generating complex reasoning chains. To efficiently enhance medical reasoning, we propose MedSSR, a Medical Knowledge-enhanced data Synthesis and Semi-supervised Reinforcement learning framework. Our framework first employs rare disease knowledge to synthesize distribution-controllable reasoning questions. We then utilize the policy model itself to generate high-quality pseudo-labels. This enables a two-stage, intrinsic-to-extrinsic training paradigm: self-supervised RL on the pseudo-labeled synthetic data, followed by supervised RL on the human-annotated real data. MedSSR scales model training efficiently without relying on costly trace distillation. Extensive experiments on Qwen and Llama demonstrate that our method outperforms existing methods across ten medical benchmarks, achieving up to +5.93% gain on rare-disease tasks. Our code is available at https://github.com/tdlhl/MedSSR.

Vision disorders significantly impact millions of lives, altering how visual information is processed and perceived. In this work, a computational framework was developed using the BrokenEyes system to simulate five common eye disorders: Age-related macular degeneration, cataract, glaucoma, refractive errors, and diabetic retinopathy and analyze their effects on neural-like feature representations in deep learning models. Leveraging a combination of human and non-human datasets, models trained under normal and disorder-specific conditions revealed critical disruptions in feature maps, particularly for cataract and glaucoma, which align with known neural processing challenges in these conditions. Evaluation metrics such as activation energy and cosine similarity quantified the severity of these distortions, providing insights into the interplay between degraded visual inputs and learned representations.

We explore the emergence of intelligent behavior in artificial systems by investigating how the complexity of rule-based systems influences the capabilities of models trained to predict these rules. Our study focuses on elementary cellular automata (ECA), simple yet powerful one-dimensional systems that generate behaviors ranging from trivial to highly complex. By training distinct Large Language Models (LLMs) on different ECAs, we evaluated the relationship between the complexity of the rules' behavior and the intelligence exhibited by the LLMs, as reflected in their performance on downstream tasks. Our findings reveal that rules with higher complexity lead to models exhibiting greater intelligence, as demonstrated by their performance on reasoning and chess move prediction tasks. Both uniform and periodic systems, and often also highly chaotic systems, resulted in poorer downstream performance, highlighting a sweet spot of complexity conducive to intelligence. We conjecture that intelligence arises from the ability to predict complexity and that creating intelligence may require only exposure to complexity.

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.

Solving the inverse problem is the key step in evaluating the capacity of a physical model to describe real phenomena. In medical image computing, it aligns with the classical theme of image-based model personalization. Traditionally, a solution to the problem is obtained by performing either sampling or variational inference based methods. Both approaches aim to identify a set of free physical model parameters that results in a simulation best matching an empirical observation. When applied to brain tumor modeling, one of the instances of image-based model personalization in medical image computing, the overarching drawback of the methods is the time complexity for finding such a set. In a clinical setting with limited time between imaging and diagnosis or even intervention, this time complexity may prove critical. As the history of quantitative science is the history of compression, we align in this paper with the historical tendency and propose a method compressing complex traditional strategies for solving an inverse problem into a simple database query task. We evaluated different ways of performing the database query task assessing the trade-off between accuracy and execution time. On the exemplary task of brain tumor growth modeling, we prove that the proposed method achieves one order speed-up compared to existing approaches for solving the inverse problem. The resulting compute time offers critical means for relying on more complex and, hence, realistic models, for integrating image preprocessing and inverse modeling even deeper, or for implementing the current model into a clinical workflow.

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.

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.

Case definitions are essential for effectively communicating public health threats. However, the absence of a standardized, machine-readable format poses significant challenges to interoperability, epidemiological research, the exchange of qualitative data, and the effective application of computational analysis methods, including artificial intelligence (AI). This complicates comparisons and collaborations across organizations and regions, limits data integration, and hinders technological innovation in public health. To address these issues, we propose the first open, machine-readable format for representing case and syndrome definitions. Additionally, we introduce the first comprehensive dataset of standardized case definitions and tools to convert existing human-readable definitions into machine-readable formats. We also provide an accessible online platform for browsing, analyzing, and contributing new definitions, available at https://opensyndrome.org. The Open Syndrome Definition format enables consistent, scalable use of case definitions across systems, unlocking AI's potential to strengthen public health preparedness and response. The source code for the format can be found at https://github.com/OpenSyndrome/schema under the MIT license.

Cancer has relational information residing at varying scales, modalities, and resolutions of the acquired data, such as radiology, pathology, genomics, proteomics, and clinical records. Integrating diverse data types can improve the accuracy and reliability of cancer diagnosis and treatment. There can be disease-related information that is too subtle for humans or existing technological tools to discern visually. Traditional methods typically focus on partial or unimodal information about biological systems at individual scales and fail to encapsulate the complete spectrum of the heterogeneous nature of data. Deep neural networks have facilitated the development of sophisticated multimodal data fusion approaches that can extract and integrate relevant information from multiple sources. Recent deep learning frameworks such as Graph Neural Networks (GNNs) and Transformers have shown remarkable success in multimodal learning. This review article provides an in-depth analysis of the state-of-the-art in GNNs and Transformers for multimodal data fusion in oncology settings, highlighting notable research studies and their findings. We also discuss the foundations of multimodal learning, inherent challenges, and opportunities for integrative learning in oncology. By examining the current state and potential future developments of multimodal data integration in oncology, we aim to demonstrate the promising role that multimodal neural networks can play in cancer prevention, early detection, and treatment through informed oncology practices in personalized settings.

Mental health disorders are one of the most serious diseases in the world. Most people with such a disease lack access to adequate care, which highlights the importance of training models for the diagnosis and treatment of mental health disorders. However, in the mental health domain, privacy concerns limit the accessibility of personalized treatment data, making it challenging to build powerful models. In this paper, we introduce MentalArena, a self-play framework to train language models by generating domain-specific personalized data, where we obtain a better model capable of making a personalized diagnosis and treatment (as a therapist) and providing information (as a patient). To accurately model human-like mental health patients, we devise Symptom Encoder, which simulates a real patient from both cognition and behavior perspectives. To address intent bias during patient-therapist interactions, we propose Symptom Decoder to compare diagnosed symptoms with encoded symptoms, and dynamically manage the dialogue between patient and therapist according to the identified deviations. We evaluated MentalArena against 6 benchmarks, including biomedicalQA and mental health tasks, compared to 6 advanced models. Our models, fine-tuned on both GPT-3.5 and Llama-3-8b, significantly outperform their counterparts, including GPT-4o. We hope that our work can inspire future research on personalized care. Code is available in https://github.com/Scarelette/MentalArena/tree/main

The rapid evolution of artificial intelligence (AI), together with the increased availability of social media and news for epidemiological surveillance, are marking a pivotal moment in epidemiology and public health research. Leveraging the power of generative AI, we use an ensemble approach which incorporates multiple Large Language Models (LLMs) to extract valuable actionable epidemiological information from the World Health Organization (WHO) Disease Outbreak News (DONs). DONs is a collection of regular reports on global outbreaks curated by the WHO and the adopted decision-making processes to respond to them. The extracted information is made available in a daily-updated dataset and a knowledge graph, referred to as eKG, derived to provide a nuanced representation of the public health domain knowledge. We provide an overview of this new dataset and describe the structure of eKG, along with the services and tools used to access and utilize the data that we are building on top. These innovative data resources open altogether new opportunities for epidemiological research, and the analysis and surveillance of disease outbreaks.

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.

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.

Phenotyping is fundamental to rare disease diagnosis, but manual curation of structured phenotypes from clinical notes is labor-intensive and difficult to scale. Existing artificial intelligence approaches typically optimize individual components of phenotyping but do not operationalize the full clinical workflow of extracting features from clinical text, standardizing them to Human Phenotype Ontology (HPO) terms, and prioritizing diagnostically informative HPO terms. We developed RARE-PHENIX, an end-to-end AI framework for rare disease phenotyping that integrates large language model-based phenotype extraction, ontology-grounded standardization to HPO terms, and supervised ranking of diagnostically informative phenotypes. We trained RARE-PHENIX using data from 2,671 patients across 11 Undiagnosed Diseases Network clinical sites, and externally validated it on 16,357 real-world clinical notes from Vanderbilt University Medical Center. Using clinician-curated HPO terms as the gold standard, RARE-PHENIX consistently outperformed a state-of-the-art deep learning baseline (PhenoBERT) across ontology-based similarity and precision-recall-F1 metrics in end-to-end evaluation (i.e., ontology-based similarity of 0.70 vs. 0.58). Ablation analyses demonstrated performance improvements with the addition of each module in RARE-PHENIX (extraction, standardization, and prioritization), supporting the value of modeling the full clinical phenotyping workflow. By modeling phenotyping as a clinically aligned workflow rather than a single extraction task, RARE-PHENIX provides structured, ranked phenotypes that are more concordant with clinician curation and has the potential to support human-in-the-loop rare disease diagnosis in real-world settings.

When a text is translated, does the translation retain the complexity of the original? We introduce ComplexityMT, a new challenge for assessing how text complexity and machine translation interact with and influence each other, using the Common European Framework of Reference for Languages (CEFR) levels as the measure of text complexity. Across six languages, including Arabic, Dutch, English, French, Hindi, and Russian, we evaluate three open-weight models, one closed model, and a commercial machine translation system on two tasks: i) correlation of CEFR with translation difficulty, and ii) shifts in CEFR levels of the source texts. Our experiments show that higher CEFR levels make texts more difficult to translate, and that machine translation shifts the CEFR level of the target text compared to the original source, for most languages. These findings provide new insights for researchers and practitioners working on multilingual pedagogical content generation and machine translation difficulty estimation.

Chronic Obstructive Pulmonary Disease (COPD), a major chronic respiratory disease with persistent airflow limitation, is a leading global cause of disability and mortality. Respiratory spirogram time series, routinely collected during pulmonary function tests (PFTs), play a critical role in the early detection of repsiratory diseases and in monitoring lung function over time. However, most current AI models for COPD diagnosis are limited to outputting classification results without providing a rationale for their diagnostic process, while current Large Language Models (LLMs) cannot understand spirograms yet, which severely limits their clinical trust and adoption. To tackle this challenge, we leverage a cohort of 234,028 individuals from the UK Biobank (UKB) to propose SpiroLLM, the first multimodal large language model that can understand spirogram. The model extracts morphological features from respiratory curves via a SpiroEncoder and aligns them with PFT numerical values in a unified latent space using a SpiroProjector, ultimately empowering a large language model to generate a comprehensive diagnostic report. Experimental results confirm that SpiroLLM achieved a diagnostic AUROC of 0.8980 (95% CI: 0.8820-0.9132). In a robustness test with missing core data, it maintained a 100% valid response rate, far surpassing the 13.4% of a text-only model and showcasing the superiority of its multimodal design. This work demonstrates the substantial potential of deeply fusing physiological signals with large language models, establishing a new paradigm for the next generation of interpretable and reliable clinical decision support tools.

In the general domain, large multimodal models (LMMs) have achieved significant advancements, yet challenges persist in applying them to specific fields, especially agriculture. As the backbone of the global economy, agriculture confronts numerous challenges, with pests and diseases being particularly concerning due to their complexity, variability, rapid spread, and high resistance. This paper specifically addresses these issues. We construct the first multimodal instruction-following dataset in the agricultural domain, covering over 221 types of pests and diseases with approximately 400,000 data entries. This dataset aims to explore and address the unique challenges in pest and disease control. Based on this dataset, we propose a knowledge-infused training method to develop Agri-LLaVA, an agricultural multimodal conversation system. To accelerate progress in this field and inspire more researchers to engage, we design a diverse and challenging evaluation benchmark for agricultural pests and diseases. Experimental results demonstrate that Agri-LLaVA excels in agricultural multimodal conversation and visual understanding, providing new insights and approaches to address agricultural pests and diseases. By open-sourcing our dataset and model, we aim to promote research and development in LMMs within the agricultural domain and make significant contributions to tackle the challenges of agricultural pests and diseases. All resources can be found at https://github.com/Kki2Eve/Agri-LLaVA.

Learning to represent free text is a core task in many clinical machine learning (ML) applications, as clinical text contains observations and plans not otherwise available for inference. State-of-the-art methods use large language models developed with immense computational resources and training data; however, applying these models is challenging because of the highly varying syntax and vocabulary in clinical free text. Structured information such as International Classification of Disease (ICD) codes often succinctly abstracts the most important facts of a clinical encounter and yields good performance, but is often not as available as clinical text in real-world scenarios. We propose a multi-view learning framework that jointly learns from codes and text to combine the availability and forward-looking nature of text and better performance of ICD codes. The learned text embeddings can be used as inputs to predictive algorithms independent of the ICD codes during inference. Our approach uses a Graph Neural Network (GNN) to process ICD codes, and Bi-LSTM to process text. We apply Deep Canonical Correlation Analysis (DCCA) to enforce the two views to learn a similar representation of each patient. In experiments using planned surgical procedure text, our model outperforms BERT models fine-tuned to clinical data, and in experiments using diverse text in MIMIC-III, our model is competitive to a fine-tuned BERT at a tiny fraction of its computational effort.

This paper explores the advancements and applications of large-scale models in the medical field, with a particular focus on Medical Large Models (MedLMs). These models, encompassing Large Language Models (LLMs), Vision Models, 3D Large Models, and Multimodal Models, are revolutionizing healthcare by enhancing disease prediction, diagnostic assistance, personalized treatment planning, and drug discovery. The integration of graph neural networks in medical knowledge graphs and drug discovery highlights the potential of Large Graph Models (LGMs) in understanding complex biomedical relationships. The study also emphasizes the transformative role of Vision-Language Models (VLMs) and 3D Large Models in medical image analysis, anatomical modeling, and prosthetic design. Despite the challenges, these technologies are setting new benchmarks in medical innovation, improving diagnostic accuracy, and paving the way for personalized healthcare solutions. This paper aims to provide a comprehensive overview of the current state and future directions of large models in medicine, underscoring their significance in advancing global health.

Integrating Large Language Models (LLMs) in healthcare diagnosis demands systematic frameworks that can handle complex medical scenarios while maintaining specialized expertise. We present KG4Diagnosis, a novel hierarchical multi-agent framework that combines LLMs with automated knowledge graph construction, encompassing 362 common diseases across medical specialties. Our framework mirrors real-world medical systems through a two-tier architecture: a general practitioner (GP) agent for initial assessment and triage, coordinating with specialized agents for in-depth diagnosis in specific domains. The core innovation lies in our end-to-end knowledge graph generation methodology, incorporating: (1) semantic-driven entity and relation extraction optimized for medical terminology, (2) multi-dimensional decision relationship reconstruction from unstructured medical texts, and (3) human-guided reasoning for knowledge expansion. KG4Diagnosis serves as an extensible foundation for specialized medical diagnosis systems, with capabilities to incorporate new diseases and medical knowledge. The framework's modular design enables seamless integration of domain-specific enhancements, making it valuable for developing targeted medical diagnosis systems. We provide architectural guidelines and protocols to facilitate adoption across medical contexts.

Providing effective treatment and making informed clinical decisions are essential goals of modern medicine and clinical care. We are interested in simulating disease dynamics for clinical decision-making, leveraging recent advances in large generative models. To this end, we introduce the Medical World Model (MeWM), the first world model in medicine that visually predicts future disease states based on clinical decisions. MeWM comprises (i) vision-language models to serve as policy models, and (ii) tumor generative models as dynamics models. The policy model generates action plans, such as clinical treatments, while the dynamics model simulates tumor progression or regression under given treatment conditions. Building on this, we propose the inverse dynamics model that applies survival analysis to the simulated post-treatment tumor, enabling the evaluation of treatment efficacy and the selection of the optimal clinical action plan. As a result, the proposed MeWM simulates disease dynamics by synthesizing post-treatment tumors, with state-of-the-art specificity in Turing tests evaluated by radiologists. Simultaneously, its inverse dynamics model outperforms medical-specialized GPTs in optimizing individualized treatment protocols across all metrics. Notably, MeWM improves clinical decision-making for interventional physicians, boosting F1-score in selecting the optimal TACE protocol by 13%, paving the way for future integration of medical world models as the second readers.

We present a general computational theory of cancer and its developmental dynamics. The theory is based on a theory of the architecture and function of developmental control networks which guide the formation of multicellular organisms. Cancer networks are special cases of developmental control networks. Cancer results from transformations of normal developmental networks. Our theory generates a natural classification of all possible cancers based on their network architecture. Each cancer network has a unique topology and semantics and developmental dynamics that result in distinct clinical tumor phenotypes. We apply this new theory with a series of proof of concept cases for all the basic cancer types. These cases have been computationally modeled, their behavior simulated and mathematically described using a multicellular systems biology approach. There are fascinating correspondences between the dynamic developmental phenotype of computationally modeled {\em in silico} cancers and natural {\em in vivo} cancers. The theory lays the foundation for a new research paradigm for understanding and investigating cancer. The theory of cancer networks implies that new diagnostic methods and new treatments to cure cancer will become possible.

The outbreak of COVID-19 has highlighted the intricate interplay between public health and economic stability on a global scale. This study proposes a novel reinforcement learning framework designed to optimize health and economic outcomes during pandemics. The framework leverages the SIR model, integrating both lockdown measures (via a stringency index) and vaccination strategies to simulate disease dynamics. The stringency index, indicative of the severity of lockdown measures, influences both the spread of the disease and the economic health of a country. Developing nations, which bear a disproportionate economic burden under stringent lockdowns, are the primary focus of our study. By implementing reinforcement learning, we aim to optimize governmental responses and strike a balance between the competing costs associated with public health and economic stability. This approach also enhances transparency in governmental decision-making by establishing a well-defined reward function for the reinforcement learning agent. In essence, this study introduces an innovative and ethical strategy to navigate the challenge of balancing public health and economic stability amidst infectious disease outbreaks.

Reliable epidemiological reasoning requires synthesizing study evidence to infer disease burden, transmission dynamics, and intervention effects at the population level. Existing medical question answering benchmarks primarily emphasize clinical knowledge or patient-level reasoning, yet few systematically evaluate evidence-grounded epidemiological inference. We present EpiQAL, the first diagnostic benchmark for epidemiological question answering across diverse diseases, comprising three subsets built from open-access literature. The subsets respectively evaluate text-grounded factual recall, multi-step inference linking document evidence with epidemiological principles, and conclusion reconstruction with the Discussion section withheld. Construction combines expert-designed taxonomy guidance, multi-model verification, and retrieval-based difficulty control. Experiments on ten open models reveal that current LLMs show limited performance on epidemiological reasoning, with multi-step inference posing the greatest challenge. Model rankings shift across subsets, and scale alone does not predict success. Chain-of-Thought prompting benefits multi-step inference but yields mixed results elsewhere. EpiQAL provides fine-grained diagnostic signals for evidence grounding, inferential reasoning, and conclusion reconstruction.

We aim to present a comprehensive overview of the latest advancements in utilizing Large Language Models (LLMs) within the healthcare sector, emphasizing their transformative impact across various medical domains. LLMs have become pivotal in supporting healthcare, including physicians, healthcare providers, and patients. Our review provides insight into the applications of Large Language Models (LLMs) in healthcare, specifically focusing on diagnostic and treatment-related functionalities. We shed light on how LLMs are applied in cancer care, dermatology, dental care, neurodegenerative disorders, and mental health, highlighting their innovative contributions to medical diagnostics and patient care. Throughout our analysis, we explore the challenges and opportunities associated with integrating LLMs in healthcare, recognizing their potential across various medical specialties despite existing limitations. Additionally, we offer an overview of handling diverse data types within the medical field.

Systematic literature reviews are essential for synthesizing scientific evidence but are costly, difficult to scale and time-intensive, creating bottlenecks for evidence-based policy. We study whether large language models can automate the complete systematic review workflow, from article retrieval, article screening, data extraction to report synthesis. Applied to epidemiological reviews of nine WHO-designated priority pathogens and validated against expert-curated ground truth, our open-source agentic pipeline (AgentSLR) achieves performance comparable to human researchers while reducing review time from approximately 7 weeks to 20 hours (a 58x speed-up). Our comparison of five frontier models reveals that performance on SLR is driven less by model size or inference cost than by each model's distinctive capabilities. Through human-in-the-loop validation, we identify key failure modes. Our results demonstrate that agentic AI can substantially accelerate scientific evidence synthesis in specialised domains.

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.

The global ramifications of the COVID-19 pandemic remain significant, exerting persistent pressure on nations even three years after its initial outbreak. Deep learning models have shown promise in improving COVID-19 diagnostics but require diverse and larger-scale datasets to improve performance. In this paper, we introduce COVIDx CXR-4, an expanded multi-institutional open-source benchmark dataset for chest X-ray image-based computer-aided COVID-19 diagnostics. COVIDx CXR-4 expands significantly on the previous COVIDx CXR-3 dataset by increasing the total patient cohort size by greater than 2.66 times, resulting in 84,818 images from 45,342 patients across multiple institutions. We provide extensive analysis on the diversity of the patient demographic, imaging metadata, and disease distributions to highlight potential dataset biases. To the best of the authors' knowledge, COVIDx CXR-4 is the largest and most diverse open-source COVID-19 CXR dataset and is made publicly available as part of an open initiative to advance research to aid clinicians against the COVID-19 disease.

Clinical diagnosis is a highly specialized discipline requiring both domain expertise and strict adherence to rigorous guidelines. While current AI-driven medical research predominantly focuses on knowledge graphs or natural text pretraining paradigms to incorporate medical knowledge, these approaches primarily rely on implicitly encoded knowledge within model parameters, neglecting task-specific knowledge required by diverse downstream tasks. To address this limitation, we propose Retrieval-Augmented Diagnosis (RAD), a novel framework that explicitly injects external knowledge into multimodal models directly on downstream tasks. Specifically, RAD operates through three key mechanisms: retrieval and refinement of disease-centered knowledge from multiple medical sources, a guideline-enhanced contrastive loss that constrains the latent distance between multi-modal features and guideline knowledge, and the dual transformer decoder that employs guidelines as queries to steer cross-modal fusion, aligning the models with clinical diagnostic workflows from guideline acquisition to feature extraction and decision-making. Moreover, recognizing the lack of quantitative evaluation of interpretability for multimodal diagnostic models, we introduce a set of criteria to assess the interpretability from both image and text perspectives. Extensive evaluations across four datasets with different anatomies demonstrate RAD's generalizability, achieving state-of-the-art performance. Furthermore, RAD enables the model to concentrate more precisely on abnormal regions and critical indicators, ensuring evidence-based, trustworthy diagnosis. Our code is available at https://github.com/tdlhl/RAD.

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.

This research paper investigates the effectiveness of simple linear models versus complex machine learning techniques in breast cancer diagnosis, emphasizing the importance of interpretability and computational efficiency in the medical domain. We focus on Logistic Regression (LR), Decision Trees (DT), and Support Vector Machines (SVM) and optimize their performance using the UCI Machine Learning Repository dataset. Our findings demonstrate that the simpler linear model, LR, outperforms the more complex DT and SVM techniques, with a test score mean of 97.28%, a standard deviation of 1.62%, and a computation time of 35.56 ms. In comparison, DT achieved a test score mean of 93.73%, and SVM had a test score mean of 96.44%. The superior performance of LR can be attributed to its simplicity and interpretability, which provide a clear understanding of the relationship between input features and the outcome. This is particularly valuable in the medical domain, where interpretability is crucial for decision-making. Moreover, the computational efficiency of LR offers advantages in terms of scalability and real-world applicability. The results of this study highlight the power of simplicity in the context of breast cancer diagnosis and suggest that simpler linear models like LR can be more effective, interpretable, and computationally efficient than their complex counterparts, making them a more suitable choice for medical applications.

Seismic advances in generative AI algorithms for imagery, text, and other data types has led to the temptation to use synthetic data to train next-generation models. Repeating this process creates an autophagous (self-consuming) loop whose properties are poorly understood. We conduct a thorough analytical and empirical analysis using state-of-the-art generative image models of three families of autophagous loops that differ in how fixed or fresh real training data is available through the generations of training and in whether the samples from previous generation models have been biased to trade off data quality versus diversity. Our primary conclusion across all scenarios is that without enough fresh real data in each generation of an autophagous loop, future generative models are doomed to have their quality (precision) or diversity (recall) progressively decrease. We term this condition Model Autophagy Disorder (MAD), making analogy to mad cow disease.

Medical care follows complex clinical pathways that extend beyond isolated physician-patient encounters, emphasizing decision-making and transitions between different stages. Current benchmarks focusing on static exams or isolated dialogues inadequately evaluate large language models (LLMs) in dynamic clinical scenarios. We introduce CP-Env, a controllable agentic hospital environment designed to evaluate LLMs across end-to-end clinical pathways. CP-Env simulates a hospital ecosystem with patient and physician agents, constructing scenarios ranging from triage and specialist consultation to diagnostic testing and multidisciplinary team meetings for agent interaction. Following real hospital adaptive flow of healthcare, it enables branching, long-horizon task execution. We propose a three-tiered evaluation framework encompassing Clinical Efficacy, Process Competency, and Professional Ethics. Results reveal that most models struggle with pathway complexity, exhibiting hallucinations and losing critical diagnostic details. Interestingly, excessive reasoning steps can sometimes prove counterproductive, while top models tend to exhibit reduced tool dependency through internalized knowledge. CP-Env advances medical AI agents development through comprehensive end-to-end clinical evaluation. We provide the benchmark and evaluation tools for further research and development at https://github.com/SPIRAL-MED/CP_ENV.

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.

Complex prediction models such as deep learning are the output from fitting machine learning, neural networks, or AI models to a set of training data. These are now standard tools in science. A key challenge with the current generation of models is that they are highly parameterized, which makes describing and interpreting the prediction strategies difficult. We use topological data analysis to transform these complex prediction models into pictures representing a topological view. The result is a map of the predictions that enables inspection. The methods scale up to large datasets across different domains and enable us to detect labeling errors in training data, understand generalization in image classification, and inspect predictions of likely pathogenic mutations in the BRCA1 gene.

Current artificial intelligence models for medical imaging are predominantly single modality and single disease. Attempts to create multimodal and multi-disease models have resulted in inconsistent clinical accuracy. Furthermore, training these models typically requires large, labour-intensive, well-labelled datasets. We developed MerMED-FM, a state-of-the-art multimodal, multi-specialty foundation model trained using self-supervised learning and a memory module. MerMED-FM was trained on 3.3 million medical images from over ten specialties and seven modalities, including computed tomography (CT), chest X-rays (CXR), ultrasound (US), pathology patches, color fundus photography (CFP), optical coherence tomography (OCT) and dermatology images. MerMED-FM was evaluated across multiple diseases and compared against existing foundational models. Strong performance was achieved across all modalities, with AUROCs of 0.988 (OCT); 0.982 (pathology); 0.951 (US); 0.943 (CT); 0.931 (skin); 0.894 (CFP); 0.858 (CXR). MerMED-FM has the potential to be a highly adaptable, versatile, cross-specialty foundation model that enables robust medical imaging interpretation across diverse medical disciplines.

Document clustering is a text mining technique used to provide better document search and browsing in digital libraries or online corpora. A lot of research has been done on biomedical document clustering that is based on using existing ontology. But, associations and co-occurrences of the medical concepts are not well represented by using ontology. In this research, a vector representation of concepts of diseases and similarity measurement between concepts are proposed. They identify the closest concepts of diseases in the context of a corpus. Each document is represented by using the vector space model. A weight scheme is proposed to consider both local content and associations between concepts. A Self-Organizing Map is used as document clustering algorithm. The vector projection and visualization features of SOM enable visualization and analysis of the clusters distributions and relationships on the two dimensional space. The experimental results show that the proposed document clustering framework generates meaningful clusters and facilitate visualization of the clusters based on the concepts of diseases.

Chikungunya (CHIK) is a viral disease transmitted to humans through the bites of {\it Aedes} mosquitoes infected with the chikungunya virus (CHIKV). CHIKV has been imported annually to Florida in the last decade due to Miami's crucial location as a hub for international travel, particularly from Central and South America including Brazil, where CHIK is endemic. This work addresses to the geographic spread of CHIK, incorporating factors such as human movement, temperature dependency, as well as vertical transmission, and incubation periods, for different patches. Central to the model is the integration of a multi-patch framework, and in the numerical analysis it is considered human movement between endemic Brazilian states and Florida. We establish crucial correlations between the mosquito reproduction number R_{m} and the disease reproduction number R_{0} with the disease dynamics in a multi-patch environment, encompassing not only a numerical analysis but also from a theoretical perspective. Through numerical simulations, validated with real population and temperature data, it is possible to understand the disease dynamics under many different scenarios and make future projections, offering insights for potential effective control strategies, as well as addressing the timing for these strategies to be adopted.

The advancement in generative AI could be boosted with more accessible mathematics. Beyond human-AI chat, large language models (LLMs) are emerging in programming, algorithm discovery, and theorem proving, yet their genomics application is limited. This project introduces Math Agents and mathematical embedding as fresh entries to the "Moore's Law of Mathematics", using a GPT-based workflow to convert equations from literature into LaTeX and Python formats. While many digital equation representations exist, there's a lack of automated large-scale evaluation tools. LLMs are pivotal as linguistic user interfaces, providing natural language access for human-AI chat and formal languages for large-scale AI-assisted computational infrastructure. Given the infinite formal possibility spaces, Math Agents, which interact with math, could potentially shift us from "big data" to "big math". Math, unlike the more flexible natural language, has properties subject to proof, enabling its use beyond traditional applications like high-validation math-certified icons for AI alignment aims. This project aims to use Math Agents and mathematical embeddings to address the ageing issue in information systems biology by applying multiscalar physics mathematics to disease models and genomic data. Generative AI with episodic memory could help analyse causal relations in longitudinal health records, using SIR Precision Health models. Genomic data is suggested for addressing the unsolved Alzheimer's disease problem.

Large language models (LLMs) are increasingly essential in processing natural languages, yet their application is frequently compromised by biases and inaccuracies originating in their training data. In this study, we introduce Cross-Care, the first benchmark framework dedicated to assessing biases and real world knowledge in LLMs, specifically focusing on the representation of disease prevalence across diverse demographic groups. We systematically evaluate how demographic biases embedded in pre-training corpora like ThePile influence the outputs of LLMs. We expose and quantify discrepancies by juxtaposing these biases against actual disease prevalences in various U.S. demographic groups. Our results highlight substantial misalignment between LLM representation of disease prevalence and real disease prevalence rates across demographic subgroups, indicating a pronounced risk of bias propagation and a lack of real-world grounding for medical applications of LLMs. Furthermore, we observe that various alignment methods minimally resolve inconsistencies in the models' representation of disease prevalence across different languages. For further exploration and analysis, we make all data and a data visualization tool available at: www.crosscare.net.

The burgeoning field of brain health research increasingly leverages artificial intelligence (AI) to interpret and analyze neurological data. This study introduces a novel approach towards the creation of medical foundation models by integrating a large-scale multi-modal magnetic resonance imaging (MRI) dataset derived from 41,400 participants in its own. Our method involves a novel two-stage pretraining approach using vision transformers. The first stage is dedicated to encoding anatomical structures in generally healthy brains, identifying key features such as shapes and sizes of different brain regions. The second stage concentrates on spatial information, encompassing aspects like location and the relative positioning of brain structures. We rigorously evaluate our model, BrainFounder, using the Brain Tumor Segmentation (BraTS) challenge and Anatomical Tracings of Lesions After Stroke v2.0 (ATLAS v2.0) datasets. BrainFounder demonstrates a significant performance gain, surpassing the achievements of the previous winning solutions using fully supervised learning. Our findings underscore the impact of scaling up both the complexity of the model and the volume of unlabeled training data derived from generally healthy brains, which enhances the accuracy and predictive capabilities of the model in complex neuroimaging tasks with MRI. The implications of this research provide transformative insights and practical applications in healthcare and make substantial steps towards the creation of foundation models for Medical AI. Our pretrained models and training code can be found at https://github.com/lab-smile/GatorBrain.

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.

Automatic medical report generation (MRG), which possesses significant research value as it can aid radiologists in clinical diagnosis and report composition, has garnered increasing attention. Despite recent progress, generating accurate reports remains arduous due to the requirement for precise clinical comprehension and disease diagnosis inference. Furthermore, owing to the limited accessibility of medical data and the imbalanced distribution of diseases, the underrepresentation of rare diseases in training data makes large-scale medical visual language models (LVLMs) prone to hallucinations, such as omissions or fabrications, severely undermining diagnostic performance and further intensifying the challenges for MRG in practice. In this study, to effectively mitigate hallucinations in medical report generation, we propose a chain-of-medical-thought approach (CoMT), which intends to imitate the cognitive process of human doctors by decomposing diagnostic procedures. The radiological features with different importance are structured into fine-grained medical thought chains to enhance the inferential ability during diagnosis, thereby alleviating hallucination problems and enhancing the diagnostic accuracy of MRG. The code and dataset have been released at https://github.com/FRENKIE-CHIANG/CoMT.

Deep neural networks are often applied to medical images to automate the problem of medical diagnosis. However, a more clinically relevant question that practitioners usually face is how to predict the future trajectory of a disease. Current methods for prognosis or disease trajectory forecasting often require domain knowledge and are complicated to apply. In this paper, we formulate the prognosis prediction problem as a one-to-many prediction problem. Inspired by a clinical decision-making process with two agents -- a radiologist and a general practitioner -- we predict prognosis with two transformer-based components that share information with each other. The first transformer in this framework aims to analyze the imaging data, and the second one leverages its internal states as inputs, also fusing them with auxiliary clinical data. The temporal nature of the problem is modeled within the transformer states, allowing us to treat the forecasting problem as a multi-task classification, for which we propose a novel loss. We show the effectiveness of our approach in predicting the development of structural knee osteoarthritis changes and forecasting Alzheimer's disease clinical status directly from raw multi-modal data. The proposed method outperforms multiple state-of-the-art baselines with respect to performance and calibration, both of which are needed for real-world applications. An open-source implementation of our method is made publicly available at https://github.com/Oulu-IMEDS/CLIMATv2.

Automated text simplification aims to produce simple versions of complex texts. This task is especially useful in the medical domain, where the latest medical findings are typically communicated via complex and technical articles. This creates barriers for laypeople seeking access to up-to-date medical findings, consequently impeding progress on health literacy. Most existing work on medical text simplification has focused on monolingual settings, with the result that such evidence would be available only in just one language (most often, English). This work addresses this limitation via multilingual simplification, i.e., directly simplifying complex texts into simplified texts in multiple languages. We introduce MultiCochrane, the first sentence-aligned multilingual text simplification dataset for the medical domain in four languages: English, Spanish, French, and Farsi. We evaluate fine-tuned and zero-shot models across these languages, with extensive human assessments and analyses. Although models can now generate viable simplified texts, we identify outstanding challenges that this dataset might be used to address.