In this paper, an explainable deep learning-based classifier based on adaptive sinc filters for Parkinson's Disease diagnosis (PD) along with determining its severity, based on analyzing the gait cycle (SincPD) is presented. Considering the effects of PD on the gait cycle of patients, the proposed method utilizes raw data in the form of vertical Ground Reaction Force (vGRF) measured by wearable sensors placed in soles of subjects' shoes. The proposed method consists of Sinc layers that model adaptive bandpass filters to extract important frequency-bands in gait cycle of patients along with healthy subjects. Therefore, by considering these frequencies, the reasons behind the classification a person as a patient or healthy can be explained. In this method, after applying some preprocessing processes, a large model equipped with many filters is first trained. Next, to prune the extra units and reach a more explainable and parsimonious structure, the extracted filters are clusters based on their cut-off frequencies using a centroid-based clustering approach. Afterward, the medoids of the extracted clusters are considered as the final filters. Therefore, only 15 bandpass filters for each sensor are derived to classify patients and healthy subjects. Finally, the most effective filters along with the sensors are determined by comparing the energy of each filter encountering patients and healthy subjects.

Disease progression models are widely used to inform the diagnosis and treatment of many progressive diseases. However, a significant limitation of existing models is that they do not account for health disparities that can bias the observed data. To address this, we develop an interpretable Bayesian disease progression model that captures three key health disparities: certain patient populations may (1) start receiving care only when their disease is more severe, (2) experience faster disease progression even while receiving care, or (3) receive follow-up care less frequently conditional on disease severity. We show theoretically and empirically that failing to account for disparities produces biased estimates of severity (underestimating severity for disadvantaged groups, for example). On a dataset of heart failure patients, we show that our model can identify groups that face each type of health disparity, and that accounting for these disparities meaningfully shifts which patients are considered high-risk.

Coronavirus Disease 2019 (COVID-19), which emerged in 2019, has caused millions of deaths worldwide. Although effective vaccines have been developed to mitigate severe symptoms, certain populations, particularly the elderly and those with comorbidities, remain at high risk for severe outcomes and increased mortality. Consequently, early identification of the severity and clinical outcomes of the disease in these patients is vital to prevent adverse prognoses. Although traditional machine learning and deep learning models have been widely employed in this area, the potential of large language models (LLMs) remains largely unexplored. Our research focuses primarily on constructing specialized prompts and adopting multi-objective learning strategies. We started by selecting serological indicators that significantly correlate with clinical outcomes and disease severity to serve as input data for the model. Blood test samples often contain numerous missing values, and traditional models generally rely on imputation to handle these gaps in the data. In contrast, LLMs offer the advantage of robust semantic understanding. By setting prompts, we can explicitly inform the model when a feature's value is missing, without the need for imputation. For the multi-objective learning strategy, the model is designed to first predict disease severity and then predict clinical outcomes. Given that LLMs utilize both the input text and the generated tokens as input for generating the next token, the predicted severity is used as a basis for generating the clinical outcome. During the fine-tuning of the LLM, the two objectives influence and improve each other. Our experiments were implemented based on the ChatGLM model. The results demonstrate the effectiveness of LLMs in this task, suggesting promising potential for further development.

Accurate assessment of disease severity from endoscopy videos in ulcerative colitis (UC) is crucial for evaluating drug efficacy in clinical trials. Severity is often measured by the Mayo Endoscopic Subscore (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score. However, expert MES/UCEIS annotation is time-consuming and susceptible to inter-rater variability, factors addressable by automation. Automation attempts with frame-level labels face challenges in fully-supervised solutions due to the prevalence of video-level labels in clinical trials. CNN-based weakly-supervised models (WSL) with end-to-end (e2e) training lack generalization to new disease scores and ignore spatio-temporal information crucial for accurate scoring. To address these limitations, we propose "Arges", a deep learning framework that utilizes a transformer with positional encoding to incorporate spatio-temporal information from frame features to estimate disease severity scores in endoscopy video. Extracted features are derived from a foundation model (ArgesFM), pre-trained on a large diverse dataset from multiple clinical trials (61M frames, 3927 videos). We evaluate four UC disease severity scores, including MES and three UCEIS component scores. Test set evaluation indicates significant improvements, with F1 scores increasing by 4.1% for MES and 18.8%, 6.6%, 3.8% for the three UCEIS component scores compared to state-of-the-art methods. Prospective validation on previously unseen clinical trial data further demonstrates the model's successful generalization.

Age-related macular degeneration (AMD) is a major cause of blindness in older adults, severely affecting vision and quality of life. Despite advances in understanding AMD, the molecular factors driving the severity of subretinal scarring (fibrosis) remain elusive, hampering the development of effective therapies. This study introduces a machine learning-based framework to predict key genes that are strongly correlated with lesion severity and to identify potential therapeutic targets to prevent subretinal fibrosis in AMD. Using an original RNA sequencing (RNA-seq) dataset from the diseased retinas of JR5558 mice, we developed a novel and specific feature engineering technique, including pathway-based dimensionality reduction and gene-based feature expansion, to enhance prediction accuracy. Two iterative experiments were conducted by leveraging Ridge and ElasticNet regression models to assess biological relevance and gene impact. The results highlight the biological significance of several key genes and demonstrate the framework's effectiveness in identifying novel therapeutic targets. The key findings provide valuable insights for advancing drug discovery efforts and improving treatment strategies for AMD, with the potential to enhance patient outcomes by targeting the underlying genetic mechanisms of subretinal lesion development.

Reinforcement learning (RL) is a promising approach to generate treatment policies for sepsis patients in intensive care. While retrospective evaluation metrics show decreased mortality when these policies are followed, studies with clinicians suggest their recommendations are often spurious. We propose that these shortcomings may be due to lack of diversity in observed actions and outcomes in the training data, and we construct experiments to investigate the feasibility of predicting sepsis disease severity changes due to clinician actions. Preliminary results suggest incorporating action information does not significantly improve model performance, indicating that clinician actions may not be sufficiently variable to yield measurable effects on disease progression. We discuss the implications of these findings for optimizing sepsis treatment.

Many variables of interest in clinical medicine, like disease severity, are recorded using discrete ordinal categories such as normal/mild/moderate/severe. These labels are used to train and evaluate disease severity prediction models. However, ordinal categories represent a simplification of an underlying continuous severity spectrum. Using continuous scores instead of ordinal categories is more sensitive to detecting small changes in disease severity over time. Here, we present a generalized framework that accurately predicts continuously valued variables using only discrete ordinal labels during model development. We found that for three clinical prediction tasks, models that take the ordinal relationship of the training labels into account outperformed conventional multi-class classification models. Particularly the continuous scores generated by ordinal classification and regression models showed a significantly higher correlation with expert rankings of disease severity and lower mean squared errors compared to the multi-class classification models. Furthermore, the use of MC dropout significantly improved the ability of all evaluated deep learning approaches to predict continuously valued scores that truthfully reflect the underlying continuous target variable. We showed that accurate continuously valued predictions can be generated even if the model development only involves discrete ordinal labels. The novel framework has been validated on three different clinical prediction tasks and has proven to bridge the gap between discrete ordinal labels and the underlying continuously valued variables.

Multiple Sclerosis (MS) is a chronic disease developed in human brain and spinal cord, which can cause permanent damage or deterioration of the nerves. The severity of MS disease is monitored by the Expanded Disability Status Scale (EDSS), composed of several functional sub-scores. Early and accurate classification of MS disease severity is critical for slowing down or preventing disease progression via applying early therapeutic intervention strategies. Recent advances in deep learning and the wide use of Electronic Health Records (EHR) creates opportunities to apply data-driven and predictive modeling tools for this goal. Previous studies focusing on using single-modal machine learning and deep learning algorithms were limited in terms of prediction accuracy due to the data insufficiency or model simplicity. In this paper, we proposed an idea of using patients' multimodal longitudinal and longitudinal EHR data to predict multiple sclerosis disease severity at the hospital visit. This work has two important contributions. First, we describe a pilot effort to leverage structured EHR data, neuroimaging data and clinical notes to build a multi-modal deep learning framework to predict patient's MS disease severity. The proposed pipeline demonstrates up to 25% increase in terms of the area under the Area Under the Receiver Operating Characteristic curve (AUROC) compared to models using single-modal data. Second, the study also provides insights regarding the amount useful signal embedded in each data modality with respect to MS disease prediction, which may improve data collection processes.

Purpose: Lung disease assessment in precapillary pulmonary hypertension (PH) is essential for appropriate patient management. This study aims to develop an artificial intelligence (AI) deep learning model for lung texture classification in CT Pulmonary Angiography (CTPA), and evaluate its correlation with clinical assessment methods. Materials and Methods: In this retrospective study with external validation, 122 patients with pre-capillary PH were used to train (n=83), validate (n=17) and test (n=10 internal test, n=12 external test) a patch based DenseNet-121 classification model. "Normal", "Ground glass", "Ground glass with reticulation", "Honeycombing", and "Emphysema" were classified as per the Fleishner Society glossary of terms. Ground truth classes were segmented by two radiologists with patches extracted from the labelled regions. Proportion of lung volume for each texture was calculated by classifying patches throughout the entire lung volume to generate a coarse texture classification mapping throughout the lung parenchyma. AI output was assessed against diffusing capacity of carbon monoxide (DLCO) and specialist radiologist reported disease severity. Results: Micro-average AUCs for the validation, internal test, and external test were 0.92, 0.95, and 0.94, respectively. The model had consistent performance across parenchymal textures, demonstrated strong correlation with diffusing capacity of carbon monoxide (DLCO), and showed good correspondence with disease severity reported by specialist radiologists. Conclusion: The classification model demonstrates excellent performance on external validation. The clinical utility of its output has been demonstrated. This objective, repeatable measure of disease severity can aid in patient management in adjunct to radiological reporting.

Electronic health records (EHR) offer unprecedented opportunities for in-depth clinical phenotyping and prediction of clinical outcomes. Combining multiple data sources is crucial to generate a complete picture of disease prevalence, incidence and trajectories. The standard approach to combining clinical data involves collating clinical terms across different terminology systems using curated maps, which are often inaccurate and/or incomplete. Here, we propose sEHR-CE, a novel framework based on transformers to enable integrated phenotyping and analyses of heterogeneous clinical datasets without relying on these mappings. We unify clinical terminologies using textual descriptors of concepts, and represent individuals' EHR as sections of text. We then fine-tune pre-trained language models to predict disease phenotypes more accurately than non-text and single terminology approaches. We validate our approach using primary and secondary care data from the UK Biobank, a large-scale research study. Finally, we illustrate in a type 2 diabetes use case how sEHR-CE identifies individuals without diagnosis that share clinical characteristics with patients.